ID BRCA2_HUMAN Reviewed; 3418 AA. AC P51587; O00183; O15008; Q13879; Q5TBJ7; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 23-FEB-2022, sequence version 4. DT 25-MAY-2022, entry version 232. DE RecName: Full=Breast cancer type 2 susceptibility protein {ECO:0000305}; DE AltName: Full=Fanconi anemia group D1 protein; GN Name=BRCA2 {ECO:0000312|HGNC:HGNC:1101}; Synonyms=FACD, FANCD1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-2466. RX PubMed=8524414; DOI=10.1038/378789a0; RA Wooster R., Bignell G., Lancaster J., Swift S., Seal S., Mangion J., RA Collins N., Gregory S., Gumbs C., Micklem G., Barfoot R., Hamoudi R., RA Patel S., Rice C., Biggs P., Hashim Y., Smith A., Connor F., Arason A., RA Gudmundsson J., Ficenec D., Kelsell D., Ford D., Tonin P., Bishop D.T., RA Spurr N.K., Ponder B.A.J., Eeles R., Peto J., Devilee P., Cornelisse C., RA Lynch H., Narod S., Lenoir G., Egilsson V., Barkadottir R.B., Easton D.F., RA Bentley D.R., Futreal P.A., Ashworth A., Stratton M.R.; RT "Identification of the breast cancer susceptibility gene BRCA2."; RL Nature 378:789-792(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], VARIANTS HIS-372 AND PHE-599, AND VARIANT RP ALA-2466. RX PubMed=8589730; DOI=10.1038/ng0396-333; RA Tavtigian S.V., Simard J., Rommens J., Couch F., Shattuck-Eidens D., RA Neuhausen S., Merajver S., Thorlacius S., Offit K., Stoppa-Lyonnet D., RA Belanger C., Bell R., Berry S., Bogden R., Chen Q., Davis T., Dumont M., RA Frye C., Hattier T., Jammulapati S., Janecki T., Jiang P., Kehrer R., RA Leblanc J.-F., Mitchell J.T., McArthur-Morrison J., Nguyen K., Peng Y., RA Samson C., Schroeder M., Snyder S.C., Steele L., Stringfellow M., RA Stroup C., Swedlund B., Swensen J., Teng D., Thomas A., Tran T., Tran T., RA Tranchant M., Weaver-Feldhaus J., Wong A.K.C., Shizuya H., Eyfjord J.E., RA Cannon-Albright L., Labrie F., Skolnick M.H., Weber B., Kamb A., RA Goldar D.E.; RT "The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds."; RL Nat. Genet. 12:333-337(1996). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-289; GLN-322; HIS-372; RP VAL-784; SER-929; PHE-976; ILE-987; ASP-991; ASN-1561; LYS-1880; MET-1915; RP PHE-2138; ARG-2162; ARG-2440; ALA-2466; THR-2490; PRO-2835; ALA-2856; RP PHE-2944; THR-2951; ILE-3244 AND VAL-3412. RG NIEHS SNPs program; RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ALA-2466. RX PubMed=15057823; DOI=10.1038/nature02379; RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L., RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., RA Frankish A.G., Frankland J., French L., Garner P., Garnett J., RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., RA Rogers J., Ross M.T.; RT "The DNA sequence and analysis of human chromosome 13."; RL Nature 428:522-528(2004). RN [5] RP INVOLVEMENT IN PNCA2. RX PubMed=9140390; DOI=10.1038/ng0597-17; RA Ozcelik H., Schmocker B., Di Nicola N., Shi X.H., Langer B., Moore M., RA Taylor B.R., Narod S.A., Darlington G., Andrulis I.L., Gallinger S., RA Redston M.; RT "Germline BRCA2 6174delT mutations in Ashkenazi Jewish pancreatic cancer RT patients."; RL Nat. Genet. 16:17-18(1997). RN [6] RP INTERACTION WITH SEM1. RX PubMed=10373512; DOI=10.1128/mcb.19.7.4633; RA Marston N.J., Richards W.J., Hughes D., Bertwistle D., Marshall C.J., RA Ashworth A.; RT "Interaction between the product of the breast cancer susceptibility gene RT BRCA2 and DSS1, a protein functionally conserved from yeast to mammals."; RL Mol. Cell. Biol. 19:4633-4642(1999). RN [7] RP FUNCTION, AND INTERACTION WITH FANCD2. RX PubMed=15115758; DOI=10.1093/hmg/ddh135; RA Hussain S., Wilson J.B., Medhurst A.L., Hejna J., Witt E., Ananth S., RA Davies A., Masson J.-Y., Moses R., West S.C., de Winter J.P., Ashworth A., RA Jones N.J., Mathew C.G.; RT "Direct interaction of FANCD2 with BRCA2 in DNA damage response pathways."; RL Hum. Mol. Genet. 13:1241-1248(2004). RN [8] RP FUNCTION, PHOSPHORYLATION, AND INTERACTION WITH FANCD2. RX PubMed=15199141; DOI=10.1128/mcb.24.13.5850-5862.2004; RA Wang X.Z., Andreassen P.R., D'Andrea A.D.; RT "Functional interaction of monoubiquitinated FANCD2 and BRCA2/FANCD1 in RT chromatin."; RL Mol. Cell. Biol. 24:5850-5862(2004). RN [9] RP UBIQUITINATION, DEUBIQUITINATION, AND INTERACTION WITH USP11. RX PubMed=15314155; DOI=10.1128/mcb.24.17.7444-7455.2004; RA Schoenfeld A.R., Apgar S., Dolios G., Wang R., Aaronson S.A.; RT "BRCA2 is ubiquitinated in vivo and interacts with USP11, a RT deubiquitinating enzyme that exhibits prosurvival function in the cellular RT response to DNA damage."; RL Mol. Cell. Biol. 24:7444-7455(2004). RN [10] RP INVOLVEMENT IN GLM3. RX PubMed=15689453; DOI=10.1136/jmg.2004.022673; RG The famillial Wilms tumor collaboration; RA Reid S., Renwick A., Seal S., Baskcomb L., Barfoot R., Jayatilake H., RA Pritchard-Jones K., Stratton M.R., Ridolfi-Luethy A., Rahman N.; RT "Biallelic BRCA2 mutations are associated with multiple malignancies in RT childhood including familial Wilms tumour."; RL J. Med. Genet. 42:147-151(2005). RN [11] RP FUNCTION. RX PubMed=15671039; DOI=10.1074/jbc.m414669200; RA Ohashi A., Zdzienicka M.Z., Chen J., Couch F.J.; RT "FANCD2 functions independently of BRCA2 and RAD51 associated homologous RT recombination in response to DNA damage."; RL J. Biol. Chem. 280:14877-14883(2005). RN [12] RP PHOSPHORYLATION AT SER-3291 BY CDK2, INTERACTION WITH RAD51, AND RP MUTAGENESIS OF SER-3291. RX PubMed=15800615; DOI=10.1038/nature03404; RA Esashi F., Christ N., Gannon J., Liu Y., Hunt T., Jasin M., West S.C.; RT "CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for RT recombinational repair."; RL Nature 434:598-604(2005). RN [13] RP INTERACTION WITH WDR16. RX PubMed=15967112; DOI=10.1593/neo.04544; RA Silva F.P., Hamamoto R., Nakamura Y., Furukawa Y.; RT "WDRPUH, a novel WD-repeat-containing protein, is highly expressed in human RT hepatocellular carcinoma and involved in cell proliferation."; RL Neoplasia 7:348-355(2005). RN [14] RP INTERACTION WITH PALB2, AND CHARACTERIZATION OF VARIANTS BC ARG-25; CYS-31 RP AND ARG-31. RX PubMed=16793542; DOI=10.1016/j.molcel.2006.05.022; RA Xia B., Sheng Q., Nakanishi K., Ohashi A., Wu J., Christ N., Liu X., RA Jasin M., Couch F.J., Livingston D.M.; RT "Control of BRCA2 cellular and clinical functions by a nuclear partner, RT PALB2."; RL Mol. Cell 22:719-729(2006). RN [15] RP INTERACTION WITH SEM1. RX PubMed=16205630; DOI=10.1038/sj.onc.1209153; RA Li J., Zou C., Bai Y., Wazer D.E., Band V., Gao Q.; RT "DSS1 is required for the stability of BRCA2."; RL Oncogene 25:1186-1194(2006). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-755, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [17] RP INTERACTION WITH FANCD2; FANCG AND XRCC3. RX PubMed=18212739; DOI=10.1038/sj.onc.1211034; RA Wilson J.B., Yamamoto K., Marriott A.S., Hussain S., Sung P., Hoatlin M.E., RA Mathew C.G., Takata M., Thompson L.H., Kupfer G.M., Jones N.J.; RT "FANCG promotes formation of a newly identified protein complex containing RT BRCA2, FANCD2 and XRCC3."; RL Oncogene 27:3641-3652(2008). RN [18] RP FUNCTION IN RAD51-DEPENDENT DNA REPAIR, PHOSPHORYLATION AT THR-3387 BY RP CHEK1 AND CHEK2, MUTAGENESIS OF THR-3387, AND INTERACTION WITH RAD51. RX PubMed=18317453; DOI=10.1038/onc.2008.17; RA Bahassi E.M., Ovesen J.L., Riesenberg A.L., Bernstein W.Z., Hasty P.E., RA Stambrook P.J.; RT "The checkpoint kinases Chk1 and Chk2 regulate the functional associations RT between hBRCA2 and Rad51 in response to DNA damage."; RL Oncogene 27:3977-3985(2008). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN A BRCA COMPLEX RP WITH BRCA1 AND PALB2. RX PubMed=19369211; DOI=10.1073/pnas.0811159106; RA Sy S.M., Huen M.S., Chen J.; RT "PALB2 is an integral component of the BRCA complex required for homologous RT recombination repair."; RL Proc. Natl. Acad. Sci. U.S.A. 106:7155-7160(2009). RN [20] RP FUNCTION, AND INTERACTION WITH RAD51. RX PubMed=20729859; DOI=10.1038/nsmb.1904; RA Liu J., Doty T., Gibson B., Heyer W.D.; RT "Human BRCA2 protein promotes RAD51 filament formation on RPA-covered RT single-stranded DNA."; RL Nat. Struct. Mol. Biol. 17:1260-1262(2010). RN [21] RP FUNCTION, AND SUBUNIT. RX PubMed=20729858; DOI=10.1038/nsmb.1905; RA Thorslund T., McIlwraith M.J., Compton S.A., Lekomtsev S., Petronczki M., RA Griffith J.D., West S.C.; RT "The breast cancer tumor suppressor BRCA2 promotes the specific targeting RT of RAD51 to single-stranded DNA."; RL Nat. Struct. Mol. Biol. 17:1263-1265(2010). RN [22] RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, AND INTERACTION WITH RAD51 RP AND DMC1. RX PubMed=20729832; DOI=10.1038/nature09399; RA Jensen R.B., Carreira A., Kowalczykowski S.C.; RT "Purified human BRCA2 stimulates RAD51-mediated recombination."; RL Nature 467:678-683(2010). RN [23] RP FUNCTION, AND INTERACTION WITH ROCK2 AND NPM1. RX PubMed=21084279; DOI=10.1158/0008-5472.can-10-0030; RA Wang H.F., Takenaka K., Nakanishi A., Miki Y.; RT "BRCA2 and nucleophosmin coregulate centrosome amplification and form a RT complex with the Rho effector kinase ROCK2."; RL Cancer Res. 71:68-77(2011). RN [24] RP SUBCELLULAR LOCATION. RX PubMed=21276791; DOI=10.1016/j.yexcr.2011.01.021; RA Cappelli E., Townsend S., Griffin C., Thacker J.; RT "Homologous recombination proteins are associated with centrosomes and are RT required for mitotic stability."; RL Exp. Cell Res. 317:1203-1213(2011). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70; SER-445; SER-492; RP SER-1970; THR-2035; SER-2095 AND SER-3319, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [26] RP INTERACTION WITH SEM1, CHARACTERIZATION OF VARIANT BC HIS-2723, MUTAGENESIS RP OF TRP-2725, NUCLEAR EXPORT SIGNAL, AND SUBCELLULAR LOCATION. RX PubMed=24013206; DOI=10.1038/nsmb.2666; RA Jeyasekharan A.D., Liu Y., Hattori H., Pisupati V., Jonsdottir A.B., RA Rajendra E., Lee M., Sundaramoorthy E., Schlachter S., Kaminski C.F., RA Ofir-Rosenfeld Y., Sato K., Savill J., Ayoub N., Venkitaraman A.R.; RT "A cancer-associated BRCA2 mutation reveals masked nuclear export signals RT controlling localization."; RL Nat. Struct. Mol. Biol. 20:1191-1198(2013). RN [27] RP INTERACTION WITH PALB2, AND IDENTIFICATION IN A PALB2-CONTAINING HR RP COMPLEX. RX PubMed=24141787; DOI=10.1038/onc.2013.421; RA Park J.Y., Singh T.R., Nassar N., Zhang F., Freund M., Hanenberg H., RA Meetei A.R., Andreassen P.R.; RT "Breast cancer-associated missense mutants of the PALB2 WD40 domain, which RT directly binds RAD51C, RAD51 and BRCA2, disrupt DNA repair."; RL Oncogene 33:4803-4812(2014). RN [28] RP FUNCTION, AND INTERACTION WITH POLH. RX PubMed=24485656; DOI=10.1016/j.celrep.2014.01.009; RA Buisson R., Niraj J., Pauty J., Maity R., Zhao W., Coulombe Y., Sung P., RA Masson J.Y.; RT "Breast cancer proteins PALB2 and BRCA2 stimulate polymerase eta in RT recombination-associated DNA synthesis at blocked replication forks."; RL Cell Rep. 6:553-564(2014). RN [29] RP FUNCTION IN R-LOOP PROCESSING, AND INTERACTION WITH SEM1 AND PCID2. RX PubMed=24896180; DOI=10.1038/nature13374; RA Bhatia V., Barroso S.I., Garcia-Rubio M.L., Tumini E., Herrera-Moyano E., RA Aguilera A.; RT "BRCA2 prevents R-loop accumulation and associates with TREX-2 mRNA export RT factor PCID2."; RL Nature 511:362-365(2014). RN [30] RP IDENTIFICATION IN THE HR COMPLEX, INTERACTION WITH ERCC5 AND PALB2, AND RP SUBCELLULAR LOCATION. RX PubMed=26833090; DOI=10.1016/j.molcel.2015.12.026; RA Trego K.S., Groesser T., Davalos A.R., Parplys A.C., Zhao W., Nelson M.R., RA Hlaing A., Shih B., Rydberg B., Pluth J.M., Tsai M.S., Hoeijmakers J.H.J., RA Sung P., Wiese C., Campisi J., Cooper P.K.; RT "Non-catalytic Roles for XPG with BRCA1 and BRCA2 in Homologous RT Recombination and Genome Stability."; RL Mol. Cell 61:535-546(2016). RN [31] RP INTERACTION WITH PALB2. RX PubMed=28319063; DOI=10.1038/onc.2017.46; RA Foo T.K., Tischkowitz M., Simhadri S., Boshari T., Zayed N., Burke K.A., RA Berman S.H., Blecua P., Riaz N., Huo Y., Ding Y.C., Neuhausen S.L., RA Weigelt B., Reis-Filho J.S., Foulkes W.D., Xia B.; RT "Compromised BRCA1-PALB2 interaction is associated with breast cancer RT risk."; RL Oncogene 36:4161-4170(2017). RN [32] RP INTERACTION WITH HSF2BP. RX PubMed=31242413; DOI=10.1016/j.celrep.2019.05.096; RA Brandsma I., Sato K., van Rossum-Fikkert S.E., van Vliet N., Sleddens E., RA Reuter M., Odijk H., van den Tempel N., Dekkers D.H.W., Bezstarosti K., RA Demmers J.A.A., Maas A., Lebbink J., Wyman C., Essers J., van Gent D.C., RA Baarends W.M., Knipscheer P., Kanaar R., Zelensky A.N.; RT "HSF2BP Interacts with a Conserved Domain of BRCA2 and Is Required for RT Mouse Spermatogenesis."; RL Cell Rep. 27:3790.e7-3798.e7(2019). RN [33] RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1519-1551 IN COMPLEX WITH RAD51. RX PubMed=12442171; DOI=10.1038/nature01230; RA Pellegrini L., Yu D.S., Lo T., Anand S., Lee M., Blundell T.L., RA Venkitaraman A.R.; RT "Insights into DNA recombination from the structure of a RAD51-BRCA2 RT complex."; RL Nature 420:287-293(2002). RN [34] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 21-39 IN COMPLEX WITH PALB2. RX PubMed=19609323; DOI=10.1038/embor.2009.126; RA Oliver A.W., Swift S., Lord C.J., Ashworth A., Pearl L.H.; RT "Structural basis for recruitment of BRCA2 by PALB2."; RL EMBO Rep. 10:990-996(2009). RN [35] RP VARIANT OVARIAN CANCER HIS-2787, AND VARIANTS HIS-372; MET-1915 AND RP ALA-2466. RX PubMed=8665505; RA Takahashi H., Chiu H.-C., Bandera C.A., Behbakht K., Liu P.C., Couch F.J., RA Weber B.L., LiVolsi V.A., Furusato M., Rebane B.A., Cardonick A., RA Benjamin I., Morgan M.A., King S.A., Mikuta J.J., Rubin S.C., Boyd J.; RT "Mutations of the BRCA2 gene in ovarian carcinomas."; RL Cancer Res. 56:2738-2741(1996). RN [36] RP VARIANTS HIS-372; ASP-991; SER-1147; MET-1915 AND CYS-2034. RX PubMed=8673091; DOI=10.1038/ng0596-123; RA Couch F.J., Farid L.M., Deshano M.L., Tavtigian S.V., Calzone K., RA Campeau L., Peng Y., Bogden B., Chen Q., Neuhausen S., Shattuck-Eidens D., RA Godwin A.K., Daly M., Radford D.M., Sedlacek S., Rommens J., Simard J., RA Garber J., Merajver S., Weber B.L.; RT "BRCA2 germline mutations in male breast cancer cases and breast cancer RT families."; RL Nat. Genet. 13:123-125(1996). RN [37] RP VARIANT GLU-3095. RX PubMed=8640235; DOI=10.1038/ng0696-238; RA Lancaster J.M., Wooster R., Mangion J., Phelan C.M., Cochran C., Gumbs C., RA Seal S., Barfoot R., Collins N., Bignell G., Patel S., Hamoudi R., RA Larsson C., Wiseman R.W., Berchuck A., Iglehart J.D., Marks J.R., RA Ashworth A., Stratton M.R., Futreal P.A.; RT "BRCA2 mutations in primary breast and ovarian cancers."; RL Nat. Genet. 13:238-240(1996). RN [38] RP VARIANTS. RX PubMed=8640236; DOI=10.1038/ng0696-241; RA Teng D.H.-F., Bogden R., Mitchell J., Baumgard M., Bell R., Berry S., RA Davis T., Ha P.C., Kehrer R., Jammulapati S., Chen Q., Offit K., RA Skolnick M.H., Tavtigian S.V., Jhanwar S., Swedlund B., Wong A.K.C., RA Kamb A.; RT "Low incidence of BRCA2 mutations in breast carcinoma and other cancers."; RL Nat. Genet. 13:241-244(1996). RN [39] RP VARIANT BC ASN-2415. RX PubMed=8640237; DOI=10.1038/ng0696-245; RA Miki Y., Katagiri T., Kasumi F., Yoshimoto T., Nakamura Y.; RT "Mutation analysis in the BRCA2 gene in primary breast cancers."; RL Nat. Genet. 13:245-247(1996). RN [40] RP VARIANT BC ASP-2089, AND VARIANT VAL-3412. RX PubMed=9150152; RA Vehmanen P., Friedman L.S., Eerola H., Sarantaus L., Pyrhoenen S., RA Ponder B.A.J., Muhonen T., Nevanlinna H.; RT "A low proportion of BRCA2 mutations in Finnish breast cancer families."; RL Am. J. Hum. Genet. 60:1050-1058(1997). RN [41] RP VARIANT BC/PANCREAS CANCER TRP-554. RX PubMed=9654203; DOI=10.1007/s004390050738; RA Ganguly T., Dhulipala R., Godmilow L., Ganguly A.; RT "High throughput fluorescence-based conformation-sensitive gel RT electrophoresis (F-CSGE) identifies six unique BRCA2 mutations and an RT overall low incidence of BRCA2 mutations in high-risk BRCA1-negative breast RT cancer families."; RL Hum. Genet. 102:549-556(1998). RN [42] RP VARIANTS BC LEU-32; ARG-53; LEU-81; ARG-201; ALA-211; SER-222 AND THR-3118. RX PubMed=9609997; DOI=10.1007/s100380050035; RA Katagiri T., Kasumi F., Yoshimoto M., Nomizu T., Asaishi K., Abe R., RA Tsuchiya A., Sugano M., Takai S., Yoneda M., Fukutomi T., Nanba K., RA Makita M., Okazaki H., Hirata K., Okazaki M., Furutsuma Y., Morishita Y., RA Iino Y., Karino T., Ayabe H., Hara S., Kajiwara T., Houga S., Shimizu T., RA Toda M., Yamazaki Y., Uchida T., Kunitomo K., Sonoo H., Kurebayashi J., RA Shimotsuma K., Nakamura Y., Miki Y.; RT "High proportion of missense mutations of the BRCA1 and BRCA2 genes in RT Japanese breast cancer families."; RL J. Hum. Genet. 43:42-48(1998). RN [43] RP VARIANTS OVARIAN CANCER PRO-75; HIS-2502 AND HIS-3098. RX PubMed=10486320; DOI=10.1086/302583; RA Gayther S.A., Russell P., Harrington P., Antoniou A.C., Easton D.F., RA Ponder B.A.J.; RT "The contribution of germline BRCA1 and BRCA2 mutations to familial ovarian RT cancer: no evidence for other ovarian cancer-susceptibility genes."; RL Am. J. Hum. Genet. 65:1021-1029(1999). RN [44] RP VARIANTS HIS-289; HIS-372; ASP-991 AND VAL-3412. RX PubMed=10323242; DOI=10.1007/s004390050936; RA Li S.S.-L., Tseng H.-M., Yang T.-P., Liu C.-H., Teng S.-J., Huang H.-W., RA Chen L.-M., Kao H.-W., Chen J.H., Tseng J.-N., Chen A., Hou M.-F., RA Huang T.-J., Chang H.-T., Mok K.-T., Tsai J.-H.; RT "Molecular characterization of germline mutations in the BRCA1 and BRCA2 RT genes from breast cancer families in Taiwan."; RL Hum. Genet. 104:201-204(1999). RN [45] RP VARIANTS BC, AND VARIANTS. RX PubMed=9971877; DOI=10.1093/hmg/8.3.413; RA Wagner T.M.U., Hirtenlehner K., Shen P., Moeslinger R., Muhr D., RA Fleischmann E., Concin H., Doeller W., Haid A., Lang A.H., Mayer P., RA Petru E., Ropp E., Langbauer G., Kubista E., Scheiner O., Underhill P., RA Mountain J., Stierer M., Zielinski C., Oefner P.; RT "Global sequence diversity of BRCA2: analysis of 71 breast cancer families RT and 95 control individuals of worldwide populations."; RL Hum. Mol. Genet. 8:413-423(1999). RN [46] RP VARIANT BC ARG-326, AND VARIANT ILE-2728. RX PubMed=10399947; RX DOI=10.1002/(sici)1097-0215(19990730)82:3<325::aid-ijc3>3.0.co;2-g; RA Sinilnikova O.M., Egan K.M., Quinn J.L., Boutrand L., Lenoir G.M., RA Stoppa-Lyonnet D., Desjardins L., Levy C., Goldgar D., Gragoudas E.S.; RT "Germline brca2 sequence variants in patients with ocular melanoma."; RL Int. J. Cancer 82:325-328(1999). RN [47] RP VARIANT HIS-372. RX PubMed=11062481; DOI=10.1038/81691; RA Healey C.S., Dunning A.M., Teare M.D., Chase D., Parker L., Burn J., RA Chang-Claude J., Mannermaa A., Kataja V., Huntsman D.G., Pharoah P.D.P., RA Luben R.N., Easton D.F., Ponder B.A.J.; RT "A common variant in BRCA2 is associated with both breast cancer risk and RT prenatal viability."; RL Nat. Genet. 26:362-364(2000). RN [48] RP VARIANTS BC MET-729; ILE-2515 AND ILE-2728, AND VARIANTS HIS-289; HIS-372; RP ASP-991; MET-1915 AND VAL-3412. RX PubMed=10978364; DOI=10.1136/jmg.37.9.e17; RA Plaschke J., Commer T., Jacobi C., Schackert H.K., Chang-Claude J.; RT "BRCA2 germline mutations among early onset breast cancer patients RT unselected for family history of the disease."; RL J. Med. Genet. 37:E17-E17(2000). RN [49] RP VARIANTS BC ASN-1179; ILE-3124 AND GLU-3196, AND VARIANT TYR-1420. RX PubMed=11139248; DOI=10.1002/1098-1004(2001)17:1<73::aid-humu12>3.0.co;2-o; RA Kwiatkowska E., Teresiak M., Lamperska K.M., Karczewska A., Breborowicz D., RA Stawicka M., Godlewski D., Krzyzosiak W.J., Mackiewicz A.; RT "BRCA2 germline mutations in male breast cancer patients in the Polish RT population."; RL Hum. Mutat. 17:73-73(2001). RN [50] RP VARIANTS BC THR-505; TYR-1730; HIS-2135 AND CYS-2222, AND VARIANT LYS-1880. RX PubMed=11241844; DOI=10.1002/humu.7; RA Edwards S.M., Kote-Jarai Z., Hamoudi R., Eeles R.A.; RT "An improved high throughput heteroduplex mutation detection system for RT screening BRCA2 mutations-fluorescent mutation detection (F-MD)."; RL Hum. Mutat. 17:220-232(2001). RN [51] RP VARIANTS HIS-289 AND VAL-784, AND VARIANT BC GLU-3076. RX PubMed=11149425; RX DOI=10.1002/1097-0215(20010101)91:1<83::aid-ijc1013>3.0.co;2-5; RA Ikeda N., Miyoshi Y., Yoneda K., Shiba E., Sekihara Y., Kinoshita M., RA Noguchi S.; RT "Frequency of BRCA1 and BRCA2 germline mutations in Japanese breast cancer RT families."; RL Int. J. Cancer 91:83-88(2001). RN [52] RP VARIANT BC ARG-2722. RX PubMed=12145750; DOI=10.1086/342192; RA Fackenthal J.D., Cartegni L., Krainer A.R., Olopade O.I.; RT "BRCA2 T2722R is a deleterious allele that causes exon skipping."; RL Am. J. Hum. Genet. 71:625-631(2002). RN [53] RP ERRATUM OF PUBMED:12145750. RA Fackenthal J.D., Cartegni L., Krainer A.R., Olopade O.I.; RL Am. J. Hum. Genet. 73:1477-1477(2002). RN [54] RP VARIANTS BC CYS-2072; CYS-2094 AND ASN-2128. RX PubMed=12373604; DOI=10.1038/sj.bjc.6600562; RA Jakubowska A., Nej K., Huzarski T., Scott R.J., Lubinski J.; RT "BRCA2 gene mutations in families with aggregations of breast and stomach RT cancers."; RL Br. J. Cancer 87:888-891(2002). RN [55] RP VARIANT THR-192. RX PubMed=12097290; RA Murphy K.M., Brune K.A., Griffin C., Sollenberger J.E., Petersen G.M., RA Bansal R., Hruban R.H., Kern S.E.; RT "Evaluation of candidate genes MAP2K4, MADH4, ACVR1B, and BRCA2 in familial RT pancreatic cancer: deleterious BRCA2 mutations in 17%."; RL Cancer Res. 62:3789-3793(2002). RN [56] RP VARIANTS HIS-118; SER-315; ILE-1988; CYS-2842 AND SER-3300. RX PubMed=11948123; RA Hu N., Li G., Li W.-J., Wang C., Goldstein A.M., Tang Z.-Z., Roth M.J., RA Dawsey S.M., Huang J., Wang Q.-H., Ding T., Giffen C., Taylor P.R., RA Emmert-Buck M.R.; RT "Infrequent mutation in the BRCA2 gene in esophageal squamous cell RT carcinoma."; RL Clin. Cancer Res. 8:1121-1126(2002). RN [57] RP VARIANTS ALA-598; TYR-1420; CYS-2034; ILE-2728 AND THR-2951. RX PubMed=12215251; DOI=10.1089/10906570260199375; RA Deffenbaugh A.M., Frank T.S., Hoffman M., Cannon-Albright L., RA Neuhausen S.L.; RT "Characterization of common BRCA1 and BRCA2 variants."; RL Genet. Test. 6:119-121(2002). RN [58] RP VARIANTS ASP-1593 AND SER-2706. RX PubMed=12442273; DOI=10.1002/humu.9082; RA Saxena S., Szabo C.I., Chopin S., Barjhoux L., Sinilnikova O., Lenoir G., RA Goldgar D.E., Bhatanager D.; RT "BRCA1 and BRCA2 in Indian breast cancer patients."; RL Hum. Mutat. 20:473-474(2002). RN [59] RP VARIANT BC ASN-2729, AND VARIANT VAL-3412. RX PubMed=12442274; DOI=10.1002/humu.9083; RA Zhi X., Szabo C., Chopin S., Suter N., Wang Q.-S., Ostrander E.A., RA Sinilnikova O.M., Lenoir G.M., Goldgar D., Shi Y.-R.; RT "BRCA1 and BRCA2 sequence variants in Chinese breast cancer families."; RL Hum. Mutat. 20:474-474(2002). RN [60] RP VARIANTS BC CYS-42; ARG-613; LEU-2118; LEU-2293 AND ARG-2793, AND VARIANT RP ILE-3374. RX PubMed=12442275; DOI=10.1002/humu.9084; RA Ruiz-Flores P., Sinilnikova O.M., Badzioch M., Calderon-Garciduenas A.L., RA Chopin S., Fabrice O., Gonzalez-Guerrero J.F., Szabo C., Lenoir G., RA Goldgar D.E., Barrera-Saldana H.A.; RT "BRCA1 and BRCA2 mutation analysis of early-onset and familial breast RT cancer cases in Mexico."; RL Hum. Mutat. 20:474-475(2002). RN [61] RP VARIANTS BC TYR-1580 AND MET-1915. RX PubMed=11948477; DOI=10.1002/ijc.10289; RA Kwiatkowska E., Teresiak M., Breborowicz D., Mackiewicz A.; RT "Somatic mutations in the BRCA2 gene and high frequency of allelic loss of RT BRCA2 in sporadic male breast cancer."; RL Int. J. Cancer 98:943-945(2002). RN [62] RP INVOLVEMENT IN FANCD1. RX PubMed=12065746; DOI=10.1126/science.1073834; RA Howlett N.G., Taniguchi T., Olson S., Cox B., Waisfisz Q., RA de Die-Smulders C., Persky N., Grompe M., Joenje H., Pals G., Ikeda H., RA Fox E.A., D'Andrea A.D.; RT "Biallelic inactivation of BRCA2 in Fanconi anemia."; RL Science 297:606-609(2002). RN [63] RP VARIANTS HIS-289; HIS-372; GLY-462; ASP-991; SER-1279; TYR-1420; ASP-1771 RP AND ALA-2466. RX PubMed=12552570; DOI=10.1002/humu.9110; RA Hadjisavvas A., Charalambous E., Adamou A., Christodoulou C.G., RA Kyriacou K.; RT "BRCA2 germline mutations in Cypriot patients with familial breast/ovarian RT cancer."; RL Hum. Mutat. 21:171-171(2003). RN [64] RP VARIANTS BC ILE-431; LYS-1036; ARG-1106 AND VAL-1524. RX PubMed=12938098; DOI=10.1002/humu.9174; RA Meyer P., Voigtlaender T., Bartram C.R., Klaes R.; RT "Twenty-three novel BRCA1 and BRCA2 sequence alterations in breast and/or RT ovarian cancer families in Southern Germany."; RL Hum. Mutat. 22:259-259(2003). RN [65] RP VARIANTS PRO-582; PHE-1522 AND VAL-2044. RX PubMed=12624724; DOI=10.1007/s100380300020; RA Sakayori M., Kawahara M., Shiraishi K., Nomizu T., Shimada A., Kudo T., RA Abe R., Ohuchi N., Takenoshita S., Kanamaru R., Ishioka C.; RT "Evaluation of the diagnostic accuracy of the stop codon (SC) assay for RT identifying protein-truncating mutations in the BRCA1and BRCA2genes in RT familial breast cancer."; RL J. Hum. Genet. 48:130-137(2003). RN [66] RP VARIANT CYS-2034, AND VARIANT BC GLU-3076. RX PubMed=12569143; DOI=10.1093/jnci/95.3.214; RA Hahn S.A., Greenhalf B., Ellis I., Sina-Frey M., Rieder H., Korte B., RA Gerdes B., Kress R., Ziegler A., Raeburn J.A., Campra D., Gruetzmann R., RA Rehder H., Rothmund M., Schmiegel W., Neoptolemos J.P., Bartsch D.K.; RT "BRCA2 germline mutations in familial pancreatic carcinoma."; RL J. Natl. Cancer Inst. 95:214-221(2003). RN [67] RP VARIANT FANCD1 PRO-2510. RX PubMed=14670928; DOI=10.1182/blood-2003-06-1970; RA Hirsch B., Shimamura A., Moreau L., Baldinger S., Hag-alshiekh M., RA Bostrom B., Sencer S., D'Andrea A.D.; RT "Association of biallelic BRCA2/FANCD1 mutations with spontaneous RT chromosomal instability and solid tumors of childhood."; RL Blood 103:2554-2559(2004). RN [68] RP VARIANTS BC SER-60; ARG-405; HIS-448; GLY-462; GLY-2275; ARG-2353; RP LYS-2488; HIS-2723; ASN-2950; ILE-3013 AND HIS-3098, AND VARIANTS ASP-991; RP ALA-2856 AND VAL-3412. RX PubMed=15026808; DOI=10.1038/sj.bjc.6601656; RA Claes K., Poppe B., Coene I., De Paepe A., Messiaen L.; RT "BRCA1 and BRCA2 germline mutation spectrum and frequencies in Belgian RT breast/ovarian cancer families."; RL Br. J. Cancer 90:1244-1251(2004). RN [69] RP VARIANTS BC ILE-64; GLY-462; ASN-1690; ASP-1771; MET-1887; MET-1915 AND RP GLU-2456, AND VARIANTS HIS-289; HIS-372; ASP-991; SER-1279; TYR-1420; RP CYS-2108 AND ALA-2466. RX PubMed=15172753; DOI=10.1016/j.cancergencyto.2003.09.020; RA Hadjisavvas A., Charalambous E., Adamou A., Neuhausen S.L., RA Christodoulou C.G., Kyriacou K.; RT "Hereditary breast and ovarian cancer in Cyprus: identification of a RT founder BRCA2 mutation."; RL Cancer Genet. Cytogenet. 151:152-156(2004). RN [70] RP VARIANT OVARIAN CANCER CYS-42, AND VARIANTS SER-3063 AND VAL-3412. RX PubMed=14746861; DOI=10.1016/j.ejca.2003.09.016; RA Malander S., Ridderheim M., Masbaeck A., Loman N., Kristoffersson U., RA Olsson H., Nilbert M., Borg A.; RT "One in 10 ovarian cancer patients carry germ line BRCA1 or BRCA2 RT mutations: results of a prospective study in Southern Sweden."; RL Eur. J. Cancer 40:422-428(2004). RN [71] RP VARIANTS BC ILE-1679; ALA-1804; LYS-1901 AND LEU-2096. RX PubMed=14722926; DOI=10.1002/humu.9213; RA Valarmathi M.T., Sawhney M., Deo S.S.V., Shukla N.K., Das S.N.; RT "Novel germline mutations in the BRCA1 and BRCA2 genes in Indian breast and RT breast-ovarian cancer families."; RL Hum. Mutat. 23:205-205(2004). RN [72] RP VARIANT ALA-225, AND CHARACTERIZATION OF VARIANT ALA-225. RX PubMed=15300854; DOI=10.1002/humu.9267; RA Sharp A., Pichert G., Lucassen A., Eccles D.; RT "RNA analysis reveals splicing mutations and loss of expression defects in RT MLH1 and BRCA1."; RL Hum. Mutat. 24:272-272(2004). RN [73] RP VARIANTS BC THR-1445; VAL-1929 AND ALA-2031, AND VARIANTS HIS-289; HIS-372; RP VAL-784; ASP-991 AND VAL-3412. RX PubMed=15365993; DOI=10.1002/humu.9275; RA Seo J.H., Cho D.-Y., Ahn S.-H., Yoon K.-S., Kang C.-S., Cho H.M., Lee H.S., RA Choe J.J., Choi C.W., Kim B.S., Shin S.W., Kim Y.H., Kim J.S., Son G.-S., RA Lee J.-B., Koo B.H.; RT "BRCA1 and BRCA2 germline mutations in Korean patients with sporadic breast RT cancer."; RL Hum. Mutat. 24:350-350(2004). RN [74] RP VARIANTS LEU-1172; TYR-1420; PHE-2944; ASN-2950 AND ILE-3013. RX PubMed=15635067; DOI=10.1136/jmg.2004.025056; RA Kim S.-W., Lee C.S., Fey J.V., Borgen P.I., Boyd J.; RT "Prevalence of BRCA2 mutations in a hospital based series of unselected RT breast cancer cases."; RL J. Med. Genet. 42:E5-E5(2005). RN [75] RP VARIANTS HIS-2336; CYS-2502; CYS-2626; PHE-2627; PRO-2653; LYS-2659; RP VAL-2663; ARG-2722; GLY-2723; ASP-2748 AND GLU-3095. RX PubMed=17924331; DOI=10.1086/521032; RA Easton D.F., Deffenbaugh A.M., Pruss D., Frye C., Wenstrup R.J., RA Allen-Brady K., Tavtigian S.V., Monteiro A.N.A., Iversen E.S., Couch F.J., RA Goldgar D.E.; RT "A systematic genetic assessment of 1,433 sequence variants of unknown RT clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition RT genes."; RL Am. J. Hum. Genet. 81:873-883(2007). RN [76] RP VARIANTS FANCD1 HIS-2336 AND CYS-2626. RX PubMed=16825431; DOI=10.1136/jmg.2006.043257; RA Alter B.P., Rosenberg P.S., Brody L.C.; RT "Clinical and molecular features associated with biallelic mutations in RT FANCD1/BRCA2."; RL J. Med. Genet. 44:1-9(2007). RN [77] RP CHARACTERIZATION OF VARIANTS VAL-2663; GLY-2723 AND TRP-3052. RX PubMed=20513136; DOI=10.1002/humu.21267; RA Walker L.C., Whiley P.J., Couch F.J., Farrugia D.J., Healey S., RA Eccles D.M., Lin F., Butler S.A., Goff S.A., Thompson B.A., Lakhani S.R., RA Da Silva L.M., Tavtigian S.V., Goldgar D.E., Brown M.A., Spurdle A.B.; RT "Detection of splicing aberrations caused by BRCA1 and BRCA2 sequence RT variants encoding missense substitutions: implications for prediction of RT pathogenicity."; RL Hum. Mutat. 31:E1484-E1505(2010). RN [78] RP CHARACTERIZATION OF VARIANTS FANCD1 HIS-2336; PRO-2510 AND CYS-2626, RP CHARACTERIZATION OF VARIANTS THR-2490 AND ASN-2729, FUNCTION, AND RP INTERACTION WITH SEM1. RX PubMed=21719596; DOI=10.1182/blood-2010-12-324541; RA Biswas K., Das R., Alter B.P., Kuznetsov S.G., Stauffer S., North S.L., RA Burkett S., Brody L.C., Meyer S., Byrd R.A., Sharan S.K.; RT "A comprehensive functional characterization of BRCA2 variants associated RT with Fanconi anemia using mouse ES cell-based assay."; RL Blood 118:2430-2442(2011). RN [79] RP CHARACTERIZATION OF VARIANTS BC PHE-2627; PRO-2653; ARG-2722; GLY-2723; RP HIS-2723; ASN-2729; HIS-2787; PRO-2792; ARG-2793; ALA-2856; THR-2951; RP ILE-3013; TRP-3052; GLU-3076; GLU-3095; HIS-3098 AND ILE-3124, RP CHARACTERIZATION OF VARIANTS ARG-2440; ALA-2466; CYS-2842 AND SER-3063, AND RP CHARACTERIZATION OF VARIANT FANCD1 PRO-2510 AND CYS-2626. RX PubMed=23108138; DOI=10.1158/0008-5472.can-12-2081; RA Guidugli L., Pankratz V.S., Singh N., Thompson J., Erding C.A., Engel C., RA Schmutzler R., Domchek S., Nathanson K., Radice P., Singer C., Tonin P.N., RA Lindor N.M., Goldgar D.E., Couch F.J.; RT "A classification model for BRCA2 DNA binding domain missense variants RT based on homology-directed repair activity."; RL Cancer Res. 73:265-275(2013). RN [80] RP VARIANTS LEU-606 AND TYR-1420. RX PubMed=26566883; DOI=10.1136/jmedgenet-2015-103179; RA Rafiullah R., Aslamkhan M., Paramasivam N., Thiel C., Mustafa G., RA Wiemann S., Schlesner M., Wade R.C., Rappold G.A., Berkel S.; RT "Homozygous missense mutation in the LMAN2L gene segregates with RT intellectual disability in a large consanguineous Pakistani family."; RL J. Med. Genet. 53:138-144(2016). CC -!- FUNCTION: Involved in double-strand break repair and/or homologous CC recombination. Binds RAD51 and potentiates recombinational DNA repair CC by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts CC by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to CC displace replication protein-A (RPA) from ssDNA and stabilizing RAD51- CC ssDNA filaments by blocking ATP hydrolysis. Part of a PALB2-scaffolded CC HR complex containing RAD51C and which is thought to play a role in DNA CC repair by HR. May participate in S phase checkpoint activation. Binds CC selectively to ssDNA, and to ssDNA in tailed duplexes and replication CC fork structures. May play a role in the extension step after strand CC invasion at replication-dependent DNA double-strand breaks; together CC with PALB2 is involved in both POLH localization at collapsed CC replication forks and DNA polymerization activity. In concert with CC NPM1, regulates centrosome duplication. Interacts with the TREX-2 CC complex (transcription and export complex 2) subunits PCID2 and SEM1, CC and is required to prevent R-loop-associated DNA damage and thus CC transcription-associated genomic instability. Silencing of BRCA2 CC promotes R-loop accumulation at actively transcribed genes in CC replicating and non-replicating cells, suggesting that BRCA2 mediates CC the control of R-loop associated genomic instability, independently of CC its known role in homologous recombination (PubMed:24896180). CC {ECO:0000269|PubMed:15115758, ECO:0000269|PubMed:15199141, CC ECO:0000269|PubMed:15671039, ECO:0000269|PubMed:18317453, CC ECO:0000269|PubMed:20729832, ECO:0000269|PubMed:20729858, CC ECO:0000269|PubMed:20729859, ECO:0000269|PubMed:21084279, CC ECO:0000269|PubMed:21719596, ECO:0000269|PubMed:24485656, CC ECO:0000269|PubMed:24896180}. CC -!- SUBUNIT: Monomer and dimer (PubMed:20729858). Interacts with RAD51; CC regulates RAD51 recruitment and function at sites of DNA repair CC (PubMed:12442171, PubMed:15800615, PubMed:18317453, PubMed:20729832, CC PubMed:20729859). Interacts with WDR16, USP11, DMC1, ROCK2 and NPM1 CC (PubMed:15314155, PubMed:15967112, PubMed:20729832, PubMed:21084279). CC Interacts with SEM1; the interaction masks a nuclear export signal in CC BRCA2 (PubMed:10373512, PubMed:16205630, PubMed:21719596, CC PubMed:24013206). Interacts with both nonubiquitinated and CC monoubiquitinated FANCD2; this complex also includes XRCC3 and CC phosphorylated FANCG (PubMed:15115758, PubMed:15199141, CC PubMed:18212739). Part of a BRCA complex containing BRCA1, BRCA2 and CC PALB2 (PubMed:19369211). Component of the homologous recombination CC repair (HR) complex composed of ERCC5/XPG, BRCA2, PALB2, DSS1 and RAD51 CC (PubMed:26833090). Within the complex, interacts with ERCC5/XPG and CC PALB2 (PubMed:26833090). Interacts directly with PALB2 which may serve CC as a scaffold for a HR complex containing PALB2, BRCA2, RAD51C, RAD51 CC and XRCC3 (PubMed:26833090, PubMed:19369211, PubMed:24141787, CC PubMed:28319063, PubMed:16793542, PubMed:19609323). Interacts with CC BRCA1 only in the presence of PALB2 which serves as the bridging CC protein (PubMed:19369211). Interacts with POLH; the interaction is CC direct (PubMed:24485656). Interacts with the TREX-2 complex subunits CC PCID2 and SEM1 (PubMed:24896180, PubMed:21719596). Interacts with CC HSF2BP and BRME1; the interaction with HSF2BP is direct and allows the CC formation of a ternary complex (PubMed:31242413). The complex CC BRME1:HSF2BP:BRCA2 interacts with SPATA22, MEIOB and RAD51 (By CC similarity). {ECO:0000250|UniProtKB:P97929, CC ECO:0000269|PubMed:10373512, ECO:0000269|PubMed:12442171, CC ECO:0000269|PubMed:15115758, ECO:0000269|PubMed:15199141, CC ECO:0000269|PubMed:15314155, ECO:0000269|PubMed:15800615, CC ECO:0000269|PubMed:15967112, ECO:0000269|PubMed:16205630, CC ECO:0000269|PubMed:16793542, ECO:0000269|PubMed:18212739, CC ECO:0000269|PubMed:18317453, ECO:0000269|PubMed:19369211, CC ECO:0000269|PubMed:19609323, ECO:0000269|PubMed:20729832, CC ECO:0000269|PubMed:20729858, ECO:0000269|PubMed:20729859, CC ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:21719596, CC ECO:0000269|PubMed:24013206, ECO:0000269|PubMed:24141787, CC ECO:0000269|PubMed:24485656, ECO:0000269|PubMed:24896180, CC ECO:0000269|PubMed:26833090, ECO:0000269|PubMed:28319063, CC ECO:0000269|PubMed:31242413}. CC -!- INTERACTION: CC P51587; P51587: BRCA2; NbExp=3; IntAct=EBI-79792, EBI-79792; CC P51587; Q14565: DMC1; NbExp=12; IntAct=EBI-79792, EBI-930865; CC P51587; Q9BXW9: FANCD2; NbExp=16; IntAct=EBI-79792, EBI-359343; CC P51587; Q9BXW9-2: FANCD2; NbExp=3; IntAct=EBI-79792, EBI-596878; CC P51587; Q9P0W2: HMG20B; NbExp=8; IntAct=EBI-79792, EBI-713401; CC P51587; Q86YC2: PALB2; NbExp=25; IntAct=EBI-79792, EBI-1222653; CC P51587; Q9NTI5: PDS5B; NbExp=26; IntAct=EBI-79792, EBI-1175604; CC P51587; Q9Y253: POLH; NbExp=6; IntAct=EBI-79792, EBI-2827270; CC P51587; Q06609: RAD51; NbExp=46; IntAct=EBI-79792, EBI-297202; CC P51587; Q06609-1: RAD51; NbExp=12; IntAct=EBI-79792, EBI-15557721; CC P51587; P60896: SEM1; NbExp=10; IntAct=EBI-79792, EBI-79819; CC P51587; P04637: TP53; NbExp=7; IntAct=EBI-79792, EBI-366083; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:24013206, CC ECO:0000269|PubMed:26833090, ECO:0000305|PubMed:21276791}. Cytoplasm, CC cytoskeleton, microtubule organizing center, centrosome CC {ECO:0000269|PubMed:21276791}. Note=Colocalizes with ERCC5/XPG to CC nuclear foci following DNA replication stress. CC {ECO:0000269|PubMed:26833090}. CC -!- TISSUE SPECIFICITY: Highest levels of expression in breast and thymus, CC with slightly lower levels in lung, ovary and spleen. CC -!- PTM: Phosphorylated by ATM upon irradiation-induced DNA damage. CC Phosphorylation by CHEK1 and CHEK2 regulates interaction with RAD51. CC Phosphorylation at Ser-3291 by CDK1 and CDK2 is low in S phase when CC recombination is active, but increases as cells progress towards CC mitosis; this phosphorylation prevents homologous recombination- CC dependent repair during S phase and G2 by inhibiting RAD51 binding. CC {ECO:0000269|PubMed:15199141, ECO:0000269|PubMed:15800615, CC ECO:0000269|PubMed:18317453}. CC -!- PTM: Ubiquitinated in the absence of DNA damage; this does not lead to CC proteasomal degradation. In contrast, ubiquitination in response to DNA CC damage leads to proteasomal degradation. {ECO:0000269|PubMed:15314155}. CC -!- DISEASE: Breast cancer (BC) [MIM:114480]: A common malignancy CC originating from breast epithelial tissue. Breast neoplasms can be CC distinguished by their histologic pattern. Invasive ductal carcinoma is CC by far the most common type. Breast cancer is etiologically and CC genetically heterogeneous. Important genetic factors have been CC indicated by familial occurrence and bilateral involvement. Mutations CC at more than one locus can be involved in different families or even in CC the same case. {ECO:0000269|PubMed:10399947, CC ECO:0000269|PubMed:10978364, ECO:0000269|PubMed:11139248, CC ECO:0000269|PubMed:11149425, ECO:0000269|PubMed:11241844, CC ECO:0000269|PubMed:11948477, ECO:0000269|PubMed:12145750, CC ECO:0000269|PubMed:12373604, ECO:0000269|PubMed:12442274, CC ECO:0000269|PubMed:12442275, ECO:0000269|PubMed:12569143, CC ECO:0000269|PubMed:12938098, ECO:0000269|PubMed:14722926, CC ECO:0000269|PubMed:15026808, ECO:0000269|PubMed:15172753, CC ECO:0000269|PubMed:15365993, ECO:0000269|PubMed:16793542, CC ECO:0000269|PubMed:23108138, ECO:0000269|PubMed:24013206, CC ECO:0000269|PubMed:8640237, ECO:0000269|PubMed:9150152, CC ECO:0000269|PubMed:9609997, ECO:0000269|PubMed:9654203, CC ECO:0000269|PubMed:9971877}. Note=Disease susceptibility is associated CC with variants affecting the gene represented in this entry. CC -!- DISEASE: Pancreatic cancer 2 (PNCA2) [MIM:613347]: A malignant neoplasm CC of the pancreas. Tumors can arise from both the exocrine and endocrine CC portions of the pancreas, but 95% of them develop from the exocrine CC portion, including the ductal epithelium, acinar cells, connective CC tissue, and lymphatic tissue. {ECO:0000269|PubMed:9140390}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Breast-ovarian cancer, familial, 2 (BROVCA2) [MIM:612555]: A CC condition associated with familial predisposition to cancer of the CC breast and ovaries. Characteristic features in affected families are an CC early age of onset of breast cancer (often before age 50), increased CC chance of bilateral cancers (cancer that develop in both breasts, or CC both ovaries, independently), frequent occurrence of breast cancer CC among men, increased incidence of tumors of other specific organs, such CC as the prostate. Note=Disease susceptibility is associated with CC variants affecting the gene represented in this entry. CC -!- DISEASE: Fanconi anemia complementation group D1 (FANCD1) [MIM:605724]: CC A disorder affecting all bone marrow elements and resulting in anemia, CC leukopenia and thrombopenia. It is associated with cardiac, renal and CC limb malformations, dermal pigmentary changes, and a predisposition to CC the development of malignancies. At the cellular level it is associated CC with hypersensitivity to DNA-damaging agents, chromosomal instability CC (increased chromosome breakage) and defective DNA repair. CC {ECO:0000269|PubMed:12065746, ECO:0000269|PubMed:14670928, CC ECO:0000269|PubMed:16825431, ECO:0000269|PubMed:21719596, CC ECO:0000269|PubMed:23108138}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Glioma 3 (GLM3) [MIM:613029]: Gliomas are benign or malignant CC central nervous system neoplasms derived from glial cells. They CC comprise astrocytomas and glioblastoma multiforme that are derived from CC astrocytes, oligodendrogliomas derived from oligodendrocytes and CC ependymomas derived from ependymocytes. {ECO:0000269|PubMed:15689453}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- WEB RESOURCE: Name=Fanconi Anemia Mutation Database; CC URL="https://www2.rockefeller.edu/fanconi/genes/jumpd1"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/brca2/"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=BRCA2 entry; CC URL="https://en.wikipedia.org/wiki/BRCA2"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/BRCA2ID164ch13q13.html"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X95152; CAA64484.1; -; Genomic_DNA. DR EMBL; X95153; CAA64484.1; JOINED; Genomic_DNA. DR EMBL; X95154; CAA64484.1; JOINED; Genomic_DNA. DR EMBL; X95155; CAA64484.1; JOINED; Genomic_DNA. DR EMBL; X95156; CAA64484.1; JOINED; Genomic_DNA. DR EMBL; X95157; CAA64484.1; JOINED; Genomic_DNA. DR EMBL; X95158; CAA64484.1; JOINED; Genomic_DNA. DR EMBL; X95159; CAA64484.1; JOINED; Genomic_DNA. DR EMBL; X95160; CAA64484.1; JOINED; Genomic_DNA. DR EMBL; X95161; CAA64484.1; JOINED; Genomic_DNA. DR EMBL; X95162; CAA64484.1; JOINED; Genomic_DNA. DR EMBL; X95163; CAA64484.1; JOINED; Genomic_DNA. DR EMBL; X95164; CAA64484.1; JOINED; Genomic_DNA. DR EMBL; X95165; CAA64484.1; JOINED; Genomic_DNA. DR EMBL; X95166; CAA64484.1; JOINED; Genomic_DNA. DR EMBL; X95167; CAA64484.1; JOINED; Genomic_DNA. DR EMBL; X95168; CAA64484.1; JOINED; Genomic_DNA. DR EMBL; X95169; CAA64484.1; JOINED; Genomic_DNA. DR EMBL; X95170; CAA64484.1; JOINED; Genomic_DNA. DR EMBL; X95171; CAA64484.1; JOINED; Genomic_DNA. DR EMBL; X95172; CAA64484.1; JOINED; Genomic_DNA. DR EMBL; X95173; CAA64484.1; JOINED; Genomic_DNA. DR EMBL; X95174; CAA64484.1; JOINED; Genomic_DNA. DR EMBL; X95175; CAA64484.1; JOINED; Genomic_DNA. DR EMBL; X95176; CAA64484.1; JOINED; Genomic_DNA. DR EMBL; X95177; CAA64484.1; JOINED; Genomic_DNA. DR EMBL; U43746; AAB07223.1; -; mRNA. DR EMBL; AY436640; AAQ97181.1; -; Genomic_DNA. DR EMBL; AL137247; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL445212; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; Z74739; CAA98995.2; -; Genomic_DNA. DR EMBL; Z73359; CAA97728.1; -; Genomic_DNA. DR CCDS; CCDS9344.1; -. DR PIR; G02334; G02334. DR RefSeq; NP_000050.2; NM_000059.3. DR PDB; 1N0W; X-ray; 1.70 A; B=1517-1551. DR PDB; 3EU7; X-ray; 2.20 A; X=21-39. DR PDB; 6GY2; X-ray; 3.11 A; C/D=194-210. DR PDB; 6HQU; X-ray; 1.97 A; I/J/K/L/M/N=1226-1253, O=2054-2064. DR PDB; 7BDX; X-ray; 2.60 A; E/F=2291-2343. DR PDB; 7LDG; X-ray; 2.56 A; B/D=2271-2335. DR PDBsum; 1N0W; -. DR PDBsum; 3EU7; -. DR PDBsum; 6GY2; -. DR PDBsum; 6HQU; -. DR PDBsum; 7BDX; -. DR PDBsum; 7LDG; -. DR SMR; P51587; -. DR BioGRID; 107142; 236. DR ComplexPortal; CPX-845; BRCA1-PALB2-BRCA2 homologous recombination DNA repair complex. DR ComplexPortal; CPX-955; BRCC ubiquitin ligase complex. DR CORUM; P51587; -. DR DIP; DIP-24214N; -. DR ELM; P51587; -. DR IntAct; P51587; 56. DR MINT; P51587; -. DR STRING; 9606.ENSP00000369497; -. DR BindingDB; P51587; -. DR iPTMnet; P51587; -. DR PhosphoSitePlus; P51587; -. DR BioMuta; BRCA2; -. DR DMDM; 14424438; -. DR CPTAC; CPTAC-3279; -. DR CPTAC; CPTAC-3280; -. DR EPD; P51587; -. DR jPOST; P51587; -. DR MassIVE; P51587; -. DR PaxDb; P51587; -. DR PeptideAtlas; P51587; -. DR PRIDE; P51587; -. DR ProteomicsDB; 56340; -. DR Antibodypedia; 7788; 321 antibodies from 41 providers. DR DNASU; 675; -. DR Ensembl; ENST00000380152.8; ENSP00000369497.3; ENSG00000139618.17. DR Ensembl; ENST00000544455.6; ENSP00000439902.1; ENSG00000139618.17. DR Ensembl; ENST00000680887.1; ENSP00000505508.1; ENSG00000139618.17. DR GeneID; 675; -. DR KEGG; hsa:675; -. DR MANE-Select; ENST00000380152.8; ENSP00000369497.3; NM_000059.4; NP_000050.3. DR UCSC; uc001uub.2; human. DR CTD; 675; -. DR DisGeNET; 675; -. DR GeneCards; BRCA2; -. DR GeneReviews; BRCA2; -. DR HGNC; HGNC:1101; BRCA2. DR HPA; ENSG00000139618; Tissue enhanced (bone marrow, lymphoid tissue, testis). DR MalaCards; BRCA2; -. DR MIM; 114480; phenotype. DR MIM; 600185; gene. DR MIM; 605724; phenotype. DR MIM; 612555; phenotype. DR MIM; 613029; phenotype. DR MIM; 613347; phenotype. DR neXtProt; NX_P51587; -. DR Orphanet; 70567; Cholangiocarcinoma. DR Orphanet; 1333; Familial pancreatic carcinoma. DR Orphanet; 1331; Familial prostate cancer. DR Orphanet; 84; Fanconi anemia. DR Orphanet; 145; Hereditary breast and ovarian cancer syndrome. DR Orphanet; 227535; Hereditary breast cancer. DR Orphanet; 213524; Hereditary site-specific ovarian cancer syndrome. DR Orphanet; 319462; Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations. DR Orphanet; 654; Nephroblastoma. DR PharmGKB; PA25412; -. DR VEuPathDB; HostDB:ENSG00000139618; -. DR eggNOG; KOG4751; Eukaryota. DR HOGENOM; CLU_000344_0_0_1; -. DR InParanoid; P51587; -. DR OrthoDB; 257485at2759; -. DR PhylomeDB; P51587; -. DR TreeFam; TF105041; -. DR PathwayCommons; P51587; -. DR Reactome; R-HSA-5685942; HDR through Homologous Recombination (HRR). DR Reactome; R-HSA-5693554; Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA). DR Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates. DR Reactome; R-HSA-5693579; Homologous DNA Pairing and Strand Exchange. DR Reactome; R-HSA-5693616; Presynaptic phase of homologous DNA pairing and strand exchange. DR Reactome; R-HSA-912446; Meiotic recombination. DR Reactome; R-HSA-9701192; Defective HDR through Homologous Recombination (HRR) due to BRCA1 loss-of-function. DR Reactome; R-HSA-9704331; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function. DR Reactome; R-HSA-9704646; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function. DR SignaLink; P51587; -. DR SIGNOR; P51587; -. DR BioGRID-ORCS; 675; 323 hits in 1089 CRISPR screens. DR ChiTaRS; BRCA2; human. DR EvolutionaryTrace; P51587; -. DR GeneWiki; BRCA2; -. DR GenomeRNAi; 675; -. DR Pharos; P51587; Tbio. DR PRO; PR:P51587; -. DR Proteomes; UP000005640; Chromosome 13. DR RNAct; P51587; protein. DR Bgee; ENSG00000139618; Expressed in secondary oocyte and 150 other tissues. DR ExpressionAtlas; P51587; baseline and differential. DR Genevisible; P51587; HS. DR GO; GO:0033593; C:BRCA2-MAGE-D1 complex; IDA:UniProtKB. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0000781; C:chromosome, telomeric region; IDA:BHF-UCL. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:1990391; C:DNA repair complex; IPI:ComplexPortal. DR GO; GO:0000800; C:lateral element; IDA:MGI. DR GO; GO:0000152; C:nuclear ubiquitin ligase complex; IDA:ComplexPortal. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0030141; C:secretory granule; IDA:UniProtKB. DR GO; GO:0043015; F:gamma-tubulin binding; IPI:UniProtKB. DR GO; GO:0010484; F:H3 histone acetyltransferase activity; IDA:UniProtKB. DR GO; GO:0010485; F:H4 histone acetyltransferase activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0002020; F:protease binding; IPI:UniProtKB. DR GO; GO:0008022; F:protein C-terminus binding; IDA:MGI. DR GO; GO:0003697; F:single-stranded DNA binding; IDA:UniProtKB. DR GO; GO:0007420; P:brain development; IEA:Ensembl. DR GO; GO:0007569; P:cell aging; IEA:Ensembl. DR GO; GO:0071479; P:cellular response to ionizing radiation; IMP:ComplexPortal. DR GO; GO:0051298; P:centrosome duplication; IMP:UniProtKB. DR GO; GO:0006978; P:DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; IEA:Ensembl. DR GO; GO:0006302; P:double-strand break repair; IMP:UniProtKB. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IDA:UniProtKB. DR GO; GO:0070200; P:establishment of protein localization to telomere; IDA:BHF-UCL. DR GO; GO:0008585; P:female gonad development; IEA:Ensembl. DR GO; GO:0030097; P:hemopoiesis; IEA:Ensembl. DR GO; GO:0035518; P:histone H2A monoubiquitination; IC:ComplexPortal. DR GO; GO:0043966; P:histone H3 acetylation; IDA:UniProtKB. DR GO; GO:0043967; P:histone H4 acetylation; IDA:UniProtKB. DR GO; GO:0001833; P:inner cell mass cell proliferation; IEA:Ensembl. DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IEA:Ensembl. DR GO; GO:0007141; P:male meiosis I; IEA:Ensembl. DR GO; GO:1990426; P:mitotic recombination-dependent replication fork processing; IMP:BHF-UCL. DR GO; GO:0033600; P:negative regulation of mammary gland epithelial cell proliferation; IDA:UniProtKB. DR GO; GO:0006289; P:nucleotide-excision repair; IMP:UniProtKB. DR GO; GO:0001556; P:oocyte maturation; IEA:Ensembl. DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0051865; P:protein autoubiquitination; IC:ComplexPortal. DR GO; GO:0032465; P:regulation of cytokinesis; IEA:Ensembl. DR GO; GO:2000001; P:regulation of DNA damage checkpoint; IC:ComplexPortal. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central. DR GO; GO:0048478; P:replication fork protection; IEA:Ensembl. DR GO; GO:0010332; P:response to gamma radiation; IEA:Ensembl. DR GO; GO:0010225; P:response to UV-C; IEA:Ensembl. DR GO; GO:0010165; P:response to X-ray; IEA:Ensembl. DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl. DR GO; GO:0000722; P:telomere maintenance via recombination; IEA:Ensembl. DR CDD; cd04493; BRCA2DBD_OB1; 1. DR CDD; cd04495; BRCA2DBD_OB3; 1. DR DisProt; DP01869; -. DR Gene3D; 2.40.50.140; -; 3. DR IDEAL; IID00237; -. DR InterPro; IPR015525; BRCA2. DR InterPro; IPR015252; BRCA2_hlx. DR InterPro; IPR036315; BRCA2_hlx_sf. DR InterPro; IPR015187; BRCA2_OB_1. DR InterPro; IPR015188; BRCA2_OB_3. DR InterPro; IPR002093; BRCA2_repeat. DR InterPro; IPR012340; NA-bd_OB-fold. DR InterPro; IPR015205; Tower_dom. DR PANTHER; PTHR11289; PTHR11289; 1. DR Pfam; PF09169; BRCA-2_helical; 1. DR Pfam; PF09103; BRCA-2_OB1; 1. DR Pfam; PF09104; BRCA-2_OB3; 1. DR Pfam; PF00634; BRCA2; 7. DR Pfam; PF09121; Tower; 1. DR PIRSF; PIRSF002397; BRCA2; 1. DR SMART; SM01341; Tower; 1. DR SUPFAM; SSF50249; SSF50249; 3. DR SUPFAM; SSF81872; SSF81872; 1. DR PROSITE; PS50138; BRCA2_REPEAT; 8. PE 1: Evidence at protein level; KW 3D-structure; Cell cycle; Cytoplasm; Cytoskeleton; Disease variant; KW DNA damage; DNA recombination; DNA repair; DNA-binding; Fanconi anemia; KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Tumor suppressor; KW Ubl conjugation. FT CHAIN 1..3418 FT /note="Breast cancer type 2 susceptibility protein" FT /id="PRO_0000064984" FT REPEAT 1002..1036 FT /note="BRCA2 1" FT REPEAT 1212..1246 FT /note="BRCA2 2" FT REPEAT 1421..1455 FT /note="BRCA2 3" FT REPEAT 1517..1551 FT /note="BRCA2 4" FT REPEAT 1664..1698 FT /note="BRCA2 5" FT REPEAT 1837..1871 FT /note="BRCA2 6" FT REPEAT 1971..2005 FT /note="BRCA2 7" FT REPEAT 2051..2085 FT /note="BRCA2 8" FT REGION 1..40 FT /note="Interaction with PALB2" FT REGION 37..68 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 358..381 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 639..1000 FT /note="Interaction with NPM1" FT /evidence="ECO:0000269|PubMed:21084279" FT REGION 1003..2082 FT /note="Interaction with RAD51" FT /evidence="ECO:0000250|UniProtKB:P97929" FT REGION 1338..1781 FT /note="Interaction with POLH" FT /evidence="ECO:0000269|PubMed:24485656" FT REGION 1410..1595 FT /note="Required for stimulation of POLH DNA polymerization FT activity" FT REGION 2270..2337 FT /note="Interaction with HSF2BP" FT /evidence="ECO:0000269|PubMed:31242413" FT REGION 2350..2545 FT /note="Interaction with FANCD2" FT REGION 2430..2450 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2481..2832 FT /note="Interaction with SEM1" FT /evidence="ECO:0000269|PubMed:10373512, FT ECO:0000269|PubMed:16205630" FT REGION 3393..3418 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 2682..2698 FT /note="Nuclear export signal; masked by interaction with FT SEM1" FT /evidence="ECO:0000269|PubMed:24013206" FT COMPBIAS 362..378 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 3398..3418 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 70 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 445 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 492 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 755 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17525332" FT MOD_RES 1970 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 2035 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 2095 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 3291 FT /note="Phosphoserine; by CDK1 and CDK2" FT /evidence="ECO:0000269|PubMed:15800615" FT MOD_RES 3319 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 3387 FT /note="Phosphothreonine; by CHEK1 and CHEK2" FT /evidence="ECO:0000269|PubMed:18317453" FT VARIANT 25 FT /note="G -> R (in BC; abolishes interaction with PALB2; FT dbSNP:rs80358961)" FT /evidence="ECO:0000269|PubMed:16793542" FT /id="VAR_028167" FT VARIANT 31 FT /note="W -> C (in BC; abolishes interaction with PALB2; FT dbSNP:rs80359214)" FT /evidence="ECO:0000269|PubMed:16793542" FT /id="VAR_028168" FT VARIANT 31 FT /note="W -> R (in BC; abolishes interaction with PALB2; FT dbSNP:rs80359182)" FT /evidence="ECO:0000269|PubMed:16793542" FT /id="VAR_028169" FT VARIANT 32 FT /note="F -> L (in BC; dbSNP:rs397508057 and FT dbSNP:rs1555280339)" FT /evidence="ECO:0000269|PubMed:9609997" FT /id="VAR_005085" FT VARIANT 42 FT /note="Y -> C (in BC and ovarian cancer; unknown FT pathological significance; dbSNP:rs4987046)" FT /evidence="ECO:0000269|PubMed:12442275, FT ECO:0000269|PubMed:14746861" FT /id="VAR_020705" FT VARIANT 53 FT /note="K -> R (in BC; dbSNP:rs397507595)" FT /evidence="ECO:0000269|PubMed:9609997" FT /id="VAR_005086" FT VARIANT 60 FT /note="N -> S (in BC; unknown pathological significance; FT dbSNP:rs80358463)" FT /evidence="ECO:0000269|PubMed:15026808" FT /id="VAR_020706" FT VARIANT 64 FT /note="T -> I (in BC; dbSNP:rs397507615)" FT /evidence="ECO:0000269|PubMed:15172753" FT /id="VAR_032712" FT VARIANT 75 FT /note="A -> P (in ovarian cancer and renal cancer; unknown FT pathological significance; dbSNP:rs28897701)" FT /evidence="ECO:0000269|PubMed:10486320" FT /id="VAR_005087" FT VARIANT 81 FT /note="F -> L (in BC; dbSNP:rs80358507)" FT /evidence="ECO:0000269|PubMed:9609997" FT /id="VAR_005088" FT VARIANT 108 FT /note="N -> H (in dbSNP:rs80358567)" FT /id="VAR_008766" FT VARIANT 118 FT /note="R -> H (in one patient with esophageal carcinoma; FT dbSNP:rs80358603)" FT /evidence="ECO:0000269|PubMed:11948123" FT /id="VAR_032713" FT VARIANT 192 FT /note="M -> T (in one patient with pancreatic cancer; FT dbSNP:rs80358805)" FT /evidence="ECO:0000269|PubMed:12097290" FT /id="VAR_032714" FT VARIANT 201 FT /note="P -> R (in BC; dbSNP:rs397507822)" FT /evidence="ECO:0000269|PubMed:9609997" FT /id="VAR_005089" FT VARIANT 211 FT /note="V -> A (in BC)" FT /evidence="ECO:0000269|PubMed:9609997" FT /id="VAR_005090" FT VARIANT 222 FT /note="P -> S (in BC; dbSNP:rs397507873)" FT /evidence="ECO:0000269|PubMed:9609997" FT /id="VAR_005091" FT VARIANT 225 FT /note="T -> A (in one patient with BC; normal RNA FT expression and splicing; dbSNP:rs80358897)" FT /evidence="ECO:0000269|PubMed:15300854" FT /id="VAR_032715" FT VARIANT 289 FT /note="N -> H (in dbSNP:rs766173)" FT /evidence="ECO:0000269|PubMed:10323242, FT ECO:0000269|PubMed:10978364, ECO:0000269|PubMed:11149425, FT ECO:0000269|PubMed:12552570, ECO:0000269|PubMed:15172753, FT ECO:0000269|PubMed:15365993, ECO:0000269|Ref.3" FT /id="VAR_005092" FT VARIANT 315 FT /note="C -> S (in one patient with esophageal carcinoma; FT dbSNP:rs79483201)" FT /evidence="ECO:0000269|PubMed:11948123" FT /id="VAR_032716" FT VARIANT 322 FT /note="K -> Q (in dbSNP:rs11571640)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_018908" FT VARIANT 326 FT /note="S -> R (in BC; dbSNP:rs28897706)" FT /evidence="ECO:0000269|PubMed:10399947" FT /id="VAR_032717" FT VARIANT 327 FT /note="K -> E (in BC; unknown pathological significance; FT dbSNP:rs80359242)" FT /id="VAR_008767" FT VARIANT 355 FT /note="V -> L (in lung cancer)" FT /id="VAR_005093" FT VARIANT 372 FT /note="N -> H (in dbSNP:rs144848)" FT /evidence="ECO:0000269|PubMed:10323242, FT ECO:0000269|PubMed:10978364, ECO:0000269|PubMed:11062481, FT ECO:0000269|PubMed:12552570, ECO:0000269|PubMed:15057823, FT ECO:0000269|PubMed:15172753, ECO:0000269|PubMed:15365993, FT ECO:0000269|PubMed:8665505, ECO:0000269|PubMed:8673091, FT ECO:0000269|Ref.3" FT /id="VAR_005094" FT VARIANT 405 FT /note="G -> R (in BC; unknown pathological significance)" FT /evidence="ECO:0000269|PubMed:15026808" FT /id="VAR_020707" FT VARIANT 431 FT /note="T -> I (in BC; unknown pathological significance; FT dbSNP:rs876660828)" FT /evidence="ECO:0000269|PubMed:12938098" FT /id="VAR_020708" FT VARIANT 448 FT /note="R -> H (in BC; unknown pathological significance; FT dbSNP:rs80358423)" FT /evidence="ECO:0000269|PubMed:15026808" FT /id="VAR_020709" FT VARIANT 462 FT /note="E -> G (in BC; unknown pathological significance; FT dbSNP:rs56403624)" FT /evidence="ECO:0000269|PubMed:12552570, FT ECO:0000269|PubMed:15026808, ECO:0000269|PubMed:15172753" FT /id="VAR_020710" FT VARIANT 505 FT /note="I -> T (in BC; dbSNP:rs28897708)" FT /evidence="ECO:0000269|PubMed:11241844" FT /id="VAR_032718" FT VARIANT 513 FT /note="K -> R (in dbSNP:rs28897709)" FT /id="VAR_056751" FT VARIANT 554 FT /note="C -> W (in BC and pancreas cancer; FT dbSNP:rs80358451)" FT /evidence="ECO:0000269|PubMed:9654203" FT /id="VAR_005095" FT VARIANT 582 FT /note="T -> P (in dbSNP:rs80358457)" FT /evidence="ECO:0000269|PubMed:12624724" FT /id="VAR_008768" FT VARIANT 598 FT /note="T -> A (in dbSNP:rs28897710)" FT /evidence="ECO:0000269|PubMed:12215251" FT /id="VAR_020711" FT VARIANT 599 FT /note="S -> F (in dbSNP:rs1046984)" FT /evidence="ECO:0000269|PubMed:8589730" FT /id="VAR_035436" FT VARIANT 606 FT /note="P -> L (in dbSNP:rs80358469)" FT /evidence="ECO:0000269|PubMed:26566883" FT /id="VAR_076440" FT VARIANT 613 FT /note="L -> R (in BC; unknown pathological significance; FT dbSNP:rs587780646)" FT /evidence="ECO:0000269|PubMed:12442275" FT /id="VAR_020712" FT VARIANT 630 FT /note="T -> I (in ovarian cancer; dbSNP:rs80358479)" FT /id="VAR_005096" FT VARIANT 707 FT /note="D -> Y (in dbSNP:rs80358487)" FT /id="VAR_008769" FT VARIANT 728 FT /note="D -> A (in BC; dbSNP:rs757577670)" FT /id="VAR_005097" FT VARIANT 729 FT /note="I -> M (in BC; dbSNP:rs397507620)" FT /evidence="ECO:0000269|PubMed:10978364" FT /id="VAR_032719" FT VARIANT 784 FT /note="M -> V (in dbSNP:rs11571653)" FT /evidence="ECO:0000269|PubMed:11149425, FT ECO:0000269|PubMed:15365993, ECO:0000269|Ref.3" FT /id="VAR_008770" FT VARIANT 886 FT /note="N -> I (in dbSNP:rs80358526)" FT /id="VAR_008771" FT VARIANT 929 FT /note="L -> S (in dbSNP:rs2227943)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_018909" FT VARIANT 935 FT /note="D -> N (in BC; unknown pathological significance; FT dbSNP:rs28897716)" FT /id="VAR_008772" FT VARIANT 976 FT /note="S -> F (in dbSNP:rs11571656)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_018910" FT VARIANT 982 FT /note="I -> L (in dbSNP:rs28897717)" FT /id="VAR_056752" FT VARIANT 987 FT /note="N -> I (in dbSNP:rs2227944)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_018911" FT VARIANT 991 FT /note="N -> D (in dbSNP:rs1799944)" FT /evidence="ECO:0000269|PubMed:10323242, FT ECO:0000269|PubMed:10978364, ECO:0000269|PubMed:12552570, FT ECO:0000269|PubMed:15026808, ECO:0000269|PubMed:15172753, FT ECO:0000269|PubMed:15365993, ECO:0000269|PubMed:8673091, FT ECO:0000269|Ref.3" FT /id="VAR_005098" FT VARIANT 1036 FT /note="E -> K (in BC; unknown pathological significance)" FT /evidence="ECO:0000269|PubMed:12938098" FT /id="VAR_020713" FT VARIANT 1106 FT /note="S -> R (in BC; unknown pathological significance; FT dbSNP:rs1298550035)" FT /evidence="ECO:0000269|PubMed:12938098" FT /id="VAR_020714" FT VARIANT 1147 FT /note="N -> S (in dbSNP:rs1799951)" FT /evidence="ECO:0000269|PubMed:8673091" FT /id="VAR_005099" FT VARIANT 1172 FT /note="S -> L (in BC; unknown pathological significance; FT dbSNP:rs80358600)" FT /evidence="ECO:0000269|PubMed:15635067" FT /id="VAR_032720" FT VARIANT 1179 FT /note="S -> N (in BC; dbSNP:rs397507674)" FT /evidence="ECO:0000269|PubMed:11139248" FT /id="VAR_020715" FT VARIANT 1279 FT /note="N -> S (in dbSNP:rs1060502384)" FT /evidence="ECO:0000269|PubMed:12552570, FT ECO:0000269|PubMed:15172753" FT /id="VAR_020716" FT VARIANT 1286 FT /note="Missing" FT /id="VAR_008773" FT VARIANT 1290 FT /note="C -> Y (in dbSNP:rs41293485)" FT /id="VAR_008774" FT VARIANT 1302 FT /note="Missing (in BC)" FT /id="VAR_005100" FT VARIANT 1414 FT /note="T -> M (in dbSNP:rs70953664)" FT /id="VAR_008775" FT VARIANT 1420 FT /note="D -> Y (in dbSNP:rs28897727)" FT /evidence="ECO:0000269|PubMed:11139248, FT ECO:0000269|PubMed:12215251, ECO:0000269|PubMed:12552570, FT ECO:0000269|PubMed:15172753, ECO:0000269|PubMed:15635067, FT ECO:0000269|PubMed:26566883" FT /id="VAR_008776" FT VARIANT 1445 FT /note="K -> T (in BC; unknown pathological significance)" FT /evidence="ECO:0000269|PubMed:15365993" FT /id="VAR_020717" FT VARIANT 1513 FT /note="D -> N (in dbSNP:rs80358687)" FT /id="VAR_008777" FT VARIANT 1522 FT /note="L -> F (in one patient with BC; dbSNP:rs397507729)" FT /evidence="ECO:0000269|PubMed:12624724" FT /id="VAR_032721" FT VARIANT 1524 FT /note="F -> V (in BC; unknown pathological significance; FT dbSNP:rs56386506)" FT /evidence="ECO:0000269|PubMed:12938098" FT /id="VAR_020718" FT VARIANT 1529 FT /note="G -> R (in bladder cancer; dbSNP:rs28897728)" FT /id="VAR_005101" FT VARIANT 1542 FT /note="V -> M (in dbSNP:rs28897729)" FT /id="VAR_056753" FT VARIANT 1561 FT /note="H -> N (in dbSNP:rs2219594)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_018912" FT VARIANT 1580 FT /note="C -> Y (in BC; somatic mutation; dbSNP:rs398122784)" FT /evidence="ECO:0000269|PubMed:11948477" FT /id="VAR_020719" FT VARIANT 1593 FT /note="E -> D (in dbSNP:rs80358703)" FT /evidence="ECO:0000269|PubMed:12442273" FT /id="VAR_008778" FT VARIANT 1643 FT /note="V -> A (in dbSNP:rs28897731)" FT /id="VAR_056754" FT VARIANT 1679 FT /note="T -> I (in BC)" FT /evidence="ECO:0000269|PubMed:14722926" FT /id="VAR_020720" FT VARIANT 1690 FT /note="K -> N (in BC; dbSNP:rs56087561)" FT /evidence="ECO:0000269|PubMed:15172753" FT /id="VAR_032722" FT VARIANT 1730 FT /note="N -> Y (in BC; dbSNP:rs397507770)" FT /evidence="ECO:0000269|PubMed:11241844" FT /id="VAR_032723" FT VARIANT 1771 FT /note="G -> D (in BC; unknown pathological significance; FT dbSNP:rs80358755)" FT /evidence="ECO:0000269|PubMed:12552570, FT ECO:0000269|PubMed:15172753" FT /id="VAR_008779" FT VARIANT 1804 FT /note="V -> A (in BC; dbSNP:rs370252983)" FT /evidence="ECO:0000269|PubMed:14722926" FT /id="VAR_020721" FT VARIANT 1805 FT /note="N -> S (in dbSNP:rs80358765)" FT /id="VAR_008780" FT VARIANT 1880 FT /note="N -> K (in dbSNP:rs11571657)" FT /evidence="ECO:0000269|PubMed:11241844, ECO:0000269|Ref.3" FT /id="VAR_005102" FT VARIANT 1887 FT /note="T -> M (in BC; dbSNP:rs397507795)" FT /evidence="ECO:0000269|PubMed:15172753" FT /id="VAR_032724" FT VARIANT 1901 FT /note="E -> K (in BC)" FT /evidence="ECO:0000269|PubMed:14722926" FT /id="VAR_020722" FT VARIANT 1902 FT /note="D -> N (in dbSNP:rs4987048)" FT /id="VAR_008781" FT VARIANT 1915 FT /note="T -> M (in dbSNP:rs4987117)" FT /evidence="ECO:0000269|PubMed:10978364, FT ECO:0000269|PubMed:11948477, ECO:0000269|PubMed:15172753, FT ECO:0000269|PubMed:8665505, ECO:0000269|PubMed:8673091, FT ECO:0000269|Ref.3" FT /id="VAR_005103" FT VARIANT 1929 FT /note="I -> V (in BC; unknown pathological significance; FT dbSNP:rs79538375)" FT /evidence="ECO:0000269|PubMed:15365993" FT /id="VAR_020723" FT VARIANT 1979 FT /note="S -> R (in dbSNP:rs28897737)" FT /id="VAR_056755" FT VARIANT 1988 FT /note="V -> I (in one patient with esophageal carcinoma; FT somatic mutation; dbSNP:rs28897739)" FT /evidence="ECO:0000269|PubMed:11948123" FT /id="VAR_032725" FT VARIANT 2031 FT /note="T -> A (in BC; unknown pathological significance)" FT /evidence="ECO:0000269|PubMed:15365993" FT /id="VAR_020724" FT VARIANT 2034 FT /note="R -> C (in dbSNP:rs1799954)" FT /evidence="ECO:0000269|PubMed:12215251, FT ECO:0000269|PubMed:12569143, ECO:0000269|PubMed:8673091" FT /id="VAR_005104" FT VARIANT 2044 FT /note="G -> V (in one patient with BC; dbSNP:rs56191579)" FT /evidence="ECO:0000269|PubMed:12624724" FT /id="VAR_032726" FT VARIANT 2072 FT /note="S -> C (in BC; dbSNP:rs80358862)" FT /evidence="ECO:0000269|PubMed:12373604" FT /id="VAR_020725" FT VARIANT 2074 FT /note="H -> N (in dbSNP:rs34309943)" FT /id="VAR_008782" FT VARIANT 2089 FT /note="E -> D (in BC)" FT /evidence="ECO:0000269|PubMed:9150152" FT /id="VAR_008783" FT VARIANT 2094 FT /note="Y -> C (in BC; dbSNP:rs397507838)" FT /evidence="ECO:0000269|PubMed:12373604" FT /id="VAR_020726" FT VARIANT 2096 FT /note="P -> L (in BC)" FT /evidence="ECO:0000269|PubMed:14722926" FT /id="VAR_020727" FT VARIANT 2108 FT /note="R -> C (in dbSNP:rs55794205)" FT /evidence="ECO:0000269|PubMed:15172753" FT /id="VAR_032727" FT VARIANT 2116 FT /note="H -> R (in dbSNP:rs55953736)" FT /id="VAR_061563" FT VARIANT 2118 FT /note="V -> L (in BC; unknown pathological significance)" FT /evidence="ECO:0000269|PubMed:12442275" FT /id="VAR_020728" FT VARIANT 2128 FT /note="K -> N (in BC; dbSNP:rs397507847)" FT /evidence="ECO:0000269|PubMed:12373604" FT /id="VAR_020729" FT VARIANT 2135 FT /note="N -> H (in BC; dbSNP:rs80358876)" FT /evidence="ECO:0000269|PubMed:11241844" FT /id="VAR_032728" FT VARIANT 2138 FT /note="V -> F (in dbSNP:rs11571659)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_008784" FT VARIANT 2162 FT /note="K -> R (in dbSNP:rs11571660)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_018913" FT VARIANT 2222 FT /note="Y -> C (in BC; dbSNP:rs397507875)" FT /evidence="ECO:0000269|PubMed:11241844" FT /id="VAR_032729" FT VARIANT 2238 FT /note="D -> E (in dbSNP:rs28897742)" FT /id="VAR_056756" FT VARIANT 2274 FT /note="G -> V (in BC; dbSNP:rs55712212)" FT /id="VAR_005105" FT VARIANT 2275 FT /note="E -> G (in BC; unknown pathological significance)" FT /evidence="ECO:0000269|PubMed:15026808" FT /id="VAR_020730" FT VARIANT 2293 FT /note="F -> L (in BC; unknown pathological significance; FT dbSNP:rs80358912 and dbSNP:rs1381512588)" FT /evidence="ECO:0000269|PubMed:12442275" FT /id="VAR_020731" FT VARIANT 2336 FT /note="R -> H (in FANCD1; affects protein splicing and FT expression; decreases homologous recombination-mediated DNA FT repair; dbSNP:rs28897743)" FT /evidence="ECO:0000269|PubMed:16825431, FT ECO:0000269|PubMed:17924331, ECO:0000269|PubMed:21719596" FT /id="VAR_032730" FT VARIANT 2336 FT /note="R -> Q (in dbSNP:rs28897743)" FT /id="VAR_056757" FT VARIANT 2353 FT /note="G -> R (in BC; unknown pathological significance; FT dbSNP:rs80358935)" FT /evidence="ECO:0000269|PubMed:15026808" FT /id="VAR_020732" FT VARIANT 2415 FT /note="H -> N (in BC)" FT /evidence="ECO:0000269|PubMed:8640237" FT /id="VAR_005106" FT VARIANT 2421 FT /note="Q -> H (in BC)" FT /id="VAR_005107" FT VARIANT 2440 FT /note="H -> R (benign variant; no effect on FT homology-directed repair activity; dbSNP:rs4986860)" FT /evidence="ECO:0000269|PubMed:23108138, ECO:0000269|Ref.3" FT /id="VAR_018914" FT VARIANT 2447 FT /note="N -> D (in dbSNP:rs4986859)" FT /id="VAR_056758" FT VARIANT 2456 FT /note="Q -> E (in BC; dbSNP:rs397507912)" FT /evidence="ECO:0000269|PubMed:15172753" FT /id="VAR_032731" FT VARIANT 2466 FT /note="V -> A (in BC; benign variant; no effect on FT homology-directed repair activity; dbSNP:rs169547)" FT /evidence="ECO:0000269|PubMed:12552570, FT ECO:0000269|PubMed:15057823, ECO:0000269|PubMed:15172753, FT ECO:0000269|PubMed:23108138, ECO:0000269|PubMed:8524414, FT ECO:0000269|PubMed:8589730, ECO:0000269|PubMed:8665505, FT ECO:0000269|Ref.3" FT /id="VAR_008785" FT VARIANT 2480 FT /note="L -> V (in dbSNP:rs80358965)" FT /id="VAR_008786" FT VARIANT 2488 FT /note="R -> K (in BC; unknown pathological significance; FT dbSNP:rs80358968)" FT /evidence="ECO:0000269|PubMed:15026808" FT /id="VAR_020733" FT VARIANT 2490 FT /note="I -> T (benign variant; no effect on homologous FT recombination-mediated DNA repair; no effect on interaction FT with SEM1; dbSNP:rs11571707)" FT /evidence="ECO:0000269|PubMed:21719596, ECO:0000269|Ref.3" FT /id="VAR_008787" FT VARIANT 2502 FT /note="R -> C (in BC; unknown pathological significance; FT dbSNP:rs55716624)" FT /evidence="ECO:0000269|PubMed:17924331" FT /id="VAR_063911" FT VARIANT 2502 FT /note="R -> H (in ovarian cancer; unknown pathological FT significance; dbSNP:rs56070345)" FT /evidence="ECO:0000269|PubMed:10486320" FT /id="VAR_008788" FT VARIANT 2510 FT /note="L -> P (in FANCD1; hypersensitive to DNA damage; FT disrupts interaction with SEM1; decreased homology-directed FT repair activity; dbSNP:rs80358979)" FT /evidence="ECO:0000269|PubMed:14670928, FT ECO:0000269|PubMed:21719596, ECO:0000269|PubMed:23108138" FT /id="VAR_032732" FT VARIANT 2515 FT /note="T -> I (in BC; unknown pathological significance; FT dbSNP:rs28897744)" FT /evidence="ECO:0000269|PubMed:10978364" FT /id="VAR_008789" FT VARIANT 2626 FT /note="W -> C (in FANCD1; hypersensitive to DNA damage; FT reduced homology-directed repair activity; no effect on FT interaction with SEM1; dbSNP:rs80359013)" FT /evidence="ECO:0000269|PubMed:16825431, FT ECO:0000269|PubMed:17924331, ECO:0000269|PubMed:21719596, FT ECO:0000269|PubMed:23108138" FT /id="VAR_032733" FT VARIANT 2627 FT /note="I -> F (in BC; unknown pathological significance; FT reduced homology-directed repair activity; FT dbSNP:rs80359014)" FT /evidence="ECO:0000269|PubMed:17924331, FT ECO:0000269|PubMed:23108138" FT /id="VAR_063912" FT VARIANT 2653 FT /note="L -> P (in BC; unknown pathological significance; FT reduced homology-directed repair activity; FT dbSNP:rs80359022)" FT /evidence="ECO:0000269|PubMed:17924331, FT ECO:0000269|PubMed:23108138" FT /id="VAR_063913" FT VARIANT 2659 FT /note="R -> K (in BC; unknown pathological significance; FT dbSNP:rs80359027)" FT /evidence="ECO:0000269|PubMed:17924331" FT /id="VAR_063914" FT VARIANT 2663 FT /note="E -> V (probable disease-associated variant; may be FT associated with cancer susceptibility; major splicing FT aberration identified with this mutant; multifactorial FT likelihood analysis provides evidence for pathogenicity; FT dbSNP:rs80359031)" FT /evidence="ECO:0000269|PubMed:17924331, FT ECO:0000269|PubMed:20513136" FT /id="VAR_063915" FT VARIANT 2686 FT /note="L -> P (in dbSNP:rs28897746)" FT /id="VAR_056759" FT VARIANT 2706 FT /note="N -> S (in dbSNP:rs80359055)" FT /evidence="ECO:0000269|PubMed:12442273" FT /id="VAR_020734" FT VARIANT 2722 FT /note="T -> R (in BC; reduced homology-directed repair FT activity; dbSNP:rs80359062)" FT /evidence="ECO:0000269|PubMed:12145750, FT ECO:0000269|PubMed:17924331, ECO:0000269|PubMed:23108138" FT /id="VAR_018661" FT VARIANT 2723 FT /note="D -> G (in BC; has defective function consistent FT with pathogenicity; major splicing aberration identified FT with this mutant; reduced homology-directed repair FT activity; dbSNP:rs41293513)" FT /evidence="ECO:0000269|PubMed:17924331, FT ECO:0000269|PubMed:20513136, ECO:0000269|PubMed:23108138" FT /id="VAR_063916" FT VARIANT 2723 FT /note="D -> H (in BC; unknown pathological significance; FT disrupts interaction with SEM1 promoting interaction with FT XPO1 and BRCA2 cytoplasmic localization; in heterozygous FT state promotes RAD51 cytoplasmic localization; reduced FT homology-directed repair activity; dbSNP:rs41293511)" FT /evidence="ECO:0000269|PubMed:15026808, FT ECO:0000269|PubMed:23108138, ECO:0000269|PubMed:24013206" FT /id="VAR_020735" FT VARIANT 2728 FT /note="V -> I (in BC; dbSNP:rs28897749)" FT /evidence="ECO:0000269|PubMed:10399947, FT ECO:0000269|PubMed:10978364, ECO:0000269|PubMed:12215251" FT /id="VAR_020736" FT VARIANT 2729 FT /note="K -> N (in BC; unknown pathological significance; no FT effect on homologous recombination-mediated DNA repair; no FT effect on interaction with SEM1; dbSNP:rs80359065)" FT /evidence="ECO:0000269|PubMed:12442274, FT ECO:0000269|PubMed:21719596, ECO:0000269|PubMed:23108138" FT /id="VAR_020737" FT VARIANT 2748 FT /note="G -> D (in BC; unknown pathological significance; FT dbSNP:rs80359071)" FT /evidence="ECO:0000269|PubMed:17924331" FT /id="VAR_063917" FT VARIANT 2787 FT /note="R -> H (in ovarian cancer and BC; somatic mutation; FT unknown pathological significance; small decrease of FT homology-directed repair activity; dbSNP:rs80359078)" FT /evidence="ECO:0000269|PubMed:23108138, FT ECO:0000269|PubMed:8665505" FT /id="VAR_008790" FT VARIANT 2792 FT /note="L -> P (in BC; unknown pathological significance; FT decreased homology-directed repair activity; FT dbSNP:rs28897751)" FT /evidence="ECO:0000269|PubMed:23108138" FT /id="VAR_056760" FT VARIANT 2793 FT /note="G -> R (in BC; unknown pathological significance; FT decreased homology-directed repair activity; FT dbSNP:rs80359082)" FT /evidence="ECO:0000269|PubMed:12442275, FT ECO:0000269|PubMed:23108138" FT /id="VAR_020738" FT VARIANT 2835 FT /note="S -> P (in dbSNP:rs11571746)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_018915" FT VARIANT 2842 FT /note="R -> C (in one patient with esophageal carcinoma; FT somatic mutation; decreased homology-directed repair FT activity; dbSNP:rs80359104)" FT /evidence="ECO:0000269|PubMed:11948123, FT ECO:0000269|PubMed:23108138" FT /id="VAR_032734" FT VARIANT 2856 FT /note="E -> A (in BC; unknown pathological significance; no FT effect on homology-directed repair activity; FT dbSNP:rs11571747)" FT /evidence="ECO:0000269|PubMed:15026808, FT ECO:0000269|PubMed:23108138, ECO:0000269|Ref.3" FT /id="VAR_018916" FT VARIANT 2944 FT /note="I -> F (in dbSNP:rs4987047)" FT /evidence="ECO:0000269|PubMed:15635067, ECO:0000269|Ref.3" FT /id="VAR_008791" FT VARIANT 2950 FT /note="K -> N (in BC; unknown pathological significance; FT dbSNP:rs28897754)" FT /evidence="ECO:0000269|PubMed:15026808, FT ECO:0000269|PubMed:15635067" FT /id="VAR_020739" FT VARIANT 2951 FT /note="A -> T (in BC; unknown pathological significance; no FT effect on homology-directed repair activity; FT dbSNP:rs11571769)" FT /evidence="ECO:0000269|PubMed:12215251, FT ECO:0000269|PubMed:23108138, ECO:0000269|Ref.3" FT /id="VAR_008792" FT VARIANT 2969 FT /note="V -> M (in dbSNP:rs59004709)" FT /id="VAR_008793" FT VARIANT 3013 FT /note="T -> I (in BC; unknown pathological significance; no FT effect on homology-directed repair activity; FT dbSNP:rs28897755)" FT /evidence="ECO:0000269|PubMed:15026808, FT ECO:0000269|PubMed:15635067, ECO:0000269|PubMed:23108138" FT /id="VAR_020740" FT VARIANT 3052 FT /note="R -> W (in BC; has defective function consistent FT with pathogenicity; multifactorial likelihood analysis FT provides evidence for pathogenicity; reduced FT homology-directed repair activity; dbSNP:rs45580035)" FT /evidence="ECO:0000269|PubMed:20513136, FT ECO:0000269|PubMed:23108138" FT /id="VAR_063918" FT VARIANT 3063 FT /note="P -> S (in a patient with ovarian cancer; unknown FT pathological significance; no effect on homology-directed FT repair activity; dbSNP:rs80359176)" FT /evidence="ECO:0000269|PubMed:14746861, FT ECO:0000269|PubMed:23108138" FT /id="VAR_020741" FT VARIANT 3076 FT /note="G -> E (in BC; also found in pancreatic cancer; FT decreased homology-directed repair activity; FT dbSNP:rs80359187)" FT /evidence="ECO:0000269|PubMed:11149425, FT ECO:0000269|PubMed:12569143, ECO:0000269|PubMed:23108138" FT /id="VAR_020742" FT VARIANT 3095 FT /note="D -> E (in BC; unknown pathological significance; FT reduced homology-directed repair activity; FT dbSNP:rs80359198)" FT /evidence="ECO:0000269|PubMed:17924331, FT ECO:0000269|PubMed:23108138, ECO:0000269|PubMed:8640235" FT /id="VAR_005108" FT VARIANT 3098 FT /note="Y -> H (in BC and ovarian cancer; unknown FT pathological significance; no effect on homology-directed FT repair activity; dbSNP:rs41293521)" FT /evidence="ECO:0000269|PubMed:10486320, FT ECO:0000269|PubMed:15026808, ECO:0000269|PubMed:23108138" FT /id="VAR_008794" FT VARIANT 3101 FT /note="L -> R (in dbSNP:rs28897758)" FT /id="VAR_056761" FT VARIANT 3103 FT /note="I -> M (in melanoma; dbSNP:rs80359204)" FT /id="VAR_005109" FT VARIANT 3118 FT /note="M -> T (in BC; dbSNP:rs56204128)" FT /evidence="ECO:0000269|PubMed:9609997" FT /id="VAR_005110" FT VARIANT 3124 FT /note="N -> I (in BC; reduced homology-directed repair FT activity; dbSNP:rs28897759)" FT /evidence="ECO:0000269|PubMed:11139248, FT ECO:0000269|PubMed:23108138" FT /id="VAR_020743" FT VARIANT 3196 FT /note="K -> E (in BC; dbSNP:rs80359228)" FT /evidence="ECO:0000269|PubMed:11139248" FT /id="VAR_020744" FT VARIANT 3244 FT /note="V -> I (in dbSNP:rs11571831)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_018917" FT VARIANT 3257 FT /note="K -> R (in dbSNP:rs55847618)" FT /id="VAR_008795" FT VARIANT 3276 FT /note="R -> S (in dbSNP:rs80359245)" FT /id="VAR_008796" FT VARIANT 3300 FT /note="P -> S (in one patient with esophageal carcinoma; FT dbSNP:rs770868371)" FT /evidence="ECO:0000269|PubMed:11948123" FT /id="VAR_032735" FT VARIANT 3357 FT /note="T -> R (in BC; dbSNP:rs80358388)" FT /id="VAR_005111" FT VARIANT 3374 FT /note="T -> I (in dbSNP:rs56309455)" FT /evidence="ECO:0000269|PubMed:12442275" FT /id="VAR_020745" FT VARIANT 3412 FT /note="I -> V (in dbSNP:rs1801426)" FT /evidence="ECO:0000269|PubMed:10323242, FT ECO:0000269|PubMed:10978364, ECO:0000269|PubMed:12442274, FT ECO:0000269|PubMed:14746861, ECO:0000269|PubMed:15026808, FT ECO:0000269|PubMed:15365993, ECO:0000269|PubMed:9150152, FT ECO:0000269|Ref.3" FT /id="VAR_005112" FT MUTAGEN 2725 FT /note="W->A: Disrupts interaction with SEM1." FT /evidence="ECO:0000269|PubMed:24013206" FT MUTAGEN 3291 FT /note="S->E: Impaired interaction with RAD51." FT /evidence="ECO:0000269|PubMed:15800615" FT MUTAGEN 3387 FT /note="T->A: Loss of phosphorylation by CHEK1 and CHEK2 (in FT vitro)." FT /evidence="ECO:0000269|PubMed:18317453" FT CONFLICT 758 FT /note="S -> N (in Ref. 1; CAA64484)" FT /evidence="ECO:0000305" FT CONFLICT 1761..1762 FT /note="GY -> RI (in Ref. 1; CAA64484)" FT /evidence="ECO:0000305" FT CONFLICT 1767 FT /note="K -> N (in Ref. 1; CAA64484)" FT /evidence="ECO:0000305" FT CONFLICT 2536 FT /note="S -> P (in Ref. 4; CAA98995)" FT /evidence="ECO:0000305" FT CONFLICT 3216 FT /note="L -> LVS (in Ref. 4; CAA97728)" FT /evidence="ECO:0000305" FT HELIX 31..35 FT /evidence="ECO:0007829|PDB:3EU7" FT STRAND 203..206 FT /evidence="ECO:0007829|PDB:6GY2" FT STRAND 1228..1230 FT /evidence="ECO:0007829|PDB:6HQU" FT HELIX 1231..1241 FT /evidence="ECO:0007829|PDB:6HQU" FT HELIX 1520..1522 FT /evidence="ECO:0007829|PDB:1N0W" FT HELIX 1536..1541 FT /evidence="ECO:0007829|PDB:1N0W" FT TURN 1542..1546 FT /evidence="ECO:0007829|PDB:1N0W" FT STRAND 2300..2302 FT /evidence="ECO:0007829|PDB:7LDG" FT HELIX 2311..2314 FT /evidence="ECO:0007829|PDB:7LDG" FT STRAND 2315..2317 FT /evidence="ECO:0007829|PDB:7LDG" SQ SEQUENCE 3418 AA; 384230 MW; 98A48F16848D2644 CRC64; MPIGSKERPT FFEIFKTRCN KADLGPISLN WFEELSSEAP PYNSEPAEES EHKNNNYEPN LFKTPQRKPS YNQLASTPII FKEQGLTLPL YQSPVKELDK FKLDLGRNVP NSRHKSLRTV KTKMDQADDV SCPLLNSCLS ESPVVLQCTH VTPQRDKSVV CGSLFHTPKF VKGRQTPKHI SESLGAEVDP DMSWSSSLAT PPTLSSTVLI VRNEEASETV FPHDTTANVK SYFSNHDESL KKNDRFIASV TDSENTNQRE AASHGFGKTS GNSFKVNSCK DHIGKSMPNV LEDEVYETVV DTSEEDSFSL CFSKCRTKNL QKVRTSKTRK KIFHEANADE CEKSKNQVKE KYSFVSEVEP NDTDPLDSNV ANQKPFESGS DKISKEVVPS LACEWSQLTL SGLNGAQMEK IPLLHISSCD QNISEKDLLD TENKRKKDFL TSENSLPRIS SLPKSEKPLN EETVVNKRDE EQHLESHTDC ILAVKQAISG TSPVASSFQG IKKSIFRIRE SPKETFNASF SGHMTDPNFK KETEASESGL EIHTVCSQKE DSLCPNLIDN GSWPATTTQN SVALKNAGLI STLKKKTNKF IYAIHDETSY KGKKIPKDQK SELINCSAQF EANAFEAPLT FANADSGLLH SSVKRSCSQN DSEEPTLSLT SSFGTILRKC SRNETCSNNT VISQDLDYKE AKCNKEKLQL FITPEADSLS CLQEGQCEND PKSKKVSDIK EEVLAAACHP VQHSKVEYSD TDFQSQKSLL YDHENASTLI LTPTSKDVLS NLVMISRGKE SYKMSDKLKG NNYESDVELT KNIPMEKNQD VCALNENYKN VELLPPEKYM RVASPSRKVQ FNQNTNLRVI QKNQEETTSI SKITVNPDSE ELFSDNENNF VFQVANERNN LALGNTKELH ETDLTCVNEP IFKNSTMVLY GDTGDKQATQ VSIKKDLVYV LAEENKNSVK QHIKMTLGQD LKSDISLNID KIPEKNNDYM NKWAGLLGPI SNHSFGGSFR TASNKEIKLS EHNIKKSKMF FKDIEEQYPT SLACVEIVNT LALDNQKKLS KPQSINTVSA HLQSSVVVSD CKNSHITPQM LFSKQDFNSN HNLTPSQKAE ITELSTILEE SGSQFEFTQF RKPSYILQKS TFEVPENQMT ILKTTSEECR DADLHVIMNA PSIGQVDSSK QFEGTVEIKR KFAGLLKNDC NKSASGYLTD ENEVGFRGFY SAHGTKLNVS TEALQKAVKL FSDIENISEE TSAEVHPISL SSSKCHDSVV SMFKIENHND KTVSEKNNKC QLILQNNIEM TTGTFVEEIT ENYKRNTENE DNKYTAASRN SHNLEFDGSD SSKNDTVCIH KDETDLLFTD QHNICLKLSG QFMKEGNTQI KEDLSDLTFL EVAKAQEACH GNTSNKEQLT ATKTEQNIKD FETSDTFFQT ASGKNISVAK ESFNKIVNFF DQKPEELHNF SLNSELHSDI RKNKMDILSY EETDIVKHKI LKESVPVGTG NQLVTFQGQP ERDEKIKEPT LLGFHTASGK KVKIAKESLD KVKNLFDEKE QGTSEITSFS HQWAKTLKYR EACKDLELAC ETIEITAAPK CKEMQNSLNN DKNLVSIETV VPPKLLSDNL CRQTENLKTS KSIFLKVKVH ENVEKETAKS PATCYTNQSP YSVIENSALA FYTSCSRKTS VSQTSLLEAK KWLREGIFDG QPERINTADY VGNYLYENNS NSTIAENDKN HLSEKQDTYL SNSSMSNSYS YHSDEVYNDS GYLSKNKLDS GIEPVLKNVE DQKNTSFSKV ISNVKDANAY PQTVNEDICV EELVTSSSPC KNKNAAIKLS ISNSNNFEVG PPAFRIASGK IVCVSHETIK KVKDIFTDSF SKVIKENNEN KSKICQTKIM AGCYEALDDS EDILHNSLDN DECSTHSHKV FADIQSEEIL QHNQNMSGLE KVSKISPCDV SLETSDICKC SIGKLHKSVS SANTCGIFST ASGKSVQVSD ASLQNARQVF SEIEDSTKQV FSKVLFKSNE HSDQLTREEN TAIRTPEHLI SQKGFSYNVV NSSAFSGFST ASGKQVSILE SSLHKVKGVL EEFDLIRTEH SLHYSPTSRQ NVSKILPRVD KRNPEHCVNS EMEKTCSKEF KLSNNLNVEG GSSENNHSIK VSPYLSQFQQ DKQQLVLGTK VSLVENIHVL GKEQASPKNV KMEIGKTETF SDVPVKTNIE VCSTYSKDSE NYFETEAVEI AKAFMEDDEL TDSKLPSHAT HSLFTCPENE EMVLSNSRIG KRRGEPLILV GEPSIKRNLL NEFDRIIENQ EKSLKASKST PDGTIKDRRL FMHHVSLEPI TCVPFRTTKE RQEIQNPNFT APGQEFLSKS HLYEHLTLEK SSSNLAVSGH PFYQVSATRN EKMRHLITTG RPTKVFVPPF KTKSHFHRVE QCVRNINLEE NRQKQNIDGH GSDDSKNKIN DNEIHQFNKN NSNQAVAVTF TKCEEEPLDL ITSLQNARDI QDMRIKKKQR QRVFPQPGSL YLAKTSTLPR ISLKAAVGGQ VPSACSHKQL YTYGVSKHCI KINSKNAESF QFHTEDYFGK ESLWTGKGIQ LADGGWLIPS NDGKAGKEEF YRALCDTPGV DPKLISRIWV YNHYRWIIWK LAAMECAFPK EFANRCLSPE RVLLQLKYRY DTEIDRSRRS AIKKIMERDD TAAKTLVLCV SDIISLSANI SETSSNKTSS ADTQKVAIIE LTDGWYAVKA QLDPPLLAVL KNGRLTVGQK IILHGAELVG SPDACTPLEA PESLMLKISA NSTRPARWYT KLGFFPDPRP FPLPLSSLFS DGGNVGCVDV IIQRAYPIQW MEKTSSGLYI FRNEREEEKE AAKYVEAQQK RLEALFTKIQ EEFEEHEENT TKPYLPSRAL TRQQVRALQD GAELYEAVKN AADPAYLEGY FSEEQLRALN NHRQMLNDKK QAQIQLEIRK AMESAEQKEQ GLSRDVTTVW KLRIVSYSKK EKDSVILSIW RPSSDLYSLL TEGKRYRIYH LATSKSKSKS ERANIQLAAT KKTQYQQLPV SDEILFQIYQ PREPLHFSKF LDPDFQPSCS EVDLIGFVVS VVKKTGLAPF VYLSDECYNL LAIKFWIDLN EDIIKPHMLI AASNLQWRPE SKSGLLTLFA GDFSVFSASP KEGHFQETFN KMKNTVENID ILCNEAENKL MHILHANDPK WSTPTKDCTS GPYTAQIIPG TGNKLLMSSP NCEIYYQSPL SLCMAKRKSV STPVSAQMTS KSCKGEKEID DQKNCKKRRA LDFLSRLPLP PPVSPICTFV SPAAQKAFQP PRSCGTKYET PIKKKELNSP QMTPFKKFNE ISLLESNSIA DEELALINTQ ALLSGSTGEK QFISVSESTR TAPTSSEDYL RLKRRCTTSL IKEQESSQAS TEECEKNKQD TITTKKYI // ID PALB2_HUMAN Reviewed; 1186 AA. AC Q86YC2; A6NIE1; Q8N7Y6; Q8ND31; Q9H6W1; DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2003, sequence version 1. DT 25-MAY-2022, entry version 157. DE RecName: Full=Partner and localizer of BRCA2; GN Name=PALB2; Synonyms=FANCN; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Endometrium; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-440 AND 476-1186. RC TISSUE=Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION, AND RP INTERACTION WITH BRCA2. RX PubMed=16793542; DOI=10.1016/j.molcel.2006.05.022; RA Xia B., Sheng Q., Nakanishi K., Ohashi A., Wu J., Christ N., Liu X., RA Jasin M., Couch F.J., Livingston D.M.; RT "Control of BRCA2 cellular and clinical functions by a nuclear partner, RT PALB2."; RL Mol. Cell 22:719-729(2006). RN [7] RP INVOLVEMENT IN SUSCEPTIBILITY TO BREAST CANCER. RX PubMed=17287723; DOI=10.1038/nature05609; RA Erkko H., Xia B., Nikkilae J., Schleutker J., Syrjaekoski K., Mannermaa A., RA Kallioniemi A., Pylkaes K., Karppinen S.-M., Rapakko K., Miron A., RA Sheng Q., Li G., Mattila H., Bell D.W., Haber D.A., Grip M., Reiman M., RA Jukkola-Vuorinen A., Mustonen A., Kere J., Aaltonen L.A., Kosma V.-M., RA Kataja V., Soini Y., Drapkin R.I., Livingston D.M., Winqvist R.; RT "A recurrent mutation in PALB2 in Finnish cancer families."; RL Nature 446:316-319(2007). RN [8] RP INVOLVEMENT IN FANCN. RX PubMed=17200672; DOI=10.1038/ng1942; RA Xia B., Dorsman J.C., Ameziane N., de Vries Y., Rooimans M.A., Sheng Q., RA Pals G., Errami A., Gluckman E., Llera J., Wang W., Livingston D.M., RA Joenje H., de Winter J.P.; RT "Fanconi anemia is associated with a defect in the BRCA2 partner PALB2."; RL Nat. Genet. 39:159-161(2007). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-376, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [11] RP FUNCTION, SUBUNIT, AND INTERACTION WITH BRCA2. RX PubMed=19423707; DOI=10.1074/jbc.m109.016717; RA Sy S.M., Huen M.S., Zhu Y., Chen J.; RT "PALB2 regulates recombinational repair through chromatin association and RT oligomerization."; RL J. Biol. Chem. 284:18302-18310(2009). RN [12] RP FUNCTION, IDENTIFICATION IN A BRCA COMPLEX WITH BRCA1 AND BRCA2, RP INTERACTION WITH BRCA1, AND MUTAGENESIS OF LYS-14; LEU-21; TYR-28; LEU-35 RP AND GLU-42. RX PubMed=19369211; DOI=10.1073/pnas.0811159106; RA Sy S.M., Huen M.S., Chen J.; RT "PALB2 is an integral component of the BRCA complex required for homologous RT recombination repair."; RL Proc. Natl. Acad. Sci. U.S.A. 106:7155-7160(2009). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-387, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [14] RP INVOLVEMENT IN PNCA3. RX PubMed=19264984; DOI=10.1126/science.1171202; RA Jones S., Hruban R.H., Kamiyama M., Borges M., Zhang X., Parsons D.W., RA Lin J.C., Palmisano E., Brune K., Jaffee E.M., Iacobuzio-Donahue C.A., RA Maitra A., Parmigiani G., Kern S.E., Velculescu V.E., Kinzler K.W., RA Vogelstein B., Eshleman J.R., Goggins M., Klein A.P.; RT "Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility RT gene."; RL Science 324:217-217(2009). RN [15] RP INTERACTION WITH MORF4L1. RX PubMed=20332121; DOI=10.1242/jcs.060178; RA Hayakawa T., Zhang F., Hayakawa N., Ohtani Y., Shinmyozu K., Nakayama J., RA Andreassen P.R.; RT "MRG15 binds directly to PALB2 and stimulates homology-directed repair of RT chromosomal breaks."; RL J. Cell Sci. 123:1124-1130(2010). RN [16] RP FUNCTION, AND INTERACTION WITH RAD51. RX PubMed=20871615; DOI=10.1038/nsmb.1915; RA Buisson R., Dion-Cote A.M., Coulombe Y., Launay H., Cai H., Stasiak A.Z., RA Stasiak A., Xia B., Masson J.Y.; RT "Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in RT stimulating homologous recombination."; RL Nat. Struct. Mol. Biol. 17:1247-1254(2010). RN [17] RP FUNCTION, AND INTERACTION WITH RAD51 AND RAD51AP1. RX PubMed=20871616; DOI=10.1038/nsmb.1916; RA Dray E., Etchin J., Wiese C., Saro D., Williams G.J., Hammel M., Yu X., RA Galkin V.E., Liu D., Tsai M.S., Sy S.M., Schild D., Egelman E., Chen J., RA Sung P.; RT "Enhancement of RAD51 recombinase activity by the tumor suppressor PALB2."; RL Nat. Struct. Mol. Biol. 17:1255-1259(2010). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-376, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [20] RP ASSOCIATION WITH CHROMATIN, AND ASSOCIATION WITH NUCLEOSOMES. RX PubMed=22193777; DOI=10.1038/embor.2011.243; RA Bleuyard J.Y., Buisson R., Masson J.Y., Esashi F.; RT "ChAM, a novel motif that mediates PALB2 intrinsic chromatin binding and RT facilitates DNA repair."; RL EMBO Rep. 13:135-141(2012). RN [21] RP INVOLVEMENT IN SUSCEPTIBILITY TO BREAST CANCER. RX PubMed=22241545; DOI=10.1002/humu.22022; RA Tischkowitz M., Capanu M., Sabbaghian N., Li L., Liang X., Vallee M.P., RA Tavtigian S.V., Concannon P., Foulkes W.D., Bernstein L., Bernstein J.L., RA Begg C.B.; RT "Rare germline mutations in PALB2 and breast cancer risk: a population- RT based study."; RL Hum. Mutat. 33:674-680(2012). RN [22] RP FUNCTION, AND SELF-ASSOCIATION. RX PubMed=22941656; DOI=10.1093/nar/gks807; RA Buisson R., Masson J.Y.; RT "PALB2 self-interaction controls homologous recombination."; RL Nucleic Acids Res. 40:10312-10323(2012). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-172; SER-190; SER-285; RP SER-376; SER-387; SER-454; SER-660 AND SER-781, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [24] RP FUNCTION, INTERACTION WITH BRCA2; RAD51C; RAD51 AND XRCC3, MUTAGENESIS OF RP THR-1030, AND CHARACTERIZATION OF VARIANTS TRP-939 AND PRO-1143. RX PubMed=24141787; DOI=10.1038/onc.2013.421; RA Park J.Y., Singh T.R., Nassar N., Zhang F., Freund M., Hanenberg H., RA Meetei A.R., Andreassen P.R.; RT "Breast cancer-associated missense mutants of the PALB2 WD40 domain, which RT directly binds RAD51C, RAD51 and BRCA2, disrupt DNA repair."; RL Oncogene 33:4803-4812(2014). RN [25] RP FUNCTION, AND INTERACTION WITH POLH. RX PubMed=24485656; DOI=10.1016/j.celrep.2014.01.009; RA Buisson R., Niraj J., Pauty J., Maity R., Zhao W., Coulombe Y., Sung P., RA Masson J.Y.; RT "Breast cancer proteins PALB2 and BRCA2 stimulate polymerase eta in RT recombination-associated DNA synthesis at blocked replication forks."; RL Cell Rep. 6:553-564(2014). RN [26] RP IDENTIFICATION IN THE HR COMPLEX, INTERACTION WITH ERCC5 AND BRCA2, AND RP SUBCELLULAR LOCATION. RX PubMed=26833090; DOI=10.1016/j.molcel.2015.12.026; RA Trego K.S., Groesser T., Davalos A.R., Parplys A.C., Zhao W., Nelson M.R., RA Hlaing A., Shih B., Rydberg B., Pluth J.M., Tsai M.S., Hoeijmakers J.H.J., RA Sung P., Wiese C., Campisi J., Cooper P.K.; RT "Non-catalytic Roles for XPG with BRCA1 and BRCA2 in Homologous RT Recombination and Genome Stability."; RL Mol. Cell 61:535-546(2016). RN [27] RP FUNCTION, SUBUNIT, INTERACTION WITH BRCA1; BRCA2 AND RAD51, SUBCELLULAR RP LOCATION, VARIANT BC PRO-35, CHARACTERIZATION OF VARIANT BC PRO-35, AND RP CHARACTERIZATION OF VARIANTS ARG-18; CYS-28 AND HIS-37. RX PubMed=28319063; DOI=10.1038/onc.2017.46; RA Foo T.K., Tischkowitz M., Simhadri S., Boshari T., Zayed N., Burke K.A., RA Berman S.H., Blecua P., Riaz N., Huo Y., Ding Y.C., Neuhausen S.L., RA Weigelt B., Reis-Filho J.S., Foulkes W.D., Xia B.; RT "Compromised BRCA1-PALB2 interaction is associated with breast cancer RT risk."; RL Oncogene 36:4161-4170(2017). RN [28] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 835-1186 ALONE AND IN COMPLEX WITH RP A BRCA2 PEPTIDE, AND DOMAIN WD REPEATS. RX PubMed=19609323; DOI=10.1038/embor.2009.126; RA Oliver A.W., Swift S., Lord C.J., Ashworth A., Pearl L.H.; RT "Structural basis for recruitment of BRCA2 by PALB2."; RL EMBO Rep. 10:990-996(2009). RN [29] RP VARIANT [LARGE SCALE ANALYSIS] SER-864. RX PubMed=18987736; DOI=10.1038/nature07485; RA Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K., RA Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L., RA Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A., RA Abbott S., Locke D., Hillier L.W., Miner T., Fulton L., Magrini V., RA Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R., RA Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E., RA Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S., RA Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A., RA DiPersio J.F., Wilson R.K.; RT "DNA sequencing of a cytogenetically normal acute myeloid leukaemia RT genome."; RL Nature 456:66-72(2008). RN [30] RP VARIANTS TYR-46; GLY-219; CYS-334; SER-337; GLN-414; MET-425; THR-491; RP ARG-515; ARG-559; GLN-672; VAL-712; LEU-728; SER-864; ALA-917; MET-932; RP TRP-939; VAL-966; GLU-998; THR-1025; ALA-1043; GLY-1075; ALA-1105; RP HIS-1114; PRO-1143 AND TYR-1170. RX PubMed=21618343; DOI=10.1002/humu.21478; RA Hellebrand H., Sutter C., Honisch E., Gross E., Wappenschmidt B., Schem C., RA Deissler H., Ditsch N., Gress V., Kiechle M., Bartram C.R., RA Schmutzler R.K., Niederacher D., Arnold N., Meindl A.; RT "Germline mutations in the PALB2 gene are population specific and occur RT with low frequencies in familial breast cancer."; RL Hum. Mutat. 32:E2176-E2188(2011). CC -!- FUNCTION: Plays a critical role in homologous recombination repair CC (HRR) through its ability to recruit BRCA2 and RAD51 to DNA breaks CC (PubMed:16793542, PubMed:19423707, PubMed:19369211, PubMed:22941656, CC PubMed:24141787, PubMed:28319063). Strongly stimulates the DNA strand- CC invasion activity of RAD51, stabilizes the nucleoprotein filament CC against a disruptive BRC3-BRC4 polypeptide and helps RAD51 to overcome CC the suppressive effect of replication protein A (RPA) CC (PubMed:20871615). Functionally cooperates with RAD51AP1 in promoting CC of D-loop formation by RAD51 (PubMed:20871616). Serves as the molecular CC scaffold in the formation of the BRCA1-PALB2-BRCA2 complex which is CC essential for homologous recombination (PubMed:19369211). Via its WD CC repeats is proposed to scaffold a HR complex containing RAD51C and CC BRCA2 which is thought to play a role in HR-mediated DNA repair CC (PubMed:24141787). Essential partner of BRCA2 that promotes the CC localization and stability of BRCA2 (PubMed:16793542). Also enables its CC recombinational repair and checkpoint functions of BRCA2 CC (PubMed:16793542). May act by promoting stable association of BRCA2 CC with nuclear structures, allowing BRCA2 to escape the effects of CC proteasome-mediated degradation (PubMed:16793542). Binds DNA with high CC affinity for D loop, which comprises single-stranded, double-stranded CC and branched DNA structures (PubMed:20871616). May play a role in the CC extension step after strand invasion at replication-dependent DNA CC double-strand breaks; together with BRCA2 is involved in both POLH CC localization at collapsed replication forks and DNA polymerization CC activity (PubMed:24485656). {ECO:0000269|PubMed:16793542, CC ECO:0000269|PubMed:19369211, ECO:0000269|PubMed:19423707, CC ECO:0000269|PubMed:20871615, ECO:0000269|PubMed:20871616, CC ECO:0000269|PubMed:22941656, ECO:0000269|PubMed:24141787, CC ECO:0000269|PubMed:24485656, ECO:0000269|PubMed:28319063}. CC -!- SUBUNIT: Homooligomer; dissociated upon DNA damage thus allowing CC association with BRCA1 (PubMed:19423707, PubMed:28319063). CC Oligomerization is essential for its focal accumulation at DNA breaks CC (PubMed:19423707). Part of a BRCA complex containing BRCA1, BRCA2 and CC PALB2 (PubMed:19369211). Interacts with BRCA1 and this interaction is CC essential for its function in HRR (PubMed:19369211, PubMed:28319063). CC Interacts with RAD51AP1 and MORF4L1/MRG15 (PubMed:20332121, CC PubMed:20871616). Component of the homologous recombination repair (HR) CC complex composed of ERCC5/XPG, BRCA2, PALB2, DSS1 and RAD51 CC (PubMed:26833090). Within the complex, interacts with ERCC5/XPG and CC BRCA2 (PubMed:26833090). Interacts with BRCA2, RAD51C, RAD51 and XRCC3; CC the interactions are direct and it may serve as a scaffold for a HR CC complex containing PALB2, BRCA2, RAD51C, RAD51 and XRCC3 CC (PubMed:28319063, PubMed:16793542, PubMed:19423707, PubMed:19609323, CC PubMed:20871615, PubMed:20871616, PubMed:24141787). Interacts with CC POLH; the interaction is direct (PubMed:24485656). CC {ECO:0000269|PubMed:16793542, ECO:0000269|PubMed:19369211, CC ECO:0000269|PubMed:19423707, ECO:0000269|PubMed:19609323, CC ECO:0000269|PubMed:20332121, ECO:0000269|PubMed:20871615, CC ECO:0000269|PubMed:20871616, ECO:0000269|PubMed:24141787, CC ECO:0000269|PubMed:24485656, ECO:0000269|PubMed:26833090, CC ECO:0000269|PubMed:28319063}. CC -!- INTERACTION: CC Q86YC2; P38398: BRCA1; NbExp=27; IntAct=EBI-1222653, EBI-349905; CC Q86YC2; P51587: BRCA2; NbExp=25; IntAct=EBI-1222653, EBI-79792; CC Q86YC2; Q14145: KEAP1; NbExp=4; IntAct=EBI-1222653, EBI-751001; CC Q86YC2; Q9UBU8-2: MORF4L1; NbExp=3; IntAct=EBI-1222653, EBI-10288852; CC Q86YC2; Q9Y253: POLH; NbExp=7; IntAct=EBI-1222653, EBI-2827270; CC Q86YC2; Q06609: RAD51; NbExp=8; IntAct=EBI-1222653, EBI-297202; CC Q86YC2; Q96B01-2: RAD51AP1; NbExp=2; IntAct=EBI-1222653, EBI-1178743; CC Q86YC2; O43502: RAD51C; NbExp=10; IntAct=EBI-1222653, EBI-2267048; CC Q86YC2; P51784: USP11; NbExp=2; IntAct=EBI-1222653, EBI-306876; CC Q86YC2; O43542: XRCC3; NbExp=3; IntAct=EBI-1222653, EBI-2849976; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16793542, CC ECO:0000269|PubMed:26833090, ECO:0000269|PubMed:28319063}. CC Note=Colocalizes with BRCA2 and BRCA1 in nuclear foci. CC {ECO:0000269|PubMed:16793542, ECO:0000269|PubMed:28319063}. CC -!- DOMAIN: Interaction with BRCA2 occurs through a hydrophobic pocket at CC the crossover between WD repeats 4 and 5. CC {ECO:0000269|PubMed:19609323}. CC -!- DOMAIN: The coiled coil domain mediates self-association. CC {ECO:0000269|PubMed:19609323, ECO:0000269|PubMed:22941656}. CC -!- DOMAIN: The chromatin-association motif (ChAM) mediates association CC with chromatin, probably through nucleosome core particles, CC independently from binding to D loop, ssDNA or dsDNA structures. CC {ECO:0000269|PubMed:19609323, ECO:0000269|PubMed:22193777}. CC -!- DISEASE: Breast cancer (BC) [MIM:114480]: A common malignancy CC originating from breast epithelial tissue. Breast neoplasms can be CC distinguished by their histologic pattern. Invasive ductal carcinoma is CC by far the most common type. Breast cancer is etiologically and CC genetically heterogeneous. Important genetic factors have been CC indicated by familial occurrence and bilateral involvement. Mutations CC at more than one locus can be involved in different families or even in CC the same case. {ECO:0000269|PubMed:17287723, CC ECO:0000269|PubMed:22241545, ECO:0000269|PubMed:28319063}. Note=Disease CC susceptibility is associated with variants affecting the gene CC represented in this entry. Breast cancer susceptibility is strongly CC associated with PALB2 truncating mutations. Conversely, rare missense CC mutations do not strongly influence breast cancer risk CC (PubMed:22241545). {ECO:0000269|PubMed:22241545}. CC -!- DISEASE: Fanconi anemia complementation group N (FANCN) [MIM:610832]: A CC disorder affecting all bone marrow elements and resulting in anemia, CC leukopenia and thrombopenia. It is associated with cardiac, renal and CC limb malformations, dermal pigmentary changes, and a predisposition to CC the development of malignancies. At the cellular level it is associated CC with hypersensitivity to DNA-damaging agents, chromosomal instability CC (increased chromosome breakage) and defective DNA repair. CC {ECO:0000269|PubMed:17200672}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Pancreatic cancer 3 (PNCA3) [MIM:613348]: A malignant neoplasm CC of the pancreas. Tumors can arise from both the exocrine and endocrine CC portions of the pancreas, but 95% of them develop from the exocrine CC portion, including the ductal epithelium, acinar cells, connective CC tissue, and lymphatic tissue. {ECO:0000269|PubMed:19264984}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SEQUENCE CAUTION: CC Sequence=BAB15140.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AL834425; CAD39086.1; -; mRNA. DR EMBL; CR749637; CAH18431.1; -; mRNA. DR EMBL; AC008870; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471145; EAW55813.1; -; Genomic_DNA. DR EMBL; BC044254; AAH44254.1; -; mRNA. DR EMBL; AK025469; BAB15140.1; ALT_INIT; mRNA. DR EMBL; AK097533; BAC05090.1; -; mRNA. DR CCDS; CCDS32406.1; -. DR RefSeq; NP_078951.2; NM_024675.3. DR PDB; 2W18; X-ray; 1.90 A; A=835-1186. DR PDB; 3EU7; X-ray; 2.20 A; A=835-1186. DR PDBsum; 2W18; -. DR PDBsum; 3EU7; -. DR AlphaFoldDB; Q86YC2; -. DR SMR; Q86YC2; -. DR BioGRID; 122843; 78. DR ComplexPortal; CPX-845; BRCA1-PALB2-BRCA2 homologous recombination DNA repair complex. DR DIP; DIP-38427N; -. DR ELM; Q86YC2; -. DR IntAct; Q86YC2; 39. DR MINT; Q86YC2; -. DR STRING; 9606.ENSP00000261584; -. DR GlyGen; Q86YC2; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q86YC2; -. DR PhosphoSitePlus; Q86YC2; -. DR BioMuta; PALB2; -. DR DMDM; 74727919; -. DR CPTAC; CPTAC-3284; -. DR EPD; Q86YC2; -. DR jPOST; Q86YC2; -. DR MassIVE; Q86YC2; -. DR MaxQB; Q86YC2; -. DR PaxDb; Q86YC2; -. DR PeptideAtlas; Q86YC2; -. DR PRIDE; Q86YC2; -. DR ProteomicsDB; 70395; -. DR Antibodypedia; 26008; 239 antibodies from 35 providers. DR CPTC; Q86YC2; 1 antibody. DR DNASU; 79728; -. DR Ensembl; ENST00000261584.9; ENSP00000261584.4; ENSG00000083093.10. DR GeneID; 79728; -. DR KEGG; hsa:79728; -. DR MANE-Select; ENST00000261584.9; ENSP00000261584.4; NM_024675.4; NP_078951.2. DR UCSC; uc002dlx.2; human. DR CTD; 79728; -. DR DisGeNET; 79728; -. DR GeneCards; PALB2; -. DR GeneReviews; PALB2; -. DR HGNC; HGNC:26144; PALB2. DR HPA; ENSG00000083093; Low tissue specificity. DR MalaCards; PALB2; -. DR MIM; 114480; phenotype. DR MIM; 610355; gene. DR MIM; 610832; phenotype. DR MIM; 613348; phenotype. DR neXtProt; NX_Q86YC2; -. DR OpenTargets; ENSG00000083093; -. DR Orphanet; 1333; Familial pancreatic carcinoma. DR Orphanet; 84; Fanconi anemia. DR Orphanet; 145; Hereditary breast and ovarian cancer syndrome. DR Orphanet; 227535; Hereditary breast cancer. DR PharmGKB; PA162398608; -. DR VEuPathDB; HostDB:ENSG00000083093; -. DR eggNOG; ENOG502QRAP; Eukaryota. DR GeneTree; ENSGT00390000014423; -. DR HOGENOM; CLU_008217_0_0_1; -. DR InParanoid; Q86YC2; -. DR OMA; GHCQKED; -. DR OrthoDB; 710645at2759; -. DR PhylomeDB; Q86YC2; -. DR TreeFam; TF351544; -. DR PathwayCommons; Q86YC2; -. DR Reactome; R-HSA-5685942; HDR through Homologous Recombination (HRR). DR Reactome; R-HSA-5693554; Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA). DR Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates. DR Reactome; R-HSA-5693579; Homologous DNA Pairing and Strand Exchange. DR Reactome; R-HSA-9701192; Defective HDR through Homologous Recombination (HRR) due to BRCA1 loss-of-function. DR Reactome; R-HSA-9704331; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function. DR Reactome; R-HSA-9704646; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function. DR SignaLink; Q86YC2; -. DR SIGNOR; Q86YC2; -. DR BioGRID-ORCS; 79728; 209 hits in 1085 CRISPR screens. DR ChiTaRS; PALB2; human. DR EvolutionaryTrace; Q86YC2; -. DR GeneWiki; PALB2; -. DR GenomeRNAi; 79728; -. DR Pharos; Q86YC2; Tbio. DR PRO; PR:Q86YC2; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; Q86YC2; protein. DR Bgee; ENSG00000083093; Expressed in secondary oocyte and 189 other tissues. DR ExpressionAtlas; Q86YC2; baseline and differential. DR Genevisible; Q86YC2; HS. DR GO; GO:1990391; C:DNA repair complex; IPI:ComplexPortal. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IC:ComplexPortal. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB. DR GO; GO:0009887; P:animal organ morphogenesis; IEA:Ensembl. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IDA:UniProtKB. DR GO; GO:0048568; P:embryonic organ development; IEA:Ensembl. DR GO; GO:0001833; P:inner cell mass cell proliferation; IEA:Ensembl. DR GO; GO:0007498; P:mesoderm development; IEA:Ensembl. DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl. DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl. DR GO; GO:0036342; P:post-anal tail morphogenesis; IEA:Ensembl. DR GO; GO:0001756; P:somitogenesis; IEA:Ensembl. DR Gene3D; 2.130.10.10; -; 1. DR IDEAL; IID00249; -. DR InterPro; IPR042417; PALB2. DR InterPro; IPR031920; PALB2_WD40. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR InterPro; IPR036322; WD40_repeat_dom_sf. DR PANTHER; PTHR14662; PTHR14662; 1. DR Pfam; PF16756; PALB2_WD40; 1. DR SUPFAM; SSF50978; SSF50978; 1. PE 1: Evidence at protein level; KW 3D-structure; Coiled coil; Disease variant; DNA damage; DNA recombination; KW DNA repair; DNA-binding; Fanconi anemia; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; Tumor suppressor; WD repeat. FT CHAIN 1..1186 FT /note="Partner and localizer of BRCA2" FT /id="PRO_0000252391" FT REPEAT 854..915 FT /note="WD 1" FT REPEAT 917..961 FT /note="WD 2" FT REPEAT 962..1009 FT /note="WD 3" FT REPEAT 1010..1052 FT /note="WD 4" FT REPEAT 1058..1109 FT /note="WD 5" FT REPEAT 1115..1153 FT /note="WD 6" FT REPEAT 1155..1186 FT /note="WD 7" FT REGION 1..579 FT /note="DNA-binding (with the preference D loop > dsDNA > FT ssDNA)" FT REGION 1..319 FT /note="Interaction with BRCA1" FT /evidence="ECO:0000269|PubMed:19369211" FT REGION 1..200 FT /note="Interaction with RAD51" FT REGION 1..160 FT /note="Required for its oligomerization and is important FT for its focal concentration at DNA damage sites" FT REGION 52..72 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 95..157 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 252..273 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 346..365 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 395..446 FT /note="ChAM (Chromatin-association motif); required for FT chromatin association, mediates nucleosome association" FT REGION 440..525 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 679..698 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 774..798 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 775..1186 FT /note="Required for interaction with POLH and POLH DNA FT synthesis stimulation" FT /evidence="ECO:0000269|PubMed:24485656" FT REGION 853..1186 FT /note="Interaction with RAD51, BRCA2 and POLH" FT /evidence="ECO:0000269|PubMed:24485656" FT COILED 9..41 FT /evidence="ECO:0000255" FT COMPBIAS 123..144 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 446..495 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 684..698 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 172 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 190 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 285 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 376 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17525332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 387 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 454 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 660 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 781 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VARIANT 18 FT /note="K -> R (decreases double-stranded DNA FT break-initiated homologous recombination; FT dbSNP:rs138789658)" FT /evidence="ECO:0000269|PubMed:28319063" FT /id="VAR_079842" FT VARIANT 28 FT /note="Y -> C (abrogates the interaction with BRCA1; FT decreases double-stranded DNA break-initiated homologous FT recombination; reduces PALB2 and RAD51 localization to FT ionizing radiation-induced foci; may weaken FT homooligomerization; dbSNP:rs515726129)" FT /evidence="ECO:0000269|PubMed:28319063" FT /id="VAR_079843" FT VARIANT 35 FT /note="L -> P (in BC; abrogates the interaction with BRCA1; FT abrogates double-stranded DNA break-initiated homologous FT recombination; abrogates PALB2 and RAD51 localization to FT ionizing radiation-induced foci; may weaken FT homooligomerization; dbSNP:rs141047069)" FT /evidence="ECO:0000269|PubMed:28319063" FT /id="VAR_079844" FT VARIANT 37 FT /note="R -> H (decreases double-stranded DNA FT break-initiated homologous recombination; FT dbSNP:rs202194596)" FT /evidence="ECO:0000269|PubMed:28319063" FT /id="VAR_079845" FT VARIANT 46 FT /note="H -> Y" FT /evidence="ECO:0000269|PubMed:21618343" FT /id="VAR_066361" FT VARIANT 219 FT /note="D -> G (in dbSNP:rs45594034)" FT /evidence="ECO:0000269|PubMed:21618343" FT /id="VAR_066362" FT VARIANT 309 FT /note="I -> V (in dbSNP:rs3809683)" FT /id="VAR_032959" FT VARIANT 334 FT /note="Y -> C (in dbSNP:rs200620434)" FT /evidence="ECO:0000269|PubMed:21618343" FT /id="VAR_066363" FT VARIANT 337 FT /note="L -> S (in dbSNP:rs45494092)" FT /evidence="ECO:0000269|PubMed:21618343" FT /id="VAR_066364" FT VARIANT 414 FT /note="R -> Q (in dbSNP:rs749461008)" FT /evidence="ECO:0000269|PubMed:21618343" FT /id="VAR_066365" FT VARIANT 425 FT /note="V -> M (in dbSNP:rs576081828)" FT /evidence="ECO:0000269|PubMed:21618343" FT /id="VAR_066366" FT VARIANT 491 FT /note="A -> T (in dbSNP:rs577969558)" FT /evidence="ECO:0000269|PubMed:21618343" FT /id="VAR_066367" FT VARIANT 515 FT /note="K -> R (in dbSNP:rs515726072)" FT /evidence="ECO:0000269|PubMed:21618343" FT /id="VAR_066368" FT VARIANT 559 FT /note="Q -> R (in dbSNP:rs152451)" FT /evidence="ECO:0000269|PubMed:21618343" FT /id="VAR_066369" FT VARIANT 672 FT /note="E -> Q (in dbSNP:rs45532440)" FT /evidence="ECO:0000269|PubMed:21618343" FT /id="VAR_066370" FT VARIANT 712 FT /note="A -> V (in dbSNP:rs141458731)" FT /evidence="ECO:0000269|PubMed:21618343" FT /id="VAR_066371" FT VARIANT 728 FT /note="F -> L" FT /evidence="ECO:0000269|PubMed:21618343" FT /id="VAR_066372" FT VARIANT 864 FT /note="P -> S (in dbSNP:rs45568339)" FT /evidence="ECO:0000269|PubMed:18987736, FT ECO:0000269|PubMed:21618343" FT /id="VAR_054150" FT VARIANT 917 FT /note="V -> A (in dbSNP:rs763645981)" FT /evidence="ECO:0000269|PubMed:21618343" FT /id="VAR_066373" FT VARIANT 932 FT /note="V -> M (in dbSNP:rs45624036)" FT /evidence="ECO:0000269|PubMed:21618343" FT /id="VAR_066374" FT VARIANT 939 FT /note="L -> W (may be associated with breast cancer FT susceptibility; reduces interaction with BRCA2, RAD51 and FT XRCC3; decreases double-stranded DNA break-initiated FT homologous recombination; increases sensitivity to IR; FT dbSNP:rs45478192)" FT /evidence="ECO:0000269|PubMed:21618343, FT ECO:0000269|PubMed:24141787" FT /id="VAR_066375" FT VARIANT 966 FT /note="I -> V (in dbSNP:rs786204248)" FT /evidence="ECO:0000269|PubMed:21618343" FT /id="VAR_066376" FT VARIANT 998 FT /note="G -> E (may be associated with breast cancer FT susceptibility; dbSNP:rs45551636)" FT /evidence="ECO:0000269|PubMed:21618343" FT /id="VAR_066377" FT VARIANT 1025 FT /note="A -> T (in dbSNP:rs746872839)" FT /evidence="ECO:0000269|PubMed:21618343" FT /id="VAR_066378" FT VARIANT 1043 FT /note="G -> A (may be associated with breast cancer FT susceptibility; reduces interaction with BRCA2, RAD51C, FT RAD51 and XRCC3; decreases double-stranded DNA FT break-initiated homologous recombination; increases FT sensitivity to IR; dbSNP:rs377713277)" FT /evidence="ECO:0000269|PubMed:21618343" FT /id="VAR_066379" FT VARIANT 1075 FT /note="S -> G" FT /evidence="ECO:0000269|PubMed:21618343" FT /id="VAR_066380" FT VARIANT 1105 FT /note="V -> A" FT /evidence="ECO:0000269|PubMed:21618343" FT /id="VAR_066381" FT VARIANT 1114 FT /note="Q -> H (in dbSNP:rs1567206753)" FT /evidence="ECO:0000269|PubMed:21618343" FT /id="VAR_066382" FT VARIANT 1143 FT /note="L -> P (may be associated with breast cancer FT susceptibility; dbSNP:rs62625284)" FT /evidence="ECO:0000269|PubMed:21618343, FT ECO:0000269|PubMed:24141787" FT /id="VAR_066383" FT VARIANT 1170 FT /note="H -> Y (in dbSNP:rs200283306)" FT /evidence="ECO:0000269|PubMed:21618343" FT /id="VAR_066384" FT MUTAGEN 14 FT /note="K->A: Loss of interaction with BRCA1 but no effect FT on interaction with BRCA2." FT /evidence="ECO:0000269|PubMed:19369211" FT MUTAGEN 21 FT /note="L->A: Loss of interaction with BRCA1 but no effect FT on interaction with BRCA2." FT /evidence="ECO:0000269|PubMed:19369211" FT MUTAGEN 28 FT /note="Y->A: Loss of interaction with BRCA1 but no effect FT on interaction with BRCA2." FT /evidence="ECO:0000269|PubMed:19369211" FT MUTAGEN 35 FT /note="L->A: Loss of interaction with BRCA1 but no effect FT on interaction with BRCA2." FT /evidence="ECO:0000269|PubMed:19369211" FT MUTAGEN 42 FT /note="E->A: Loss of interaction with BRCA1 but no effect FT on interaction with BRCA2." FT /evidence="ECO:0000269|PubMed:19369211" FT MUTAGEN 1030 FT /note="T->I: Unstable and promotes protein degradation; FT reduces interaction with RAD51C and RAD51." FT /evidence="ECO:0000269|PubMed:24141787" FT STRAND 855..861 FT /evidence="ECO:0007829|PDB:2W18" FT STRAND 869..877 FT /evidence="ECO:0007829|PDB:2W18" FT STRAND 884..913 FT /evidence="ECO:0007829|PDB:2W18" FT STRAND 919..922 FT /evidence="ECO:0007829|PDB:2W18" FT STRAND 932..936 FT /evidence="ECO:0007829|PDB:2W18" FT STRAND 938..947 FT /evidence="ECO:0007829|PDB:2W18" FT STRAND 958..972 FT /evidence="ECO:0007829|PDB:2W18" FT TURN 973..975 FT /evidence="ECO:0007829|PDB:2W18" FT STRAND 976..984 FT /evidence="ECO:0007829|PDB:2W18" FT STRAND 988..994 FT /evidence="ECO:0007829|PDB:2W18" FT STRAND 1000..1006 FT /evidence="ECO:0007829|PDB:2W18" FT STRAND 1013..1020 FT /evidence="ECO:0007829|PDB:2W18" FT STRAND 1025..1030 FT /evidence="ECO:0007829|PDB:2W18" FT STRAND 1033..1039 FT /evidence="ECO:0007829|PDB:2W18" FT TURN 1040..1042 FT /evidence="ECO:0007829|PDB:2W18" FT STRAND 1045..1050 FT /evidence="ECO:0007829|PDB:2W18" FT STRAND 1053..1055 FT /evidence="ECO:0007829|PDB:3EU7" FT STRAND 1059..1066 FT /evidence="ECO:0007829|PDB:2W18" FT STRAND 1069..1075 FT /evidence="ECO:0007829|PDB:2W18" FT STRAND 1090..1096 FT /evidence="ECO:0007829|PDB:2W18" FT TURN 1097..1100 FT /evidence="ECO:0007829|PDB:2W18" FT STRAND 1101..1108 FT /evidence="ECO:0007829|PDB:2W18" FT STRAND 1118..1124 FT /evidence="ECO:0007829|PDB:2W18" FT STRAND 1127..1132 FT /evidence="ECO:0007829|PDB:2W18" FT STRAND 1137..1141 FT /evidence="ECO:0007829|PDB:2W18" FT TURN 1142..1144 FT /evidence="ECO:0007829|PDB:2W18" FT STRAND 1146..1151 FT /evidence="ECO:0007829|PDB:2W18" FT STRAND 1161..1164 FT /evidence="ECO:0007829|PDB:2W18" FT STRAND 1166..1174 FT /evidence="ECO:0007829|PDB:2W18" FT STRAND 1180..1185 FT /evidence="ECO:0007829|PDB:2W18" SQ SEQUENCE 1186 AA; 131295 MW; 215EC32291315FA2 CRC64; MDEPPGKPLS CEEKEKLKEK LAFLKREYSK TLARLQRAQR AEKIKHSIKK TVEEQDCLSQ QDLSPQLKHS EPKNKICVYD KLHIKTHLDE ETGEKTSITL DVGPESFNPG DGPGGLPIQR TDDTQEHFPH RVSDPSGEQK QKLPSRRKKQ QKRTFISQER DCVFGTDSLR LSGKRLKEQE EISSKNPARS PVTEIRTHLL SLKSELPDSP EPVTEINEDS VLIPPTAQPE KGVDTFLRRP NFTRATTVPL QTLSDSGSSQ HLEHIPPKGS SELTTHDLKN IRFTSPVSLE AQGKKMTVST DNLLVNKAIS KSGQLPTSSN LEANISCSLN ELTYNNLPAN ENQNLKEQNQ TEKSLKSPSD TLDGRNENLQ ESEILSQPKS LSLEATSPLS AEKHSCTVPE GLLFPAEYYV RTTRSMSNCQ RKVAVEAVIQ SHLDVKKKGF KNKNKDASKN LNLSNEETDQ SEIRMSGTCT GQPSSRTSQK LLSLTKVSSP AGPTEDNDLS RKAVAQAPGR RYTGKRKSAC TPASDHCEPL LPTSSLSIVN RSKEEVTSHK YQHEKLFIQV KGKKSRHQKE DSLSWSNSAY LSLDDDAFTA PFHRDGMLSL KQLLSFLSIT DFQLPDEDFG PLKLEKVKSC SEKPVEPFES KMFGERHLKE GSCIFPEELS PKRMDTEMED LEEDLIVLPG KSHPKRPNSQ SQHTKTGLSS SILLYTPLNT VAPDDNDRPT TDMCSPAFPI LGTTPAFGPQ GSYEKASTEV AGRTCCTPQL AHLKDSVCLA SDTKQFDSSG SPAKPHTTLQ VSGRQGQPTC DCDSVPPGTP PPIESFTFKE NQLCRNTCQE LHKHSVEQTE TAELPASDSI NPGNLQLVSE LKNPSGSCSV DVSAMFWERA GCKEPCIITA CEDVVSLWKA LDAWQWEKLY TWHFAEVPVL QIVPVPDVYN LVCVALGNLE IREIRALFCS SDDESEKQVL LKSGNIKAVL GLTKRRLVSS SGTLSDQQVE VMTFAEDGGG KENQFLMPPE ETILTFAEVQ GMQEALLGTT IMNNIVIWNL KTGQLLKKMH IDDSYQASVC HKAYSEMGLL FIVLSHPCAK ESESLRSPVF QLIVINPKTT LSVGVMLYCL PPGQAGRFLE GDVKDHCAAA ILTSGTIAIW DLLLGQCTAL LPPVSDQHWS FVKWSGTDSH LLAGQKDGNI FVYHYS // ID BCCIP_HUMAN Reviewed; 314 AA. AC Q9P287; B3KP45; Q8ND15; Q96GC4; Q9P288; DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 25-MAY-2022, entry version 166. DE RecName: Full=BRCA2 and CDKN1A-interacting protein; DE AltName: Full=P21- and CDK-associated protein 1; DE AltName: Full=Protein TOK-1; GN Name=BCCIP; Synonyms=TOK1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, INTERACTION WITH RP CDKN1A, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RC TISSUE=Brain; RX PubMed=10878006; DOI=10.1074/jbc.m003031200; RA Ono T., Kitaura H., Ugai H., Murata T., Yokoyama K.K., Iguchi-Ariga S.M.M., RA Ariga H.; RT "TOK-1, a novel p21Cip1-binding protein that cooperatively enhances p21- RT dependent inhibitory activity toward CDK2 kinase."; RL J. Biol. Chem. 275:31145-31154(2000). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2). RX PubMed=12527204; DOI=10.1016/s0378-1119(02)01098-3; RA Meng X., Liu J., Shen Z.; RT "Genomic structure of the human BCCIP gene and its expression in cancer."; RL Gene 302:139-146(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Brain; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP INTERACTION WITH BRCA2, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=11313963; DOI=10.1038/sj.onc.1204098; RA Liu J., Yuan Y., Huan J., Shen Z.; RT "Inhibition of breast and brain cancer cell growth by BCCIPalpha, an RT evolutionarily conserved nuclear protein that interacts with BRCA2."; RL Oncogene 20:336-345(2001). RN [8] RP FUNCTION, AND INTERACTION WITH CDKN1A. RX PubMed=14726710; RA Meng X., Liu J., Shen Z.; RT "Inhibition of G1 to S cell cycle progression by BCCIP beta."; RL Cell Cycle 3:343-348(2004). RN [9] RP FUNCTION. RX PubMed=15539944; DOI=10.4161/cc.3.11.1213; RA Meng X., Lu H., Shen Z.; RT "BCCIP functions through p53 to regulate the expression of p21Waf1/Cip1."; RL Cell Cycle 3:1457-1462(2004). RN [10] RP FUNCTION, INTERACTION WITH BRCA2, AND SUBCELLULAR LOCATION. RX PubMed=15713648; DOI=10.1128/mcb.25.5.1949-1957.2005; RA Lu H., Guo X., Meng X., Liu J., Allen C., Wray J., Nickoloff J.A., Shen Z.; RT "The BRCA2-interacting protein BCCIP functions in RAD51 and BRCA2 focus RT formation and homologous recombinational repair."; RL Mol. Cell. Biol. 25:1949-1957(2005). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [12] RP FUNCTION. RX PubMed=17947333; DOI=10.1093/nar/gkm732; RA Lu H., Yue J., Meng X., Nickoloff J.A., Shen Z.; RT "BCCIP regulates homologous recombination by distinct domains and RT suppresses spontaneous DNA damage."; RL Nucleic Acids Res. 35:7160-7170(2007). RN [13] RP INTERACTION WITH MTDH. RX PubMed=18440304; DOI=10.1016/j.bbrc.2008.04.084; RA Ash S.C., Yang D.Q., Britt D.E.; RT "LYRIC/AEG-1 overexpression modulates BCCIPalpha protein levels in prostate RT tumor cells."; RL Biochem. Biophys. Res. Commun. 371:333-338(2008). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-42, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-112, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [19] RP INTERACTION WITH TENT5C. RX PubMed=28931820; DOI=10.1038/s41467-017-00578-5; RA Mroczek S., Chlebowska J., Kulinski T.M., Gewartowska O., Gruchota J., RA Cysewski D., Liudkovska V., Borsuk E., Nowis D., Dziembowski A.; RT "The non-canonical poly(A) polymerase FAM46C acts as an onco-suppressor in RT multiple myeloma."; RL Nat. Commun. 8:619-619(2017). RN [20] RP FUNCTION, INTERACTION WITH DCTN1; ACTR1A AND TUBULINS, AND SUBCELLULAR RP LOCATION. RX PubMed=28394342; DOI=10.1038/onc.2017.92; RA Huhn S.C., Liu J., Ye C., Lu H., Jiang X., Feng X., Ganesan S., White E., RA Shen Z.; RT "Regulation of spindle integrity and mitotic fidelity by BCCIP."; RL Oncogene 36:4750-4766(2017). CC -!- FUNCTION: During interphase, required for microtubule organizing and CC anchoring activities. During mitosis, required for the organization and CC stabilization of the spindle pole (PubMed:28394342). Isoform 2/alpha is CC particularly important for the regulation of microtubule anchoring, CC microtubule stability, spindle architecture and spindle orientation, CC compared to isoform 1/beta (PubMed:28394342). May promote cell cycle CC arrest by enhancing the inhibition of CDK2 activity by CDKN1A. May be CC required for repair of DNA damage by homologous recombination in CC conjunction with BRCA2. May not be involved in non-homologous end CC joining (NHEJ). {ECO:0000269|PubMed:10878006, CC ECO:0000269|PubMed:14726710, ECO:0000269|PubMed:15539944, CC ECO:0000269|PubMed:15713648, ECO:0000269|PubMed:17947333, CC ECO:0000269|PubMed:28394342}. CC -!- SUBUNIT: Interacts with BRCA2, CDKN1A and MTDH/LYRIC (PubMed:10878006, CC PubMed:11313963, PubMed:14726710, PubMed:15713648, PubMed:18440304). CC Isoform 2/alpha, but not isoform 1/beta, interacts with DCTN1/p150- CC glued and ACTR1A/ARP1 (PubMed:28394342). Both isoform 1 and isoform 2 CC interact with alpha-, beta- and gamma-tubulins (PubMed:28394342). CC Interacts with TENT5C; the interaction has no effect on TENT5C poly(A) CC polymerase function (PubMed:28931820). {ECO:0000269|PubMed:10878006, CC ECO:0000269|PubMed:11313963, ECO:0000269|PubMed:14726710, CC ECO:0000269|PubMed:15713648, ECO:0000269|PubMed:18440304, CC ECO:0000269|PubMed:28394342, ECO:0000269|PubMed:28931820}. CC -!- INTERACTION: CC Q9P287; Q9HC77: CENPJ; NbExp=3; IntAct=EBI-711154, EBI-946194; CC Q9P287; Q9Y324: FCF1; NbExp=3; IntAct=EBI-711154, EBI-5455734; CC Q9P287; P82933: MRPS9; NbExp=3; IntAct=EBI-711154, EBI-721385; CC Q9P287; P01127: PDGFB; NbExp=3; IntAct=EBI-711154, EBI-1554925; CC Q9P287; Q53GL6: RALY; NbExp=3; IntAct=EBI-711154, EBI-9512693; CC Q9P287; P62829: RPL23; NbExp=7; IntAct=EBI-711154, EBI-353303; CC Q9P287; P63173: RPL38; NbExp=3; IntAct=EBI-711154, EBI-359141; CC Q9P287; P52744: ZNF138; NbExp=3; IntAct=EBI-711154, EBI-10746567; CC Q9P287; P17023: ZNF19; NbExp=3; IntAct=EBI-711154, EBI-12884200; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10878006, CC ECO:0000269|PubMed:11313963, ECO:0000269|PubMed:15713648}. Cytoplasm, CC cytoskeleton, microtubule organizing center, centrosome, centriole CC {ECO:0000269|PubMed:28394342}. Cytoplasm, cytoskeleton, spindle pole CC {ECO:0000269|PubMed:28394342}. Note=Colocalizes with BRCA2 in discrete CC nuclear foci (PubMed:15713648). In interphase, preferential localizes CC to the mother centriole (PubMed:28394342). Recruited to the spindle CC pole matrix and centrosome by microtubules and dynein/dynactin activity CC (PubMed:28394342). {ECO:0000269|PubMed:15713648, CC ECO:0000269|PubMed:28394342}. CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm, cytoskeleton, microtubule CC organizing center, centrosome {ECO:0000269|PubMed:28394342}. Cytoplasm, CC cytoskeleton, spindle pole {ECO:0000269|PubMed:28394342}. Note=Isoform CC 1/beta tends to be less abundant at, and less strongly associated with, CC centrosomes than isoform 2/alpha. {ECO:0000269|PubMed:28394342}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm, cytoskeleton, microtubule CC organizing center, centrosome {ECO:0000269|PubMed:28394342}. Cytoplasm, CC cytoskeleton, spindle pole {ECO:0000269|PubMed:28394342}. Note=Isoform CC 2/alpha tends to be more abundant at, and more strongly associated CC with, centrosomes than isoform 1/beta. {ECO:0000269|PubMed:28394342}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=Beta; CC IsoId=Q9P287-1; Sequence=Displayed; CC Name=2; Synonyms=Alpha; CC IsoId=Q9P287-2; Sequence=VSP_020540; CC Name=3; CC IsoId=Q9P287-3; Sequence=VSP_020541; CC Name=4; CC IsoId=Q9P287-4; Sequence=VSP_042023; CC -!- TISSUE SPECIFICITY: Expressed at high levels in testis and skeletal CC muscle and at lower levels in brain, heart, kidney, liver, lung, ovary, CC pancreas, placenta, and spleen. {ECO:0000269|PubMed:10878006, CC ECO:0000269|PubMed:11313963}. CC -!- DEVELOPMENTAL STAGE: Isoform 1 is expressed throughout the cell cycle. CC Isoform 2 is expressed following mitosis and peaks in the G1/S phase of CC the cell cycle. {ECO:0000269|PubMed:10878006}. CC -!- MISCELLANEOUS: HT1080 cells that constitutively express low levels of CC BCCIP display increased levels of spontaneous single-stranded DNA and CC double-strand breaks. CC -!- SIMILARITY: Belongs to the BCP1 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB040450; BAA92927.1; -; mRNA. DR EMBL; AB040451; BAA92928.1; -; mRNA. DR EMBL; AY064247; AAL55436.1; -; Genomic_DNA. DR EMBL; AY064247; AAL55438.1; -; Genomic_DNA. DR EMBL; AY064248; AAL55439.1; -; mRNA. DR EMBL; AY064249; AAL55440.1; -; mRNA. DR EMBL; AK055691; BAG51557.1; -; mRNA. DR EMBL; AL834458; CAD39118.1; -; mRNA. DR EMBL; AL360176; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC009771; AAH09771.1; -; mRNA. DR CCDS; CCDS7649.1; -. [Q9P287-2] DR CCDS; CCDS7650.1; -. [Q9P287-4] DR CCDS; CCDS7651.1; -. [Q9P287-1] DR RefSeq; NP_057651.1; NM_016567.3. [Q9P287-2] DR RefSeq; NP_510868.1; NM_078468.2. [Q9P287-1] DR RefSeq; NP_510869.1; NM_078469.2. [Q9P287-4] DR PDB; 7KYQ; X-ray; 3.06 A; A=61-314. DR PDB; 7KYS; X-ray; 2.20 A; A/B/C=61-314. DR PDBsum; 7KYQ; -. DR PDBsum; 7KYS; -. DR AlphaFoldDB; Q9P287; -. DR SMR; Q9P287; -. DR BioGRID; 121161; 113. DR CORUM; Q9P287; -. DR IntAct; Q9P287; 45. DR MINT; Q9P287; -. DR STRING; 9606.ENSP00000357748; -. DR GlyGen; Q9P287; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9P287; -. DR PhosphoSitePlus; Q9P287; -. DR BioMuta; BCCIP; -. DR DMDM; 74753124; -. DR EPD; Q9P287; -. DR jPOST; Q9P287; -. DR MassIVE; Q9P287; -. DR MaxQB; Q9P287; -. DR PaxDb; Q9P287; -. DR PeptideAtlas; Q9P287; -. DR PRIDE; Q9P287; -. DR ProteomicsDB; 83752; -. [Q9P287-1] DR ProteomicsDB; 83753; -. [Q9P287-2] DR ProteomicsDB; 83754; -. [Q9P287-3] DR ProteomicsDB; 83755; -. [Q9P287-4] DR Antibodypedia; 32428; 153 antibodies from 28 providers. DR DNASU; 56647; -. DR Ensembl; ENST00000278100.11; ENSP00000278100.6; ENSG00000107949.17. DR Ensembl; ENST00000299130.7; ENSP00000299130.3; ENSG00000107949.17. [Q9P287-4] DR Ensembl; ENST00000368759.5; ENSP00000357748.5; ENSG00000107949.17. [Q9P287-2] DR GeneID; 56647; -. DR KEGG; hsa:56647; -. DR MANE-Select; ENST00000278100.11; ENSP00000278100.6; NM_078468.3; NP_510868.1. DR UCSC; uc001ljb.5; human. [Q9P287-1] DR CTD; 56647; -. DR DisGeNET; 56647; -. DR GeneCards; BCCIP; -. DR HGNC; HGNC:978; BCCIP. DR HPA; ENSG00000107949; Low tissue specificity. DR MIM; 611883; gene. DR neXtProt; NX_Q9P287; -. DR OpenTargets; ENSG00000107949; -. DR PharmGKB; PA25290; -. DR VEuPathDB; HostDB:ENSG00000107949; -. DR eggNOG; KOG3034; Eukaryota. DR GeneTree; ENSGT00390000000696; -. DR HOGENOM; CLU_068770_1_1_1; -. DR InParanoid; Q9P287; -. DR OMA; MYTMLLE; -. DR OrthoDB; 1120393at2759; -. DR PhylomeDB; Q9P287; -. DR TreeFam; TF320301; -. DR PathwayCommons; Q9P287; -. DR SignaLink; Q9P287; -. DR BioGRID-ORCS; 56647; 392 hits in 1091 CRISPR screens. DR ChiTaRS; BCCIP; human. DR GeneWiki; BCCIP; -. DR GenomeRNAi; 56647; -. DR Pharos; Q9P287; Tbio. DR PRO; PR:Q9P287; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; Q9P287; protein. DR Bgee; ENSG00000107949; Expressed in testis and 238 other tissues. DR Genevisible; Q9P287; HS. DR GO; GO:0005814; C:centriole; IDA:UniProtKB. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0097431; C:mitotic spindle pole; IDA:UniProtKB. DR GO; GO:0019908; C:nuclear cyclin-dependent protein kinase holoenzyme complex; IDA:MGI. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0019207; F:kinase regulator activity; IDA:MGI. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0015631; F:tubulin binding; IDA:UniProtKB. DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW. DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IMP:UniProtKB. DR GO; GO:0034453; P:microtubule anchoring; IMP:UniProtKB. DR GO; GO:0000226; P:microtubule cytoskeleton organization; IMP:UniProtKB. DR GO; GO:0090307; P:mitotic spindle assembly; IMP:UniProtKB. DR GO; GO:0007052; P:mitotic spindle organization; IMP:UniProtKB. DR GO; GO:0061101; P:neuroendocrine cell differentiation; IDA:UniProtKB. DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; IDA:MGI. DR InterPro; IPR025602; BCP1_family. DR PANTHER; PTHR13261; PTHR13261; 1. DR Pfam; PF13862; BCCIP; 1. DR PIRSF; PIRSF028983; BCP1; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell cycle; Cytoplasm; Cytoskeleton; KW DNA damage; DNA repair; Nucleus; Phosphoprotein; Reference proteome. FT CHAIN 1..314 FT /note="BRCA2 and CDKN1A-interacting protein" FT /id="PRO_0000249687" FT REGION 1..56 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 59..167 FT /note="Interaction with BRCA2" FT REGION 161..259 FT /note="Interaction with CDKN1A" FT COMPBIAS 28..56 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 42 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692" FT MOD_RES 112 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 281 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9CWI3" FT VAR_SEQ 259..314 FT /note="KAILKFNYSVQEESDTCLGGKWSFDDVPMTPLRTVMLIPGDKMNEIMDKLKE FT YLSV -> EQGKPEVLGGPDTRRGLEPVPIQHNGGSRGQVTALVSLKAGLIQSRSTLSD FT FQGTFMTVGIALS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10878006, FT ECO:0000303|PubMed:12527204" FT /id="VSP_020540" FT VAR_SEQ 259..314 FT /note="KAILKFNYSVQEESDTCLGGKWSFDDVPMTPLRTVMLIPGDKMNEIMDKLKE FT YLSV -> EQGKPEVLGGPDTRRGLEPVPIQHNGWSVPPVLE (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_042023" FT VAR_SEQ 285..314 FT /note="VPMTPLRTVMLIPGDKMNEIMDKLKEYLSV -> WSVPPVLE (in FT isoform 3)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_020541" FT VARIANT 254 FT /note="E -> Q (in dbSNP:rs17153610)" FT /id="VAR_046642" FT CONFLICT 75 FT /note="K -> R (in Ref. 3; BAG51557)" FT /evidence="ECO:0000305" FT CONFLICT 230 FT /note="G -> E (in Ref. 6; AAH09771)" FT /evidence="ECO:0000305" FT STRAND 61..64 FT /evidence="ECO:0007829|PDB:7KYS" FT HELIX 68..70 FT /evidence="ECO:0007829|PDB:7KYS" FT HELIX 71..82 FT /evidence="ECO:0007829|PDB:7KYS" FT HELIX 89..98 FT /evidence="ECO:0007829|PDB:7KYS" FT TURN 99..102 FT /evidence="ECO:0007829|PDB:7KYQ" FT STRAND 104..108 FT /evidence="ECO:0007829|PDB:7KYS" FT STRAND 126..132 FT /evidence="ECO:0007829|PDB:7KYS" FT TURN 133..138 FT /evidence="ECO:0007829|PDB:7KYS" FT HELIX 140..156 FT /evidence="ECO:0007829|PDB:7KYS" FT HELIX 159..169 FT /evidence="ECO:0007829|PDB:7KYS" FT STRAND 172..174 FT /evidence="ECO:0007829|PDB:7KYQ" FT STRAND 176..183 FT /evidence="ECO:0007829|PDB:7KYS" FT HELIX 189..191 FT /evidence="ECO:0007829|PDB:7KYS" FT HELIX 192..208 FT /evidence="ECO:0007829|PDB:7KYS" FT HELIX 212..214 FT /evidence="ECO:0007829|PDB:7KYS" FT STRAND 217..227 FT /evidence="ECO:0007829|PDB:7KYS" FT STRAND 247..250 FT /evidence="ECO:0007829|PDB:7KYS" FT HELIX 253..259 FT /evidence="ECO:0007829|PDB:7KYS" FT STRAND 261..267 FT /evidence="ECO:0007829|PDB:7KYS" FT STRAND 288..297 FT /evidence="ECO:0007829|PDB:7KYS" FT HELIX 298..300 FT /evidence="ECO:0007829|PDB:7KYS" FT HELIX 301..312 FT /evidence="ECO:0007829|PDB:7KYS" SQ SEQUENCE 314 AA; 35979 MW; 203CA32F7BE0A806 CRC64; MASRSKRRAV ESGVPQPPDP PVQRDEEEEK EVENEDEDDD DSDKEKDEED EVIDEEVNIE FEAYSLSDND YDGIKKLLQQ LFLKAPVNTA ELTDLLIQQN HIGSVIKQTD VSEDSNDDMD EDEVFGFISL LNLTERKGTQ CVEQIQELVL RFCEKNCEKS MVEQLDKFLN DTTKPVGLLL SERFINVPPQ IALPMYQQLQ KELAGAHRTN KPCGKCYFYL LISKTFVEAG KNNSKKKPSN KKKAALMFAN AEEEFFYEKA ILKFNYSVQE ESDTCLGGKW SFDDVPMTPL RTVMLIPGDK MNEIMDKLKE YLSV // ID EMSY_HUMAN Reviewed; 1322 AA. AC Q7Z589; B7ZKT8; B7ZKU0; B7ZKU2; Q17RM7; Q4G109; Q8NBU6; Q8TE50; Q9H8I9; AC Q9NRH0; DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot. DT 24-MAY-2004, sequence version 2. DT 25-MAY-2022, entry version 173. DE RecName: Full=BRCA2-interacting transcriptional repressor EMSY {ECO:0000312|HGNC:HGNC:18071}; GN Name=EMSY {ECO:0000312|HGNC:HGNC:18071}; Synonyms=C11orf30; GN ORFNames=GL002; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, RP INVOLVEMENT IN CANCER, INTERACTION WITH BRCA2; CBX1 AND ZMYND11, AND RP MUTAGENESIS OF 100-VAL--LEU-102 AND LEU-106. RX PubMed=14651845; DOI=10.1016/s0092-8674(03)00930-9; RA Hughes-Davies L., Huntsman D., Ruas M., Fuks F., Bye J., Chin S.-F., RA Milner J., Brown L.A., Hsu F., Gilks B., Nielsen T., Schulzer M., Chia S., RA Ragaz J., Cahn A., Linger L., Ozdag H., Cattaneo E., Jordanova E.S., RA Schuuring E., Yu D.S., Venkitaraman A., Ponder B., Doherty A., Aparicio S., RA Bentley D., Theillet C., Ponting C.P., Caldas C., Kouzarides T.; RT "EMSY links the BRCA2 pathway to sporadic breast and ovarian cancer."; RL Cell 115:523-535(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3; 4; 5; 6 AND 7), AND RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1082-1322 (ISOFORM 1). RC TISSUE=Brain, Testis, and Urinary bladder; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 861-1322 (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 861-1322 (ISOFORM 2). RC TISSUE=Brain; RA Guo J.H., Zan Q., Yu L.; RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1115-1322 (ISOFORM 1). RC TISSUE=Liver; RA Li Y., Wu T., Xu S., Ren S., Chen Z., Han Z.; RT "A novel gene expressed in human liver non-tumor tissues."; RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases. RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1136, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-209 AND SER-1136, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [11] RP FUNCTION, IDENTIFICATION IN A NUCLEAR RECEPTOR HORMONE COMPLEX, AND RP INTERACTION WITH ZNF335; CCAR2; ASH2L; RBBP5. RX PubMed=19131338; DOI=10.1074/jbc.m805872200; RA Garapaty S., Xu C.F., Trojer P., Mahajan M.A., Neubert T.A., Samuels H.H.; RT "Identification and characterization of a novel nuclear protein complex RT involved in nuclear hormone receptor-mediated gene regulation."; RL J. Biol. Chem. 284:7542-7552(2009). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-207, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [13] RP GLYCOSYLATION AT SER-228; SER-236; THR-271; THR-501; THR-506; SER-557 AND RP THR-1120. RX PubMed=20068230; DOI=10.1126/scisignal.2000526; RA Wang Z., Udeshi N.D., Slawson C., Compton P.D., Sakabe K., Cheung W.D., RA Shabanowitz J., Hunt D.F., Hart G.W.; RT "Extensive crosstalk between O-GlcNAcylation and phosphorylation regulates RT cytokinesis."; RL Sci. Signal. 3:RA2-RA2(2010). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-209 AND SER-1136, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-209, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-207; SER-209; SER-238 AND RP SER-1136, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [18] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-108, AND INTERACTION WITH RP ZMYND11. RX PubMed=15947784; DOI=10.1038/sj.embor.7400415; RA Ekblad C.M.S., Chavali G.B., Basu B.P., Freund S.M.V., Veprintsev D., RA Hughes-Davies L., Kouzarides T., Doherty A.J., Itzhaki L.S.; RT "Binding of EMSY to HP1beta: implications for recruitment of HP1beta and RT BS69."; RL EMBO Rep. 6:675-680(2005). RN [19] RP X-RAY CRYSTALLOGRAPHY (1.1 ANGSTROMS) OF 1-100, AND SUBUNIT. RX PubMed=15978617; DOI=10.1016/j.jmb.2005.05.047; RA Chavali G.B., Ekblad C.M., Basu B.P., Brissett N.C., Veprintsev D., RA Hughes-Davies L., Kouzarides T., Itzhaki L.S., Doherty A.J.; RT "Crystal structure of the ENT domain of human EMSY."; RL J. Mol. Biol. 350:964-973(2005). RN [20] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 9-139 IN COMPLEX WITH CBX1. RX PubMed=16615912; DOI=10.1016/j.str.2006.01.007; RA Huang Y., Myers M.P., Xu R.-M.; RT "Crystal structure of the HP1-EMSY complex reveals an unusual mode of HP1 RT binding."; RL Structure 14:703-712(2006). CC -!- FUNCTION: Regulator which is able to repress transcription, possibly CC via its interaction with a multiprotein chromatin remodeling complex CC that modifies the chromatin (PubMed:14651845). Its interaction with CC BRCA2 suggests that it may play a central role in the DNA repair CC function of BRCA2 (PubMed:14651845). Mediates ligand-dependent CC transcriptional activation by nuclear hormone receptors CC (PubMed:19131338). {ECO:0000269|PubMed:14651845, CC ECO:0000269|PubMed:19131338}. CC -!- SUBUNIT: Homodimer (PubMed:15978617). Interacts with the CC transactivation domain of BRCA2 (PubMed:14651845). Interacts with CBX1 CC (via chromoshadow domain) (PubMed:14651845, PubMed:16615912). Interacts CC with ZMYND11 (PubMed:14651845, PubMed:15947784). Does not interact with CC CBX3 or CBX5 (PubMed:14651845). Component of a nuclear receptor- CC mediated transcription complex composed of at least ZNF335, CCAR2 and CC EMSY; the complex stimulates the transcription of nuclear receptor CC target genes such as SOX9 and HOXA1 (PubMed:19131338). Within the CC complex interacts with CCAR2 and ZNF335 (PubMed:19131338). Components CC of this complex may associate with components of a histone methylation CC complex to form a complex at least composed of ZNF335, HCFC1, CCAR2, CC EMSY, MKI67, RBBP5, ASH2L and WDR5 (PubMed:19131338). Within this CC complex, interacts with ASH2L and RBBP5 (PubMed:19131338). CC {ECO:0000269|PubMed:14651845, ECO:0000269|PubMed:15947784, CC ECO:0000269|PubMed:15978617, ECO:0000269|PubMed:16615912, CC ECO:0000269|PubMed:19131338}. CC -!- INTERACTION: CC Q7Z589; P83916: CBX1; NbExp=3; IntAct=EBI-6598631, EBI-78129; CC Q7Z589; P35638-2: DDIT3; NbExp=3; IntAct=EBI-6598631, EBI-10173632; CC Q7Z589; O15015: ZNF646; NbExp=3; IntAct=EBI-6598631, EBI-745608; CC Q7Z589-5; Q96BJ3: AIDA; NbExp=3; IntAct=EBI-11989522, EBI-4401674; CC Q7Z589-5; Q5SYC1: CLVS2; NbExp=3; IntAct=EBI-11989522, EBI-12357161; CC Q7Z589-5; P35638: DDIT3; NbExp=3; IntAct=EBI-11989522, EBI-742651; CC Q7Z589-5; Q9NRI5-2: DISC1; NbExp=3; IntAct=EBI-11989522, EBI-11988027; CC Q7Z589-5; O43681: GET3; NbExp=3; IntAct=EBI-11989522, EBI-2515857; CC Q7Z589-5; Q8N485: LIX1; NbExp=3; IntAct=EBI-11989522, EBI-10694501; CC Q7Z589-5; P25786: PSMA1; NbExp=3; IntAct=EBI-11989522, EBI-359352; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14651845}. CC Note=Localizes to DNA damage markers in irradiated cells, suggesting CC that it participates in DNA repair process. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=7; CC Name=1; CC IsoId=Q7Z589-1; Sequence=Displayed; CC Name=2; CC IsoId=Q7Z589-2; Sequence=VSP_010431; CC Name=3; CC IsoId=Q7Z589-3; Sequence=VSP_020774, VSP_020775; CC Name=4; CC IsoId=Q7Z589-4; Sequence=VSP_054139, VSP_054140, VSP_054143; CC Name=5; CC IsoId=Q7Z589-5; Sequence=VSP_054140; CC Name=6; CC IsoId=Q7Z589-6; Sequence=VSP_054139, VSP_054141, VSP_054142; CC Name=7; CC IsoId=Q7Z589-7; Sequence=VSP_054139, VSP_054140; CC -!- PTM: O-glycosylated during cytokinesis at sites identical or close to CC phosphorylation sites, this interferes with the phosphorylation status. CC {ECO:0000269|PubMed:20068230}. CC -!- MISCELLANEOUS: Defects in EMSY may be a cause of sporadic breast cancer CC and higher-grade ovarian cancers. Overexpressed through amplification CC almost exclusively in sporadic breast cancer (13%) and higher-grade CC ovarian cancer (17%). Amplification is associated with worse survival, CC particularly in node-negative breast cancer, suggesting that it may be CC of prognostic value. CC -!- MISCELLANEOUS: Was named EMSY by PubMed:14651845 because the protein CC sequence contains the word 'SISTER', after the first author's sister, CC who is a breast cancer nurse. CC -!- SEQUENCE CAUTION: CC Sequence=AAF86947.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAH29375.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAL65260.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAB14627.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/C11ORF30ID173.html"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AJ430203; CAD22881.1; -; mRNA. DR EMBL; AP002360; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP003165; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471076; EAW74998.1; -; Genomic_DNA. DR EMBL; BC029375; AAH29375.1; ALT_INIT; mRNA. DR EMBL; BC033404; AAH33404.1; -; mRNA. DR EMBL; BC117265; AAI17266.1; -; mRNA. DR EMBL; BC143370; AAI43371.1; -; mRNA. DR EMBL; BC143374; AAI43375.1; -; mRNA. DR EMBL; BC143376; AAI43377.1; -; mRNA. DR EMBL; AK023651; BAB14627.1; ALT_INIT; mRNA. DR EMBL; AY070433; AAL65260.1; ALT_INIT; mRNA. DR EMBL; AF226047; AAF86947.1; ALT_INIT; mRNA. DR CCDS; CCDS73349.1; -. [Q7Z589-7] DR CCDS; CCDS73350.1; -. [Q7Z589-4] DR CCDS; CCDS73351.1; -. [Q7Z589-5] DR CCDS; CCDS8244.1; -. [Q7Z589-1] DR RefSeq; NP_001287871.1; NM_001300942.1. [Q7Z589-7] DR RefSeq; NP_001287872.1; NM_001300943.1. [Q7Z589-5] DR RefSeq; NP_001287873.1; NM_001300944.1. [Q7Z589-4] DR RefSeq; NP_064578.2; NM_020193.4. [Q7Z589-1] DR PDB; 1UTU; X-ray; 2.00 A; A/B=1-108. DR PDB; 1UZ3; X-ray; 1.10 A; A/B=1-100. DR PDB; 2FMM; X-ray; 1.80 A; E=9-139. DR PDBsum; 1UTU; -. DR PDBsum; 1UZ3; -. DR PDBsum; 2FMM; -. DR AlphaFoldDB; Q7Z589; -. DR SMR; Q7Z589; -. DR BioGRID; 121270; 97. DR CORUM; Q7Z589; -. DR DIP; DIP-29099N; -. DR IntAct; Q7Z589; 66. DR MINT; Q7Z589; -. DR STRING; 9606.ENSP00000433205; -. DR GlyConnect; 1657; 2 N-Linked glycans (1 site), 1 O-Linked glycan (9 sites). DR GlyGen; Q7Z589; 55 sites, 2 N-linked glycans (1 site), 2 O-linked glycans (54 sites). DR iPTMnet; Q7Z589; -. DR PhosphoSitePlus; Q7Z589; -. DR BioMuta; EMSY; -. DR DMDM; 47605660; -. DR EPD; Q7Z589; -. DR jPOST; Q7Z589; -. DR MassIVE; Q7Z589; -. DR MaxQB; Q7Z589; -. DR PaxDb; Q7Z589; -. DR PeptideAtlas; Q7Z589; -. DR PRIDE; Q7Z589; -. DR ProteomicsDB; 61157; -. DR ProteomicsDB; 7194; -. DR ProteomicsDB; 7195; -. DR ProteomicsDB; 7196; -. DR Antibodypedia; 31192; 177 antibodies from 27 providers. DR DNASU; 56946; -. DR Ensembl; ENST00000334736.7; ENSP00000334130.3; ENSG00000158636.16. DR Ensembl; ENST00000524767.5; ENSP00000433205.1; ENSG00000158636.16. [Q7Z589-7] DR Ensembl; ENST00000525038.5; ENSP00000436968.1; ENSG00000158636.16. [Q7Z589-4] DR Ensembl; ENST00000525919.5; ENSP00000432010.1; ENSG00000158636.16. [Q7Z589-5] DR Ensembl; ENST00000529032.5; ENSP00000432327.1; ENSG00000158636.16. DR Ensembl; ENST00000533248.5; ENSP00000433634.1; ENSG00000158636.16. [Q7Z589-6] DR Ensembl; ENST00000533988.5; ENSP00000434665.1; ENSG00000158636.16. [Q7Z589-3] DR GeneID; 56946; -. DR KEGG; hsa:56946; -. DR UCSC; uc001oxj.4; human. [Q7Z589-1] DR CTD; 56946; -. DR DisGeNET; 56946; -. DR GeneCards; EMSY; -. DR HGNC; HGNC:18071; EMSY. DR HPA; ENSG00000158636; Low tissue specificity. DR MIM; 608574; gene. DR neXtProt; NX_Q7Z589; -. DR OpenTargets; ENSG00000158636; -. DR PharmGKB; PA134904392; -. DR VEuPathDB; HostDB:ENSG00000158636; -. DR eggNOG; KOG4675; Eukaryota. DR GeneTree; ENSGT00390000009554; -. DR HOGENOM; CLU_197021_0_0_1; -. DR InParanoid; Q7Z589; -. DR OMA; EYITTEC; -. DR OrthoDB; 150416at2759; -. DR PhylomeDB; Q7Z589; -. DR TreeFam; TF332401; -. DR PathwayCommons; Q7Z589; -. DR SignaLink; Q7Z589; -. DR SIGNOR; Q7Z589; -. DR BioGRID-ORCS; 56946; 46 hits in 1051 CRISPR screens. DR ChiTaRS; EMSY; human. DR EvolutionaryTrace; Q7Z589; -. DR GeneWiki; C11orf30; -. DR GenomeRNAi; 56946; -. DR Pharos; Q7Z589; Tbio. DR PRO; PR:Q7Z589; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q7Z589; protein. DR Bgee; ENSG00000158636; Expressed in corpus callosum and 219 other tissues. DR ExpressionAtlas; Q7Z589; baseline and differential. DR Genevisible; Q7Z589; HS. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl. DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW. DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:InterPro. DR Gene3D; 1.10.1240.40; -; 1. DR IDEAL; IID00281; -. DR InterPro; IPR033482; EMSY. DR InterPro; IPR005491; ENT_dom. DR InterPro; IPR036142; ENT_dom-like_sf. DR PANTHER; PTHR16500; PTHR16500; 1. DR Pfam; PF03735; ENT; 1. DR SMART; SM01191; ENT; 1. DR SUPFAM; SSF158639; SSF158639; 1. DR PROSITE; PS51138; ENT; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Chromatin regulator; DNA damage; KW DNA repair; Glycoprotein; Nucleus; Phosphoprotein; Reference proteome; KW Repressor; Transcription; Transcription regulation. FT CHAIN 1..1322 FT /note="BRCA2-interacting transcriptional repressor EMSY" FT /id="PRO_0000086968" FT DOMAIN 16..100 FT /note="ENT" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00476" FT REGION 1..478 FT /note="Interaction with BRCA2" FT /evidence="ECO:0000269|PubMed:14651845" FT REGION 104..108 FT /note="Interaction with ZMYND11" FT REGION 148..178 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 192..215 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 417..444 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 698..736 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1205..1231 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1290..1322 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 417..438 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1205..1223 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1307..1322 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 207 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 209 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 213 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8BMB0" FT MOD_RES 238 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 818 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8BMB0" FT MOD_RES 821 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8BMB0" FT MOD_RES 1136 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT CARBOHYD 228 FT /note="O-linked (GlcNAc) serine" FT /evidence="ECO:0000269|PubMed:20068230" FT CARBOHYD 236 FT /note="O-linked (GlcNAc) serine" FT /evidence="ECO:0000269|PubMed:20068230" FT CARBOHYD 271 FT /note="O-linked (GlcNAc) threonine" FT /evidence="ECO:0000269|PubMed:20068230" FT CARBOHYD 501 FT /note="O-linked (GlcNAc) threonine" FT /evidence="ECO:0000269|PubMed:20068230" FT CARBOHYD 506 FT /note="O-linked (GlcNAc) threonine" FT /evidence="ECO:0000269|PubMed:20068230" FT CARBOHYD 557 FT /note="O-linked (GlcNAc) serine" FT /evidence="ECO:0000269|PubMed:20068230" FT CARBOHYD 1120 FT /note="O-linked (GlcNAc) threonine" FT /evidence="ECO:0000269|PubMed:20068230" FT VAR_SEQ 82 FT /note="N -> K (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_020774" FT VAR_SEQ 82 FT /note="N -> KMNLSLYLGERPSYS (in isoform 4, isoform 6 and FT isoform 7)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_054139" FT VAR_SEQ 83..1322 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_020775" FT VAR_SEQ 140 FT /note="E -> EV (in isoform 4, isoform 5 and isoform 7)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_054140" FT VAR_SEQ 733..747 FT /note="SQPVVHVIASRRQDW -> AVVISGEISSPPLFS (in isoform 6)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_054141" FT VAR_SEQ 748..852 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_054142" FT VAR_SEQ 839..852 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_054143" FT VAR_SEQ 1091..1257 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.6" FT /id="VSP_010431" FT MUTAGEN 100..102 FT /note="VPL->APA: Abolishes interaction with CBX1." FT /evidence="ECO:0000269|PubMed:14651845" FT MUTAGEN 106 FT /note="L->A: Abolishes interaction with ZMYND11." FT /evidence="ECO:0000269|PubMed:14651845" FT HELIX 7..9 FT /evidence="ECO:0007829|PDB:1UZ3" FT HELIX 13..38 FT /evidence="ECO:0007829|PDB:1UZ3" FT HELIX 43..55 FT /evidence="ECO:0007829|PDB:1UZ3" FT HELIX 60..71 FT /evidence="ECO:0007829|PDB:1UZ3" FT HELIX 74..84 FT /evidence="ECO:0007829|PDB:1UZ3" FT HELIX 90..97 FT /evidence="ECO:0007829|PDB:1UZ3" FT STRAND 98..103 FT /evidence="ECO:0007829|PDB:2FMM" FT HELIX 108..110 FT /evidence="ECO:0007829|PDB:2FMM" FT STRAND 112..116 FT /evidence="ECO:0007829|PDB:2FMM" FT STRAND 122..124 FT /evidence="ECO:0007829|PDB:2FMM" SQ SEQUENCE 1322 AA; 141468 MW; 7F8C95E8BA0FC9F0 CRC64; MPVVWPTLLD LSRDECKRIL RKLELEAYAG VISALRAQGD LTKEKKDLLG ELSKVLSIST ERHRAEVRRA VNDERLTTIA HNMSGPNSSS EWSIEGRRLV PLMPRLVPQT AFTVTANAVA NAAIQHNASL PVPAETGSKE VVCYSYTSTT STPTSTPVPS GSIATVKSPR PASPASNVVV LPSGSTVYVK SVSCSDEDEK PRKRRRTNSS SSSPVVLKEV PKAVVPVSKT ITVPVSGSPK MSNIMQSIAN SLPPHMSPVK ITFTKPSTQT TNTTTQKVII VTTSPSSTFV PNILSKSHNY AAVTKLVPTS VIASTTQKPP VVITASQSSL VSNSSSGSSS STPSPIPNTV AVTAVVSSTP SVVMSTVAQG VSTSAIKMAS TRLPSPKSLV SAPTQILAQF PKQHQQSPKQ QLYQVQQQTQ QQVAQPSPVS HQQQPQQSPL PPGIKPTIQI KQESGVKIIT QQVQPSKILP KPVTATLPTS SNSPIMVVSS NGAIMTTKLV TTPTGTQATY TRPTVSPSIG RMAATPGAAT YVKTTSGSII TVVPKSLATL GGKIISSNIV SGTTTKITTI PMTSKPNVIV VQKTTGKGTT IQGLPGKNVV TTLLNAGGEK TIQTVPTGAK PAILTATRPI TKMIVTQPKG IGSTVQPAAK IIPTKIVYGQ QGKTQVLIKP KPVTFQATVV SEQTRQLVTE TLQQASRVAE AGNSSIQEGK EEPQNYTDSS SSSTESSQSS QDSQPVVHVI ASRRQDWSEH EIAMETSPTI IYQDVSSESQ SATSTIKALL ELQQTTVKEK LESKPRQPTI DLSQMAVPIQ MTQEKRHSPE SPSIAVVESE LVAEYITTER TDEGTEVAFP LLVSHRSQPQ QPSQPQRTLL QHVAQSQTAT QTSVVVKSIP ASSPGAITHI MQQALSSHTA FTKHSEELGT EEGEVEEMDT LDPQTGLFYR SALTQSQSAK QQKLSQPPLE QTQLQVKTLQ CFQTKQKQTI HLQADQLQHK LPQMPQLSIR HQKLTPLQQE QAQPKPDVQH TQHPMVAKDR QLPTLMAQPP QTVVQVLAVK TTQQLPKLQQ APNQPKIYVQ PQTPQSQMSL PASSEKQTAS QVEQPIITQG SSVTKITFEG RQPPTVTKIT GGSSVPKLTS PVTSISPIQA SEKTAVSDIL KMSLMEAQID TNVEHMIVDP PKKALATSML TGEAGSLPST HMVVAGMANS TPQQQKCRES CSSPSTVGSS LTTRKIDPPA VPATGQFMRI QNVGQKKAEE SPAEIIIQAI PQYAIPCHSS SNVVVEPSGL LELNNFTSQQ LDDEETAMEQ DIDSSTEDGT EPSPSQSSAE RS // ID RA51C_HUMAN Reviewed; 376 AA. AC O43502; O43503; Q3B783; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1998, sequence version 1. DT 25-MAY-2022, entry version 189. DE RecName: Full=DNA repair protein RAD51 homolog 3; DE Short=R51H3; DE AltName: Full=RAD51 homolog C; DE AltName: Full=RAD51-like protein 2; GN Name=RAD51C; Synonyms=RAD51L2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RX PubMed=9469824; DOI=10.1093/nar/26.5.1179; RA Dosanjh M.K., Collins D.W., Fan W., Lennon G.G., Albala J.S., Shen Z., RA Schild D.; RT "Isolation and characterization of RAD51C, a new human member of the RAD51 RT family of related genes."; RL Nucleic Acids Res. 26:1179-1184(1998). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-144; CYS-249 AND RP ALA-287. RG NIEHS SNPs program; RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP IDENTIFICATION IN THE BCDX2 COMPLEX WITH RAD51B; RAD51D AND XRCC2, AND RP IDENTIFICATION IN THE CX3 COMPLEX WITH XRCC3. RX PubMed=11751635; DOI=10.1101/gad.947001; RA Masson J.Y., Tarsounas M.C., Stasiak A.Z., Stasiak A., Shah R., RA McIlwraith M.J., Benson F.E., West S.C.; RT "Identification and purification of two distinct complexes containing the RT five RAD51 paralogs."; RL Genes Dev. 15:3296-3307(2001). RN [7] RP FUNCTION, AND INTERACTION WITH RAD51B. RX PubMed=11751636; DOI=10.1101/gad.935501; RA Sigurdsson S., Van Komen S., Bussen W., Schild D., Albala J.S., Sung P.; RT "Mediator function of the human Rad51B-Rad51C complex in Rad51/RPA- RT catalyzed DNA strand exchange."; RL Genes Dev. 15:3308-3318(2001). RN [8] RP INTERACTION WITH RAD51B, AND SUBUNIT. RX PubMed=11744692; DOI=10.1074/jbc.m108306200; RA Miller K.A., Yoshikawa D.M., McConnell I.R., Clark R., Schild D., RA Albala J.S.; RT "RAD51C interacts with RAD51B and is central to a larger protein complex in RT vivo exclusive of RAD51."; RL J. Biol. Chem. 277:8406-8411(2002). RN [9] RP IDENTIFICATION IN A COMPLEX WITH RAD51B; RAD51D AND XRCC2. RX PubMed=11842112; DOI=10.1093/nar/30.4.1001; RA Wiese C., Collins D.W., Albala J.S., Thompson L.H., Kronenberg A., RA Schild D.; RT "Interactions involving the Rad51 paralogs Rad51C and XRCC3 in human RT cells."; RL Nucleic Acids Res. 30:1001-1008(2002). RN [10] RP IDENTIFICATION IN A COMPLEX WITH RAD51B; RAD51D AND XRCC2, AND INTERACTION RP WITH XRCC3. RX PubMed=11842113; DOI=10.1093/nar/30.4.1009; RA Liu N., Schild D., Thelen M.P., Thompson L.H.; RT "Involvement of Rad51C in two distinct protein complexes of Rad51 paralogs RT in human cells."; RL Nucleic Acids Res. 30:1009-1015(2002). RN [11] RP INTERACTION WITH RAD51 AND RAD51B. RX PubMed=12427746; DOI=10.1074/jbc.m211038200; RA Lio Y.-C., Mazin A.V., Kowalczykowski S.C., Chen D.J.; RT "Complex formation by the human Rad51B and Rad51C DNA repair proteins and RT their activities in vitro."; RL J. Biol. Chem. 278:2469-2478(2003). RN [12] RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-131. RX PubMed=12966089; DOI=10.1074/jbc.m308621200; RA French C.A., Tambini C.E., Thacker J.; RT "Identification of functional domains in the RAD51L2 (RAD51C) protein and RT its requirement for gene conversion."; RL J. Biol. Chem. 278:45445-45450(2003). RN [13] RP INTERACTION WITH RAD51B; RAD51D AND XRCC3. RX PubMed=14704354; DOI=10.1093/nar/gkg925; RA Miller K.A., Sawicka D., Barsky D., Albala J.S.; RT "Domain mapping of the Rad51 paralog protein complexes."; RL Nucleic Acids Res. 32:169-178(2004). RN [14] RP FUNCTION, AND MUTAGENESIS OF LYS-131. RX PubMed=14716019; DOI=10.1126/science.1093037; RA Liu Y., Masson J.Y., Shah R., O'Regan P., West S.C.; RT "RAD51C is required for Holliday junction processing in mammalian cells."; RL Science 303:243-246(2004). RN [15] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=16215984; DOI=10.1002/jcb.20640; RA Bennett B.T., Knight K.L.; RT "Cellular localization of human Rad51C and regulation of ubiquitin-mediated RT proteolysis of Rad51."; RL J. Cell. Biochem. 96:1095-1109(2005). RN [16] RP FUNCTION, AND INTERACTION WITH RAD51. RX PubMed=16395335; DOI=10.1038/sj.emboj.7600914; RA Rodrigue A., Lafrance M., Gauthier M.C., McDonald D., Hendzel M., RA West S.C., Jasin M., Masson J.Y.; RT "Interplay between human DNA repair proteins at a unique double-strand RT break in vivo."; RL EMBO J. 25:222-231(2006). RN [17] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=19783859; DOI=10.1074/jbc.m109.024646; RA Gildemeister O.S., Sage J.M., Knight K.L.; RT "Cellular redistribution of Rad51 in response to DNA damage: novel role for RT Rad51C."; RL J. Biol. Chem. 284:31945-31952(2009). RN [18] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=19451272; DOI=10.1083/jcb.200811079; RA Badie S., Liao C., Thanasoula M., Barber P., Hill M.A., Tarsounas M.; RT "RAD51C facilitates checkpoint signaling by promoting CHK2 RT phosphorylation."; RL J. Cell Biol. 185:587-600(2009). RN [19] RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION. RX PubMed=20413593; DOI=10.1074/jbc.m109.099846; RA Sage J.M., Gildemeister O.S., Knight K.L.; RT "Discovery of a novel function for human Rad51: maintenance of the RT mitochondrial genome."; RL J. Biol. Chem. 285:18984-18990(2010). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [21] RP INTERACTION WITH SWSAP1. RX PubMed=21965664; DOI=10.1074/jbc.m111.271080; RA Liu T., Wan L., Wu Y., Chen J., Huang J.; RT "hSWS1.SWSAP1 is an evolutionarily conserved complex required for efficient RT homologous recombination repair."; RL J. Biol. Chem. 286:41758-41766(2011). RN [22] RP FUNCTION IN MITOTIC CELL PROGRESSION. RX PubMed=23108668; DOI=10.1242/jcs.114595; RA Rodrigue A., Coulombe Y., Jacquet K., Gagne J.P., Roques C., Gobeil S., RA Poirier G., Masson J.Y.; RT "The RAD51 paralogs ensure cellular protection against mitotic defects and RT aneuploidy."; RL J. Cell Sci. 126:348-359(2013). RN [23] RP INTERACTION WITH HELQ. RX PubMed=24005041; DOI=10.1093/nar/gkt676; RA Luebben S.W., Kawabata T., Akre M.K., Lee W.L., Johnson C.S., RA O'Sullivan M.G., Shima N.; RT "Helq acts in parallel to Fancc to suppress replication-associated genome RT instability."; RL Nucleic Acids Res. 41:10283-10297(2013). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [25] RP FUNCTION OF THE BCDX2 COMPLEX, AND FUNCTION OF THE CX3 COMPLEX. RX PubMed=23149936; DOI=10.1128/mcb.00465-12; RA Chun J., Buechelmaier E.S., Powell S.N.; RT "Rad51 paralog complexes BCDX2 and CX3 act at different stages in the RT BRCA1-BRCA2-dependent homologous recombination pathway."; RL Mol. Cell. Biol. 33:387-395(2013). RN [26] RP INTERACTION WITH BRCA2; RAD51 AND PALB2, IDENTIFICATION IN A RP PALB2-CONTAINING HR COMPLEX, CHARACTERIZATION OF VARIANT BROVCA3 PHE-138, RP CHARACTERIZATION OF VARIANT ASN-159, AND CHARACTERIZATION OF VARIANT FANCO RP HIS-258. RX PubMed=24141787; DOI=10.1038/onc.2013.421; RA Park J.Y., Singh T.R., Nassar N., Zhang F., Freund M., Hanenberg H., RA Meetei A.R., Andreassen P.R.; RT "Breast cancer-associated missense mutants of the PALB2 WD40 domain, which RT directly binds RAD51C, RAD51 and BRCA2, disrupt DNA repair."; RL Oncogene 33:4803-4812(2014). RN [27] RP ELECTRON MICROSCOPY OF THE BCDX2 AND CX3 COMPLEXES, AND DNA-BINDING OF THE RP BCDX2 AND CX3 COMPLEXES. RX PubMed=20207730; DOI=10.1074/jbc.m109.074286; RA Compton S.A., Ozgur S., Griffith J.D.; RT "Ring-shaped Rad51 paralog protein complexes bind Holliday junctions and RT replication forks as visualized by electron microscopy."; RL J. Biol. Chem. 285:13349-13356(2010). RN [28] RP VARIANT FANCO HIS-258, AND CHARACTERIZATION OF VARIANT FANCO HIS-258. RX PubMed=20400963; DOI=10.1038/ng.570; RA Vaz F., Hanenberg H., Schuster B., Barker K., Wiek C., Erven V., RA Neveling K., Endt D., Kesterton I., Autore F., Fraternali F., Freund M., RA Hartmann L., Grimwade D., Roberts R.G., Schaal H., Mohammed S., Rahman N., RA Schindler D., Mathew C.G.; RT "Mutation of the RAD51C gene in a Fanconi anemia-like disorder."; RL Nat. Genet. 42:406-409(2010). RN [29] RP VARIANTS ARG-3; THR-126; ASN-159; ALA-169; SER-264; VAL-264; ALA-287 AND RP GLN-366, AND VARIANTS BROVCA3 VAL-125 AND PHE-138. RX PubMed=20400964; DOI=10.1038/ng.569; RA Meindl A., Hellebrand H., Wiek C., Erven V., Wappenschmidt B., RA Niederacher D., Freund M., Lichtner P., Hartmann L., Schaal H., Ramser J., RA Honisch E., Kubisch C., Wichmann H.E., Kast K., Deissler H., Engel C., RA Muller-Myhsok B., Neveling K., Kiechle M., Mathew C.G., Schindler D., RA Schmutzler R.K., Hanenberg H.; RT "Germline mutations in breast and ovarian cancer pedigrees establish RAD51C RT as a human cancer susceptibility gene."; RL Nat. Genet. 42:410-414(2010). RN [30] RP VARIANTS LEU-52; PHE-103 DEL; VAL-114; THR-126; ALA-169; THR-175; CYS-249; RP VAL-262 AND SER-264, AND VARIANTS BROVCA3 GLU-162; PRO-178 AND ALA-287. RX PubMed=21990120; DOI=10.1002/humu.21625; RG Kathleen Cuningham foundation consortium for research into familial breast cancer (kConFab); RA Thompson E.R., Boyle S.E., Johnson J., Ryland G.L., Sawyer S., Choong D.Y., RA Chenevix-Trench G., Trainer A.H., Lindeman G.J., Mitchell G., James P.A., RA Campbell I.G.; RT "Analysis of RAD51C germline mutations in high-risk breast and ovarian RT cancer families and ovarian cancer patients."; RL Hum. Mutat. 33:95-99(2012). CC -!- FUNCTION: Essential for the homologous recombination (HR) pathway of CC DNA repair. Involved in the homologous recombination repair (HRR) CC pathway of double-stranded DNA breaks arising during DNA replication or CC induced by DNA-damaging agents. Part of the RAD51 paralog protein CC complexes BCDX2 and CX3 which act at different stages of the BRCA1- CC BRCA2-dependent HR pathway. Upon DNA damage, BCDX2 seems to act CC downstream of BRCA2 recruitment and upstream of RAD51 recruitment; CX3 CC seems to act downstream of RAD51 recruitment; both complexes bind CC predominantly to the intersection of the four duplex arms of the CC Holliday junction (HJ) and to junction of replication forks. The BCDX2 CC complex was originally reported to bind single-stranded DNA, single- CC stranded gaps in duplex DNA and specifically to nicks in duplex DNA. CC The BCDX2 subcomplex RAD51B:RAD51C exhibits single-stranded DNA- CC dependent ATPase activity suggesting an involvement in early stages of CC the HR pathway. Involved in RAD51 foci formation in response to DNA CC damage suggesting an involvement in early stages of HR probably in the CC invasion step. Has an early function in DNA repair in facilitating CC phosphorylation of the checkpoint kinase CHEK2 and thereby transduction CC of the damage signal, leading to cell cycle arrest and HR activation. CC Participates in branch migration and HJ resolution and thus is CC important for processing HR intermediates late in the DNA repair CC process; the function may be linked to the CX3 complex. Part of a CC PALB2-scaffolded HR complex containing BRCA2 and which is thought to CC play a role in DNA repair by HR. Protects RAD51 from ubiquitin-mediated CC degradation that is enhanced following DNA damage. Plays a role in CC regulating mitochondrial DNA copy number under conditions of oxidative CC stress in the presence of RAD51 and XRCC3. Contributes to DNA cross- CC link resistance, sister chromatid cohesion and genomic stability. CC Involved in maintaining centrosome number in mitosis. CC {ECO:0000269|PubMed:14716019, ECO:0000269|PubMed:16215984, CC ECO:0000269|PubMed:16395335, ECO:0000269|PubMed:19451272, CC ECO:0000269|PubMed:19783859, ECO:0000269|PubMed:20413593, CC ECO:0000269|PubMed:23108668, ECO:0000269|PubMed:23149936}. CC -!- SUBUNIT: Part of the RAD51 paralog protein complexes BCDX2 and CX3; the CC complexes have a ring-like structure arranged into a flat disc around a CC central channel (PubMed:12427746, PubMed:11751635, PubMed:11751636, CC PubMed:11842112, PubMed:11842113, PubMed:14704354). The BCDX2 complex CC consits of RAD51B, RAD51C, RAD51D and XRCC2; the CX3 complex consists CC of RAD51C and XRCC3 (PubMed:11751635, PubMed:11842113, CC PubMed:14704354). The BCDX2 subcomplex RAD51B:RAD51C interacts with CC RAD51 (PubMed:12427746, PubMed:16395335). Interacts with SWSAP1; CC involved in homologous recombination repair (PubMed:21965664). CC Interacts directly with PALB2 which may serve as a scaffold for a HR CC complex containing PALB2, BRCA2, RAD51C, RAD51 and XRCC3 CC (PubMed:24141787). Interacts with HELQ (PubMed:24005041). CC {ECO:0000269|PubMed:11751635, ECO:0000269|PubMed:11751636, CC ECO:0000269|PubMed:11842112, ECO:0000269|PubMed:11842113, CC ECO:0000269|PubMed:12427746, ECO:0000269|PubMed:14704354, CC ECO:0000269|PubMed:16395335, ECO:0000269|PubMed:21965664, CC ECO:0000269|PubMed:24005041, ECO:0000269|PubMed:24141787}. CC -!- INTERACTION: CC O43502; Q8TDG4: HELQ; NbExp=6; IntAct=EBI-2267048, EBI-2802156; CC O43502; Q86YC2: PALB2; NbExp=10; IntAct=EBI-2267048, EBI-1222653; CC O43502; Q06609: RAD51; NbExp=6; IntAct=EBI-2267048, EBI-297202; CC O43502; O15315: RAD51B; NbExp=12; IntAct=EBI-2267048, EBI-2824089; CC O43502; O75771: RAD51D; NbExp=6; IntAct=EBI-2267048, EBI-1055693; CC O43502; Q6NVH7: SWSAP1; NbExp=2; IntAct=EBI-2267048, EBI-5281637; CC O43502; O43543: XRCC2; NbExp=3; IntAct=EBI-2267048, EBI-3918457; CC O43502; O43542: XRCC3; NbExp=11; IntAct=EBI-2267048, EBI-2849976; CC O43502-2; Q9NZD8: SPG21; NbExp=3; IntAct=EBI-14233893, EBI-742688; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12966089, CC ECO:0000269|PubMed:16215984}. Cytoplasm {ECO:0000269|PubMed:16215984}. CC Cytoplasm, perinuclear region {ECO:0000269|PubMed:16215984}. CC Mitochondrion {ECO:0000269|PubMed:20413593}. Note=DNA damage induces an CC increase in nuclear levels. Accumulates in DNA damage induced nuclear CC foci or RAD51C foci which is formed during the S or G2 phase of cell CC cycle. Accumulation at DNA lesions requires the presence of NBN/NBS1, CC ATM and RPA. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O43502-1; Sequence=Displayed; CC Name=2; CC IsoId=O43502-2; Sequence=VSP_043656, VSP_043657; CC -!- TISSUE SPECIFICITY: Expressed in a variety of tissues, with highest CC expression in testis, heart muscle, spleen and prostate. CC -!- INDUCTION: Stress-induced increase in the mitochondrial levels is seen. CC {ECO:0000269|PubMed:20413593}. CC -!- DISEASE: Fanconi anemia complementation group O (FANCO) [MIM:613390]: A CC disorder affecting all bone marrow elements and resulting in anemia, CC leukopenia and thrombopenia. It is associated with cardiac, renal and CC limb malformations, dermal pigmentary changes, and a predisposition to CC the development of malignancies. At the cellular level it is associated CC with hypersensitivity to DNA-damaging agents, chromosomal instability CC (increased chromosome breakage) and defective DNA repair. CC {ECO:0000269|PubMed:20400963, ECO:0000269|PubMed:24141787}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Breast-ovarian cancer, familial, 3 (BROVCA3) [MIM:613399]: A CC condition associated with familial predisposition to cancer of the CC breast and ovaries. Characteristic features in affected families are an CC early age of onset of breast cancer (often before age 50), increased CC chance of bilateral cancers (cancer that develop in both breasts, or CC both ovaries, independently), frequent occurrence of breast cancer CC among men, increased incidence of tumors of other specific organs, such CC as the prostate. {ECO:0000269|PubMed:20400964, CC ECO:0000269|PubMed:21990120, ECO:0000269|PubMed:24141787}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the RecA family. RAD51 subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/rad51c/"; CC -!- WEB RESOURCE: Name=RAD51 homolog C (S.cerevisiae) (RAD51C); Note=Leiden CC Open Variation Database (LOVD); CC URL="https://databases.lovd.nl/shared/genes/RAD51C"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF029669; AAC39604.1; -; mRNA. DR EMBL; AF029670; AAC39605.1; -; mRNA. DR EMBL; AY623112; AAT38108.1; -; Genomic_DNA. DR EMBL; AC011195; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC025521; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471109; EAW94432.1; -; Genomic_DNA. DR EMBL; BC107753; AAI07754.1; -; mRNA. DR CCDS; CCDS11611.1; -. [O43502-1] DR CCDS; CCDS45745.1; -. [O43502-2] DR RefSeq; NP_002867.1; NM_002876.3. [O43502-2] DR RefSeq; NP_478123.1; NM_058216.2. [O43502-1] DR AlphaFoldDB; O43502; -. DR SMR; O43502; -. DR BioGRID; 111826; 53. DR CORUM; O43502; -. DR DIP; DIP-41247N; -. DR IntAct; O43502; 20. DR MINT; O43502; -. DR STRING; 9606.ENSP00000336701; -. DR GlyGen; O43502; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O43502; -. DR PhosphoSitePlus; O43502; -. DR BioMuta; RAD51C; -. DR CPTAC; CPTAC-3250; -. DR CPTAC; CPTAC-3287; -. DR EPD; O43502; -. DR jPOST; O43502; -. DR MassIVE; O43502; -. DR MaxQB; O43502; -. DR PaxDb; O43502; -. DR PeptideAtlas; O43502; -. DR PRIDE; O43502; -. DR ProteomicsDB; 48995; -. [O43502-1] DR ProteomicsDB; 48996; -. [O43502-2] DR Antibodypedia; 18441; 388 antibodies from 35 providers. DR CPTC; O43502; 2 antibodies. DR DNASU; 5889; -. DR Ensembl; ENST00000337432.9; ENSP00000336701.4; ENSG00000108384.15. DR Ensembl; ENST00000421782.3; ENSP00000391450.2; ENSG00000108384.15. [O43502-2] DR GeneID; 5889; -. DR KEGG; hsa:5889; -. DR MANE-Select; ENST00000337432.9; ENSP00000336701.4; NM_058216.3; NP_478123.1. DR UCSC; uc002iwt.3; human. [O43502-1] DR CTD; 5889; -. DR DisGeNET; 5889; -. DR GeneCards; RAD51C; -. DR GeneReviews; RAD51C; -. DR HGNC; HGNC:9820; RAD51C. DR HPA; ENSG00000108384; Low tissue specificity. DR MalaCards; RAD51C; -. DR MIM; 602774; gene. DR MIM; 613390; phenotype. DR MIM; 613399; phenotype. DR neXtProt; NX_O43502; -. DR OpenTargets; ENSG00000108384; -. DR Orphanet; 84; Fanconi anemia. DR Orphanet; 145; Hereditary breast and ovarian cancer syndrome. DR PharmGKB; PA34177; -. DR VEuPathDB; HostDB:ENSG00000108384; -. DR eggNOG; KOG1434; Eukaryota. DR GeneTree; ENSGT00940000156805; -. DR InParanoid; O43502; -. DR OMA; RLILYWN; -. DR OrthoDB; 1345899at2759; -. DR PhylomeDB; O43502; -. DR TreeFam; TF101220; -. DR PathwayCommons; O43502; -. DR Reactome; R-HSA-5685942; HDR through Homologous Recombination (HRR). DR Reactome; R-HSA-5693554; Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA). DR Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates. DR Reactome; R-HSA-5693579; Homologous DNA Pairing and Strand Exchange. DR Reactome; R-HSA-5693616; Presynaptic phase of homologous DNA pairing and strand exchange. DR Reactome; R-HSA-912446; Meiotic recombination. DR Reactome; R-HSA-9701192; Defective HDR through Homologous Recombination (HRR) due to BRCA1 loss-of-function. DR Reactome; R-HSA-9704331; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function. DR Reactome; R-HSA-9704646; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function. DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production. DR SignaLink; O43502; -. DR SIGNOR; O43502; -. DR BioGRID-ORCS; 5889; 537 hits in 1089 CRISPR screens. DR ChiTaRS; RAD51C; human. DR GeneWiki; RAD51C; -. DR GenomeRNAi; 5889; -. DR Pharos; O43502; Tbio. DR PRO; PR:O43502; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; O43502; protein. DR Bgee; ENSG00000108384; Expressed in female gonad and 231 other tissues. DR ExpressionAtlas; O43502; baseline and differential. DR Genevisible; O43502; HS. DR GO; GO:0030054; C:cell junction; IDA:HPA. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0033063; C:Rad51B-Rad51C-Rad51D-XRCC2 complex; IDA:UniProtKB. DR GO; GO:0033065; C:Rad51C-XRCC3 complex; IDA:UniProtKB. DR GO; GO:0005657; C:replication fork; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0008094; F:ATP-dependent activity, acting on DNA; IEA:InterPro. DR GO; GO:0008821; F:crossover junction endodeoxyribonuclease activity; IEA:Ensembl. DR GO; GO:0003677; F:DNA binding; TAS:ProtInc. DR GO; GO:0006310; P:DNA recombination; IDA:UniProtKB. DR GO; GO:0006281; P:DNA repair; IDA:UniProtKB. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IMP:UniProtKB. DR GO; GO:0007066; P:female meiosis sister chromatid cohesion; IEA:Ensembl. DR GO; GO:0007141; P:male meiosis I; IEA:Ensembl. DR GO; GO:0000707; P:meiotic DNA recombinase assembly; IBA:GO_Central. DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; IMP:UniProtKB. DR GO; GO:0007131; P:reciprocal meiotic recombination; IBA:GO_Central. DR GO; GO:0007062; P:sister chromatid cohesion; ISS:UniProtKB. DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl. DR GO; GO:0000722; P:telomere maintenance via recombination; IEA:Ensembl. DR CDD; cd01123; Rad51_DMC1_radA; 1. DR Gene3D; 3.40.50.300; -; 1. DR InterPro; IPR013632; DNA_recomb/repair_Rad51_C. DR InterPro; IPR016467; DNA_recomb/repair_RecA-like. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR033925; Rad51_DMC1_RadA. DR InterPro; IPR020588; RecA_ATP-bd. DR Pfam; PF08423; Rad51; 1. DR PIRSF; PIRSF005856; Rad51; 1. DR SUPFAM; SSF52540; SSF52540; 1. DR PROSITE; PS50162; RECA_2; 1. PE 1: Evidence at protein level; KW Alternative splicing; ATP-binding; Cytoplasm; Disease variant; DNA damage; KW DNA recombination; DNA repair; DNA-binding; Fanconi anemia; Mitochondrion; KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome. FT CHAIN 1..376 FT /note="DNA repair protein RAD51 homolog 3" FT /id="PRO_0000122941" FT NP_BIND 125..132 FT /note="ATP" FT /evidence="ECO:0000255" FT REGION 1..126 FT /note="Required for Holliday junction resolution activity" FT REGION 79..136 FT /note="Interaction with RAD51B, RAD51D and XRCC3" FT /evidence="ECO:0000269|PubMed:14704354" FT MOTIF 366..370 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT MOD_RES 20 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 135 FT /note="C -> W (in isoform 2)" FT /evidence="ECO:0000303|PubMed:9469824" FT /id="VSP_043656" FT VAR_SEQ 136..376 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:9469824" FT /id="VSP_043657" FT VARIANT 3 FT /note="G -> R (in dbSNP:rs376403182)" FT /evidence="ECO:0000269|PubMed:20400964" FT /id="VAR_063837" FT VARIANT 52 FT /note="I -> L (in dbSNP:rs730881927)" FT /evidence="ECO:0000269|PubMed:21990120" FT /id="VAR_068014" FT VARIANT 103 FT /note="Missing" FT /evidence="ECO:0000269|PubMed:21990120" FT /id="VAR_068015" FT VARIANT 114 FT /note="G -> V (in dbSNP:rs1555593767)" FT /evidence="ECO:0000269|PubMed:21990120" FT /id="VAR_068016" FT VARIANT 125 FT /note="G -> V (in BROVCA3; dbSNP:rs267606998)" FT /evidence="ECO:0000269|PubMed:20400964" FT /id="VAR_063838" FT VARIANT 126 FT /note="A -> T (in dbSNP:rs61758784)" FT /evidence="ECO:0000269|PubMed:20400964, FT ECO:0000269|PubMed:21990120" FT /id="VAR_063839" FT VARIANT 138 FT /note="L -> F (in BROVCA3; reduces interaction with BRCA2 FT and to a lesser extent with PALB2 and RAD51; FT dbSNP:rs267606999)" FT /evidence="ECO:0000269|PubMed:20400964, FT ECO:0000269|PubMed:24141787" FT /id="VAR_063840" FT VARIANT 144 FT /note="I -> T (in dbSNP:rs28363307)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_020518" FT VARIANT 159 FT /note="D -> N (reduces interaction with BRCA2 and to a FT lesser extent with PALB2 and RAD51)" FT /evidence="ECO:0000269|PubMed:20400964, FT ECO:0000269|PubMed:24141787" FT /id="VAR_063841" FT VARIANT 162 FT /note="G -> E (in BROVCA3; dbSNP:rs35151472)" FT /evidence="ECO:0000269|PubMed:21990120" FT /id="VAR_068017" FT VARIANT 169 FT /note="V -> A (in dbSNP:rs587780256)" FT /evidence="ECO:0000269|PubMed:20400964, FT ECO:0000269|PubMed:21990120" FT /id="VAR_063842" FT VARIANT 175 FT /note="A -> T (in dbSNP:rs587780838)" FT /evidence="ECO:0000269|PubMed:21990120" FT /id="VAR_068018" FT VARIANT 178 FT /note="Q -> P (in BROVCA3)" FT /evidence="ECO:0000269|PubMed:21990120" FT /id="VAR_068019" FT VARIANT 249 FT /note="R -> C (in dbSNP:rs28363311)" FT /evidence="ECO:0000269|PubMed:21990120, ECO:0000269|Ref.2" FT /id="VAR_020519" FT VARIANT 258 FT /note="R -> H (in FANCO; possibly hypomorphic allele; FT reduces interaction with BRCA2 and to a lesser extent with FT PALB2 and RAD51; dbSNP:rs267606997)" FT /evidence="ECO:0000269|PubMed:20400963, FT ECO:0000269|PubMed:24141787" FT /id="VAR_064032" FT VARIANT 262 FT /note="L -> V (in dbSNP:rs149331537)" FT /evidence="ECO:0000269|PubMed:21990120" FT /id="VAR_068020" FT VARIANT 264 FT /note="G -> S (in dbSNP:rs147241704)" FT /evidence="ECO:0000269|PubMed:20400964, FT ECO:0000269|PubMed:21990120" FT /id="VAR_063843" FT VARIANT 264 FT /note="G -> V (in dbSNP:rs1283065191)" FT /evidence="ECO:0000269|PubMed:20400964" FT /id="VAR_063844" FT VARIANT 287 FT /note="T -> A (in BROVCA3; dbSNP:rs28363317)" FT /evidence="ECO:0000269|PubMed:20400964, FT ECO:0000269|PubMed:21990120, ECO:0000269|Ref.2" FT /id="VAR_020520" FT VARIANT 366 FT /note="R -> Q (in dbSNP:rs577852020)" FT /evidence="ECO:0000269|PubMed:20400964" FT /id="VAR_063845" FT MUTAGEN 131 FT /note="K->A: Significant loss of function; abolishes FT Holliday junction resolution activity." FT /evidence="ECO:0000269|PubMed:12966089, FT ECO:0000269|PubMed:14716019" FT MUTAGEN 131 FT /note="K->R: Partial loss of function." FT /evidence="ECO:0000269|PubMed:12966089, FT ECO:0000269|PubMed:14716019" SQ SEQUENCE 376 AA; 42190 MW; 3AAADD3C1C0851E0 CRC64; MRGKTFRFEM QRDLVSFPLS PAVRVKLVSA GFQTAEELLE VKPSELSKEV GISKAEALET LQIIRRECLT NKPRYAGTSE SHKKCTALEL LEQEHTQGFI ITFCSALDDI LGGGVPLMKT TEICGAPGVG KTQLCMQLAV DVQIPECFGG VAGEAVFIDT EGSFMVDRVV DLATACIQHL QLIAEKHKGE EHRKALEDFT LDNILSHIYY FRCRDYTELL AQVYLLPDFL SEHSKVRLVI VDGIAFPFRH DLDDLSLRTR LLNGLAQQMI SLANNHRLAV ILTNQMTTKI DRNQALLVPA LGESWGHAAT IRLIFHWDRK QRLATLYKSP SQKECTVLFQ IKPQGFRDTV VTSACSLQTE GSLSTRKRSR DPEEEL // ID HM20B_HUMAN Reviewed; 317 AA. AC Q9P0W2; A6NMS5; D6W616; Q6IBP8; Q8NBD5; Q9HD21; Q9Y491; Q9Y4A2; DT 04-JAN-2005, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 25-MAY-2022, entry version 173. DE RecName: Full=SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1-related; DE Short=SMARCE1-related protein; DE AltName: Full=BRCA2-associated factor 35; DE AltName: Full=HMG box-containing protein 20B; DE AltName: Full=HMG domain-containing protein 2; DE AltName: Full=HMG domain-containing protein HMGX2; DE AltName: Full=Sox-like transcriptional factor; DE AltName: Full=Structural DNA-binding protein BRAF35; GN Name=HMG20B; Synonyms=BRAF35, HMGX2, HMGXB2, SMARCE1R; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RX PubMed=10773667; DOI=10.1159/000015486; RA Sumoy L., Carim-Todd L., Escarceller M., Nadal M., Gratacos M., RA Pujana M.A., Estivill X., Peral B.; RT "HMG20A and HMG20B map to human chromosomes 15q24 and 19p13.3 and RT constitute a distinct class of HMG-box genes with ubiquitous expression."; RL Cytogenet. Cell Genet. 88:62-67(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH BRCA2, AND RP SUBCELLULAR LOCATION. RX PubMed=11207365; DOI=10.1016/s0092-8674(01)00209-4; RA Marmorstein L.Y., Kinev A.V., Chan G.K.T., Bochar D.A., Beniya H., RA Epstein J.A., Yen T.J., Shiekhattar R.; RT "A human BRCA2 complex containing a structural DNA binding component RT influences cell cycle progression."; RL Cell 104:247-257(2001). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=11997092; DOI=10.1016/s0167-4781(01)00373-6; RA Lee Y.M., Shin H., Choi W., Ahn S., Kim W.; RT "Characterization of human SMARCE1r high-mobility-group protein."; RL Biochim. Biophys. Acta 1574:269-276(2002). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=12083779; DOI=10.1016/s0006-291x(02)00624-1; RA Wang C., McCarty I.M., Balazs L., Li Y., Steiner M.S.; RT "Cloning a cDNA encoding an alternatively spliced protein of BRCA2- RT associated factor 35."; RL Biochem. Biophys. Res. Commun. 295:129-135(2002). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Cerebellum; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Pancreas, Placenta, Skin, and Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 97-317 (ISOFORM 1). RC TISSUE=Heart; RA Suzuki H., Schullery D., Shnyreva M.G., Ostrowski J., Denisenko O., RA Mochizuki S., Bomsztyk K.; RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 103-317 (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [11] RP IDENTIFICATION AS A COMPONENT OF A HISTONE DEACETYLASE COMPLEX, AND RP MUTAGENESIS OF LYS-116. RX PubMed=12032298; DOI=10.1073/pnas.112008599; RA Hakimi M.-A., Bochar D.A., Chenoweth J., Lane W.S., Mandel G., RA Shiekhattar R.; RT "A core-BRAF35 complex containing histone deacetylase mediates repression RT of neuronal-specific genes."; RL Proc. Natl. Acad. Sci. U.S.A. 99:7420-7425(2002). RN [12] RP IDENTIFICATION IN THE BHC COMPLEX WITH GSE1; GTF2I; HDAC1; HDAC2; KDM1A; RP PHF21A; RCOR1; ZMYM2; ZMYM3 AND ZNF217. RX PubMed=12493763; DOI=10.1074/jbc.m208992200; RA Hakimi M.-A., Dong Y., Lane W.S., Speicher D.W., Shiekhattar R.; RT "A candidate X-linked mental retardation gene is a component of a new RT family of histone deacetylase-containing complexes."; RL J. Biol. Chem. 278:7234-7239(2003). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-160, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [14] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-31, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [15] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-31, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). CC -!- FUNCTION: Required for correct progression through G2 phase of the cell CC cycle and entry into mitosis. Required for RCOR1/CoREST mediated CC repression of neuronal specific gene promoters. CC -!- SUBUNIT: Component of a BHC histone deacetylase complex that contains CC HDAC1, HDAC2, HMG20B/BRAF35, KDM1A, RCOR1/CoREST and PHF21A/BHC80. The CC BHC complex may also contain ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I. CC Interacts with the BRCA2 tumor suppressor protein. Interacts with DTNB CC (By similarity). {ECO:0000250|UniProtKB:Q9Z104, CC ECO:0000269|PubMed:11207365, ECO:0000269|PubMed:12493763}. CC -!- INTERACTION: CC Q9P0W2; Q86V38: ATN1; NbExp=3; IntAct=EBI-713401, EBI-11954292; CC Q9P0W2; P51587: BRCA2; NbExp=8; IntAct=EBI-713401, EBI-79792; CC Q9P0W2; Q9NWQ9: C14orf119; NbExp=3; IntAct=EBI-713401, EBI-725606; CC Q9P0W2; Q68D86: CCDC102B; NbExp=6; IntAct=EBI-713401, EBI-10171570; CC Q9P0W2; Q96JN2-2: CCDC136; NbExp=3; IntAct=EBI-713401, EBI-10171416; CC Q9P0W2; P02489: CRYAA; NbExp=3; IntAct=EBI-713401, EBI-6875961; CC Q9P0W2; P30040: ERP29; NbExp=6; IntAct=EBI-713401, EBI-946830; CC Q9P0W2; Q9NP66: HMG20A; NbExp=6; IntAct=EBI-713401, EBI-740641; CC Q9P0W2; P42858: HTT; NbExp=3; IntAct=EBI-713401, EBI-466029; CC Q9P0W2; Q92876: KLK6; NbExp=3; IntAct=EBI-713401, EBI-2432309; CC Q9P0W2; P19012: KRT15; NbExp=3; IntAct=EBI-713401, EBI-739566; CC Q9P0W2; O76015: KRT38; NbExp=6; IntAct=EBI-713401, EBI-1047263; CC Q9P0W2; P61970: NUTF2; NbExp=3; IntAct=EBI-713401, EBI-591778; CC Q9P0W2; O75928-2: PIAS2; NbExp=5; IntAct=EBI-713401, EBI-348567; CC Q9P0W2; Q96KQ4: PPP1R13B; NbExp=3; IntAct=EBI-713401, EBI-1105153; CC Q9P0W2; O75971-2: SNAPC5; NbExp=3; IntAct=EBI-713401, EBI-12004298; CC Q9P0W2; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-713401, EBI-5235340; CC Q9P0W2; Q8N0S2: SYCE1; NbExp=3; IntAct=EBI-713401, EBI-6872807; CC Q9P0W2; Q9UBB9: TFIP11; NbExp=3; IntAct=EBI-713401, EBI-1105213; CC Q9P0W2; Q86WV8: TSC1; NbExp=3; IntAct=EBI-713401, EBI-12806590; CC Q9P0W2; Q8N6Y0: USHBP1; NbExp=3; IntAct=EBI-713401, EBI-739895; CC -!- SUBCELLULAR LOCATION: Nucleus. Chromosome. Note=Localized to condensed CC chromosomes in mitosis in conjunction with BRCA2. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9P0W2-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9P0W2-2; Sequence=VSP_037131; CC Name=3; CC IsoId=Q9P0W2-3; Sequence=VSP_037132; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in adult tissues. CC {ECO:0000269|PubMed:10773667, ECO:0000269|PubMed:11997092}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC26860.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAC26860.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAH21585.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF146223; AAF66707.1; -; mRNA. DR EMBL; AL355709; CAB90809.2; -; mRNA. DR EMBL; AF331191; AAG60060.1; -; mRNA. DR EMBL; AF288679; AAG01174.1; -; mRNA. DR EMBL; AF072165; AAF76253.1; -; mRNA. DR EMBL; AK090733; BAC03510.1; -; mRNA. DR EMBL; AC005786; AAC62837.1; -; Genomic_DNA. DR EMBL; CH471139; EAW69306.1; -; Genomic_DNA. DR EMBL; CH471139; EAW69307.1; -; Genomic_DNA. DR EMBL; CH471139; EAW69308.1; -; Genomic_DNA. DR EMBL; BC002552; AAH02552.1; -; mRNA. DR EMBL; BC003505; AAH03505.2; -; mRNA. DR EMBL; BC004408; AAH04408.2; -; mRNA. DR EMBL; BC021585; AAH21585.1; ALT_INIT; mRNA. DR EMBL; AF072836; AAC26860.1; ALT_SEQ; mRNA. DR EMBL; CR456754; CAG33035.1; -; mRNA. DR CCDS; CCDS45919.1; -. [Q9P0W2-1] DR RefSeq; NP_006330.2; NM_006339.2. [Q9P0W2-1] DR AlphaFoldDB; Q9P0W2; -. DR SMR; Q9P0W2; -. DR BioGRID; 115642; 53. DR CORUM; Q9P0W2; -. DR IntAct; Q9P0W2; 62. DR MINT; Q9P0W2; -. DR STRING; 9606.ENSP00000328269; -. DR GlyGen; Q9P0W2; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9P0W2; -. DR PhosphoSitePlus; Q9P0W2; -. DR BioMuta; HMG20B; -. DR EPD; Q9P0W2; -. DR jPOST; Q9P0W2; -. DR MassIVE; Q9P0W2; -. DR MaxQB; Q9P0W2; -. DR PaxDb; Q9P0W2; -. DR PeptideAtlas; Q9P0W2; -. DR PRIDE; Q9P0W2; -. DR ProteomicsDB; 83610; -. [Q9P0W2-1] DR ProteomicsDB; 83611; -. [Q9P0W2-2] DR ProteomicsDB; 83612; -. [Q9P0W2-3] DR Antibodypedia; 23254; 304 antibodies from 34 providers. DR DNASU; 10362; -. DR Ensembl; ENST00000333651.11; ENSP00000328269.6; ENSG00000064961.19. DR GeneID; 10362; -. DR KEGG; hsa:10362; -. DR MANE-Select; ENST00000333651.11; ENSP00000328269.6; NM_006339.3; NP_006330.2. DR UCSC; uc002lya.4; human. [Q9P0W2-1] DR CTD; 10362; -. DR DisGeNET; 10362; -. DR GeneCards; HMG20B; -. DR HGNC; HGNC:5002; HMG20B. DR HPA; ENSG00000064961; Low tissue specificity. DR MIM; 605535; gene. DR neXtProt; NX_Q9P0W2; -. DR OpenTargets; ENSG00000064961; -. DR PharmGKB; PA29332; -. DR VEuPathDB; HostDB:ENSG00000064961; -. DR eggNOG; KOG0381; Eukaryota. DR GeneTree; ENSGT00940000161213; -. DR InParanoid; Q9P0W2; -. DR OMA; NIDRYMH; -. DR OrthoDB; 1458939at2759; -. DR PhylomeDB; Q9P0W2; -. DR TreeFam; TF106440; -. DR PathwayCommons; Q9P0W2; -. DR Reactome; R-HSA-3214815; HDACs deacetylate histones. DR Reactome; R-HSA-9679191; Potential therapeutics for SARS. DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production. DR SignaLink; Q9P0W2; -. DR SIGNOR; Q9P0W2; -. DR BioGRID-ORCS; 10362; 13 hits in 1103 CRISPR screens. DR ChiTaRS; HMG20B; human. DR GeneWiki; HMG20B; -. DR GenomeRNAi; 10362; -. DR Pharos; Q9P0W2; Tbio. DR PRO; PR:Q9P0W2; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q9P0W2; protein. DR Bgee; ENSG00000064961; Expressed in lower esophagus muscularis layer and 223 other tissues. DR ExpressionAtlas; Q9P0W2; baseline and differential. DR Genevisible; Q9P0W2; HS. DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell. DR GO; GO:0016604; C:nuclear body; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW. DR GO; GO:0033234; P:negative regulation of protein sumoylation; IEA:Ensembl. DR GO; GO:0045666; P:positive regulation of neuron differentiation; IEA:Ensembl. DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central. DR GO; GO:0035914; P:skeletal muscle cell differentiation; IEA:Ensembl. DR Gene3D; 1.10.30.10; -; 1. DR InterPro; IPR009071; HMG_box_dom. DR InterPro; IPR036910; HMG_box_dom_sf. DR Pfam; PF00505; HMG_box; 1. DR SMART; SM00398; HMG; 1. DR SUPFAM; SSF47095; SSF47095; 1. DR PROSITE; PS50118; HMG_BOX_2; 1. PE 1: Evidence at protein level; KW Alternative splicing; Cell cycle; Chromatin regulator; Chromosome; KW Coiled coil; DNA-binding; Isopeptide bond; Nucleus; Phosphoprotein; KW Reference proteome; Transcription; Transcription regulation; KW Ubl conjugation. FT CHAIN 1..317 FT /note="SWI/SNF-related matrix-associated actin-dependent FT regulator of chromatin subfamily E member 1-related" FT /id="PRO_0000048575" FT DNA_BIND 70..138 FT /note="HMG box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00267" FT REGION 1..71 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 190..257 FT /evidence="ECO:0000255" FT COMPBIAS 35..55 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 160 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CROSSLNK 31 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:28112733" FT VAR_SEQ 1..102 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12083779" FT /id="VSP_037131" FT VAR_SEQ 83..106 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_037132" FT MUTAGEN 116 FT /note="K->I: Loss of DNA binding activity of the BHC FT histone deacetylase complex." FT /evidence="ECO:0000269|PubMed:12032298" FT CONFLICT 11..12 FT /note="AA -> SS (in Ref. 3; AAG01174)" FT /evidence="ECO:0000305" FT CONFLICT 174 FT /note="G -> D (in Ref. 10; CAG33035)" FT /evidence="ECO:0000305" FT CONFLICT 223 FT /note="H -> Q (in Ref. 9; AAC26860)" FT /evidence="ECO:0000305" FT CONFLICT 270 FT /note="G -> D (in Ref. 5; BAC03510)" FT /evidence="ECO:0000305" SQ SEQUENCE 317 AA; 35813 MW; ADFCF71C47F8CD2D CRC64; MSHGPKQPGA AAAPAGGKAP GQHGGFVVTV KQERGEGPRA GEKGSHEEEP VKKRGWPKGK KRKKILPNGP KAPVTGYVRF LNERREQIRT RHPDLPFPEI TKMLGAEWSK LQPTEKQRYL DEAEREKQQY MKELRAYQQS EAYKMCTEKI QEKKIKKEDS SSGLMNTLLN GHKGGDCDGF STFDVPIFTE EFLDQNKARE AELRRLRKMN VAFEEQNAVL QRHTQSMSSA RERLEQELAL EERRTLALQQ QLQAVRQALT ASFASLPVPG TGETPTLGTL DFYMARLHGA IERDPAQHEK LIVRIKEILA QVASEHL // ID XRCC3_HUMAN Reviewed; 346 AA. AC O43542; O43568; Q9BU18; DT 03-APR-2002, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1998, sequence version 1. DT 25-MAY-2022, entry version 182. DE RecName: Full=DNA repair protein XRCC3; DE AltName: Full=X-ray repair cross-complementing protein 3; GN Name=XRCC3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANT MET-241. RC TISSUE=Cervix carcinoma; RX PubMed=9660962; DOI=10.1016/s1097-2765(00)80078-7; RA Liu N., Lamerdin J.E., Tebbs R.S., Schild D., Tucker J.D., Shen M.R., RA Brookman K.W., Siciliano M.J., Walter C.A., Fan W., Narayana L.S., RA Zhou Z.-Q., Adamson A.W., Sorensen K.J., Chen D.J., Jones N.J., RA Thompson L.H.; RT "XRCC2 and XRCC3, new human Rad51-family members, promote chromosome RT stability and protect against DNA cross-links and other damages."; RL Mol. Cell 1:783-793(1998). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-94 AND MET-241. RG NIEHS SNPs program; RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lymph, Muscle, and Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP IDENTIFICATION IN THE CX3 COMPLEX WITH XRCC3. RX PubMed=11751635; DOI=10.1101/gad.947001; RA Masson J.Y., Tarsounas M.C., Stasiak A.Z., Stasiak A., Shah R., RA McIlwraith M.J., Benson F.E., West S.C.; RT "Identification and purification of two distinct complexes containing the RT five RAD51 paralogs."; RL Genes Dev. 15:3296-3307(2001). RN [5] RP INVOLVEMENT IN BC SUSCEPTIBILITY. RX PubMed=12023982; DOI=10.1093/hmg/11.12.1399; RA Kuschel B., Auranen A., McBride S., Novik K.L., Antoniou A., RA Lipscombe J.M., Day N.E., Easton D.F., Ponder B.A., Pharoah P.D., RA Dunning A.; RT "Variants in DNA double-strand break repair genes and breast cancer RT susceptibility."; RL Hum. Mol. Genet. 11:1399-1407(2002). RN [6] RP IDENTIFICATION IN THE CX3 COMPLEX WITH XRCC3. RX PubMed=11744692; DOI=10.1074/jbc.m108306200; RA Miller K.A., Yoshikawa D.M., McConnell I.R., Clark R., Schild D., RA Albala J.S.; RT "RAD51C interacts with RAD51B and is central to a larger protein complex in RT vivo exclusive of RAD51."; RL J. Biol. Chem. 277:8406-8411(2002). RN [7] RP INTERACTION WITH RAD51 AND RAD51C. RX PubMed=11842113; DOI=10.1093/nar/30.4.1009; RA Liu N., Schild D., Thelen M.P., Thompson L.H.; RT "Involvement of Rad51C in two distinct protein complexes of Rad51 paralogs RT in human cells."; RL Nucleic Acids Res. 30:1009-1015(2002). RN [8] RP INTERACTION WITH RAD51C. RX PubMed=14704354; DOI=10.1093/nar/gkg925; RA Miller K.A., Sawicka D., Barsky D., Albala J.S.; RT "Domain mapping of the Rad51 paralog protein complexes."; RL Nucleic Acids Res. 32:169-178(2004). RN [9] RP FUNCTION. RX PubMed=14716019; DOI=10.1126/science.1093037; RA Liu Y., Masson J.Y., Shah R., O'Regan P., West S.C.; RT "RAD51C is required for Holliday junction processing in mammalian cells."; RL Science 303:243-246(2004). RN [10] RP SUBCELLULAR LOCATION. RX PubMed=16215984; DOI=10.1002/jcb.20640; RA Bennett B.T., Knight K.L.; RT "Cellular localization of human Rad51C and regulation of ubiquitin-mediated RT proteolysis of Rad51."; RL J. Cell. Biochem. 96:1095-1109(2005). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [12] RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION. RX PubMed=20413593; DOI=10.1074/jbc.m109.099846; RA Sage J.M., Gildemeister O.S., Knight K.L.; RT "Discovery of a novel function for human Rad51: maintenance of the RT mitochondrial genome."; RL J. Biol. Chem. 285:18984-18990(2010). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [14] RP INTERACTION WITH SWSAP1 AND ZSWIM7. RX PubMed=21965664; DOI=10.1074/jbc.m111.271080; RA Liu T., Wan L., Wu Y., Chen J., Huang J.; RT "hSWS1.SWSAP1 is an evolutionarily conserved complex required for efficient RT homologous recombination repair."; RL J. Biol. Chem. 286:41758-41766(2011). RN [15] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [16] RP FUNCTION IN HOLLIDAY JUNCTION RESOLUTION. RX PubMed=23108668; DOI=10.1242/jcs.114595; RA Rodrigue A., Coulombe Y., Jacquet K., Gagne J.P., Roques C., Gobeil S., RA Poirier G., Masson J.Y.; RT "The RAD51 paralogs ensure cellular protection against mitotic defects and RT aneuploidy."; RL J. Cell Sci. 126:348-359(2013). RN [17] RP FUNCTION OF THE CX3 COMPLEX. RX PubMed=23149936; DOI=10.1128/mcb.00465-12; RA Chun J., Buechelmaier E.S., Powell S.N.; RT "Rad51 paralog complexes BCDX2 and CX3 act at different stages in the RT BRCA1-BRCA2-dependent homologous recombination pathway."; RL Mol. Cell. Biol. 33:387-395(2013). RN [18] RP INTERACTION WITH PALB2, AND IDENTIFICATION IN A PALB2-CONTAINING HR RP COMPLEX. RX PubMed=24141787; DOI=10.1038/onc.2013.421; RA Park J.Y., Singh T.R., Nassar N., Zhang F., Freund M., Hanenberg H., RA Meetei A.R., Andreassen P.R.; RT "Breast cancer-associated missense mutants of the PALB2 WD40 domain, which RT directly binds RAD51C, RAD51 and BRCA2, disrupt DNA repair."; RL Oncogene 33:4803-4812(2014). RN [19] RP ELECTRON MICROSCOPY OF THE CX3 COMPLEX, AND DNA-BINDING OF THE CX3 COMPLEX. RX PubMed=20207730; DOI=10.1074/jbc.m109.074286; RA Compton S.A., Ozgur S., Griffith J.D.; RT "Ring-shaped Rad51 paralog protein complexes bind Holliday junctions and RT replication forks as visualized by electron microscopy."; RL J. Biol. Chem. 285:13349-13356(2010). RN [20] RP VARIANT CMM6 MET-241. RX PubMed=11059748; RA Winsey S.L., Haldar N.A., Marsh H.P., Bunce M., Marshall S.E., Harris A.L., RA Wojnarowska F., Welsh K.I.; RT "A variant within the DNA repair gene XRCC3 is associated with the RT development of melanoma skin cancer."; RL Cancer Res. 60:5612-5616(2000). CC -!- FUNCTION: Involved in the homologous recombination repair (HRR) pathway CC of double-stranded DNA, thought to repair chromosomal fragmentation, CC translocations and deletions. Part of the RAD51 paralog protein complex CC CX3 which acts in the BRCA1-BRCA2-dependent HR pathway. Upon DNA CC damage, CX3 acts downstream of RAD51 recruitment; the complex binds CC predominantly to the intersection of the four duplex arms of the CC Holliday junction (HJ) and to junctions of replication forks. Involved CC in HJ resolution and thus in processing HR intermediates late in the CC DNA repair process; the function may be linked to the CX3 complex and CC seems to involve GEN1 during mitotic cell cycle progression. Part of a CC PALB2-scaffolded HR complex containing BRCA2 and RAD51C and which is CC thought to play a role in DNA repair by HR. Plays a role in regulating CC mitochondrial DNA copy number under conditions of oxidative stress in CC the presence of RAD51 and RAD51C. {ECO:0000269|PubMed:14716019, CC ECO:0000269|PubMed:20413593, ECO:0000269|PubMed:23108668, CC ECO:0000269|PubMed:23149936}. CC -!- SUBUNIT: Interacts with RAD51C and RAD51. Part of the CX3 complex CC consisting of RAD51C and XRCC3; the complex has a ring-like structure CC arranged into a flat disc around a central channel; CX3 can interact CC with RAD51 in vitro. Forms a complex with FANCD2, BRCA2 and CC phosphorylated FANCG. Interacts with SWSAP1 and ZSWIM7; involved in CC homologous recombination repair. Interacts directly with PALB2 which CC may serve as a scaffold for a HR complex containing PALB2, BRCA2, CC RAD51C, RAD51 and XRCC3. {ECO:0000269|PubMed:11744692, CC ECO:0000269|PubMed:11751635, ECO:0000269|PubMed:11842113, CC ECO:0000269|PubMed:14704354, ECO:0000269|PubMed:21965664, CC ECO:0000269|PubMed:24141787}. CC -!- INTERACTION: CC O43542; Q86YC2: PALB2; NbExp=3; IntAct=EBI-2849976, EBI-1222653; CC O43542; Q06609: RAD51; NbExp=5; IntAct=EBI-2849976, EBI-297202; CC O43542; O43502: RAD51C; NbExp=11; IntAct=EBI-2849976, EBI-2267048; CC O43542; Q6NVH7: SWSAP1; NbExp=2; IntAct=EBI-2849976, EBI-5281637; CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Cytoplasm, perinuclear CC region. Mitochondrion. Note=Accumulates in discrete nuclear foci prior CC to DNA damage, and these foci persist throughout the time course of DNA CC repair. CC -!- INDUCTION: Stress-induced increase in the mitochondrial levels is seen. CC {ECO:0000269|PubMed:20413593}. CC -!- DISEASE: Breast cancer (BC) [MIM:114480]: A common malignancy CC originating from breast epithelial tissue. Breast neoplasms can be CC distinguished by their histologic pattern. Invasive ductal carcinoma is CC by far the most common type. Breast cancer is etiologically and CC genetically heterogeneous. Important genetic factors have been CC indicated by familial occurrence and bilateral involvement. Mutations CC at more than one locus can be involved in different families or even in CC the same case. {ECO:0000269|PubMed:12023982}. Note=Disease CC susceptibility is associated with variants affecting the gene CC represented in this entry. CC -!- DISEASE: Melanoma, cutaneous malignant 6 (CMM6) [MIM:613972]: A CC malignant neoplasm of melanocytes, arising de novo or from a pre- CC existing benign nevus, which occurs most often in the skin but also may CC involve other sites. {ECO:0000269|PubMed:11059748}. Note=Disease CC susceptibility is associated with variants affecting the gene CC represented in this entry. CC -!- SIMILARITY: Belongs to the RecA family. RAD51 subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/XRCC3ID335ch14q32.html"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/xrcc3/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF035586; AAC05368.1; -; mRNA. DR EMBL; AF037222; AAC04805.1; -; Genomic_DNA. DR EMBL; AF508041; AAM23015.1; -; Genomic_DNA. DR EMBL; BC001036; AAH01036.1; -; mRNA. DR EMBL; BC002949; AAH02949.1; -; mRNA. DR EMBL; BC011725; AAH11725.1; -; mRNA. DR CCDS; CCDS9984.1; -. DR RefSeq; NP_001093588.1; NM_001100118.1. DR RefSeq; NP_001093589.1; NM_001100119.1. DR RefSeq; NP_005423.1; NM_005432.3. DR RefSeq; XP_005268103.1; XM_005268046.2. DR RefSeq; XP_011535440.1; XM_011537138.2. DR AlphaFoldDB; O43542; -. DR SMR; O43542; -. DR BioGRID; 113351; 173. DR CORUM; O43542; -. DR DIP; DIP-42016N; -. DR IntAct; O43542; 149. DR MINT; O43542; -. DR STRING; 9606.ENSP00000451974; -. DR iPTMnet; O43542; -. DR PhosphoSitePlus; O43542; -. DR BioMuta; XRCC3; -. DR EPD; O43542; -. DR jPOST; O43542; -. DR MassIVE; O43542; -. DR PaxDb; O43542; -. DR PeptideAtlas; O43542; -. DR PRIDE; O43542; -. DR ProteomicsDB; 49041; -. DR Antibodypedia; 14778; 599 antibodies from 35 providers. DR DNASU; 7517; -. DR Ensembl; ENST00000352127.11; ENSP00000343392.7; ENSG00000126215.14. DR Ensembl; ENST00000553264.5; ENSP00000451974.1; ENSG00000126215.14. DR Ensembl; ENST00000554913.5; ENSP00000451362.1; ENSG00000126215.14. DR Ensembl; ENST00000555055.6; ENSP00000452598.1; ENSG00000126215.14. DR GeneID; 7517; -. DR KEGG; hsa:7517; -. DR MANE-Select; ENST00000555055.6; ENSP00000452598.1; NM_005432.4; NP_005423.1. DR CTD; 7517; -. DR DisGeNET; 7517; -. DR GeneCards; XRCC3; -. DR HGNC; HGNC:12830; XRCC3. DR HPA; ENSG00000126215; Low tissue specificity. DR MalaCards; XRCC3; -. DR MIM; 114480; phenotype. DR MIM; 600675; gene. DR MIM; 613972; phenotype. DR neXtProt; NX_O43542; -. DR OpenTargets; ENSG00000126215; -. DR PharmGKB; PA37422; -. DR VEuPathDB; HostDB:ENSG00000126215; -. DR eggNOG; KOG1564; Eukaryota. DR GeneTree; ENSGT00930000151053; -. DR HOGENOM; CLU_041732_1_0_1; -. DR InParanoid; O43542; -. DR OMA; PCLGLQW; -. DR OrthoDB; 1341207at2759; -. DR PhylomeDB; O43542; -. DR TreeFam; TF101203; -. DR PathwayCommons; O43542; -. DR Reactome; R-HSA-5685942; HDR through Homologous Recombination (HRR). DR Reactome; R-HSA-5693554; Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA). DR Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates. DR Reactome; R-HSA-5693579; Homologous DNA Pairing and Strand Exchange. DR SignaLink; O43542; -. DR SIGNOR; O43542; -. DR BioGRID-ORCS; 7517; 516 hits in 1084 CRISPR screens. DR ChiTaRS; XRCC3; human. DR GeneWiki; XRCC3; -. DR GenomeRNAi; 7517; -. DR Pharos; O43542; Tbio. DR PRO; PR:O43542; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; O43542; protein. DR Bgee; ENSG00000126215; Expressed in left lobe of thyroid gland and 132 other tissues. DR ExpressionAtlas; O43542; baseline and differential. DR Genevisible; O43542; HS. DR GO; GO:0000781; C:chromosome, telomeric region; IC:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0033065; C:Rad51C-XRCC3 complex; IDA:UniProtKB. DR GO; GO:0005657; C:replication fork; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0008094; F:ATP-dependent activity, acting on DNA; IEA:InterPro. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0006974; P:cellular response to DNA damage stimulus; TAS:ProtInc. DR GO; GO:0006310; P:DNA recombination; TAS:ProtInc. DR GO; GO:0006281; P:DNA repair; IGI:BHF-UCL. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IMP:UniProtKB. DR GO; GO:0045003; P:double-strand break repair via synthesis-dependent strand annealing; IBA:GO_Central. DR GO; GO:0036297; P:interstrand cross-link repair; IMP:ParkinsonsUK-UCL. DR GO; GO:0090267; P:positive regulation of mitotic cell cycle spindle assembly checkpoint; IMP:UniProtKB. DR GO; GO:0010824; P:regulation of centrosome duplication; IMP:UniProtKB. DR GO; GO:0071140; P:resolution of mitotic recombination intermediates; IMP:UniProtKB. DR GO; GO:0010033; P:response to organic substance; IEA:Ensembl. DR GO; GO:0090656; P:t-circle formation; IMP:BHF-UCL. DR GO; GO:0000722; P:telomere maintenance via recombination; IMP:BHF-UCL. DR GO; GO:0090737; P:telomere maintenance via telomere trimming; IGI:BHF-UCL. DR GO; GO:0090657; P:telomeric loop disassembly; TAS:BHF-UCL. DR CDD; cd01123; Rad51_DMC1_radA; 1. DR Gene3D; 3.40.50.300; -; 1. DR InterPro; IPR013632; DNA_recomb/repair_Rad51_C. DR InterPro; IPR016467; DNA_recomb/repair_RecA-like. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR033925; Rad51_DMC1_RadA. DR InterPro; IPR020588; RecA_ATP-bd. DR Pfam; PF08423; Rad51; 1. DR PIRSF; PIRSF005856; Rad51; 1. DR SUPFAM; SSF52540; SSF52540; 1. DR PROSITE; PS50162; RECA_2; 1. PE 1: Evidence at protein level; KW Acetylation; ATP-binding; Cytoplasm; Disease variant; DNA damage; KW DNA recombination; DNA repair; DNA-binding; Mitochondrion; KW Nucleotide-binding; Nucleus; Reference proteome. FT CHAIN 1..346 FT /note="DNA repair protein XRCC3" FT /id="PRO_0000122951" FT NP_BIND 107..114 FT /note="ATP" FT /evidence="ECO:0000255" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22814378" FT VARIANT 94 FT /note="R -> H (in dbSNP:rs3212057)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_020405" FT VARIANT 241 FT /note="T -> M (in CMM6; risk factor for disease FT development; dbSNP:rs861539)" FT /evidence="ECO:0000269|PubMed:11059748, FT ECO:0000269|PubMed:9660962, ECO:0000269|Ref.2" FT /id="VAR_013006" FT VARIANT 271 FT /note="G -> R (in dbSNP:rs28903080)" FT /id="VAR_029295" FT VARIANT 302 FT /note="R -> H (in dbSNP:rs28903081)" FT /id="VAR_029296" SQ SEQUENCE 346 AA; 37850 MW; 4DDF3B163C3B3332 CRC64; MDLDLLDLNP RIIAAIKKAK LKSVKEVLHF SGPDLKRLTN LSSPEVWHLL RTASLHLRGS SILTALQLHQ QKERFPTQHQ RLSLGCPVLD ALLRGGLPLD GITELAGRSS AGKTQLALQL CLAVQFPRQH GGLEAGAVYI CTEDAFPHKR LQQLMAQQPR LRTDVPGELL QKLRFGSQIF IEHVADVDTL LECVNKKVPV LLSRGMARLV VIDSVAAPFR CEFDSQASAP RARHLQSLGA TLRELSSAFQ SPVLCINQVT EAMEEQGAAH GPLGFWDERV SPALGITWAN QLLVRLLADR LREEEAALGC PARTLRVLSA PHLPPSSCSY TISAEGVRGT PGTQSH // ID BRME1_HUMAN Reviewed; 668 AA. AC Q0VDD7; Q13411; Q8N825; Q96D63; Q9BU49; DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot. DT 24-JUL-2007, sequence version 2. DT 25-MAY-2022, entry version 126. DE RecName: Full=Break repair meiotic recombinase recruitment factor 1 {ECO:0000305}; DE AltName: Full=Pre-T/NK cell-associated protein 3B3; GN Name=BRME1 {ECO:0000312|HGNC:HGNC:28153}; Synonyms=C19orf57; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 123-668 (ISOFORM 1), AND VARIANTS ARG-267 AND RP ARG-500. RC TISSUE=Lung, and Mammary gland; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP IDENTIFICATION. RX PubMed=8228263; RA Ranes-Goldberg M.G., Hori T., Mohan-Peterson S., Spits H.; RT "Identification of human pre-T/NK cell-associated genes."; RL J. Immunol. 151:5810-5821(1993). RN [4] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-370, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-370, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). CC -!- FUNCTION: Meiotic recombination factor component of recombination CC bridges involved in meiotic double-strand break repair. Modulates the CC localization of recombinases DMC1:RAD51 to meiotic double-strand break CC (DSB) sites through the interaction with and stabilization of the CC BRCA2:HSF2BP complex during meiotic recombination. Indispensable for CC the DSB repair, homologous synapsis, and crossover formation that are CC needed for progression past metaphase I, is essential for CC spermatogenesis and male fertility. {ECO:0000250|UniProtKB:Q6DIA7}. CC -!- SUBUNIT: Interacts with HSF2BP (via N-terminus) and BRCA2; the CC interaction with HSF2BP is direct and allows the formation of a ternary CC complex. The complex BRME1:HSF2BP:BRCA2 interacts with SPATA22, MEIOB CC and RAD51. {ECO:0000250|UniProtKB:Q6DIA7}. CC -!- INTERACTION: CC Q0VDD7; Q13155: AIMP2; NbExp=8; IntAct=EBI-741210, EBI-745226; CC Q0VDD7; Q8WUW1: BRK1; NbExp=3; IntAct=EBI-741210, EBI-2837444; CC Q0VDD7; P50990: CCT8; NbExp=3; IntAct=EBI-741210, EBI-356507; CC Q0VDD7; Q9BT78: COPS4; NbExp=2; IntAct=EBI-741210, EBI-742413; CC Q0VDD7; Q9UBT7: CTNNAL1; NbExp=3; IntAct=EBI-741210, EBI-514206; CC Q0VDD7; Q8IZU0: FAM9B; NbExp=3; IntAct=EBI-741210, EBI-10175124; CC Q0VDD7; Q68CZ6: HAUS3; NbExp=3; IntAct=EBI-741210, EBI-2558217; CC Q0VDD7; Q86YM7: HOMER1; NbExp=3; IntAct=EBI-741210, EBI-746815; CC Q0VDD7; O60333-2: KIF1B; NbExp=3; IntAct=EBI-741210, EBI-10975473; CC Q0VDD7; O76015: KRT38; NbExp=3; IntAct=EBI-741210, EBI-1047263; CC Q0VDD7; Q6A162: KRT40; NbExp=3; IntAct=EBI-741210, EBI-10171697; CC Q0VDD7; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-741210, EBI-10172290; CC Q0VDD7; P60411: KRTAP10-9; NbExp=4; IntAct=EBI-741210, EBI-10172052; CC Q0VDD7; P28331-2: NDUFS1; NbExp=3; IntAct=EBI-741210, EBI-6190702; CC Q0VDD7; Q9BVL2: NUP58; NbExp=3; IntAct=EBI-741210, EBI-2811583; CC Q0VDD7; P60900: PSMA6; NbExp=3; IntAct=EBI-741210, EBI-357793; CC Q0VDD7; Q06455-4: RUNX1T1; NbExp=3; IntAct=EBI-741210, EBI-10224192; CC Q0VDD7; P61764: STXBP1; NbExp=3; IntAct=EBI-741210, EBI-960169; CC Q0VDD7; P36406: TRIM23; NbExp=4; IntAct=EBI-741210, EBI-740098; CC Q0VDD7; Q99576-3: TSC22D3; NbExp=3; IntAct=EBI-741210, EBI-10294415; CC Q0VDD7; P02766: TTR; NbExp=3; IntAct=EBI-741210, EBI-711909; CC Q0VDD7; O76024: WFS1; NbExp=3; IntAct=EBI-741210, EBI-720609; CC Q0VDD7-2; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-12040255, EBI-10173507; CC Q0VDD7-2; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-12040255, EBI-3867333; CC Q0VDD7-2; Q15323: KRT31; NbExp=3; IntAct=EBI-12040255, EBI-948001; CC Q0VDD7-2; O76011: KRT34; NbExp=3; IntAct=EBI-12040255, EBI-1047093; CC Q0VDD7-2; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-12040255, EBI-10171774; CC Q0VDD7-2; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-12040255, EBI-22310682; CC -!- SUBCELLULAR LOCATION: Chromosome {ECO:0000250|UniProtKB:Q6DIA7}. CC Note=During meiosis, recruited to chromosomes and localizes on CC recombination sites in a double-strand break-dependent manner. First CC appears on the chromosome axis at leptotene. Along with the progression CC of meiotic recombination, released from the axis to form bridge-like CC structures linking homolog axes before they are synapsed. Finally, CC located between synapsed homolog axes and on the synaptonemal complex CC (SC). {ECO:0000250|UniProtKB:Q6DIA7}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q0VDD7-1; Sequence=Displayed; CC Name=2; CC IsoId=Q0VDD7-2; Sequence=VSP_027044; CC -!- SEQUENCE CAUTION: CC Sequence=AAB02340.1; Type=Erroneous translation; Note=Wrong choice of frame.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK097431; BAC05049.1; -; mRNA. DR EMBL; BC002891; AAH02891.2; -; mRNA. DR EMBL; BC012945; AAH12945.2; -; mRNA. DR EMBL; BC119719; AAI19720.1; -; mRNA. DR EMBL; L17327; AAB02340.1; ALT_SEQ; mRNA. DR CCDS; CCDS12299.1; -. [Q0VDD7-2] DR RefSeq; NP_001332773.1; NM_001345844.1. [Q0VDD7-2] DR RefSeq; NP_077299.3; NM_024323.4. [Q0VDD7-2] DR AlphaFoldDB; Q0VDD7; -. DR BioGRID; 122590; 51. DR IntAct; Q0VDD7; 41. DR MINT; Q0VDD7; -. DR STRING; 9606.ENSP00000254336; -. DR iPTMnet; Q0VDD7; -. DR PhosphoSitePlus; Q0VDD7; -. DR BioMuta; C19orf57; -. DR DMDM; 158564134; -. DR jPOST; Q0VDD7; -. DR MassIVE; Q0VDD7; -. DR MaxQB; Q0VDD7; -. DR PaxDb; Q0VDD7; -. DR PeptideAtlas; Q0VDD7; -. DR PRIDE; Q0VDD7; -. DR ProteomicsDB; 58818; -. [Q0VDD7-1] DR ProteomicsDB; 58819; -. [Q0VDD7-2] DR Antibodypedia; 50171; 41 antibodies from 14 providers. DR DNASU; 79173; -. DR Ensembl; ENST00000346736.6; ENSP00000254336.1; ENSG00000132016.12. [Q0VDD7-2] DR Ensembl; ENST00000586783.6; ENSP00000465822.1; ENSG00000132016.12. DR Ensembl; ENST00000672170.1; ENSP00000500215.1; ENSG00000288152.1. DR Ensembl; ENST00000672786.1; ENSP00000500761.1; ENSG00000288152.1. [Q0VDD7-2] DR GeneID; 79173; -. DR KEGG; hsa:79173; -. DR MANE-Select; ENST00000586783.6; ENSP00000465822.1; NM_001345843.2; NP_001332772.2. DR UCSC; uc002mxk.2; human. [Q0VDD7-1] DR CTD; 79173; -. DR GeneCards; BRME1; -. DR HGNC; HGNC:28153; BRME1. DR HPA; ENSG00000132016; Tissue enhanced (testis). DR MIM; 619276; gene. DR neXtProt; NX_Q0VDD7; -. DR OpenTargets; ENSG00000132016; -. DR PharmGKB; PA162378679; -. DR VEuPathDB; HostDB:ENSG00000132016; -. DR eggNOG; ENOG502SVQQ; Eukaryota. DR GeneTree; ENSGT00390000016855; -. DR HOGENOM; CLU_029361_0_0_1; -. DR InParanoid; Q0VDD7; -. DR OMA; HETQEPT; -. DR OrthoDB; 573895at2759; -. DR PhylomeDB; Q0VDD7; -. DR TreeFam; TF337646; -. DR PathwayCommons; Q0VDD7; -. DR SignaLink; Q0VDD7; -. DR BioGRID-ORCS; 79173; 4 hits in 1049 CRISPR screens. DR ChiTaRS; C19orf57; human. DR GenomeRNAi; 79173; -. DR Pharos; Q0VDD7; Tdark. DR PRO; PR:Q0VDD7; -. DR Proteomes; UP000005640; Chromosome 19. DR Proteomes; UP000005640; Unplaced. DR RNAct; Q0VDD7; protein. DR Bgee; ENSG00000132016; Expressed in sural nerve and 118 other tissues. DR ExpressionAtlas; Q0VDD7; baseline and differential. DR Genevisible; Q0VDD7; HS. DR GO; GO:0005694; C:chromosome; ISS:UniProtKB. DR GO; GO:1990918; P:double-strand break repair involved in meiotic recombination; ISS:UniProtKB. DR GO; GO:0007144; P:female meiosis I; ISS:UniProtKB. DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB. DR InterPro; IPR031441; Brme1. DR PANTHER; PTHR14583; PTHR14583; 1. DR Pfam; PF15710; Brme1; 1. PE 1: Evidence at protein level; KW Alternative splicing; Chromosome; Meiosis; Phosphoprotein; KW Reference proteome. FT CHAIN 1..668 FT /note="Break repair meiotic recombinase recruitment factor FT 1" FT /id="PRO_0000295737" FT REGION 1..142 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 155..333 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 349..465 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 482..521 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 642..668 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 110..127 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 168..185 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 212..252 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 306..332 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 370 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT VAR_SEQ 588..619 FT /note="RTFVGIQASEASRMEDATNVVRGLIVELSNLN -> S (in isoform FT 2)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_027044" FT VARIANT 267 FT /note="G -> R (in dbSNP:rs2305775)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_033356" FT VARIANT 500 FT /note="Q -> R (in dbSNP:rs3803892)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_033357" FT CONFLICT 491 FT /note="D -> E (in Ref. 2; AAI19720)" FT /evidence="ECO:0000305" SQ SEQUENCE 668 AA; 69556 MW; 64E4242D2B5C6507 CRC64; MTKRKKLRTS GEGLCPPKPL KNPRLGDFYG DPQSSMLGCL HHPEEPEGKL GPVPSTQQHG EEPGKAVSSS PDEETGSPCR LLRQPEKEPA PLPPSQNSFG RFVPQFAKSR KTVTRKEEMK DEDRGSGAFS LETIAESSAQ SPGCQLLVET LGVPLQEATE LGDPTQADSA RPEQSSQSPV QAVPGSGDSQ PDDPPDRGTG LSASQRASQD HLSEQGADDS KPETDRVPGD GGQKEHLPSI DSEGEKPDRG APQEGGAQRT AGAGLPGGPQ EEGDGVPCTP ASAPTSGPAP GLGPASWCLE PGSVAQGSPD PQQTPSRMGR EGEGTHSSLG CSSLGMVVIA DLSTDPTELE ERALEVAGPD GQASAISPAS PRRKAADGGH RRALPGCTSL TGETTGESGE AGQDGKPPGD VLVGPTASLA LAPGSGESMM GAGDSGHASP DTGPCVNQKQ EPGPAQEEAE LGGQNLERDL EGFRVSPQAS VVLEHREIAD DPLQEPGAQQ GIPDTTSELA GQRDHLPHSA DQGTWADSLA VELDFLLDSQ IQDALDASDF EAPPEQLFPS GNKPGPCWPG PSSHANGDPV AVAKAQPRTF VGIQASEASR MEDATNVVRG LIVELSNLNR LIMGTHRDLE AFKRLNYRKT KLGGKAPLPY PSKGPGNIPR GDPPWREL // ID RAD51_HUMAN Reviewed; 339 AA. AC Q06609; B0FXP0; B2R8T6; Q6FHX9; Q6ZNA8; Q9BV60; DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1994, sequence version 1. DT 25-MAY-2022, entry version 232. DE RecName: Full=DNA repair protein RAD51 homolog 1 {ECO:0000305}; DE Short=HsRAD51; DE Short=hRAD51; DE AltName: Full=RAD51 homolog A; GN Name=RAD51 {ECO:0000312|HGNC:HGNC:9817}; Synonyms=RAD51A, RECA; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=8358431; DOI=10.1038/ng0793-239; RA Shinohara A., Ogawa H., Matsuda Y., Ushio N., Ikeo K., Ogawa T.; RT "Cloning of human, mouse and fission yeast recombination genes homologous RT to RAD51 and recA."; RL Nat. Genet. 4:239-243(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Testis; RX PubMed=8479919; DOI=10.1093/nar/21.7.1665; RA Yoshimura Y., Morita T., Yamamoto A., Matsushiro A.; RT "Cloning and sequence of the human RecA-like gene cDNA."; RL Nucleic Acids Res. 21:1665-1665(1993). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=10493508; RA Schmutte C., Tombline G., Rhiem K., Sadoff M.M., Schmutzler R., RA von Deimling A., Fishel R.; RT "Characterization of the human Rad51 genomic locus and examination of RT tumors with 15q14-15 loss of heterozygosity (LOH)."; RL Cancer Res. 59:4564-4569(1999). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=11535547; RA Wang W.W., Spurdle A.B., Kolachana P., Bove B., Modan B., Ebbers S.M., RA Suthers G., Tucker M.A., Kaufman D.J., Doody M.M., Tarone R.E., Daly M., RA Levavi H., Pierce H., Chetrit A., Yechezkel G.H., Chenevix-Trench G., RA Offit K., Godwin A.K., Struewing J.P.; RT "A single nucleotide polymorphism in the 5' untranslated region of RAD51 RT and risk of cancer among BRCA1/2 mutation carriers."; RL Cancer Epidemiol. Biomarkers Prev. 10:955-960(2001). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION OF ISOFORMS 1 AND 3, RP TISSUE SPECIFICITY (ISOFORMS 1 AND 3), SUBCELLULAR LOCATION (ISOFORMS 1 AND RP 3), AND MUTAGENESIS (ISOFORM 3). RX PubMed=18417535; DOI=10.1093/nar/gkn171; RA Park J.Y., Yoo H.W., Kim B.R., Park R., Choi S.Y., Kim Y.; RT "Identification of a novel human Rad51 variant that promotes DNA strand RT exchange."; RL Nucleic Acids Res. 36:3226-3234(2008). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NIEHS SNPs program; RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4). RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16572171; DOI=10.1038/nature04601; RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S., RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.; RT "Analysis of the DNA sequence and duplication history of human chromosome RT 15."; RL Nature 440:671-675(2006). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [12] RP CHARACTERIZATION. RX PubMed=7988572; DOI=10.1002/j.1460-2075.1994.tb06914.x; RA Benson F.E., Stasiak A., West S.C.; RT "Purification and characterization of the human Rad51 protein, an analogue RT of E. coli RecA."; RL EMBO J. 13:5764-5771(1994). RN [13] RP INTERACTION WITH RAD54L. RX PubMed=9321665; DOI=10.1093/nar/25.20.4106; RA Golub E.I., Kovalenko O.V., Gupta R.C., Ward D.C., Radding C.M.; RT "Interaction of human recombination proteins Rad51 and Rad54."; RL Nucleic Acids Res. 25:4106-4110(1997). RN [14] RP INTERACTION WITH RAD51AP1. RX PubMed=9396801; DOI=10.1093/nar/25.24.4946; RA Kovalenko O.V., Golub E.I., Bray-Ward P., Ward D.C., Radding C.M.; RT "A novel nucleic acid-binding protein that interacts with human rad51 RT recombinase."; RL Nucleic Acids Res. 25:4946-4953(1997). RN [15] RP INTERACTION WITH RAD51AP1, AND SUBCELLULAR LOCATION. RX PubMed=9192668; DOI=10.1073/pnas.94.13.6927; RA Mizuta R., LaSalle J.M., Cheng H.-L., Shinohara A., Ogawa H., RA Copeland N.G., Jenkins N.A., Lalande M., Alt F.W.; RT "RAB22 and RAB163/mouse BRCA2: proteins that specifically interact with the RT RAD51 protein."; RL Proc. Natl. Acad. Sci. U.S.A. 94:6927-6932(1997). RN [16] RP INTERACTION WITH ABL1, AND PHOSPHORYLATION AT TYR-54. RX PubMed=9461559; DOI=10.1074/jbc.273.7.3799; RA Yuan Z.M., Huang Y., Ishiko T., Nakada S., Utsugisawa T., Kharbanda S., RA Wang R., Sung P., Shinohara A., Weichselbaum R., Kufe D.; RT "Regulation of Rad51 function by c-Abl in response to DNA damage."; RL J. Biol. Chem. 273:3799-3802(1998). RN [17] RP INTERACTION WITH RAD54B. RX PubMed=10851248; DOI=10.1074/jbc.m910306199; RA Tanaka K., Hiramoto T., Fukuda T., Miyagawa K.; RT "A novel human Rad54 homologue, Rad54B, associates with Rad51."; RL J. Biol. Chem. 275:26316-26321(2000). RN [18] RP FUNCTION. RX PubMed=12205100; DOI=10.1074/jbc.m208004200; RA Sigurdsson S., Van Komen S., Petukhova G., Sung P.; RT "Homologous DNA pairing by human recombination factors Rad51 and Rad54."; RL J. Biol. Chem. 277:42790-42794(2002). RN [19] RP INTERACTION WITH XRCC3. RX PubMed=11842113; DOI=10.1093/nar/30.4.1009; RA Liu N., Schild D., Thelen M.P., Thompson L.H.; RT "Involvement of Rad51C in two distinct protein complexes of Rad51 paralogs RT in human cells."; RL Nucleic Acids Res. 30:1009-1015(2002). RN [20] RP INTERACTION WITH RAD51B AND RAD51C. RX PubMed=12427746; DOI=10.1074/jbc.m211038200; RA Lio Y.-C., Mazin A.V., Kowalczykowski S.C., Chen D.J.; RT "Complex formation by the human Rad51B and Rad51C DNA repair proteins and RT their activities in vitro."; RL J. Biol. Chem. 278:2469-2478(2003). RN [21] RP SELF-ASSOCIATION, INTERACTION WITH BRCA2, AND MUTAGENESIS OF RP 208-SER-ALA-209. RX PubMed=14580352; DOI=10.1016/s1097-2765(03)00394-0; RA Yu D.S., Sonoda E., Takeda S., Huang C.L., Pellegrini L., Blundell T.L., RA Venkitaraman A.R.; RT "Dynamic control of Rad51 recombinase by self-association and interaction RT with BRCA2."; RL Mol. Cell 12:1029-1041(2003). RN [22] RP SUBCELLULAR LOCATION. RX PubMed=16215984; DOI=10.1002/jcb.20640; RA Bennett B.T., Knight K.L.; RT "Cellular localization of human Rad51C and regulation of ubiquitin-mediated RT proteolysis of Rad51."; RL J. Cell. Biochem. 96:1095-1109(2005). RN [23] RP INTERACTION WITH CHEK1, SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-309, RP AND MUTAGENESIS OF THR-309. RX PubMed=15665856; DOI=10.1038/ncb1212; RA Soerensen C.S., Hansen L.T., Dziegielewski J., Syljuaesen R.G., Lundin C., RA Bartek J., Helleday T.; RT "The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous RT recombination repair."; RL Nat. Cell Biol. 7:195-201(2005). RN [24] RP INTERACTION WITH RAD51AP2. RX PubMed=16990250; DOI=10.1093/nar/gkl665; RA Kovalenko O.V., Wiese C., Schild D.; RT "RAD51AP2, a novel vertebrate- and meiotic-specific protein, shares a RT conserved RAD51-interacting C-terminal domain with RAD51AP1/PIR51."; RL Nucleic Acids Res. 34:5081-5092(2006). RN [25] RP INTERACTION WITH NABP2. RX PubMed=18449195; DOI=10.1038/nature06883; RA Richard D.J., Bolderson E., Cubeddu L., Wadsworth R.I.M., Savage K., RA Sharma G.G., Nicolette M.L., Tsvetanov S., McIlwraith M.J., Pandita R.K., RA Takeda S., Hay R.T., Gautier J., West S.C., Paull T.T., Pandita T.K., RA White M.F., Khanna K.K.; RT "Single-stranded DNA-binding protein hSSB1 is critical for genomic RT stability."; RL Nature 453:677-681(2008). RN [26] RP SUBCELLULAR LOCATION. RX PubMed=19783859; DOI=10.1074/jbc.m109.024646; RA Gildemeister O.S., Sage J.M., Knight K.L.; RT "Cellular redistribution of Rad51 in response to DNA damage: novel role for RT Rad51C."; RL J. Biol. Chem. 284:31945-31952(2009). RN [27] RP INTERACTION WITH RECQL5, AND FUNCTION. RX PubMed=20348101; DOI=10.1074/jbc.m110.110478; RA Schwendener S., Raynard S., Paliwal S., Cheng A., Kanagaraj R., RA Shevelev I., Stark J.M., Sung P., Janscak P.; RT "Physical interaction of RECQ5 helicase with RAD51 facilitates its anti- RT recombinase activity."; RL J. Biol. Chem. 285:15739-15745(2010). RN [28] RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION. RX PubMed=20413593; DOI=10.1074/jbc.m109.099846; RA Sage J.M., Gildemeister O.S., Knight K.L.; RT "Discovery of a novel function for human Rad51: maintenance of the RT mitochondrial genome."; RL J. Biol. Chem. 285:18984-18990(2010). RN [29] RP INTERACTION WITH RPA1. RX PubMed=20705237; DOI=10.1016/j.molcel.2010.07.021; RA Dou H., Huang C., Singh M., Carpenter P.B., Yeh E.T.; RT "Regulation of DNA repair through desumoylation and sumoylation of RT replication protein A complex."; RL Mol. Cell 39:333-345(2010). RN [30] RP INTERACTION WITH POLN. RX PubMed=19995904; DOI=10.1128/mcb.01124-09; RA Moldovan G.L., Madhavan M.V., Mirchandani K.D., McCaffrey R.M., RA Vinciguerra P., D'Andrea A.D.; RT "DNA polymerase POLN participates in cross-link repair and homologous RT recombination."; RL Mol. Cell. Biol. 30:1088-1096(2010). RN [31] RP INTERACTION WITH RECQL5, AND FUNCTION. RX PubMed=20231364; DOI=10.1128/mcb.01583-09; RA Islam M.N., Fox D. III, Guo R., Enomoto T., Wang W.; RT "RecQL5 promotes genome stabilization through two parallel RT mechanisms--interacting with RNA polymerase II and acting as a helicase."; RL Mol. Cell. Biol. 30:2460-2472(2010). RN [32] RP INTERACTION WITH RPA2, AND SUBCELLULAR LOCATION. RX PubMed=20154705; DOI=10.1038/nsmb.1769; RA Lee D.H., Pan Y., Kanner S., Sung P., Borowiec J.A., Chowdhury D.; RT "A PP4 phosphatase complex dephosphorylates RPA2 to facilitate DNA repair RT via homologous recombination."; RL Nat. Struct. Mol. Biol. 17:365-372(2010). RN [33] RP INTERACTION WITH PALB2. RX PubMed=20871615; DOI=10.1038/nsmb.1915; RA Buisson R., Dion-Cote A.M., Coulombe Y., Launay H., Cai H., Stasiak A.Z., RA Stasiak A., Xia B., Masson J.Y.; RT "Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in RT stimulating homologous recombination."; RL Nat. Struct. Mol. Biol. 17:1247-1254(2010). RN [34] RP SUBCELLULAR LOCATION. RX PubMed=21276791; DOI=10.1016/j.yexcr.2011.01.021; RA Cappelli E., Townsend S., Griffin C., Thacker J.; RT "Homologous recombination proteins are associated with centrosomes and are RT required for mitotic stability."; RL Exp. Cell Res. 317:1203-1213(2011). RN [35] RP INTERACTION WITH SWI5 AND SFR1. RX PubMed=21252223; DOI=10.1074/jbc.m110.207290; RA Yuan J., Chen J.; RT "The role of human SWI5-MEI5 complex in homologous recombination repair."; RL J. Biol. Chem. 286:9888-9893(2011). RN [36] RP INTERACTION WITH SWSAP1. RX PubMed=21965664; DOI=10.1074/jbc.m111.271080; RA Liu T., Wan L., Wu Y., Chen J., Huang J.; RT "hSWS1.SWSAP1 is an evolutionarily conserved complex required for efficient RT homologous recombination repair."; RL J. Biol. Chem. 286:41758-41766(2011). RN [37] RP INVOLVEMENT IN MRMV2. RX PubMed=22305526; DOI=10.1016/j.ajhg.2011.12.002; RA Depienne C., Bouteiller D., Meneret A., Billot S., Groppa S., Klebe S., RA Charbonnier-Beaupel F., Corvol J.C., Saraiva J.P., Brueggemann N., RA Bhatia K., Cincotta M., Brochard V., Flamand-Roze C., Carpentier W., RA Meunier S., Marie Y., Gaussen M., Stevanin G., Wehrle R., Vidailhet M., RA Klein C., Dusart I., Brice A., Roze E.; RT "RAD51 haploinsufficiency causes congenital mirror movements in humans."; RL Am. J. Hum. Genet. 90:301-307(2012). RN [38] RP INTERACTION WITH PARPBP. RX PubMed=22153967; DOI=10.1016/j.molcel.2011.11.010; RA Moldovan G.L., Dejsuphong D., Petalcorin M.I., Hofmann K., Takeda S., RA Boulton S.J., D'Andrea A.D.; RT "Inhibition of homologous recombination by the PCNA-interacting protein RT PARI."; RL Mol. Cell 45:75-86(2012). RN [39] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [40] RP INTERACTION WITH MCM9 AND MCM8, AND SUBCELLULAR LOCATION. RX PubMed=23401855; DOI=10.1128/mcb.01503-12; RA Park J., Long D.T., Lee K.Y., Abbas T., Shibata E., Negishi M., Luo Y., RA Schimenti J.C., Gambus A., Walter J.C., Dutta A.; RT "The MCM8-MCM9 complex promotes RAD51 recruitment at DNA damage sites to RT facilitate homologous recombination."; RL Mol. Cell. Biol. 33:1632-1644(2013). RN [41] RP MUTAGENESIS OF 208-SER-ALA-209, AND NUCLEAR EXPORT SIGNAL. RX PubMed=24013206; DOI=10.1038/nsmb.2666; RA Jeyasekharan A.D., Liu Y., Hattori H., Pisupati V., Jonsdottir A.B., RA Rajendra E., Lee M., Sundaramoorthy E., Schlachter S., Kaminski C.F., RA Ofir-Rosenfeld Y., Sato K., Savill J., Ayoub N., Venkitaraman A.R.; RT "A cancer-associated BRCA2 mutation reveals masked nuclear export signals RT controlling localization."; RL Nat. Struct. Mol. Biol. 20:1191-1198(2013). RN [42] RP INTERACTION WITH FBH1, UBIQUITINATION AT LYS-58 AND LYS-64, AND MUTAGENESIS RP OF LYS-58 AND LYS-64. RX PubMed=23393192; DOI=10.1093/nar/gkt056; RA Masuda-Ozawa T., Hoang T., Seo Y.S., Chen L.F., Spies M.; RT "Single-molecule sorting reveals how ubiquitylation affects substrate RT recognition and activities of FBH1 helicase."; RL Nucleic Acids Res. 41:3576-3587(2013). RN [43] RP INTERACTION WITH PALB2, AND IDENTIFICATION IN A PALB2-CONTAINING HR RP COMPLEX. RX PubMed=24141787; DOI=10.1038/onc.2013.421; RA Park J.Y., Singh T.R., Nassar N., Zhang F., Freund M., Hanenberg H., RA Meetei A.R., Andreassen P.R.; RT "Breast cancer-associated missense mutants of the PALB2 WD40 domain, which RT directly binds RAD51C, RAD51 and BRCA2, disrupt DNA repair."; RL Oncogene 33:4803-4812(2014). RN [44] RP FUNCTION, INTERACTION WITH FIGNL1; RAD51AP1 AND SWI5, SUBCELLULAR LOCATION, RP AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=23754376; DOI=10.1073/pnas.1220662110; RA Yuan J., Chen J.; RT "FIGNL1-containing protein complex is required for efficient homologous RT recombination repair."; RL Proc. Natl. Acad. Sci. U.S.A. 110:10640-10645(2013). RN [45] RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH BLM AND SPIDR, INTERACTION WITH RP SPIDR, AND SUBCELLULAR LOCATION. RX PubMed=23509288; DOI=10.1073/pnas.1220921110; RA Wan L., Han J., Liu T., Dong S., Xie F., Chen H., Huang J.; RT "Scaffolding protein SPIDR/KIAA0146 connects the Bloom syndrome helicase RT with homologous recombination repair."; RL Proc. Natl. Acad. Sci. U.S.A. 110:10646-10651(2013). RN [46] RP FUNCTION, INVOLVEMENT IN FANCR, VARIANT FANCR PRO-131, AND CHARACTERIZATION RP OF VARIANT FANCR PRO-131. RX PubMed=26253028; DOI=10.1016/j.molcel.2015.07.009; RA Wang A.T., Kim T., Wagner J.E., Conti B.A., Lach F.P., Huang A.L., RA Molina H., Sanborn E.M., Zierhut H., Cornes B.K., Abhyankar A., Sougnez C., RA Gabriel S.B., Auerbach A.D., Kowalczykowski S.C., Smogorzewska A.; RT "A dominant mutation in human RAD51 reveals its function in DNA interstrand RT crosslink repair independent of homologous recombination."; RL Mol. Cell 59:478-490(2015). RN [47] RP INTERACTION WITH POLQ. RX PubMed=25642963; DOI=10.1038/nature14184; RA Ceccaldi R., Liu J.C., Amunugama R., Hajdu I., Primack B., Petalcorin M.I., RA O'Connor K.W., Konstantinopoulos P.A., Elledge S.J., Boulton S.J., RA Yusufzai T., D'Andrea A.D.; RT "Homologous-recombination-deficient tumours are dependent on Poltheta- RT mediated repair."; RL Nature 518:258-262(2015). RN [48] RP IDENTIFICATION IN THE HRR COMPLEX, AND SUBCELLULAR LOCATION. RX PubMed=26833090; DOI=10.1016/j.molcel.2015.12.026; RA Trego K.S., Groesser T., Davalos A.R., Parplys A.C., Zhao W., Nelson M.R., RA Hlaing A., Shih B., Rydberg B., Pluth J.M., Tsai M.S., Hoeijmakers J.H.J., RA Sung P., Wiese C., Campisi J., Cooper P.K.; RT "Non-catalytic Roles for XPG with BRCA1 and BRCA2 in Homologous RT Recombination and Genome Stability."; RL Mol. Cell 61:535-546(2016). RN [49] RP FUNCTION, INTERACTION WITH RFWD3, AND UBIQUITINATION. RX PubMed=28575658; DOI=10.1016/j.molcel.2017.04.022; RA Inano S., Sato K., Katsuki Y., Kobayashi W., Tanaka H., Nakajima K., RA Nakada S., Miyoshi H., Knies K., Takaori-Kondo A., Schindler D., Ishiai M., RA Kurumizaka H., Takata M.; RT "RFWD3-mediated ubiquitination promotes timely removal of both RPA and RT RAD51 from dna damage sites to facilitate homologous recombination."; RL Mol. Cell 66:622-634(2017). RN [50] RP INTERACTION WITH HELQ. RX PubMed=34937945; DOI=10.1038/s41586-021-04261-0; RA Anand R., Buechelmaier E., Belan O., Newton M., Vancevska A., RA Kaczmarczyk A., Takaki T., Rueda D.S., Powell S.N., Boulton S.J.; RT "HELQ is a dual-function DSB repair enzyme modulated by RPA and RAD51."; RL Nature 0:0-0(2021). RN [51] RP STRUCTURE BY NMR OF 1-114. RX PubMed=10390347; DOI=10.1006/jmbi.1999.2904; RA Aihara H., Ito Y., Kurumizaka H., Yokoyama S., Shibata T.; RT "The N-terminal domain of the human Rad51 protein binds DNA: structure and RT a DNA binding surface as revealed by NMR."; RL J. Mol. Biol. 290:495-504(1999). RN [52] RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 97-339 IN COMPLEX WITH BRCA2, RP FUNCTION, SUBUNIT, MUTAGENESIS OF PHE-86 AND ALA-89, SUBCELLULAR LOCATION, RP AND INTERACTION WITH BRCA2. RX PubMed=12442171; DOI=10.1038/nature01230; RA Pellegrini L., Yu D.S., Lo T., Anand S., Lee M., Blundell T.L., RA Venkitaraman A.R.; RT "Insights into DNA recombination from the structure of a RAD51-BRCA2 RT complex."; RL Nature 420:287-293(2002). RN [53] RP VARIANT BC GLN-150. RX PubMed=10807537; DOI=10.1007/s100380050199; RA Kato M., Yano K., Matsuo F., Saito H., Katagiri T., Kurumizaka H., RA Yoshimoto M., Kasumi F., Akiyama F., Sakamoto G., Nagawa H., Nakamura Y., RA Miki Y.; RT "Identification of Rad51 alteration in patients with bilateral breast RT cancer."; RL J. Hum. Genet. 45:133-137(2000). RN [54] RP INVOLVEMENT IN FANCR, VARIANT FANCR THR-293, CHARACTERIZATION OF VARIANT RP FANCR THR-293, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=26681308; DOI=10.1038/ncomms9829; RA Ameziane N., May P., Haitjema A., van de Vrugt H.J., RA van Rossum-Fikkert S.E., Ristic D., Williams G.J., Balk J., Rockx D., RA Li H., Rooimans M.A., Oostra A.B., Velleuer E., Dietrich R., RA Bleijerveld O.B., Maarten Altelaar A.F., Meijers-Heijboer H., Joenje H., RA Glusman G., Roach J., Hood L., Galas D., Wyman C., Balling R., RA den Dunnen J., de Winter J.P., Kanaar R., Gelinas R., Dorsman J.C.; RT "A novel Fanconi anaemia subtype associated with a dominant-negative RT mutation in RAD51."; RL Nat. Commun. 6:8829-8829(2015). RN [55] RP CHARACTERIZATION OF VARIANT BC GLN-150. RX PubMed=25539919; DOI=10.1093/nar/gku1337; RA Chen J., Morrical M.D., Donigan K.A., Weidhaas J.B., Sweasy J.B., RA Averill A.M., Tomczak J.A., Morrical S.W.; RT "Tumor-associated mutations in a conserved structural motif alter physical RT and biochemical properties of human RAD51 recombinase."; RL Nucleic Acids Res. 43:1098-1111(2015). CC -!- FUNCTION: Plays an important role in homologous strand exchange, a key CC step in DNA repair through homologous recombination (HR) CC (PubMed:28575658). Binds to single and double-stranded DNA and exhibits CC DNA-dependent ATPase activity. Catalyzes the recognition of homology CC and strand exchange between homologous DNA partners to form a joint CC molecule between a processed DNA break and the repair template. Binds CC to single-stranded DNA in an ATP-dependent manner to form nucleoprotein CC filaments which are essential for the homology search and strand CC exchange (PubMed:26681308). Part of a PALB2-scaffolded HR complex CC containing BRCA2 and RAD51C and which is thought to play a role in DNA CC repair by HR. Plays a role in regulating mitochondrial DNA copy number CC under conditions of oxidative stress in the presence of RAD51C and CC XRCC3. Also involved in interstrand cross-link repair CC (PubMed:26253028). {ECO:0000269|PubMed:12205100, CC ECO:0000269|PubMed:12442171, ECO:0000269|PubMed:18417535, CC ECO:0000269|PubMed:20231364, ECO:0000269|PubMed:20348101, CC ECO:0000269|PubMed:20413593, ECO:0000269|PubMed:23509288, CC ECO:0000269|PubMed:23754376, ECO:0000269|PubMed:26253028, CC ECO:0000269|PubMed:26681308, ECO:0000269|PubMed:28575658}. CC -!- SUBUNIT: Forms linear homooligomers, giving rise to a RAD51 CC nucleoprotein filament, which is essential for strand-pairing reactions CC during DNA recombination. Interacts with BRCA1 and either directly or CC indirectly with p53. Interacts with XRCC3, RAD54L and RAD54B. Interacts CC with the BCDX2 subcomplex RAD51C:RAD51B. Component of the homologous CC recombination repair (HR) complex composed of ERCC5/XPG, BRCA2, PALB2, CC DSS1 and RAD51 (PubMed:26833090). Interacts directly with PALB2 which CC may serve as a scaffold for a HR complex containing PALB2, BRCA2, CC RAD51C, RAD51 and XRCC3. Interacts with RAD51AP1 and RAD51AP2. CC Interacts with CHEK1, and this may require prior phosphorylation of CC CHEK1. Interacts with the MND1-PSMC3IP heterodimer. Found in a complex, CC at least composed of BLM, RAD51 and SPIDR; the complex formation is CC mediated by SPIDR. Interacts with SPIDR; the interaction is direct and CC recruits RAD51 to DNA damage sites. Interacts with FIGNL1 (via N- CC terminal one-half region); the interaction is direct. Interacts with CC RAD51AP1 (via C-terminal region); the interaction is direct. Interacts CC with NABP2, RPA1, PALB2 and RAD51. Interacts with SWI5/C9orf119, and at CC lower level with SFR1/MEIR5. Interacts with hyperphosphorylated RPA2; CC this interaction is necessary for efficient recruitment to chromatin in CC response to DNA damage. Interacts with SWSAP1; involved in homologous CC recombination repair. Interacts with PARPBP, BRCA2 and RECQL5; these CC interactions interfere with the formation of the RAD51-DNA homologous CC recombination structure. Interacts with POLQ; POLQ acts as an inhibitor CC of homology-recombination repair (HR) pathway by limiting RAD51 CC accumulation at resected ends (PubMed:25642963). Interacts with FBH1 CC (PubMed:23393192). Interacts with POLN (PubMed:19995904). Interacts CC with RFWD3 (PubMed:28575658). Interacts with the MCM8-MCM9 complex; the CC interaction recruits RAD51 to DNA damage sites (PubMed:23401855). CC Component of a multiprotein complex with MEIOB and SPATA22. Interacts CC with the complex BRME1:HSF2BP:BRCA2 (By similarity). Interacts with CC HELQ; stimulating HELQ DNA helicase activity and ability to unwing DNA CC (PubMed:34937945). {ECO:0000250|UniProtKB:Q08297, CC ECO:0000269|PubMed:10851248, ECO:0000269|PubMed:11842113, CC ECO:0000269|PubMed:12427746, ECO:0000269|PubMed:12442171, CC ECO:0000269|PubMed:14580352, ECO:0000269|PubMed:15665856, CC ECO:0000269|PubMed:16990250, ECO:0000269|PubMed:18449195, CC ECO:0000269|PubMed:19995904, ECO:0000269|PubMed:20154705, CC ECO:0000269|PubMed:20231364, ECO:0000269|PubMed:20348101, CC ECO:0000269|PubMed:20705237, ECO:0000269|PubMed:20871615, CC ECO:0000269|PubMed:21252223, ECO:0000269|PubMed:21965664, CC ECO:0000269|PubMed:22153967, ECO:0000269|PubMed:23393192, CC ECO:0000269|PubMed:23401855, ECO:0000269|PubMed:23509288, CC ECO:0000269|PubMed:23754376, ECO:0000269|PubMed:24141787, CC ECO:0000269|PubMed:25642963, ECO:0000269|PubMed:26833090, CC ECO:0000269|PubMed:28575658, ECO:0000269|PubMed:34937945, CC ECO:0000269|PubMed:9192668, ECO:0000269|PubMed:9321665, CC ECO:0000269|PubMed:9396801, ECO:0000269|PubMed:9461559}. CC -!- INTERACTION: CC Q06609; P51587: BRCA2; NbExp=46; IntAct=EBI-297202, EBI-79792; CC Q06609; O14757: CHEK1; NbExp=3; IntAct=EBI-297202, EBI-974488; CC Q06609; Q00341: HDLBP; NbExp=2; IntAct=EBI-297202, EBI-1049478; CC Q06609; Q13007: IL24; NbExp=2; IntAct=EBI-297202, EBI-3915542; CC Q06609; Q96KN1: LRATD2; NbExp=4; IntAct=EBI-297202, EBI-9057780; CC Q06609; Q14676: MDC1; NbExp=3; IntAct=EBI-297202, EBI-495644; CC Q06609; P11245: NAT2; NbExp=4; IntAct=EBI-297202, EBI-9057228; CC Q06609; Q9BZ95: NSD3; NbExp=4; IntAct=EBI-297202, EBI-3390132; CC Q06609; Q86YC2: PALB2; NbExp=8; IntAct=EBI-297202, EBI-1222653; CC Q06609; O75417-1: POLQ; NbExp=3; IntAct=EBI-297202, EBI-16141065; CC Q06609; Q06609: RAD51; NbExp=11; IntAct=EBI-297202, EBI-297202; CC Q06609; Q96B01-2: RAD51AP1; NbExp=6; IntAct=EBI-297202, EBI-1178743; CC Q06609; Q96B01-3: RAD51AP1; NbExp=6; IntAct=EBI-297202, EBI-1178748; CC Q06609; O43502: RAD51C; NbExp=6; IntAct=EBI-297202, EBI-2267048; CC Q06609; P43351: RAD52; NbExp=3; IntAct=EBI-297202, EBI-706448; CC Q06609; Q14159: SPIDR; NbExp=6; IntAct=EBI-297202, EBI-11318692; CC Q06609; Q6NVH7: SWSAP1; NbExp=2; IntAct=EBI-297202, EBI-5281637; CC Q06609; P04637: TP53; NbExp=2; IntAct=EBI-297202, EBI-366083; CC Q06609; O43542: XRCC3; NbExp=5; IntAct=EBI-297202, EBI-2849976; CC Q06609-1; P51587: BRCA2; NbExp=12; IntAct=EBI-15557721, EBI-79792; CC Q06609-1; Q06609-1: RAD51; NbExp=4; IntAct=EBI-15557721, EBI-15557721; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12442171, CC ECO:0000269|PubMed:15665856, ECO:0000269|PubMed:18417535, CC ECO:0000269|PubMed:19783859, ECO:0000269|PubMed:23401855, CC ECO:0000269|PubMed:23509288, ECO:0000269|PubMed:26681308, CC ECO:0000269|PubMed:26833090, ECO:0000269|PubMed:9192668}. Cytoplasm CC {ECO:0000269|PubMed:16215984, ECO:0000269|PubMed:26681308}. Cytoplasm, CC perinuclear region. Mitochondrion matrix {ECO:0000269|PubMed:20413593}. CC Chromosome {ECO:0000269|PubMed:23401855}. Cytoplasm, cytoskeleton, CC microtubule organizing center, centrosome CC {ECO:0000269|PubMed:21276791}. Note=Colocalizes with RAD51AP1 and RPA2 CC to multiple nuclear foci upon induction of DNA damage CC (PubMed:20154705). DNA damage induces an increase in nuclear levels CC (PubMed:20154705). Together with FIGNL1, redistributed in discrete CC nuclear DNA damage-induced foci after ionizing radiation (IR) or CC camptothecin (CPT) treatment (PubMed:23754376). Accumulated at sites of CC DNA damage in a SPIDR-dependent manner (PubMed:23509288). Recruited at CC sites of DNA damage in a MCM9-MCM8-dependent manner (PubMed:23401855). CC Colocalizes with ERCC5/XPG to nuclear foci in S phase CC (PubMed:26833090). {ECO:0000269|PubMed:20154705, CC ECO:0000269|PubMed:23401855, ECO:0000269|PubMed:23509288, CC ECO:0000269|PubMed:23754376, ECO:0000269|PubMed:26833090}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q06609-1; Sequence=Displayed; CC Name=2; CC IsoId=Q06609-2; Sequence=VSP_005556; CC Name=3; CC IsoId=Q06609-3; Sequence=VSP_041724, VSP_041725; CC Name=4; CC IsoId=Q06609-4; Sequence=VSP_043655; CC -!- TISSUE SPECIFICITY: Highly expressed in testis and thymus, followed by CC small intestine, placenta, colon, pancreas and ovary. Weakly expressed CC in breast. CC -!- INDUCTION: Stress-induced increase in the mitochondrial levels is seen. CC {ECO:0000269|PubMed:20413593}. CC -!- DOMAIN: The nuclear localization may reside in the C-terminus (between CC 259 and 339 AA). CC -!- PTM: Ubiquitinated by the SCF(FBH1) E3 ubiquitin ligase complex, CC regulating RAD51 subcellular location and preventing its association CC with DNA. Ubiquitinated by RFWD3 in response to DNA damage: CC ubiquitination leads to degradation by the proteasome, promoting CC homologous recombination (PubMed:28575658). CC {ECO:0000269|PubMed:23393192, ECO:0000269|PubMed:28575658}. CC -!- PTM: Phosphorylated. Phosphorylation of Thr-309 by CHEK1 may enhance CC association with chromatin at sites of DNA damage and promote DNA CC repair by homologous recombination. Phosphorylation by ABL1 inhibits CC function. {ECO:0000269|PubMed:15665856, ECO:0000269|PubMed:9461559}. CC -!- DISEASE: Breast cancer (BC) [MIM:114480]: A common malignancy CC originating from breast epithelial tissue. Breast neoplasms can be CC distinguished by their histologic pattern. Invasive ductal carcinoma is CC by far the most common type. Breast cancer is etiologically and CC genetically heterogeneous. Important genetic factors have been CC indicated by familial occurrence and bilateral involvement. Mutations CC at more than one locus can be involved in different families or even in CC the same case. {ECO:0000269|PubMed:10807537, CC ECO:0000269|PubMed:25539919}. Note=Disease susceptibility is associated CC with variants affecting the gene represented in this entry. CC -!- DISEASE: Mirror movements 2 (MRMV2) [MIM:614508]: A disorder CC characterized by contralateral involuntary movements that mirror CC voluntary ones. While mirror movements are occasionally found in young CC children, persistence beyond the age of 10 is abnormal. Mirror CC movements occur more commonly in the upper extremities. CC {ECO:0000269|PubMed:22305526}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Fanconi anemia, complementation group R (FANCR) [MIM:617244]: CC A disorder affecting all bone marrow elements and resulting in anemia, CC leukopenia and thrombopenia. It is associated with cardiac, renal and CC limb malformations, dermal pigmentary changes, and a predisposition to CC the development of malignancies. At the cellular level it is associated CC with hypersensitivity to DNA-damaging agents, chromosomal instability CC (increased chromosome breakage) and defective DNA repair. CC {ECO:0000269|PubMed:26253028, ECO:0000269|PubMed:26681308}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: [Isoform 3]: Mutagenesis of Arg-264 to Ala inhibits CC nuclear localization. Mutagenesis of Lys-264 to Gln inhibits nuclear CC localization. Deletion of 254-Arg-Lys-255 inhibits nuclear CC localization. {ECO:0000269|PubMed:18417535}. CC -!- SIMILARITY: Belongs to the RecA family. RAD51 subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/rad51/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D13804; BAA02962.1; -; mRNA. DR EMBL; D14134; BAA03189.1; -; mRNA. DR EMBL; AF165094; AAD49705.1; -; Genomic_DNA. DR EMBL; AF165088; AAD49705.1; JOINED; Genomic_DNA. DR EMBL; AF165089; AAD49705.1; JOINED; Genomic_DNA. DR EMBL; AF165090; AAD49705.1; JOINED; Genomic_DNA. DR EMBL; AF165091; AAD49705.1; JOINED; Genomic_DNA. DR EMBL; AF165092; AAD49705.1; JOINED; Genomic_DNA. DR EMBL; AF165093; AAD49705.1; JOINED; Genomic_DNA. DR EMBL; AF233744; AAF69145.1; -; Genomic_DNA. DR EMBL; AF233740; AAF69145.1; JOINED; Genomic_DNA. DR EMBL; AF233741; AAF69145.1; JOINED; Genomic_DNA. DR EMBL; AF233742; AAF69145.1; JOINED; Genomic_DNA. DR EMBL; AF236021; AAF69145.1; JOINED; Genomic_DNA. DR EMBL; AF233743; AAF69145.1; JOINED; Genomic_DNA. DR EMBL; EU362635; ABY59731.1; -; mRNA. DR EMBL; AY196785; AAN87149.1; -; Genomic_DNA. DR EMBL; AK131299; BAD18467.1; -; mRNA. DR EMBL; AK291969; BAF84658.1; -; mRNA. DR EMBL; AK313503; BAG36283.1; -; mRNA. DR EMBL; CR536559; CAG38796.1; -; mRNA. DR EMBL; AC012476; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC022405; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471125; EAW92434.1; -; Genomic_DNA. DR EMBL; CH471125; EAW92432.1; -; Genomic_DNA. DR EMBL; CH471125; EAW92435.1; -; Genomic_DNA. DR EMBL; BC001459; AAH01459.1; -; mRNA. DR CCDS; CCDS10062.1; -. [Q06609-1] DR CCDS; CCDS53931.1; -. [Q06609-4] DR CCDS; CCDS53932.1; -. [Q06609-3] DR PIR; I58295; I58295. DR RefSeq; NP_001157741.1; NM_001164269.1. [Q06609-4] DR RefSeq; NP_001157742.1; NM_001164270.1. [Q06609-3] DR RefSeq; NP_002866.2; NM_002875.4. [Q06609-1] DR RefSeq; NP_597994.3; NM_133487.3. [Q06609-4] DR RefSeq; XP_006720689.1; XM_006720626.3. [Q06609-1] DR RefSeq; XP_011520159.1; XM_011521857.2. [Q06609-1] DR RefSeq; XP_011520160.1; XM_011521858.2. [Q06609-1] DR RefSeq; XP_011520161.1; XM_011521859.2. [Q06609-1] DR RefSeq; XP_011520162.1; XM_011521860.2. [Q06609-1] DR RefSeq; XP_011520163.1; XM_011521861.2. [Q06609-3] DR PDB; 1B22; NMR; -; A=1-114. DR PDB; 1N0W; X-ray; 1.70 A; A=97-339. DR PDB; 5H1B; EM; 4.40 A; A/B/C=1-339. DR PDB; 5H1C; EM; 4.50 A; A/B/C=1-339. DR PDB; 5JZC; EM; 4.20 A; A/B/C/D/E/F/G=1-339. DR PDB; 5NP7; EM; 4.20 A; A/B/C/D/E/F/G=1-339. DR PDB; 5NWL; X-ray; 3.93 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N=1-339. DR PDB; 7C9A; EM; 3.43 A; A/B/C=1-339. DR PDBsum; 1B22; -. DR PDBsum; 1N0W; -. DR PDBsum; 5H1B; -. DR PDBsum; 5H1C; -. DR PDBsum; 5JZC; -. DR PDBsum; 5NP7; -. DR PDBsum; 5NWL; -. DR PDBsum; 7C9A; -. DR AlphaFoldDB; Q06609; -. DR BMRB; Q06609; -. DR SMR; Q06609; -. DR BioGRID; 111825; 235. DR ComplexPortal; CPX-955; BRCC ubiquitin ligase complex. DR CORUM; Q06609; -. DR DIP; DIP-462N; -. DR ELM; Q06609; -. DR IntAct; Q06609; 129. DR MINT; Q06609; -. DR BindingDB; Q06609; -. DR ChEMBL; CHEMBL2034807; -. DR DrugBank; DB12742; Amuvatinib. DR DrugBank; DB04395; Phosphoaminophosphonic Acid-Adenylate Ester. DR iPTMnet; Q06609; -. DR PhosphoSitePlus; Q06609; -. DR BioMuta; RAD51; -. DR DMDM; 548663; -. DR EPD; Q06609; -. DR jPOST; Q06609; -. DR MassIVE; Q06609; -. DR MaxQB; Q06609; -. DR PeptideAtlas; Q06609; -. DR PRIDE; Q06609; -. DR ProteomicsDB; 58464; -. [Q06609-1] DR ProteomicsDB; 58465; -. [Q06609-2] DR ProteomicsDB; 58466; -. [Q06609-3] DR ProteomicsDB; 58467; -. [Q06609-4] DR Antibodypedia; 4162; 954 antibodies from 44 providers. DR DNASU; 5888; -. DR Ensembl; ENST00000267868.8; ENSP00000267868.3; ENSG00000051180.17. DR Ensembl; ENST00000382643.7; ENSP00000372088.3; ENSG00000051180.17. [Q06609-4] DR Ensembl; ENST00000423169.6; ENSP00000406602.2; ENSG00000051180.17. [Q06609-3] DR Ensembl; ENST00000532743.6; ENSP00000433924.2; ENSG00000051180.17. DR Ensembl; ENST00000557850.5; ENSP00000454176.1; ENSG00000051180.17. [Q06609-2] DR Ensembl; ENST00000645673.2; ENSP00000493712.2; ENSG00000051180.17. [Q06609-4] DR GeneID; 5888; -. DR KEGG; hsa:5888; -. DR MANE-Select; ENST00000267868.8; ENSP00000267868.3; NM_002875.5; NP_002866.2. DR UCSC; uc001zmi.5; human. [Q06609-1] DR CTD; 5888; -. DR DisGeNET; 5888; -. DR GeneCards; RAD51; -. DR GeneReviews; RAD51; -. DR HGNC; HGNC:9817; RAD51. DR HPA; ENSG00000051180; Tissue enhanced (lymphoid tissue, testis). DR MalaCards; RAD51; -. DR MIM; 114480; phenotype. DR MIM; 179617; gene. DR MIM; 614508; phenotype. DR MIM; 617244; phenotype. DR neXtProt; NX_Q06609; -. DR OpenTargets; ENSG00000051180; -. DR Orphanet; 238722; Familial congenital mirror movements. DR Orphanet; 84; Fanconi anemia. DR Orphanet; 145; Hereditary breast and ovarian cancer syndrome. DR PharmGKB; PA34176; -. DR VEuPathDB; HostDB:ENSG00000051180; -. DR GeneTree; ENSGT00940000156157; -. DR HOGENOM; CLU_041732_3_0_1; -. DR InParanoid; Q06609; -. DR OMA; TFRIYLR; -. DR OrthoDB; 877394at2759; -. DR PhylomeDB; Q06609; -. DR TreeFam; TF101218; -. DR BRENDA; 3.6.4.B7; 2681. DR PathwayCommons; Q06609; -. DR Reactome; R-HSA-5685938; HDR through Single Strand Annealing (SSA). DR Reactome; R-HSA-5685942; HDR through Homologous Recombination (HRR). DR Reactome; R-HSA-5693554; Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA). DR Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates. DR Reactome; R-HSA-5693579; Homologous DNA Pairing and Strand Exchange. DR Reactome; R-HSA-5693616; Presynaptic phase of homologous DNA pairing and strand exchange. DR Reactome; R-HSA-8953750; Transcriptional Regulation by E2F6. DR Reactome; R-HSA-912446; Meiotic recombination. DR Reactome; R-HSA-9701192; Defective HDR through Homologous Recombination (HRR) due to BRCA1 loss-of-function. DR Reactome; R-HSA-9704331; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function. DR Reactome; R-HSA-9704646; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function. DR SignaLink; Q06609; -. DR SIGNOR; Q06609; -. DR BioGRID-ORCS; 5888; 773 hits in 1097 CRISPR screens. DR ChiTaRS; RAD51; human. DR EvolutionaryTrace; Q06609; -. DR GeneWiki; RAD51; -. DR GenomeRNAi; 5888; -. DR Pharos; Q06609; Tchem. DR PRO; PR:Q06609; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; Q06609; protein. DR Bgee; ENSG00000051180; Expressed in testis and 153 other tissues. DR ExpressionAtlas; Q06609; baseline and differential. DR Genevisible; Q06609; HS. DR GO; GO:0000785; C:chromatin; IDA:UniProtKB. DR GO; GO:0000781; C:chromosome, telomeric region; IDA:BHF-UCL. DR GO; GO:0000793; C:condensed chromosome; ISS:UniProtKB. DR GO; GO:0000794; C:condensed nuclear chromosome; ISS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0000800; C:lateral element; IDA:MGI. DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell. DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0000228; C:nuclear chromosome; IDA:UniProtKB. DR GO; GO:0000152; C:nuclear ubiquitin ligase complex; IDA:ComplexPortal. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0016605; C:PML body; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0035861; C:site of double-strand break; IDA:MGI. DR GO; GO:0005524; F:ATP binding; IDA:MGI. DR GO; GO:0008094; F:ATP-dependent activity, acting on DNA; IBA:GO_Central. DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB. DR GO; GO:0070182; F:DNA polymerase binding; IPI:UniProtKB. DR GO; GO:0000150; F:DNA strand exchange activity; IBA:GO_Central. DR GO; GO:0003690; F:double-stranded DNA binding; IDA:UniProtKB. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB. DR GO; GO:0003697; F:single-stranded DNA binding; IDA:UniProtKB. DR GO; GO:0017116; F:single-stranded DNA helicase activity; IDA:UniProtKB. DR GO; GO:0072757; P:cellular response to camptothecin; IDA:UniProtKB. DR GO; GO:0072719; P:cellular response to cisplatin; IEA:Ensembl. DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB. DR GO; GO:0071480; P:cellular response to gamma radiation; IEA:Ensembl. DR GO; GO:0072711; P:cellular response to hydroxyurea; IEA:Ensembl. DR GO; GO:0071479; P:cellular response to ionizing radiation; IDA:UniProtKB. DR GO; GO:0070192; P:chromosome organization involved in meiotic cell cycle; IBA:GO_Central. DR GO; GO:0000730; P:DNA recombinase assembly; IMP:UniProtKB. DR GO; GO:0006310; P:DNA recombination; TAS:UniProtKB. DR GO; GO:0006281; P:DNA repair; TAS:ProtInc. DR GO; GO:0006268; P:DNA unwinding involved in DNA replication; IDA:UniProtKB. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IDA:UniProtKB. DR GO; GO:0035518; P:histone H2A monoubiquitination; IC:ComplexPortal. DR GO; GO:0036297; P:interstrand cross-link repair; IMP:UniProtKB. DR GO; GO:0051321; P:meiotic cell cycle; ISS:UniProtKB. DR GO; GO:0006312; P:mitotic recombination; IBA:GO_Central. DR GO; GO:1990426; P:mitotic recombination-dependent replication fork processing; IEA:InterPro. DR GO; GO:0051106; P:positive regulation of DNA ligation; IDA:UniProtKB. DR GO; GO:0051865; P:protein autoubiquitination; IC:ComplexPortal. DR GO; GO:0007131; P:reciprocal meiotic recombination; IBA:GO_Central. DR GO; GO:2000001; P:regulation of DNA damage checkpoint; IC:ComplexPortal. DR GO; GO:0010569; P:regulation of double-strand break repair via homologous recombination; IDA:UniProtKB. DR GO; GO:0001932; P:regulation of protein phosphorylation; IEA:Ensembl. DR GO; GO:0031297; P:replication fork processing; IDA:UniProtKB. DR GO; GO:1990414; P:replication-born double-strand break repair via sister chromatid exchange; IEA:Ensembl. DR GO; GO:1904631; P:response to glucoside; IEA:Ensembl. DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl. DR GO; GO:0010165; P:response to X-ray; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0042148; P:strand invasion; IBA:GO_Central. DR GO; GO:0000722; P:telomere maintenance via recombination; ISS:BHF-UCL. DR GO; GO:0010833; P:telomere maintenance via telomere lengthening; ISS:BHF-UCL. DR CDD; cd01123; Rad51_DMC1_radA; 1. DR DisProt; DP01622; -. DR Gene3D; 3.40.50.300; -; 1. DR IDEAL; IID00241; -. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR011941; DNA_recomb/repair_Rad51. DR InterPro; IPR013632; DNA_recomb/repair_Rad51_C. DR InterPro; IPR016467; DNA_recomb/repair_RecA-like. DR InterPro; IPR010995; DNA_repair_Rad51/TF_NusA_a-hlx. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR033925; Rad51_DMC1_RadA. DR InterPro; IPR020588; RecA_ATP-bd. DR InterPro; IPR020587; RecA_monomer-monomer_interface. DR Pfam; PF08423; Rad51; 1. DR PIRSF; PIRSF005856; Rad51; 1. DR SMART; SM00382; AAA; 1. DR SUPFAM; SSF47794; SSF47794; 1. DR SUPFAM; SSF52540; SSF52540; 1. DR TIGRFAMs; TIGR02239; recomb_RAD51; 1. DR PROSITE; PS50162; RECA_2; 1. DR PROSITE; PS50163; RECA_3; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Chromosome; KW Cytoplasm; Cytoskeleton; Disease variant; DNA damage; DNA recombination; KW DNA repair; DNA-binding; Fanconi anemia; Isopeptide bond; Mitochondrion; KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; KW Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:22814378" FT CHAIN 2..339 FT /note="DNA repair protein RAD51 homolog 1" FT /id="PRO_0000122932" FT DOMAIN 48..77 FT /note="HhH" FT NP_BIND 127..134 FT /note="ATP" FT /evidence="ECO:0000250" FT REGION 184..257 FT /note="Interaction with PALB2" FT MOTIF 245..260 FT /note="Nuclear export signal; masked by the interaction FT with BRCA2" FT /evidence="ECO:0000305|PubMed:24013206" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:22814378" FT MOD_RES 54 FT /note="Phosphotyrosine; by ABL1" FT /evidence="ECO:0000269|PubMed:9461559" FT MOD_RES 309 FT /note="Phosphothreonine; by CHEK1" FT /evidence="ECO:0000269|PubMed:15665856" FT CROSSLNK 58 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:23393192" FT CROSSLNK 64 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:23393192" FT VAR_SEQ 76..114 FT /note="AEAAKLVPMGFTTATEFHQRRSEIIQITTGSKELDKLLQ -> TESRSVARL FT ECNSVILVYCTLRLSGSSDSPASASRVVGTT (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043655" FT VAR_SEQ 77..173 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_005556" FT VAR_SEQ 259..284 FT /note="FGVAVVITNQVVAQVDGAAMFAADPK -> IVSEERKRGNQNLQNLRLSLSS FT (in isoform 3)" FT /evidence="ECO:0000303|PubMed:18417535" FT /id="VSP_041724" FT VAR_SEQ 285..339 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:18417535" FT /id="VSP_041725" FT VARIANT 131 FT /note="T -> P (in FANCR; causes dominant negative loss of FT function in interstrand cross-link repair; shows high basal FT DNA-independent ATPase activity; results in decreased DNA FT binding)" FT /evidence="ECO:0000269|PubMed:26253028" FT /id="VAR_076870" FT VARIANT 150 FT /note="R -> Q (in BC; decreased ATPase activity in the FT presence of stoichiometric ss-DNA concentrations with FT respect to RAD51; 3 to 4-fold decrease of affinity for ATP; FT dbSNP:rs121917739)" FT /evidence="ECO:0000269|PubMed:10807537, FT ECO:0000269|PubMed:25539919" FT /id="VAR_010899" FT VARIANT 293 FT /note="A -> T (in FANCR; dominant negative; impaired FT function in DNA repair via homologous recombination; FT impaired DNA-binding and formation of nucleoprotein FT filaments; impaired DNA-dependent ATPase activity; no FT effect on subcellular location; dbSNP:rs1057519413)" FT /evidence="ECO:0000269|PubMed:26681308" FT /id="VAR_076593" FT MUTAGEN 58 FT /note="K->R: Impaired ubiquitination; when associated with FT R-64." FT /evidence="ECO:0000269|PubMed:23393192" FT MUTAGEN 64 FT /note="K->R: Impaired ubiquitination; when associated with FT R-58." FT /evidence="ECO:0000269|PubMed:23393192" FT MUTAGEN 86 FT /note="F->A: Loss of homooligomerization." FT /evidence="ECO:0000269|PubMed:12442171" FT MUTAGEN 89 FT /note="A->E: Loss of homooligomerization." FT /evidence="ECO:0000269|PubMed:12442171" FT MUTAGEN 208..209 FT /note="SA->LE: Disrupts interaction with BRCA2, no effect FT on homooligomerization, promotes interaction with XPO1 and FT cytoplasmic localization." FT /evidence="ECO:0000269|PubMed:14580352, FT ECO:0000269|PubMed:24013206" FT MUTAGEN 309 FT /note="T->A: Confers hypersensitivity to hydroxyurea." FT /evidence="ECO:0000269|PubMed:15665856" FT CONFLICT 313 FT /note="K -> Q (in Ref. 1; BAA02962)" FT /evidence="ECO:0000305" FT HELIX 25..30 FT /evidence="ECO:0007829|PDB:7C9A" FT HELIX 35..43 FT /evidence="ECO:0007829|PDB:7C9A" FT HELIX 49..53 FT /evidence="ECO:0007829|PDB:7C9A" FT STRAND 54..56 FT /evidence="ECO:0007829|PDB:1B22" FT HELIX 57..61 FT /evidence="ECO:0007829|PDB:7C9A" FT TURN 62..65 FT /evidence="ECO:0007829|PDB:1B22" FT HELIX 68..76 FT /evidence="ECO:0007829|PDB:7C9A" FT HELIX 78..81 FT /evidence="ECO:0007829|PDB:7C9A" FT HELIX 89..95 FT /evidence="ECO:0007829|PDB:7C9A" FT TURN 96..98 FT /evidence="ECO:0007829|PDB:7C9A" FT HELIX 107..112 FT /evidence="ECO:0007829|PDB:1N0W" FT TURN 113..115 FT /evidence="ECO:0007829|PDB:1N0W" FT STRAND 116..118 FT /evidence="ECO:0007829|PDB:1N0W" FT STRAND 121..126 FT /evidence="ECO:0007829|PDB:1N0W" FT STRAND 128..131 FT /evidence="ECO:0007829|PDB:7C9A" FT HELIX 133..143 FT /evidence="ECO:0007829|PDB:1N0W" FT HELIX 148..150 FT /evidence="ECO:0007829|PDB:1N0W" FT STRAND 154..164 FT /evidence="ECO:0007829|PDB:1N0W" FT HELIX 168..177 FT /evidence="ECO:0007829|PDB:1N0W" FT HELIX 182..187 FT /evidence="ECO:0007829|PDB:1N0W" FT STRAND 189..193 FT /evidence="ECO:0007829|PDB:1N0W" FT HELIX 197..213 FT /evidence="ECO:0007829|PDB:1N0W" FT STRAND 216..222 FT /evidence="ECO:0007829|PDB:1N0W" FT TURN 223..225 FT /evidence="ECO:0007829|PDB:7C9A" FT HELIX 226..228 FT /evidence="ECO:0007829|PDB:1N0W" FT HELIX 238..259 FT /evidence="ECO:0007829|PDB:1N0W" FT STRAND 262..267 FT /evidence="ECO:0007829|PDB:1N0W" FT STRAND 285..288 FT /evidence="ECO:0007829|PDB:7C9A" FT HELIX 289..295 FT /evidence="ECO:0007829|PDB:7C9A" FT STRAND 298..304 FT /evidence="ECO:0007829|PDB:1N0W" FT STRAND 309..314 FT /evidence="ECO:0007829|PDB:1N0W" FT STRAND 318..320 FT /evidence="ECO:0007829|PDB:7C9A" FT STRAND 323..330 FT /evidence="ECO:0007829|PDB:1N0W" FT STRAND 333..335 FT /evidence="ECO:0007829|PDB:1N0W" SQ SEQUENCE 339 AA; 36966 MW; 26578E6206DEDEDA CRC64; MAMQMQLEAN ADTSVEEESF GPQPISRLEQ CGINANDVKK LEEAGFHTVE AVAYAPKKEL INIKGISEAK ADKILAEAAK LVPMGFTTAT EFHQRRSEII QITTGSKELD KLLQGGIETG SITEMFGEFR TGKTQICHTL AVTCQLPIDR GGGEGKAMYI DTEGTFRPER LLAVAERYGL SGSDVLDNVA YARAFNTDHQ TQLLYQASAM MVESRYALLI VDSATALYRT DYSGRGELSA RQMHLARFLR MLLRLADEFG VAVVITNQVV AQVDGAAMFA ADPKKPIGGN IIAHASTTRL YLRKGRGETR ICKIYDSPCL PEAEAMFAIN ADGVGDAKD // ID PCID2_HUMAN Reviewed; 399 AA. AC Q5JVF3; A6NK09; Q3ZCX1; Q5TC57; Q5TC58; Q9H7K1; Q9HBZ7; Q9NUK6; Q9NVY1; AC Q9NW44; Q9NWH3; DT 10-JAN-2006, integrated into UniProtKB/Swiss-Prot. DT 10-JAN-2006, sequence version 2. DT 25-MAY-2022, entry version 155. DE RecName: Full=PCI domain-containing protein 2; DE AltName: Full=CSN12-like protein; GN Name=PCID2; ORFNames=HT004; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4). RC TISSUE=Embryo, Ovary, Placenta, Spleen, and Teratocarcinoma; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Hypothalamus; RA Peng Y., Li N., Jia J., Xu S., Han Z., Fu G., Chen Z.; RT "A novel gene expressed in human hypothalamus."; RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057823; DOI=10.1038/nature02379; RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L., RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., RA Frankish A.G., Frankland J., French L., Garner P., Garnett J., RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., RA Rogers J., Ross M.T.; RT "The DNA sequence and analysis of human chromosome 13."; RL Nature 428:522-528(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Eye, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP PROTEIN SEQUENCE OF 2-20; 83-93; 117-128 AND 250-259, CLEAVAGE OF INITIATOR RP METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Ovarian carcinoma; RA Bienvenut W.V.; RL Submitted (JAN-2010) to UniProtKB. RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [7] RP IDENTIFICATION IN THE TREX-2 COMPLEX. RX PubMed=22307388; DOI=10.1093/nar/gks059; RA Jani D., Lutz S., Hurt E., Laskey R.A., Stewart M., Wickramasinghe V.O.; RT "Functional and structural characterization of the mammalian TREX-2 complex RT that links transcription with nuclear messenger RNA export."; RL Nucleic Acids Res. 40:4562-4573(2012). RN [8] RP FUNCTION, IDENTIFICATION IN THE TREX-2 COMPLEX, AND SUBCELLULAR LOCATION. RX PubMed=23591820; DOI=10.1242/jcs.118000; RA Umlauf D., Bonnet J., Waharte F., Fournier M., Stierle M., Fischer B., RA Brino L., Devys D., Tora L.; RT "The human TREX-2 complex is stably associated with the nuclear pore RT basket."; RL J. Cell Sci. 126:2656-2667(2013). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-45, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [10] RP INTERACTION WITH BRCA2. RX PubMed=24896180; DOI=10.1038/nature13374; RA Bhatia V., Barroso S.I., Garcia-Rubio M.L., Tumini E., Herrera-Moyano E., RA Aguilera A.; RT "BRCA2 prevents R-loop accumulation and associates with TREX-2 mRNA export RT factor PCID2."; RL Nature 511:362-365(2014). CC -!- FUNCTION: Required for B-cell survival through the regulation of the CC expression of cell-cycle checkpoint MAD2L1 protein during B cell CC differentiation (By similarity). As a component of the TREX-2 complex, CC involved in the export of mRNAs to the cytoplasm through the nuclear CC pores (PubMed:22307388) (Probable). Binds and stabilizes BRCA2 and is CC thus involved in the control of R-loop-associated DNA damage and CC transcription-associated genomic instability. R-loop accumulation does CC not increase in PCID2-depleted cells (PubMed:24896180). CC {ECO:0000250|UniProtKB:Q8BFV2, ECO:0000269|PubMed:22307388, CC ECO:0000269|PubMed:24896180, ECO:0000305|PubMed:23591820}. CC -!- SUBUNIT: Component of the nuclear pore complex (NPC)-associated TREX-2 CC complex (transcription and export complex 2), composed of at least CC GANP, 2 copies of ENY2, PCID2, SEM1/DSS1, and either centrin CETN2 or CC centrin CETN3. The TREX-2 complex also associates with ALYREF/ALY and CC with the nucleoporin NUP153 (PubMed:22307388, PubMed:23591820). CC Interacts with BRCA2 (PubMed:24896180). {ECO:0000269|PubMed:22307388, CC ECO:0000269|PubMed:23591820, ECO:0000269|PubMed:24896180}. CC -!- INTERACTION: CC Q5JVF3; Q9UKT9: IKZF3; NbExp=3; IntAct=EBI-1051701, EBI-747204; CC Q5JVF3; Q96PV6: LENG8; NbExp=3; IntAct=EBI-1051701, EBI-739546; CC Q5JVF3; P60896: SEM1; NbExp=3; IntAct=EBI-1051701, EBI-79819; CC Q5JVF3-1; P60896: SEM1; NbExp=3; IntAct=EBI-15970419, EBI-79819; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23591820}. Nucleus, CC nuclear pore complex {ECO:0000269|PubMed:23591820}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q5JVF3-1; Sequence=Displayed; CC Name=2; CC IsoId=Q5JVF3-2; Sequence=VSP_016843; CC Name=3; CC IsoId=Q5JVF3-3; Sequence=VSP_016845; CC Name=4; CC IsoId=Q5JVF3-4; Sequence=VSP_016844; CC -!- SIMILARITY: Belongs to the CSN12 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAG09695.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=BAB15768.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK000888; BAA91407.1; -; mRNA. DR EMBL; AK001185; BAA91542.1; -; mRNA. DR EMBL; AK001302; BAA91611.1; -; mRNA. DR EMBL; AK002167; BAA92118.1; -; mRNA. DR EMBL; AK023313; BAB14521.1; -; mRNA. DR EMBL; AK024478; BAB15768.1; ALT_INIT; mRNA. DR EMBL; AF183426; AAG09695.1; ALT_FRAME; mRNA. DR EMBL; AL136221; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL137002; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC016614; AAH16614.1; -; mRNA. DR EMBL; BC031246; AAH31246.1; -; mRNA. DR CCDS; CCDS58301.1; -. [Q5JVF3-2] DR CCDS; CCDS58302.1; -. [Q5JVF3-4] DR CCDS; CCDS9532.2; -. [Q5JVF3-1] DR RefSeq; NP_001120674.1; NM_001127202.3. [Q5JVF3-1] DR RefSeq; NP_001120675.1; NM_001127203.3. [Q5JVF3-1] DR RefSeq; NP_001245142.1; NM_001258213.2. [Q5JVF3-2] DR RefSeq; NP_001307584.1; NM_001320655.1. [Q5JVF3-2] DR RefSeq; NP_001307585.1; NM_001320656.1. [Q5JVF3-4] DR RefSeq; NP_001307586.1; NM_001320657.1. DR RefSeq; NP_001307589.1; NM_001320660.1. DR RefSeq; NP_060856.2; NM_018386.4. [Q5JVF3-1] DR RefSeq; XP_016876153.1; XM_017020664.1. [Q5JVF3-2] DR PDB; 3T5X; X-ray; 2.12 A; A=201-399. DR PDBsum; 3T5X; -. DR AlphaFoldDB; Q5JVF3; -. DR SMR; Q5JVF3; -. DR BioGRID; 120908; 61. DR DIP; DIP-50497N; -. DR IntAct; Q5JVF3; 25. DR MINT; Q5JVF3; -. DR GlyGen; Q5JVF3; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q5JVF3; -. DR MetOSite; Q5JVF3; -. DR PhosphoSitePlus; Q5JVF3; -. DR SwissPalm; Q5JVF3; -. DR BioMuta; PCID2; -. DR DMDM; 85681034; -. DR EPD; Q5JVF3; -. DR jPOST; Q5JVF3; -. DR MassIVE; Q5JVF3; -. DR MaxQB; Q5JVF3; -. DR PaxDb; Q5JVF3; -. DR PeptideAtlas; Q5JVF3; -. DR PRIDE; Q5JVF3; -. DR ProteomicsDB; 63327; -. [Q5JVF3-1] DR ProteomicsDB; 63328; -. [Q5JVF3-2] DR ProteomicsDB; 63329; -. [Q5JVF3-3] DR ProteomicsDB; 63330; -. [Q5JVF3-4] DR Antibodypedia; 25858; 96 antibodies from 15 providers. DR DNASU; 55795; -. DR Ensembl; ENST00000246505.9; ENSP00000246505.5; ENSG00000126226.22. [Q5JVF3-4] DR Ensembl; ENST00000337344.9; ENSP00000337405.4; ENSG00000126226.22. DR Ensembl; ENST00000375457.2; ENSP00000364606.2; ENSG00000126226.22. [Q5JVF3-2] DR Ensembl; ENST00000375459.5; ENSP00000364608.1; ENSG00000126226.22. [Q5JVF3-2] DR Ensembl; ENST00000375477.5; ENSP00000364626.1; ENSG00000126226.22. DR Ensembl; ENST00000375479.6; ENSP00000364628.2; ENSG00000126226.22. DR Ensembl; ENST00000622406.4; ENSP00000479494.1; ENSG00000126226.22. [Q5JVF3-4] DR GeneID; 55795; -. DR KEGG; hsa:55795; -. DR MANE-Select; ENST00000337344.9; ENSP00000337405.4; NM_001127202.4; NP_001120674.1. DR UCSC; uc058ylr.1; human. [Q5JVF3-1] DR CTD; 55795; -. DR DisGeNET; 55795; -. DR GeneCards; PCID2; -. DR HGNC; HGNC:25653; PCID2. DR HPA; ENSG00000126226; Low tissue specificity. DR MIM; 613713; gene. DR neXtProt; NX_Q5JVF3; -. DR OpenTargets; ENSG00000126226; -. DR PharmGKB; PA144596397; -. DR VEuPathDB; HostDB:ENSG00000126226; -. DR GeneTree; ENSGT00390000001101; -. DR HOGENOM; CLU_031567_2_0_1; -. DR InParanoid; Q5JVF3; -. DR OMA; TYLIPCH; -. DR PhylomeDB; Q5JVF3; -. DR TreeFam; TF106136; -. DR PathwayCommons; Q5JVF3; -. DR SignaLink; Q5JVF3; -. DR BioGRID-ORCS; 55795; 755 hits in 1086 CRISPR screens. DR ChiTaRS; PCID2; human. DR GenomeRNAi; 55795; -. DR Pharos; Q5JVF3; Tbio. DR PRO; PR:Q5JVF3; -. DR Proteomes; UP000005640; Chromosome 13. DR RNAct; Q5JVF3; protein. DR Bgee; ENSG00000126226; Expressed in oocyte and 232 other tissues. DR ExpressionAtlas; Q5JVF3; baseline and differential. DR Genevisible; Q5JVF3; HS. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0044615; C:nuclear pore nuclear basket; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0070390; C:transcription export complex 2; IDA:UniProtKB. DR GO; GO:0003690; F:double-stranded DNA binding; IBA:GO_Central. DR GO; GO:0003723; F:RNA binding; IBA:GO_Central. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:2000117; P:negative regulation of cysteine-type endopeptidase activity; IMP:UniProtKB. DR GO; GO:0071028; P:nuclear mRNA surveillance; IBA:GO_Central. DR GO; GO:0016973; P:poly(A)+ mRNA export from nucleus; IBA:GO_Central. DR GO; GO:0045579; P:positive regulation of B cell differentiation; IEA:Ensembl. DR GO; GO:0090267; P:positive regulation of mitotic cell cycle spindle assembly checkpoint; IMP:UniProtKB. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB. DR GO; GO:0000973; P:posttranscriptional tethering of RNA polymerase II gene DNA at nuclear periphery; IBA:GO_Central. DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW. DR GO; GO:0043488; P:regulation of mRNA stability; IMP:UniProtKB. DR GO; GO:0048536; P:spleen development; ISS:UniProtKB. DR GO; GO:0006368; P:transcription elongation from RNA polymerase II promoter; IBA:GO_Central. DR Gene3D; 1.10.10.10; -; 1. DR InterPro; IPR045114; Csn12-like. DR InterPro; IPR000717; PCI_dom. DR InterPro; IPR036388; WH-like_DNA-bd_sf. DR PANTHER; PTHR12732; PTHR12732; 1. DR Pfam; PF01399; PCI; 1. DR PROSITE; PS50250; PCI; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; KW Direct protein sequencing; mRNA transport; Nuclear pore complex; Nucleus; KW Phosphoprotein; Protein transport; Reference proteome; Translocation; KW Transport. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|Ref.5" FT CHAIN 2..399 FT /note="PCI domain-containing protein 2" FT /id="PRO_0000121029" FT DOMAIN 210..391 FT /note="PCI" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01185" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000269|Ref.5" FT MOD_RES 45 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..12 FT /note="MAHITINQYLQQ -> MRLTDVVQQL (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_016843" FT VAR_SEQ 89 FT /note="Q -> QYPLSFMAAVPHRTHAVDYLGLETRKHWASCSFLQLERNDSVLEQKL FT VSALSLGT (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_016844" FT VAR_SEQ 92..114 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_016845" FT CONFLICT 74 FT /note="N -> D (in Ref. 4; AAH31246)" FT /evidence="ECO:0000305" FT CONFLICT 87 FT /note="I -> L (in Ref. 1; BAA91407)" FT /evidence="ECO:0000305" FT CONFLICT 106 FT /note="P -> L (in Ref. 2; AAG09695)" FT /evidence="ECO:0000305" FT CONFLICT 129 FT /note="K -> E (in Ref. 2; AAG09695)" FT /evidence="ECO:0000305" FT CONFLICT 145 FT /note="L -> M (in Ref. 1; BAA91407)" FT /evidence="ECO:0000305" FT CONFLICT 180 FT /note="F -> I (in Ref. 1; BAA91611)" FT /evidence="ECO:0000305" FT CONFLICT 313 FT /note="I -> T (in Ref. 1; BAA92118)" FT /evidence="ECO:0000305" FT HELIX 206..222 FT /evidence="ECO:0007829|PDB:3T5X" FT HELIX 226..239 FT /evidence="ECO:0007829|PDB:3T5X" FT HELIX 245..261 FT /evidence="ECO:0007829|PDB:3T5X" FT HELIX 268..273 FT /evidence="ECO:0007829|PDB:3T5X" FT HELIX 277..279 FT /evidence="ECO:0007829|PDB:3T5X" FT HELIX 280..288 FT /evidence="ECO:0007829|PDB:3T5X" FT HELIX 291..300 FT /evidence="ECO:0007829|PDB:3T5X" FT HELIX 302..307 FT /evidence="ECO:0007829|PDB:3T5X" FT HELIX 311..315 FT /evidence="ECO:0007829|PDB:3T5X" FT HELIX 317..333 FT /evidence="ECO:0007829|PDB:3T5X" FT STRAND 336..339 FT /evidence="ECO:0007829|PDB:3T5X" FT HELIX 340..349 FT /evidence="ECO:0007829|PDB:3T5X" FT HELIX 357..369 FT /evidence="ECO:0007829|PDB:3T5X" FT STRAND 375..378 FT /evidence="ECO:0007829|PDB:3T5X" FT TURN 379..382 FT /evidence="ECO:0007829|PDB:3T5X" FT STRAND 383..386 FT /evidence="ECO:0007829|PDB:3T5X" FT HELIX 395..397 FT /evidence="ECO:0007829|PDB:3T5X" SQ SEQUENCE 399 AA; 46030 MW; 8D23273361F00E18 CRC64; MAHITINQYL QQVYEAIDSR DGASCAELVS FKHPHVANPR LQMASPEEKC QQVLEPPYDE MFAAHLRCTY AVGNHDFIEA YKCQTVIVQS FLRAFQAHKE ENWALPVMYA VALDLRVFAN NADQQLVKKG KSKVGDMLEK AAELLMSCFR VCASDTRAGI EDSKKWGMLF LVNQLFKIYF KINKLHLCKP LIRAIDSSNL KDDYSTAQRV TYKYYVGRKA MFDSDFKQAE EYLSFAFEHC HRSSQKNKRM ILIYLLPVKM LLGHMPTVEL LKKYHLMQFA EVTRAVSEGN LLLLHEALAK HEAFFIRCGI FLILEKLKII TYRNLFKKVY LLLKTHQLSL DAFLVALKFM QVEDVDIDEV QCILANLIYM GHVKGYISHQ HQKLVVSKQN PFPPLSTVC // ID FACD2_HUMAN Reviewed; 1451 AA. AC Q9BXW9; Q2LA86; Q69YP9; Q6PJN7; Q9BQ06; Q9H9T9; DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot. DT 26-NOV-2014, sequence version 2. DT 25-MAY-2022, entry version 186. DE RecName: Full=Fanconi anemia group D2 protein; DE Short=Protein FACD2; GN Name=FANCD2; Synonyms=FACD; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), FUNCTION, RP TISSUE SPECIFICITY, VARIANTS FANCD2 TRP-302 AND HIS-1236, AND VARIANT RP LEU-714. RC TISSUE=Lymphoblast; RX PubMed=11239453; DOI=10.1016/s1097-2765(01)00172-1; RA Timmers C., Taniguchi T., Hejna J., Reifsteck C., Lucas L., Bruun D., RA Thayer M., Cox B., Olson S., D'Andrea A.D., Moses R., Grompe M.; RT "Positional cloning of a novel Fanconi anemia gene, FANCD2."; RL Mol. Cell 7:241-248(2001). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-33; MET-61; HIS-65; RP MET-172; ALA-193; GLN-328; VAL-446; ARG-456; PRO-623; LEU-714; ARG-865 AND RP VAL-901. RG NIEHS SNPs program; RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 161-860 (ISOFORM 1). RC TISSUE=Teratocarcinoma; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 502-1451 (ISOFORM 3). RC TISSUE=Melanoma; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [6] RP FUNCTION, SUBCELLULAR LOCATION, UBIQUITINATION AT LYS-561, MUTAGENESIS OF RP LYS-561, INTERACTION WITH BRCA1, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=11239454; DOI=10.1016/s1097-2765(01)00173-3; RA Garcia-Higuera I., Taniguchi T., Ganesan S., Meyn M.S., Timmers C., RA Hejna J., Grompe M., D'Andrea A.D.; RT "Interaction of the Fanconi anemia proteins and BRCA1 in a common RT pathway."; RL Mol. Cell 7:249-262(2001). RN [7] RP FUNCTION, UBIQUITINATION, AND MUTAGENESIS OF LYS-561. RX PubMed=12239151; DOI=10.1182/blood-2002-01-0278; RA Taniguchi T., Garcia-Higuera I., Andreassen P.R., Gregory R.C., Grompe M., RA D'Andrea A.D.; RT "S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with RT BRCA1 and RAD51."; RL Blood 100:2414-2420(2002). RN [8] RP FUNCTION, PHOSPHORYLATION AT SER-222 AND SER-1404, MUTAGENESIS OF SER-222; RP LYS-561; SER-1257; SER-1401; SER-1404 AND SER-1418, AND IDENTIFICATION BY RP MASS SPECTROMETRY. RX PubMed=12086603; DOI=10.1016/s0092-8674(02)00747-x; RA Taniguchi T., Garcia-Higuera I., Xu B., Andreassen P.R., Gregory R.C., RA Kim S.-T., Lane W.S., Kastan M.B., D'Andrea A.D.; RT "Convergence of the Fanconi anemia and ataxia telangiectasia signaling RT pathways."; RL Cell 109:459-472(2002). RN [9] RP SUBCELLULAR LOCATION, AND INTERACTION WITH FANCE. RX PubMed=12093742; DOI=10.1093/emboj/cdf355; RA Pace P., Johnson M., Tan W.M., Mosedale G., Sng C., Hoatlin M.E., RA de Winter J.P., Joenje H., Gergely F., Patel K.J.; RT "FANCE: the link between Fanconi anaemia complex assembly and activity."; RL EMBO J. 21:3414-3423(2002). RN [10] RP INTERACTION WITH FANCE. RX PubMed=12649160; DOI=10.1182/blood-2002-11-3517; RA Gordon S.M., Buchwald M.; RT "Fanconi anemia protein complex: mapping protein interactions in the yeast RT 2- and 3-hybrid systems."; RL Blood 102:136-141(2003). RN [11] RP INTERACTION WITH MEN1, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=12874027; RA Jin S., Mao H., Schnepp R.W., Sykes S.M., Silva A.C., D'Andrea A.D., RA Hua X.; RT "Menin associates with FANCD2, a protein involved in repair of DNA RT damage."; RL Cancer Res. 63:4204-4210(2003). RN [12] RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND FUNCTION. RX PubMed=14517836; DOI=10.1002/path.1450; RA Hoelzel M., van Diest P.J., Bier P., Wallisch M., Hoatlin M.E., Joenje H., RA de Winter J.P.; RT "FANCD2 protein is expressed in proliferating cells of human tissues that RT are cancer-prone in Fanconi anaemia."; RL J. Pathol. 201:198-203(2003). RN [13] RP UBIQUITINATION BY FANCL. RX PubMed=12973351; DOI=10.1038/ng1241; RA Meetei A.R., de Winter J.P., Medhurst A.L., Wallisch M., Waisfisz Q., RA van de Vrugt H.J., Oostra A.B., Yan Z., Ling C., Bishop C.E., Hoatlin M.E., RA Joenje H., Wang W.; RT "A novel ubiquitin ligase is deficient in Fanconi anemia."; RL Nat. Genet. 35:165-170(2003). RN [14] RP PHOSPHORYLATION BY ATR. RX PubMed=14988723; DOI=10.1038/sj.emboj.7600113; RA Pichierri P., Rosselli F.; RT "The DNA crosslink-induced S-phase checkpoint depends on ATR-CHK1 and ATR- RT NBS1-FANCD2 pathways."; RL EMBO J. 23:1178-1187(2004). RN [15] RP INTERACTION WITH BLM. RX PubMed=15257300; DOI=10.1038/sj.emboj.7600277; RA Pichierri P., Franchitto A., Rosselli F.; RT "BLM and the FANC proteins collaborate in a common pathway in response to RT stalled replication forks."; RL EMBO J. 23:3154-3163(2004). RN [16] RP FUNCTION, PHOSPHORYLATION BY ATR, AND UBIQUITINATION. RX PubMed=15314022; DOI=10.1101/gad.1196104; RA Andreassen P.R., D'Andrea A.D., Taniguchi T.; RT "ATR couples FANCD2 monoubiquitination to the DNA-damage response."; RL Genes Dev. 18:1958-1963(2004). RN [17] RP FUNCTION, AND INTERACTION WITH BRCA2. RX PubMed=15115758; DOI=10.1093/hmg/ddh135; RA Hussain S., Wilson J.B., Medhurst A.L., Hejna J., Witt E., Ananth S., RA Davies A., Masson J.-Y., Moses R., West S.C., de Winter J.P., Ashworth A., RA Jones N.J., Mathew C.G.; RT "Direct interaction of FANCD2 with BRCA2 in DNA damage response pathways."; RL Hum. Mol. Genet. 13:1241-1248(2004). RN [18] RP FUNCTION. RX PubMed=15377654; DOI=10.1074/jbc.m407160200; RA Freie B.W., Ciccone S.L.M., Li X., Plett P.A., Orschell C.M., Srour E.F., RA Hanenberg H., Schindler D., Lee S.-H., Clapp D.W.; RT "A role for the Fanconi anemia C protein in maintaining the DNA damage- RT induced G2 checkpoint."; RL J. Biol. Chem. 279:50986-50993(2004). RN [19] RP UBIQUITINATION, AND INTERACTION WITH BRCA2. RX PubMed=15199141; DOI=10.1128/mcb.24.13.5850-5862.2004; RA Wang X.Z., Andreassen P.R., D'Andrea A.D.; RT "Functional interaction of monoubiquitinated FANCD2 and BRCA2/FANCD1 in RT chromatin."; RL Mol. Cell. Biol. 24:5850-5862(2004). RN [20] RP UBIQUITINATION. RX PubMed=15502827; DOI=10.1038/ng1458; RA Meetei A.R., Levitus M., Xue Y., Medhurst A.L., Zwaan M., Ling C., RA Rooimans M.A., Bier P., Hoatlin M., Pals G., de Winter J.P., Wang W., RA Joenje H.; RT "X-linked inheritance of Fanconi anemia complementation group B."; RL Nat. Genet. 36:1219-1224(2004). RN [21] RP FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-561, AND CHARACTERIZATION RP (ISOFORM 2). RX PubMed=15454491; DOI=10.1182/blood-2003-11-3997; RA Montes de Oca R., Andreassen P.R., Margossian S.P., Gregory R.C., RA Taniguchi T., Wang X.Z., Houghtaling S., Grompe M., D'Andrea A.D.; RT "Regulated interaction of the Fanconi anemia protein, FANCD2, with RT chromatin."; RL Blood 105:1003-1009(2005). RN [22] RP FUNCTION. RX PubMed=15661754; DOI=10.1093/hmg/ddi065; RA Howlett N.G., Taniguchi T., Durkin S.G., D'Andrea A.D., Glover T.W.; RT "The Fanconi anemia pathway is required for the DNA replication stress RT response and for the regulation of common fragile site stability."; RL Hum. Mol. Genet. 14:693-701(2005). RN [23] RP FUNCTION. RX PubMed=15671039; DOI=10.1074/jbc.m414669200; RA Ohashi A., Zdzienicka M.Z., Chen J., Couch F.J.; RT "FANCD2 functions independently of BRCA2 and RAD51 associated homologous RT recombination in response to DNA damage."; RL J. Biol. Chem. 280:14877-14883(2005). RN [24] RP INTERACTION WITH USP1, AND DEUBIQUITINATION. RX PubMed=15694335; DOI=10.1016/j.molcel.2005.01.008; RA Nijman S.M.B., Huang T.T., Dirac A.M.G., Brummelkamp T.R., Kerkhoven R.M., RA D'Andrea A.D., Bernards R.; RT "The deubiquitinating enzyme USP1 regulates the Fanconi Anemia pathway."; RL Mol. Cell 17:331-339(2005). RN [25] RP UBIQUITINATION. RX PubMed=16116422; DOI=10.1038/ng1626; RA Meetei A.R., Medhurst A.L., Ling C., Xue Y., Singh T.R., Bier P., RA Steltenpool J., Stone S., Dokal I., Mathew C.G., Hoatlin M., Joenje H., RA de Winter J.P., Wang W.; RT "A human ortholog of archaeal DNA repair protein Hef is defective in RT Fanconi anemia complementation group M."; RL Nat. Genet. 37:958-963(2005). RN [26] RP FUNCTION, AND MUTAGENESIS OF SER-222 AND LYS-561. RX PubMed=15650050; DOI=10.1073/pnas.0407796102; RA Nakanishi K., Yang Y.-G., Pierce A.J., Taniguchi T., Digweed M., RA D'Andrea A.D., Wang Z.-Q., Jasin M.; RT "Human Fanconi anemia monoubiquitination pathway promotes homologous DNA RT repair."; RL Proc. Natl. Acad. Sci. U.S.A. 102:1110-1115(2005). RN [27] RP UBIQUITINATION. RX PubMed=16916645; DOI=10.1016/j.molcel.2006.06.024; RA Machida Y.J., Machida Y., Chen Y., Gurtan A.M., Kupfer G.M., D'Andrea A.D., RA Dutta A.; RT "UBE2T is the E2 in the Fanconi anemia pathway and undergoes negative RT autoregulation."; RL Mol. Cell 23:589-596(2006). RN [28] RP INTERACTION WITH FANCI. RX PubMed=17412408; DOI=10.1016/j.cell.2007.03.009; RA Smogorzewska A., Matsuoka S., Vinciguerra P., McDonald E.R. III, RA Hurov K.E., Luo J., Ballif B.A., Gygi S.P., Hofmann K., D'Andrea A.D., RA Elledge S.J.; RT "Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog RT required for DNA repair."; RL Cell 129:289-301(2007). RN [29] RP INTERACTION WITH FANCI. RX PubMed=17460694; DOI=10.1038/nsmb1252; RA Sims A.E., Spiteri E., Sims R.J. III, Arita A.G., Lach F.P., Landers T., RA Wurm M., Freund M., Neveling K., Hanenberg H., Auerbach A.D., Huang T.T.; RT "FANCI is a second monoubiquitinated member of the Fanconi anemia RT pathway."; RL Nat. Struct. Mol. Biol. 14:564-567(2007). RN [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-592 AND SER-1412, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [31] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [32] RP UBIQUITINATION AT LYS-561, AND MUTAGENESIS OF LYS-561. RX PubMed=19111657; DOI=10.1016/j.molcel.2008.12.003; RA Alpi A.F., Pace P.E., Babu M.M., Patel K.J.; RT "Mechanistic insight into site-restricted monoubiquitination of FANCD2 by RT Ube2t, FANCL, and FANCI."; RL Mol. Cell 32:767-777(2008). RN [33] RP INTERACTION WITH BRCA2; FANCG AND XRCC3. RX PubMed=18212739; DOI=10.1038/sj.onc.1211034; RA Wilson J.B., Yamamoto K., Marriott A.S., Hussain S., Sung P., Hoatlin M.E., RA Mathew C.G., Takata M., Thompson L.H., Kupfer G.M., Jones N.J.; RT "FANCG promotes formation of a newly identified protein complex containing RT BRCA2, FANCD2 and XRCC3."; RL Oncogene 27:3641-3652(2008). RN [34] RP INTERACTION WITH DCLRE1B. RX PubMed=18469862; DOI=10.1038/onc.2008.139; RA Bae J.B., Mukhopadhyay S.S., Liu L., Zhang N., Tan J., Akhter S., Liu X., RA Shen X., Li L., Legerski R.J.; RT "Snm1B/Apollo mediates replication fork collapse and S Phase checkpoint RT activation in response to DNA interstrand cross-links."; RL Oncogene 27:5045-5056(2008). RN [35] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1412, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [36] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [37] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [38] RP SUBCELLULAR LOCATION. RX PubMed=19465922; DOI=10.1038/ncb1882; RA Chan K.L., Palmai-Pallag T., Ying S., Hickson I.D.; RT "Replication stress induces sister-chromatid bridging at fragile site loci RT in mitosis."; RL Nat. Cell Biol. 11:753-760(2009). RN [39] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=19465921; DOI=10.1038/ncb1883; RA Naim V., Rosselli F.; RT "The FANC pathway and BLM collaborate during mitosis to prevent micro- RT nucleation and chromosome abnormalities."; RL Nat. Cell Biol. 11:761-768(2009). RN [40] RP UBIQUITINATION AT LYS-561, INTERACTION WITH MTMR15, AND MUTAGENESIS OF RP LYS-561. RX PubMed=20603015; DOI=10.1016/j.cell.2010.06.021; RA MacKay C., Declais A.C., Lundin C., Agostinho A., Deans A.J., RA MacArtney T.J., Hofmann K., Gartner A., West S.C., Helleday T., RA Lilley D.M., Rouse J.; RT "Identification of KIAA1018/FAN1, a DNA repair nuclease recruited to DNA RT damage by monoubiquitinated FANCD2."; RL Cell 142:65-76(2010). RN [41] RP UBIQUITINATION AT LYS-561, INTERACTION WITH MTMR15, AND MUTAGENESIS OF RP LYS-561. RX PubMed=20603016; DOI=10.1016/j.cell.2010.06.022; RA Kratz K., Schopf B., Kaden S., Sendoel A., Eberhard R., Lademann C., RA Cannavo E., Sartori A.A., Hengartner M.O., Jiricny J.; RT "Deficiency of FANCD2-associated nuclease KIAA1018/FAN1 sensitizes cells to RT interstrand crosslinking agents."; RL Cell 142:77-88(2010). RN [42] RP UBIQUITINATION AT LYS-561, INTERACTION WITH MTMR15, AND MUTAGENESIS OF RP LYS-561. RX PubMed=20603073; DOI=10.1016/j.molcel.2010.06.023; RA Smogorzewska A., Desetty R., Saito T.T., Schlabach M., Lach F.P., RA Sowa M.E., Clark A.B., Kunkel T.A., Harper J.W., Colaiacovo M.P., RA Elledge S.J.; RT "A genetic screen identifies FAN1, a Fanconi anemia-associated nuclease RT necessary for DNA interstrand crosslink repair."; RL Mol. Cell 39:36-47(2010). RN [43] RP INTERACTION WITH POLN. RX PubMed=19995904; DOI=10.1128/mcb.01124-09; RA Moldovan G.L., Madhavan M.V., Mirchandani K.D., McCaffrey R.M., RA Vinciguerra P., D'Andrea A.D.; RT "DNA polymerase POLN participates in cross-link repair and homologous RT recombination."; RL Mol. Cell. Biol. 30:1088-1096(2010). RN [44] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-8; SER-594; SER-717; RP SER-1412; SER-1423; THR-1426 AND SER-1435, VARIANT [LARGE SCALE ANALYSIS] RP LEU-714, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [45] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [46] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1435, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [47] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-592; SER-1257 AND SER-1412, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [48] RP FUNCTION, INTERACTION WITH UHRF1 AND UHRF2, SUBCELLULAR LOCATION, AND RP UBIQUITINATION. RX PubMed=30335751; DOI=10.1371/journal.pgen.1007643; RA Motnenko A., Liang C.C., Yang D., Lopez-Martinez D., Yoshikawa Y., Zhan B., RA Ward K.E., Tian J., Haas W., Spingardi P., Kessler B.M., Kriaucionis S., RA Gygi S.P., Cohn M.A.; RT "Identification of UHRF2 as a novel DNA interstrand crosslink sensor RT protein."; RL PLoS Genet. 14:e1007643-e1007643(2018). CC -!- FUNCTION: Required for maintenance of chromosomal stability. Promotes CC accurate and efficient pairing of homologs during meiosis. Involved in CC the repair of DNA double-strand breaks, both by homologous CC recombination and single-strand annealing. May participate in S phase CC and G2 phase checkpoint activation upon DNA damage. Plays a role in CC preventing breakage and loss of missegregating chromatin at the end of CC cell division, particularly after replication stress. Required for the CC targeting, or stabilization, of BLM to non-centromeric abnormal CC structures induced by replicative stress. Promotes BRCA2/FANCD1 loading CC onto damaged chromatin. May also be involved in B-cell immunoglobulin CC isotype switching. {ECO:0000269|PubMed:11239453, CC ECO:0000269|PubMed:11239454, ECO:0000269|PubMed:12086603, CC ECO:0000269|PubMed:12239151, ECO:0000269|PubMed:14517836, CC ECO:0000269|PubMed:15115758, ECO:0000269|PubMed:15314022, CC ECO:0000269|PubMed:15377654, ECO:0000269|PubMed:15454491, CC ECO:0000269|PubMed:15650050, ECO:0000269|PubMed:15661754, CC ECO:0000269|PubMed:15671039, ECO:0000269|PubMed:19465921, CC ECO:0000269|PubMed:30335751}. CC -!- SUBUNIT: Interacts directly with FANCE and FANCI. Interacts with USP1 CC and MEN1. The ubiquitinated form specifically interacts with BRCA1 and CC BLM. Both the nonubiquitinated and the monoubiquitinated forms interact CC with BRCA2; this interaction is mediated by phosphorylated FANCG and CC the complex also includes XCCR3. The ubiquitinated form specifically CC interacts with MTMR15/FAN1 (via UBZ-type zinc finger), leading to CC recruit MTMR15/FAN1 to sites of DNA damage. Interacts with CC DCLRE1B/Apollo (PubMed:11239454, PubMed:12093742, PubMed:12649160, CC PubMed:12874027, PubMed:15115758, PubMed:15199141, PubMed:15257300, CC PubMed:15694335, PubMed:17412408, PubMed:17460694, PubMed:18212739, CC PubMed:18469862, PubMed:20603015, PubMed:20603016, PubMed:20603073). CC Interacts with POLN (PubMed:19995904). Interacts with UHRF1 and UHRF2; CC these interactions promote FANCD2 activation (PubMed:30335751). CC {ECO:0000269|PubMed:11239454, ECO:0000269|PubMed:12093742, CC ECO:0000269|PubMed:12649160, ECO:0000269|PubMed:12874027, CC ECO:0000269|PubMed:15115758, ECO:0000269|PubMed:15199141, CC ECO:0000269|PubMed:15257300, ECO:0000269|PubMed:15694335, CC ECO:0000269|PubMed:17412408, ECO:0000269|PubMed:17460694, CC ECO:0000269|PubMed:18212739, ECO:0000269|PubMed:18469862, CC ECO:0000269|PubMed:19995904, ECO:0000269|PubMed:20603015, CC ECO:0000269|PubMed:20603016, ECO:0000269|PubMed:20603073, CC ECO:0000269|PubMed:30335751}. CC -!- INTERACTION: CC Q9BXW9; P51587: BRCA2; NbExp=16; IntAct=EBI-359343, EBI-79792; CC Q9BXW9; P49716: CEBPD; NbExp=8; IntAct=EBI-359343, EBI-7962058; CC Q9BXW9; Q9NVI1: FANCI; NbExp=2; IntAct=EBI-359343, EBI-1013291; CC Q9BXW9; Q16658: FSCN1; NbExp=6; IntAct=EBI-359343, EBI-351076; CC Q9BXW9; O00255: MEN1; NbExp=4; IntAct=EBI-359343, EBI-592789; CC Q9BXW9; P49959: MRE11; NbExp=6; IntAct=EBI-359343, EBI-396513; CC Q9BXW9; O60934: NBN; NbExp=6; IntAct=EBI-359343, EBI-494844; CC Q9BXW9-2; P51587: BRCA2; NbExp=3; IntAct=EBI-596878, EBI-79792; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11239454, CC ECO:0000269|PubMed:12093742, ECO:0000269|PubMed:19465921, CC ECO:0000269|PubMed:19465922, ECO:0000269|PubMed:30335751}. CC Note=Concentrates in nuclear foci during S phase and upon genotoxic CC stress. At the onset of mitosis, excluded from chromosomes and diffuses CC into the cytoplasm, returning to the nucleus at the end of cell CC division. Observed in a few spots localized in pairs on the sister CC chromatids of mitotic chromosome arms and not centromeres, one on each CC chromatids. These foci coincide with common fragile sites and could be CC sites of replication fork stalling. The foci are frequently interlinked CC through BLM-associated ultra-fine DNA bridges. Following aphidicolin CC treatment, targets chromatid gaps and breaks. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=2; CC IsoId=Q9BXW9-2; Sequence=Displayed; CC Name=1; CC IsoId=Q9BXW9-1; Sequence=VSP_057198; CC Name=3; CC IsoId=Q9BXW9-3; Sequence=VSP_013885, VSP_013886; CC Name=4; CC IsoId=Q9BXW9-4; Sequence=VSP_013883, VSP_013884; CC -!- TISSUE SPECIFICITY: Highly expressed in germinal center cells of the CC spleen, tonsil, and reactive lymph nodes, and in the proliferating CC basal layer of squamous epithelium of tonsil, esophagus, oropharynx, CC larynx and cervix. Expressed in cytotrophoblastic cells of the placenta CC and exocrine cells of the pancreas (at protein level). Highly expressed CC in testis, where expression is restricted to maturing spermatocytes. CC {ECO:0000269|PubMed:11239453, ECO:0000269|PubMed:14517836, CC ECO:0000269|PubMed:15454491}. CC -!- DEVELOPMENTAL STAGE: Highly expressed in fetal oocytes, and in CC hematopoietic cells of the fetal liver and bone marrow (at protein CC level). {ECO:0000269|PubMed:14517836}. CC -!- DOMAIN: The C-terminal 24 residues of isoform 2 are required for its CC function. CC -!- PTM: Monoubiquitinated on Lys-561 during S phase and upon genotoxic CC stress by FANCL in complex with E2 ligases UBE2T or UBE2W (isoform 1 CC and isoform 2). Deubiquitinated by USP1 as cells enter G2/M, or once CC DNA repair is completed. Monoubiquitination requires the joint CC intervention of the FANC core complex, including FANCA, FANCB, FANCC, CC FANCE, FANCF, FANCG, and FANCM, and proteins involved in cell cycle CC checkpoints and DNA repair, including RPA1, ATR, CHEK1 and BRCA1, and CC is mediated by FANCL/PHF9. Ubiquitination is required for binding to CC chromatin, interaction with BRCA1, BRCA2 and MTMR15/FAN1, DNA repair, CC and normal cell cycle progression, but not for phosphorylation on Ser- CC 222 or interaction with MEN1. {ECO:0000269|PubMed:11239454, CC ECO:0000269|PubMed:12086603, ECO:0000269|PubMed:15694335, CC ECO:0000269|PubMed:19111657, ECO:0000269|PubMed:20603015, CC ECO:0000269|PubMed:20603016, ECO:0000269|PubMed:20603073, CC ECO:0000269|PubMed:30335751}. CC -!- PTM: Phosphorylated in response to various genotoxic stresses by ATM CC and/or ATR. Upon ionizing radiation, phosphorylated by ATM on Ser-222 CC and Ser-1404. Phosphorylation on Ser-222 is required for S-phase CC checkpoint activation, but not for ubiquitination, foci formation, or CC DNA repair. In contrast, phosphorylation by ATR on other sites may be CC required for ubiquitination and foci formation. CC {ECO:0000269|PubMed:12086603, ECO:0000269|PubMed:15694335}. CC -!- DISEASE: Fanconi anemia complementation group D2 (FANCD2) [MIM:227646]: CC A disorder affecting all bone marrow elements and resulting in anemia, CC leukopenia and thrombopenia. It is associated with cardiac, renal and CC limb malformations, dermal pigmentary changes, and a predisposition to CC the development of malignancies. At the cellular level it is associated CC with hypersensitivity to DNA-damaging agents, chromosomal instability CC (increased chromosome breakage) and defective DNA repair. CC {ECO:0000269|PubMed:11239453}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 1]: Less abundant than isoform 2, may be not CC functional. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAB14132.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/FADID103.html"; CC -!- WEB RESOURCE: Name=Fanconi Anemia Mutation Database; CC URL="https://www2.rockefeller.edu/fanconi/genes/jumpd2"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/fancd2/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF230336; AAL05980.1; -; mRNA. DR EMBL; AF273251; AAK18772.1; -; Genomic_DNA. DR EMBL; AF273222; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273223; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273227; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273231; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273235; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273243; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273241; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273239; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273245; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273246; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273247; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273248; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273249; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273250; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273236; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273237; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273238; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273224; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273226; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273228; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273230; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273232; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273234; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273240; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273242; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273244; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273233; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273229; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273225; AAK18772.1; JOINED; Genomic_DNA. DR EMBL; AF273251; AAK18773.1; -; Genomic_DNA. DR EMBL; AF273222; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273223; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273224; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273225; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273226; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273227; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273228; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273229; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273230; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273231; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273232; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273233; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273234; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273235; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273236; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273237; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273238; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273239; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273240; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273241; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273242; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273243; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273244; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273245; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273246; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273247; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273248; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273249; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF273250; AAK18773.1; JOINED; Genomic_DNA. DR EMBL; AF340183; AAK15369.1; -; mRNA. DR EMBL; DQ341263; ABC67466.1; -; Genomic_DNA. DR EMBL; BC013582; AAH13582.1; -; mRNA. DR EMBL; AK022613; BAB14132.1; ALT_INIT; mRNA. DR EMBL; AL832427; CAH10647.1; -; mRNA. DR CCDS; CCDS2595.1; -. [Q9BXW9-1] DR CCDS; CCDS33696.1; -. [Q9BXW9-2] DR RefSeq; NP_001018125.1; NM_001018115.2. [Q9BXW9-2] DR RefSeq; NP_001306913.1; NM_001319984.1. [Q9BXW9-2] DR RefSeq; NP_149075.2; NM_033084.4. [Q9BXW9-1] DR PDB; 6VAA; EM; 3.35 A; B=1-1451. DR PDB; 6VAD; EM; 3.35 A; B=1-1451. DR PDB; 6VAE; EM; 3.50 A; B=1-1451. DR PDB; 6VAF; EM; 3.90 A; B=1-1451. DR PDB; 7AY1; EM; 3.70 A; B=1-1451. DR PDB; 7KZQ; EM; 4.20 A; V=1-1451. DR PDB; 7KZR; EM; 4.20 A; V=1-1451. DR PDB; 7KZS; EM; 4.20 A; V=1-1451. DR PDB; 7KZT; EM; 4.20 A; V=1-1451. DR PDB; 7KZV; EM; 4.20 A; V=1-1451. DR PDBsum; 6VAA; -. DR PDBsum; 6VAD; -. DR PDBsum; 6VAE; -. DR PDBsum; 6VAF; -. DR PDBsum; 7AY1; -. DR PDBsum; 7KZQ; -. DR PDBsum; 7KZR; -. DR PDBsum; 7KZS; -. DR PDBsum; 7KZT; -. DR PDBsum; 7KZV; -. DR AlphaFoldDB; Q9BXW9; -. DR SMR; Q9BXW9; -. DR BioGRID; 108474; 849. DR ComplexPortal; CPX-6264; Fanconi anemia ID complex. DR CORUM; Q9BXW9; -. DR DIP; DIP-27606N; -. DR DIP; DIP-29382N; -. DR IntAct; Q9BXW9; 65. DR MINT; Q9BXW9; -. DR STRING; 9606.ENSP00000287647; -. DR ChEMBL; CHEMBL2157857; -. DR iPTMnet; Q9BXW9; -. DR PhosphoSitePlus; Q9BXW9; -. DR BioMuta; FANCD2; -. DR DMDM; 67461071; -. DR CPTAC; CPTAC-3227; -. DR CPTAC; CPTAC-3228; -. DR CPTAC; CPTAC-3229; -. DR EPD; Q9BXW9; -. DR jPOST; Q9BXW9; -. DR MassIVE; Q9BXW9; -. DR MaxQB; Q9BXW9; -. DR PaxDb; Q9BXW9; -. DR PeptideAtlas; Q9BXW9; -. DR PRIDE; Q9BXW9; -. DR ProteomicsDB; 79531; -. [Q9BXW9-2] DR ProteomicsDB; 79532; -. [Q9BXW9-2] DR ProteomicsDB; 79533; -. [Q9BXW9-3] DR ProteomicsDB; 79534; -. [Q9BXW9-4] DR Antibodypedia; 10521; 639 antibodies from 39 providers. DR CPTC; Q9BXW9; 2 antibodies. DR DNASU; 2177; -. DR Ensembl; ENST00000287647.7; ENSP00000287647.3; ENSG00000144554.13. [Q9BXW9-1] DR Ensembl; ENST00000419585.5; ENSP00000398754.1; ENSG00000144554.13. DR Ensembl; ENST00000431693.1; ENSP00000399354.1; ENSG00000144554.13. [Q9BXW9-4] DR Ensembl; ENST00000675286.1; ENSP00000502379.1; ENSG00000144554.13. DR GeneID; 2177; -. DR KEGG; hsa:2177; -. DR MANE-Select; ENST00000675286.1; ENSP00000502379.1; NM_001018115.3; NP_001018125.1. DR UCSC; uc003buw.4; human. [Q9BXW9-2] DR CTD; 2177; -. DR DisGeNET; 2177; -. DR GeneCards; FANCD2; -. DR GeneReviews; FANCD2; -. DR HGNC; HGNC:3585; FANCD2. DR HPA; ENSG00000144554; Tissue enhanced (bone). DR MalaCards; FANCD2; -. DR MIM; 227646; phenotype. DR MIM; 613984; gene. DR neXtProt; NX_Q9BXW9; -. DR OpenTargets; ENSG00000144554; -. DR Orphanet; 84; Fanconi anemia. DR PharmGKB; PA27999; -. DR VEuPathDB; HostDB:ENSG00000144554; -. DR eggNOG; KOG4712; Eukaryota. DR GeneTree; ENSGT00390000016970; -. DR HOGENOM; CLU_002068_1_0_1; -. DR InParanoid; Q9BXW9; -. DR OMA; EFFFDIV; -. DR OrthoDB; 979208at2759; -. DR TreeFam; TF101106; -. DR PathwayCommons; Q9BXW9; -. DR Reactome; R-HSA-6783310; Fanconi Anemia Pathway. DR Reactome; R-HSA-6796648; TP53 Regulates Transcription of DNA Repair Genes. DR SignaLink; Q9BXW9; -. DR SIGNOR; Q9BXW9; -. DR BioGRID-ORCS; 2177; 89 hits in 1088 CRISPR screens. DR ChiTaRS; FANCD2; human. DR GeneWiki; FANCD2; -. DR GenomeRNAi; 2177; -. DR Pharos; Q9BXW9; Tbio. DR PRO; PR:Q9BXW9; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q9BXW9; protein. DR Bgee; ENSG00000144554; Expressed in female gonad and 162 other tissues. DR ExpressionAtlas; Q9BXW9; baseline and differential. DR Genevisible; Q9BXW9; HS. DR GO; GO:0000785; C:chromatin; IC:ComplexPortal. DR GO; GO:0000793; C:condensed chromosome; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:1990391; C:DNA repair complex; IPI:ComplexPortal. DR GO; GO:0016604; C:nuclear body; IDA:HPA. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:ParkinsonsUK-UCL. DR GO; GO:0070182; F:DNA polymerase binding; IPI:UniProtKB. DR GO; GO:0048854; P:brain morphogenesis; IEA:Ensembl. DR GO; GO:0034599; P:cellular response to oxidative stress; IEA:Ensembl. DR GO; GO:1990918; P:double-strand break repair involved in meiotic recombination; IBA:GO_Central. DR GO; GO:0007276; P:gamete generation; IEA:Ensembl. DR GO; GO:0007129; P:homologous chromosome pairing at meiosis; IBA:GO_Central. DR GO; GO:0036297; P:interstrand cross-link repair; IBA:GO_Central. DR GO; GO:0031573; P:mitotic intra-S DNA damage checkpoint signaling; IBA:GO_Central. DR GO; GO:0097150; P:neuronal stem cell population maintenance; IEA:Ensembl. DR GO; GO:2000348; P:regulation of CD40 signaling pathway; IEA:Ensembl. DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; IEA:Ensembl. DR GO; GO:0050727; P:regulation of inflammatory response; IEA:Ensembl. DR GO; GO:0045589; P:regulation of regulatory T cell differentiation; IEA:Ensembl. DR GO; GO:0010332; P:response to gamma radiation; IDA:UniProtKB. DR CDD; cd11721; FANCD2; 1. DR InterPro; IPR029448; FANCD2. DR PANTHER; PTHR32086; PTHR32086; 1. DR Pfam; PF14631; FancD2; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell cycle; Disease variant; KW DNA damage; DNA repair; Fanconi anemia; Isopeptide bond; Nucleus; KW Phosphoprotein; Reference proteome; Ubl conjugation. FT CHAIN 1..1451 FT /note="Fanconi anemia group D2 protein" FT /id="PRO_0000087168" FT REGION 1..291 FT /note="Interaction with FANCE" FT REGION 1..37 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 248..359 FT /note="Interaction with BRCA2" FT REGION 868..906 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1396..1451 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1..26 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1415..1430 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1431..1451 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 8 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 222 FT /note="Phosphoserine; by ATM" FT /evidence="ECO:0000269|PubMed:12086603" FT MOD_RES 592 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17525332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 594 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 717 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 1257 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1401 FT /note="Phosphoserine; by ATM" FT /evidence="ECO:0000305" FT MOD_RES 1404 FT /note="Phosphoserine; by ATM" FT /evidence="ECO:0000269|PubMed:12086603" FT MOD_RES 1412 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17525332, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1423 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 1426 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 1435 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692" FT CROSSLNK 561 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:11239454, FT ECO:0000269|PubMed:19111657, ECO:0000269|PubMed:20603015, FT ECO:0000269|PubMed:20603016, ECO:0000269|PubMed:20603073" FT VAR_SEQ 232..241 FT /note="SDLLIENTSL -> RWINPLSSSK (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_013883" FT VAR_SEQ 242..1451 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_013884" FT VAR_SEQ 1229..1249 FT /note="HTFVVFFRVMMAELEKTVKKI -> FMKRNSSTGTWLFETSVSSST (in FT isoform 3)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_013885" FT VAR_SEQ 1250..1451 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_013886" FT VAR_SEQ 1428..1451 FT /note="DGEEDEVSAGEKEQDSDESYDDSD -> VSLQNPPESGTDGCILLIVLSWWS FT RTLPTYVYCQMLLCPFPFPP (in isoform 1)" FT /id="VSP_057198" FT VARIANT 33 FT /note="K -> R (in dbSNP:rs34691009)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025827" FT VARIANT 61 FT /note="T -> M (in dbSNP:rs35110529)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025828" FT VARIANT 65 FT /note="Q -> H (in dbSNP:rs36084488)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025829" FT VARIANT 126 FT /note="S -> G (in FANCD2; dbSNP:rs764507146)" FT /id="VAR_022559" FT VARIANT 172 FT /note="I -> M (in dbSNP:rs35173688)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025830" FT VARIANT 193 FT /note="T -> A (in dbSNP:rs34936017)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025831" FT VARIANT 302 FT /note="R -> W (in FANCD2; dbSNP:rs121917787)" FT /evidence="ECO:0000269|PubMed:11239453" FT /id="VAR_022560" FT VARIANT 328 FT /note="R -> Q (in dbSNP:rs35625434)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025832" FT VARIANT 446 FT /note="L -> V (in dbSNP:rs34557223)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025833" FT VARIANT 456 FT /note="L -> R (in dbSNP:rs35782247)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025834" FT VARIANT 623 FT /note="Q -> P (in dbSNP:rs36070315)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025835" FT VARIANT 714 FT /note="P -> L (in dbSNP:rs3864017)" FT /evidence="ECO:0000269|PubMed:11239453, ECO:0000269|Ref.2, FT ECO:0007744|PubMed:20068231" FT /id="VAR_022561" FT VARIANT 865 FT /note="K -> R (in dbSNP:rs35546777)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025836" FT VARIANT 901 FT /note="G -> V (in dbSNP:rs35495399)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_025837" FT VARIANT 1236 FT /note="R -> H (in FANCD2; no effect on ubiquitination; FT dbSNP:rs121917786)" FT /evidence="ECO:0000269|PubMed:11239453" FT /id="VAR_022562" FT MUTAGEN 222 FT /note="S->A: Reduces phosphorylation by ATM. No effect on FT ubiquitination, foci formation or DNA repair ability, but FT impairs S-phase checkpoint activation." FT /evidence="ECO:0000269|PubMed:12086603, FT ECO:0000269|PubMed:15650050" FT MUTAGEN 561 FT /note="K->R: Abolishes ubiquitination; impairs chromatin FT binding, foci formation and DNA repair. Abolishes FT interaction with MTMR15/FAN1. No effect on S-222 FT phosphorylation by ATM." FT /evidence="ECO:0000269|PubMed:11239454, FT ECO:0000269|PubMed:12086603, ECO:0000269|PubMed:12239151, FT ECO:0000269|PubMed:15454491, ECO:0000269|PubMed:15650050, FT ECO:0000269|PubMed:19111657, ECO:0000269|PubMed:20603015, FT ECO:0000269|PubMed:20603016, ECO:0000269|PubMed:20603073" FT MUTAGEN 1257 FT /note="S->A: No effect on phosphorylation by ATM." FT /evidence="ECO:0000269|PubMed:12086603" FT MUTAGEN 1401 FT /note="S->A: Reduces phosphorylation by ATM; when FT associated with A-1404 and A-1418." FT /evidence="ECO:0000269|PubMed:12086603" FT MUTAGEN 1404 FT /note="S->A: Reduces phosphorylation by ATM; when FT associated with A-1401 and A-1418." FT /evidence="ECO:0000269|PubMed:12086603" FT MUTAGEN 1418 FT /note="S->A: Reduces phosphorylation by ATM; when FT associated with A-1401 and A-1404." FT /evidence="ECO:0000269|PubMed:12086603" FT CONFLICT 257 FT /note="N -> D (in Ref. 4; BAB14132)" FT /evidence="ECO:0000305" FT CONFLICT 557 FT /note="L -> S (in Ref. 4; BAB14132)" FT /evidence="ECO:0000305" FT CONFLICT 589 FT /note="R -> G (in Ref. 4; BAB14132)" FT /evidence="ECO:0000305" FT HELIX 47..55 FT /evidence="ECO:0007829|PDB:6VAA" FT STRAND 62..64 FT /evidence="ECO:0007829|PDB:6VAA" FT STRAND 67..70 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 72..85 FT /evidence="ECO:0007829|PDB:6VAA" FT STRAND 86..88 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 89..103 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 107..114 FT /evidence="ECO:0007829|PDB:6VAA" FT STRAND 115..119 FT /evidence="ECO:0007829|PDB:6VAA" FT STRAND 131..134 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 135..140 FT /evidence="ECO:0007829|PDB:6VAA" FT TURN 143..145 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 146..154 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 158..160 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 172..178 FT /evidence="ECO:0007829|PDB:6VAA" FT TURN 179..182 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 189..202 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 205..213 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 215..218 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 221..223 FT /evidence="ECO:0007829|PDB:6VAE" FT HELIX 224..237 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 242..251 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 256..268 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 270..272 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 275..277 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 278..287 FT /evidence="ECO:0007829|PDB:6VAA" FT STRAND 291..293 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 294..304 FT /evidence="ECO:0007829|PDB:6VAA" FT STRAND 307..309 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 340..355 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 359..369 FT /evidence="ECO:0007829|PDB:6VAA" FT STRAND 373..375 FT /evidence="ECO:0007829|PDB:6VAE" FT HELIX 379..390 FT /evidence="ECO:0007829|PDB:6VAA" FT TURN 393..395 FT /evidence="ECO:0007829|PDB:6VAD" FT HELIX 396..407 FT /evidence="ECO:0007829|PDB:6VAA" FT TURN 408..410 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 414..424 FT /evidence="ECO:0007829|PDB:6VAA" FT TURN 425..428 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 429..431 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 432..439 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 441..443 FT /evidence="ECO:0007829|PDB:6VAA" FT STRAND 444..447 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 448..464 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 467..482 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 486..502 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 504..508 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 511..515 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 516..520 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 526..540 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 543..545 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 550..563 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 568..585 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 605..622 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 625..641 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 648..663 FT /evidence="ECO:0007829|PDB:6VAA" FT STRAND 665..667 FT /evidence="ECO:0007829|PDB:6VAA" FT STRAND 681..684 FT /evidence="ECO:0007829|PDB:6VAA" FT STRAND 687..689 FT /evidence="ECO:0007829|PDB:6VAA" FT STRAND 691..698 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 700..706 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 730..745 FT /evidence="ECO:0007829|PDB:6VAA" FT TURN 750..752 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 753..757 FT /evidence="ECO:0007829|PDB:6VAA" FT STRAND 760..762 FT /evidence="ECO:0007829|PDB:6VAA" FT STRAND 769..771 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 777..799 FT /evidence="ECO:0007829|PDB:6VAA" FT STRAND 800..802 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 806..832 FT /evidence="ECO:0007829|PDB:6VAA" FT TURN 843..845 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 846..850 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 917..923 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 930..937 FT /evidence="ECO:0007829|PDB:6VAA" FT TURN 943..945 FT /evidence="ECO:0007829|PDB:6VAE" FT HELIX 962..980 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 1004..1006 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 1009..1019 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 1021..1041 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 1052..1073 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 1076..1079 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 1084..1095 FT /evidence="ECO:0007829|PDB:6VAA" FT TURN 1096..1098 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 1107..1119 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 1120..1123 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 1129..1142 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 1152..1164 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 1171..1175 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 1179..1192 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 1196..1207 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 1210..1213 FT /evidence="ECO:0007829|PDB:6VAA" FT STRAND 1222..1225 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 1230..1246 FT /evidence="ECO:0007829|PDB:6VAA" FT STRAND 1254..1256 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 1258..1280 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 1281..1283 FT /evidence="ECO:0007829|PDB:6VAD" FT HELIX 1289..1315 FT /evidence="ECO:0007829|PDB:6VAA" FT STRAND 1316..1319 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 1321..1348 FT /evidence="ECO:0007829|PDB:6VAA" FT TURN 1351..1354 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 1357..1375 FT /evidence="ECO:0007829|PDB:6VAA" FT HELIX 1381..1383 FT /evidence="ECO:0007829|PDB:6VAE" SQ SEQUENCE 1451 AA; 164128 MW; BF931980ADA67405 CRC64; MVSKRRLSKS EDKESLTEDA SKTRKQPLSK KTKKSHIANE VEENDSIFVK LLKISGIILK TGESQNQLAV DQIAFQKKLF QTLRRHPSYP KIIEEFVSGL ESYIEDEDSF RNCLLSCERL QDEEASMGAS YSKSLIKLLL GIDILQPAII KTLFEKLPEY FFENKNSDEI NIPRLIVSQL KWLDRVVDGK DLTTKIMQLI SIAPENLQHD IITSLPEILG DSQHADVGKE LSDLLIENTS LTVPILDVLS SLRLDPNFLL KVRQLVMDKL SSIRLEDLPV IIKFILHSVT AMDTLEVISE LREKLDLQHC VLPSRLQASQ VKLKSKGRAS SSGNQESSGQ SCIILLFDVI KSAIRYEKTI SEAWIKAIEN TASVSEHKVF DLVMLFIIYS TNTQTKKYID RVLRNKIRSG CIQEQLLQST FSVHYLVLKD MCSSILSLAQ SLLHSLDQSI ISFGSLLYKY AFKFFDTYCQ QEVVGALVTH ICSGNEAEVD TALDVLLELV VLNPSAMMMN AVFVKGILDY LDNISPQQIR KLFYVLSTLA FSKQNEASSH IQDDMHLVIR KQLSSTVFKY KLIGIIGAVT MAGIMAADRS ESPSLTQERA NLSDEQCTQV TSLLQLVHSC SEQSPQASAL YYDEFANLIQ HEKLDPKALE WVGHTICNDF QDAFVVDSCV VPEGDFPFPV KALYGLEEYD TQDGIAINLL PLLFSQDFAK DGGPVTSQES GQKLVSPLCL APYFRLLRLC VERQHNGNLE EIDGLLDCPI FLTDLEPGEK LESMSAKERS FMCSLIFLTL NWFREIVNAF CQETSPEMKG KVLTRLKHIV ELQIILEKYL AVTPDYVPPL GNFDVETLDI TPHTVTAISA KIRKKGKIER KQKTDGSKTS SSDTLSEEKN SECDPTPSHR GQLNKEFTGK EEKTSLLLHN SHAFFRELDI EVFSILHCGL VTKFILDTEM HTEATEVVQL GPPELLFLLE DLSQKLESML TPPIARRVPF LKNKGSRNIG FSHLQQRSAQ EIVHCVFQLL TPMCNHLENI HNYFQCLAAE NHGVVDGPGV KVQEYHIMSS CYQRLLQIFH GLFAWSGFSQ PENQNLLYSA LHVLSSRLKQ GEHSQPLEEL LSQSVHYLQN FHQSIPSFQC ALYLIRLLMV ILEKSTASAQ NKEKIASLAR QFLCRVWPSG DKEKSNISND QLHALLCIYL EHTESILKAI EEIAGVGVPE LINSPKDASS STFPTLTRHT FVVFFRVMMA ELEKTVKKIE PGTAADSQQI HEEKLLYWNM AVRDFSILIN LIKVFDSHPV LHVCLKYGRL FVEAFLKQCM PLLDFSFRKH REDVLSLLET FQLDTRLLHH LCGHSKIHQD TRLTQHVPLL KKTLELLVCR VKAMLTLNNC REAFWLGNLK NRDLQGEEIK SQNSQESTAD ESEDDMSSQA SKSKATEDGE EDEVSAGEKE QDSDESYDDS D // ID SEM1_HUMAN Reviewed; 70 AA. AC P60896; Q13437; Q61067; DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot. DT 13-APR-2004, sequence version 1. DT 25-MAY-2022, entry version 157. DE RecName: Full=26S proteasome complex subunit SEM1; DE AltName: Full=26S proteasome complex subunit DSS1; DE AltName: Full=Deleted in split hand/split foot protein 1; DE AltName: Full=Split hand/foot deleted protein 1; DE AltName: Full=Split hand/foot malformation type 1 protein; GN Name=SEM1 {ECO:0000312|HGNC:HGNC:10845}; GN Synonyms=C7orf76, DSS1, SHFDG1, SHFM1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8733122; DOI=10.1093/hmg/5.5.571; RA Crackower M.A., Scherer S.W., Rommens J.M., Hui C.-C., Poorkaj P., RA Soder S., Cobben J.M., Hudgins L., Evans J.P., Tsui L.-C.; RT "Characterization of the split hand/split foot malformation locus SHFM1 at RT 7q21.3-q22.1 and analysis of a candidate gene for its expression during RT limb development."; RL Hum. Mol. Genet. 5:571-579(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP FUNCTION. RX PubMed=1317798; DOI=10.1111/j.1432-1033.1992.tb16961.x; RA Kanayama H.O., Tamura T., Ugai S., Kagawa S., Tanahashi N., Yoshimura T., RA Tanaka K., Ichihara A.; RT "Demonstration that a human 26S proteolytic complex consists of a RT proteasome and multiple associated protein components and hydrolyzes ATP RT and ubiquitin-ligated proteins by closely linked mechanisms."; RL Eur. J. Biochem. 206:567-578(1992). RN [5] RP INTERACTION WITH BRCA2. RX PubMed=10373512; DOI=10.1128/mcb.19.7.4633; RA Marston N.J., Richards W.J., Hughes D., Bertwistle D., Marshall C.J., RA Ashworth A.; RT "Interaction between the product of the breast cancer susceptibility gene RT BRCA2 and DSS1, a protein functionally conserved from yeast to mammals."; RL Mol. Cell. Biol. 19:4633-4642(1999). RN [6] RP FUNCTION. RX PubMed=15117943; DOI=10.1074/jbc.m403165200; RA Sone T., Saeki Y., Toh-e A., Yokosawa H.; RT "Sem1p is a novel subunit of the 26S proteasome from Saccharomyces RT cerevisiae."; RL J. Biol. Chem. 279:28807-28816(2004). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17323924; DOI=10.1021/bi061994u; RA Wang X., Chen C.-F., Baker P.R., Chen P.-L., Kaiser P., Huang L.; RT "Mass spectrometric characterization of the affinity-purified human 26S RT proteasome complex."; RL Biochemistry 46:3553-3565(2007). RN [8] RP INTERACTION WITH BRCA2. RX PubMed=21719596; DOI=10.1182/blood-2010-12-324541; RA Biswas K., Das R., Alter B.P., Kuznetsov S.G., Stauffer S., North S.L., RA Burkett S., Brody L.C., Meyer S., Byrd R.A., Sharan S.K.; RT "A comprehensive functional characterization of BRCA2 variants associated RT with Fanconi anemia using mouse ES cell-based assay."; RL Blood 118:2430-2442(2011). RN [9] RP INTERACTION WITH TREX-2 COMPLEX. RX PubMed=22307388; DOI=10.1093/nar/gks059; RA Jani D., Lutz S., Hurt E., Laskey R.A., Stewart M., Wickramasinghe V.O.; RT "Functional and structural characterization of the mammalian TREX-2 complex RT that links transcription with nuclear messenger RNA export."; RL Nucleic Acids Res. 40:4562-4573(2012). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [11] RP FUNCTION. RX PubMed=24896180; DOI=10.1038/nature13374; RA Bhatia V., Barroso S.I., Garcia-Rubio M.L., Tumini E., Herrera-Moyano E., RA Aguilera A.; RT "BRCA2 prevents R-loop accumulation and associates with TREX-2 mRNA export RT factor PCID2."; RL Nature 511:362-365(2014). RN [12] RP IDENTIFICATION IN THE HR COMPLEX, AND SUBCELLULAR LOCATION. RX PubMed=26833090; DOI=10.1016/j.molcel.2015.12.026; RA Trego K.S., Groesser T., Davalos A.R., Parplys A.C., Zhao W., Nelson M.R., RA Hlaing A., Shih B., Rydberg B., Pluth J.M., Tsai M.S., Hoeijmakers J.H.J., RA Sung P., Wiese C., Campisi J., Cooper P.K.; RT "Non-catalytic Roles for XPG with BRCA1 and BRCA2 in Homologous RT Recombination and Genome Stability."; RL Mol. Cell 61:535-546(2016). RN [13] RP X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) IN COMPLEX WITH BRCA2. RX PubMed=12228710; DOI=10.1126/science.297.5588.1837; RA Yang H., Jeffrey P.D., Miller J., Kinnucan E., Sun Y., Thoma N.H., RA Zheng N., Chen P.L., Lee W.H., Pavletich N.P.; RT "BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA RT structure."; RL Science 297:1837-1848(2002). RN [14] RP STRUCTURE BY ELECTRON MICROSCOPY (3.50 ANGSTROMS) OF 1-389, AND SUBUNIT. RX PubMed=27428775; DOI=10.1038/nsmb.3273; RA Huang X., Luan B., Wu J., Shi Y.; RT "An atomic structure of the human 26S proteasome."; RL Nat. Struct. Mol. Biol. 23:778-785(2016). RN [15] RP STRUCTURE BY ELECTRON MICROSCOPY (4.50 ANGSTROMS) OF 1-389, AND SUBUNIT. RX PubMed=27342858; DOI=10.1073/pnas.1608050113; RA Schweitzer A., Aufderheide A., Rudack T., Beck F., Pfeifer G., RA Plitzko J.M., Sakata E., Schulten K., Foerster F., Baumeister W.; RT "Structure of the human 26S proteasome at a resolution of 3.9 Aa."; RL Proc. Natl. Acad. Sci. U.S.A. 113:7816-7821(2016). CC -!- FUNCTION: Component of the 26S proteasome, a multiprotein complex CC involved in the ATP-dependent degradation of ubiquitinated proteins. CC This complex plays a key role in the maintenance of protein homeostasis CC by removing misfolded or damaged proteins, which could impair cellular CC functions, and by removing proteins whose functions are no longer CC required. Therefore, the proteasome participates in numerous cellular CC processes, including cell cycle progression, apoptosis, or DNA damage CC repair (PubMed:15117943). Component of the TREX-2 complex CC (transcription and export complex 2), composed of at least ENY2, GANP, CC PCID2, SEM1, and either centrin CETN2 or CETN3 (PubMed:22307388). The CC TREX-2 complex functions in docking export-competent ribonucleoprotein CC particles (mRNPs) to the nuclear entrance of the nuclear pore complex CC (nuclear basket). TREX-2 participates in mRNA export and accurate CC chromatin positioning in the nucleus by tethering genes to the nuclear CC periphery. Binds and stabilizes BRCA2 and is thus involved in the CC control of R-loop-associated DNA damage and thus transcription- CC associated genomic instability. R-loop accumulation increases in SEM1- CC depleted cells. {ECO:0000269|PubMed:1317798, CC ECO:0000269|PubMed:15117943, ECO:0000269|PubMed:22307388, CC ECO:0000269|PubMed:24896180}. CC -!- SUBUNIT: Component of the 19S proteasome regulatory particle complex. CC The 26S proteasome consists of a 20S core particle (CP) and two 19S CC regulatory subunits (RP). The regulatory particle is made of a lid CC composed of 9 subunits including SEM1, a base containing 6 ATPases and CC few additional components (PubMed:27428775, PubMed:27342858). Belongs CC to the TREX-2 complex (transcription and export complex 2), composed of CC at least ENY2, GANP, PCID2, SEM1, and either centrin CETN2 or CETN3 CC (PubMed:22307388). Component of the homologous recombination repair CC (HR) complex composed of ERCC5/XPG, BRCA2, PALB2, DSS1 and RAD51 CC (PubMed:26833090). Interacts with the C-terminal of BRCA2 CC (PubMed:10373512, PubMed:21719596). {ECO:0000269|PubMed:10373512, CC ECO:0000269|PubMed:12228710, ECO:0000269|PubMed:21719596, CC ECO:0000269|PubMed:22307388, ECO:0000269|PubMed:26833090, CC ECO:0000269|PubMed:27342858, ECO:0000269|PubMed:27428775}. CC -!- INTERACTION: CC P60896; P51587: BRCA2; NbExp=10; IntAct=EBI-79819, EBI-79792; CC P60896; Q01658: DR1; NbExp=3; IntAct=EBI-79819, EBI-750300; CC P60896; P35637: FUS; NbExp=3; IntAct=EBI-79819, EBI-400434; CC P60896; P28799: GRN; NbExp=3; IntAct=EBI-79819, EBI-747754; CC P60896; Q00403: GTF2B; NbExp=3; IntAct=EBI-79819, EBI-389564; CC P60896; Q9Y5Q9: GTF3C3; NbExp=3; IntAct=EBI-79819, EBI-1054873; CC P60896; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-79819, EBI-1055254; CC P60896; Q5S007: LRRK2; NbExp=3; IntAct=EBI-79819, EBI-5323863; CC P60896; P35240-4: NF2; NbExp=3; IntAct=EBI-79819, EBI-1014514; CC P60896; Q5JVF3: PCID2; NbExp=3; IntAct=EBI-79819, EBI-1051701; CC P60896; Q5JVF3-1: PCID2; NbExp=3; IntAct=EBI-79819, EBI-15970419; CC P60896; O43242: PSMD3; NbExp=3; IntAct=EBI-79819, EBI-357622; CC P60896; P00441: SOD1; NbExp=3; IntAct=EBI-79819, EBI-990792; CC P60896; Q6NUL7: SPTLC1; NbExp=3; IntAct=EBI-79819, EBI-25912847; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26833090}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage; Named isoforms=2; CC Name=1; CC IsoId=P60896-1; Sequence=Displayed; CC Name=2; CC IsoId=Q6ZVN7-1; Sequence=External; CC -!- TISSUE SPECIFICITY: Expressed in limb bud, craniofacial primordia and CC skin. CC -!- SIMILARITY: Belongs to the DSS1/SEM1 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U41515; AAA91179.1; -; mRNA. DR EMBL; AC073230; AAQ93368.1; -; Genomic_DNA. DR EMBL; BC032782; AAH32782.1; -; mRNA. DR CCDS; CCDS5646.1; -. [P60896-1] DR PIR; G02284; G02284. DR RefSeq; NP_006295.1; NM_006304.1. [P60896-1] DR PDB; 1IYJ; X-ray; 3.40 A; A/C=1-70. DR PDB; 1MIU; X-ray; 3.10 A; B=1-70. DR PDB; 1MJE; X-ray; 3.50 A; B=1-70. DR PDB; 3T5X; X-ray; 2.12 A; B=1-70. DR PDB; 5GJQ; EM; 4.50 A; Y=1-70. DR PDB; 5GJR; EM; 3.50 A; AB/Y=1-70. DR PDB; 5L4K; EM; 4.50 A; Y=1-70. DR PDB; 5LN3; EM; 6.80 A; Y=1-70. DR PDB; 5M32; EM; 3.80 A; s=1-70. DR PDB; 5T0C; EM; 3.80 A; Ae/Be=1-70. DR PDB; 5T0G; EM; 4.40 A; e=1-70. DR PDB; 5T0H; EM; 6.80 A; e=1-70. DR PDB; 5T0I; EM; 8.00 A; e=1-70. DR PDB; 5T0J; EM; 8.00 A; e=1-70. DR PDB; 5VFR; EM; 4.90 A; e=1-70. DR PDB; 5VFT; EM; 7.00 A; e=1-70. DR PDB; 5VGZ; EM; 3.70 A; e=1-70. DR PDB; 5VHF; EM; 5.70 A; e=1-70. DR PDB; 5VHH; EM; 6.10 A; e=1-70. DR PDB; 5VHI; EM; 6.80 A; e=1-70. DR PDB; 5VHS; EM; 8.80 A; e=38-70. DR PDB; 6MSB; EM; 3.00 A; e=1-70. DR PDB; 6MSD; EM; 3.20 A; e=1-70. DR PDB; 6MSG; EM; 3.50 A; e=1-70. DR PDB; 6MSH; EM; 3.60 A; e=1-70. DR PDB; 6MSJ; EM; 3.30 A; e=1-70. DR PDB; 6MSK; EM; 3.20 A; e=1-70. DR PDB; 6WJD; EM; 4.80 A; e=1-70. DR PDB; 6WJN; EM; 5.70 A; e=1-70. DR PDBsum; 1IYJ; -. DR PDBsum; 1MIU; -. DR PDBsum; 1MJE; -. DR PDBsum; 3T5X; -. DR PDBsum; 5GJQ; -. DR PDBsum; 5GJR; -. DR PDBsum; 5L4K; -. DR PDBsum; 5LN3; -. DR PDBsum; 5M32; -. DR PDBsum; 5T0C; -. DR PDBsum; 5T0G; -. DR PDBsum; 5T0H; -. DR PDBsum; 5T0I; -. DR PDBsum; 5T0J; -. DR PDBsum; 5VFR; -. DR PDBsum; 5VFT; -. DR PDBsum; 5VGZ; -. DR PDBsum; 5VHF; -. DR PDBsum; 5VHH; -. DR PDBsum; 5VHI; -. DR PDBsum; 5VHS; -. DR PDBsum; 6MSB; -. DR PDBsum; 6MSD; -. DR PDBsum; 6MSG; -. DR PDBsum; 6MSH; -. DR PDBsum; 6MSJ; -. DR PDBsum; 6MSK; -. DR PDBsum; 6WJD; -. DR PDBsum; 6WJN; -. DR AlphaFoldDB; P60896; -. DR SMR; P60896; -. DR BioGRID; 113692; 139. DR ComplexPortal; CPX-5993; 26S Proteasome complex. DR CORUM; P60896; -. DR DIP; DIP-31023N; -. DR IntAct; P60896; 85. DR MINT; P60896; -. DR ChEMBL; CHEMBL2364701; -. DR iPTMnet; P60896; -. DR PhosphoSitePlus; P60896; -. DR BioMuta; SEM1; -. DR jPOST; P60896; -. DR MassIVE; P60896; -. DR PaxDb; P60896; -. DR PeptideAtlas; P60896; -. DR PRIDE; P60896; -. DR ProteomicsDB; 57235; -. DR Antibodypedia; 30181; 150 antibodies from 27 providers. DR DNASU; 7979; -. DR Ensembl; ENST00000248566.4; ENSP00000248566.2; ENSG00000127922.10. DR GeneID; 7979; -. DR KEGG; hsa:7979; -. DR MANE-Select; ENST00000248566.4; ENSP00000248566.2; NM_006304.2; NP_006295.1. DR CTD; 7979; -. DR DisGeNET; 7979; -. DR GeneCards; SEM1; -. DR HGNC; HGNC:10845; SEM1. DR HPA; ENSG00000127922; Low tissue specificity. DR MalaCards; SEM1; -. DR MIM; 601285; gene. DR neXtProt; NX_P60896; -. DR OpenTargets; ENSG00000127922; -. DR Orphanet; 2440; Isolated split hand-split foot malformation. DR PharmGKB; PA35749; -. DR VEuPathDB; HostDB:ENSG00000127922; -. DR GeneTree; ENSGT00940000163409; -. DR InParanoid; P60896; -. DR OMA; TLWENNW; -. DR PhylomeDB; P60896; -. DR TreeFam; TF314699; -. DR PathwayCommons; P60896; -. DR Reactome; R-HSA-1169091; Activation of NF-kappaB in B cells. DR Reactome; R-HSA-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha. DR Reactome; R-HSA-1236974; ER-Phagosome pathway. DR Reactome; R-HSA-1236978; Cross-presentation of soluble exogenous antigens (endosomes). DR Reactome; R-HSA-174084; Autodegradation of Cdh1 by Cdh1:APC/C. DR Reactome; R-HSA-174113; SCF-beta-TrCP mediated degradation of Emi1. DR Reactome; R-HSA-174154; APC/C:Cdc20 mediated degradation of Securin. DR Reactome; R-HSA-174178; APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1. DR Reactome; R-HSA-174184; Cdc20:Phospho-APC/C mediated degradation of Cyclin A. DR Reactome; R-HSA-180534; Vpu mediated degradation of CD4. DR Reactome; R-HSA-180585; Vif-mediated degradation of APOBEC3G. DR Reactome; R-HSA-187577; SCF(Skp2)-mediated degradation of p27/p21. DR Reactome; R-HSA-195253; Degradation of beta-catenin by the destruction complex. DR Reactome; R-HSA-202424; Downstream TCR signaling. DR Reactome; R-HSA-211733; Regulation of activated PAK-2p34 by proteasome mediated degradation. DR Reactome; R-HSA-2467813; Separation of Sister Chromatids. DR Reactome; R-HSA-2871837; FCERI mediated NF-kB activation. DR Reactome; R-HSA-349425; Autodegradation of the E3 ubiquitin ligase COP1. DR Reactome; R-HSA-350562; Regulation of ornithine decarboxylase (ODC). DR Reactome; R-HSA-382556; ABC-family proteins mediated transport. DR Reactome; R-HSA-450408; AUF1 (hnRNP D0) binds and destabilizes mRNA. DR Reactome; R-HSA-4608870; Asymmetric localization of PCP proteins. DR Reactome; R-HSA-4641257; Degradation of AXIN. DR Reactome; R-HSA-4641258; Degradation of DVL. DR Reactome; R-HSA-5358346; Hedgehog ligand biogenesis. DR Reactome; R-HSA-5362768; Hh mutants are degraded by ERAD. DR Reactome; R-HSA-5607761; Dectin-1 mediated noncanonical NF-kB signaling. DR Reactome; R-HSA-5607764; CLEC7A (Dectin-1) signaling. DR Reactome; R-HSA-5610780; Degradation of GLI1 by the proteasome. DR Reactome; R-HSA-5610783; Degradation of GLI2 by the proteasome. DR Reactome; R-HSA-5610785; GLI3 is processed to GLI3R by the proteasome. DR Reactome; R-HSA-5632684; Hedgehog 'on' state. DR Reactome; R-HSA-5658442; Regulation of RAS by GAPs. DR Reactome; R-HSA-5668541; TNFR2 non-canonical NF-kB pathway. DR Reactome; R-HSA-5676590; NIK-->noncanonical NF-kB signaling. DR Reactome; R-HSA-5678895; Defective CFTR causes cystic fibrosis. DR Reactome; R-HSA-5687128; MAPK6/MAPK4 signaling. DR Reactome; R-HSA-5689603; UCH proteinases. DR Reactome; R-HSA-5689880; Ub-specific processing proteases. DR Reactome; R-HSA-68827; CDT1 association with the CDC6:ORC:origin complex. DR Reactome; R-HSA-68949; Orc1 removal from chromatin. DR Reactome; R-HSA-69017; CDK-mediated phosphorylation and removal of Cdc6. DR Reactome; R-HSA-69481; G2/M Checkpoints. DR Reactome; R-HSA-69601; Ubiquitin Mediated Degradation of Phosphorylated Cdc25A. DR Reactome; R-HSA-75815; Ubiquitin-dependent degradation of Cyclin D. DR Reactome; R-HSA-8852276; The role of GTSE1 in G2/M progression after G2 checkpoint. DR Reactome; R-HSA-8854050; FBXL7 down-regulates AURKA during mitotic entry and in early mitosis. DR Reactome; R-HSA-8932339; ROS sensing by NFE2L2. DR Reactome; R-HSA-8939236; RUNX1 regulates transcription of genes involved in differentiation of HSCs. DR Reactome; R-HSA-8939902; Regulation of RUNX2 expression and activity. DR Reactome; R-HSA-8941858; Regulation of RUNX3 expression and activity. DR Reactome; R-HSA-8948751; Regulation of PTEN stability and activity. DR Reactome; R-HSA-8951664; Neddylation. DR Reactome; R-HSA-9010553; Regulation of expression of SLITs and ROBOs. DR Reactome; R-HSA-9020702; Interleukin-1 signaling. DR Reactome; R-HSA-9604323; Negative regulation of NOTCH4 signaling. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; P60896; -. DR SIGNOR; P60896; -. DR BioGRID-ORCS; 7979; 665 hits in 1077 CRISPR screens. DR ChiTaRS; SHFM1; human. DR EvolutionaryTrace; P60896; -. DR GeneWiki; SHFM1; -. DR GenomeRNAi; 7979; -. DR Pharos; P60896; Tbio. DR PRO; PR:P60896; -. DR Proteomes; UP000005640; Chromosome 7. DR Bgee; ENSG00000127922; Expressed in testis and 239 other tissues. DR ExpressionAtlas; P60896; baseline and differential. DR Genevisible; P60896; HS. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0000502; C:proteasome complex; IDA:UniProtKB. DR GO; GO:0008541; C:proteasome regulatory particle, lid subcomplex; IEA:InterPro. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IEA:Ensembl. DR GO; GO:0006406; P:mRNA export from nucleus; IEA:InterPro. DR GO; GO:0043248; P:proteasome assembly; IEA:InterPro. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IC:ComplexPortal. DR DisProt; DP00617; -. DR InterPro; IPR007834; DSS1_SEM1. DR PANTHER; PTHR16771; PTHR16771; 1. DR Pfam; PF05160; DSS1_SEM1; 1. DR SMART; SM01385; DSS1_SEM1; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative promoter usage; Nucleus; Proteasome; KW Reference proteome. FT CHAIN 1..70 FT /note="26S proteasome complex subunit SEM1" FT /id="PRO_0000122961" FT VARIANT 17 FT /note="D -> G (in dbSNP:rs1802882)" FT /id="VAR_012003" FT HELIX 10..12 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 21..23 FT /evidence="ECO:0007829|PDB:1MJE" FT HELIX 42..44 FT /evidence="ECO:0007829|PDB:3T5X" FT HELIX 51..62 FT /evidence="ECO:0007829|PDB:3T5X" SQ SEQUENCE 70 AA; 8278 MW; 0E0F58D2F3D9F723 CRC64; MSEKKQPVDL GLLEEDDEFE EFPAEDWAGL DEDEDAHVWE DNWDDDNVED DFSNQLRAEL EKHGYKMETS // ID DMC1_HUMAN Reviewed; 340 AA. AC Q14565; A8K9A2; B4DMW6; Q08AI1; Q99498; Q9UH11; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 27-APR-2001, sequence version 2. DT 25-MAY-2022, entry version 191. DE RecName: Full=Meiotic recombination protein DMC1/LIM15 homolog; GN Name=DMC1; Synonyms=DMC1H, LIM15; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Testis; RX PubMed=8590282; DOI=10.1093/dnares/2.4.183; RA Sato S., Seki N., Hotta Y., Tabata S.; RT "Expression profiles of a human gene identified as a structural homologue RT of meiosis-specific recA-like genes."; RL DNA Res. 2:183-185(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Testis; RX PubMed=8602360; DOI=10.1093/nar/24.3.470; RA Habu T., Taki T., West A., Nishimune Y., Morita T.; RT "The mouse and human homologs of DMC1, the yeast meiosis-specific RT homologous recombination gene, have a common unique form of exon-skipped RT transcript in meiosis."; RL Nucleic Acids Res. 24:470-477(1996). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84; RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., RA Beare D.M., Dunham I.; RT "A genome annotation-driven approach to cloning the human ORFeome."; RL Genome Biol. 5:R84.1-R84.11(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Heart, and Thymus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-200. RG NIEHS SNPs program; RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP INTERACTION WITH BRCA2. RX PubMed=20729832; DOI=10.1038/nature09399; RA Jensen R.B., Carreira A., Kowalczykowski S.C.; RT "Purified human BRCA2 stimulates RAD51-mediated recombination."; RL Nature 467:678-683(2010). RN [9] RP INTERACTION WITH RAD51AP1. RX PubMed=21903585; DOI=10.1074/jbc.m111.290015; RA Dunlop M.H., Dray E., Zhao W., Tsai M.S., Wiese C., Schild D., Sung P.; RT "RAD51-associated protein 1 (RAD51AP1) interacts with the meiotic RT recombinase DMC1 through a conserved motif."; RL J. Biol. Chem. 286:37328-37334(2011). RN [10] RP FUNCTION, AND INTERACTION WITH RAD51AP1. RX PubMed=21307306; DOI=10.1073/pnas.1016454108; RA Dray E., Dunlop M.H., Kauppi L., San Filippo J., Wiese C., Tsai M.S., RA Begovic S., Schild D., Jasin M., Keeney S., Sung P.; RT "Molecular basis for enhancement of the meiotic DMC1 recombinase by RAD51 RT associated protein 1 (RAD51AP1)."; RL Proc. Natl. Acad. Sci. U.S.A. 108:3560-3565(2011). RN [11] RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS), SUBUNIT, DNA-BINDING SITES, AND RP MUTAGENESIS OF ARG-230; PHE-233; ARG-236; ARG-242; GLU-258 AND ARG-311. RX PubMed=15125839; DOI=10.1016/s1097-2765(04)00218-7; RA Kinebuchi T., Kagawa W., Enomoto R., Tanaka K., Miyagawa K., Shibata T., RA Kurumizaka H., Yokoyama S.; RT "Structural basis for octameric ring formation and DNA interaction of the RT human homologous-pairing protein Dmc1."; RL Mol. Cell 14:363-374(2004). CC -!- FUNCTION: Participates in meiotic recombination, specifically in CC homologous strand assimilation, which is required for the resolution of CC meiotic double-strand breaks. {ECO:0000269|PubMed:21307306}. CC -!- SUBUNIT: Double stacked ring-shaped homooctamer (PubMed:15125839). CC Interacts with BRCA2 (PubMed:20729832). Interacts with the MND1-PSMC3IP CC heterodimer (By similarity). Interacts with RAD51AP1; the interaction CC is direct and stimulates DMC1-mediated homologous recombination CC (PubMed:21307306, PubMed:21903585). {ECO:0000250|UniProtKB:Q61880, CC ECO:0000269|PubMed:15125839, ECO:0000269|PubMed:20729832, CC ECO:0000269|PubMed:21307306, ECO:0000269|PubMed:21903585}. CC -!- INTERACTION: CC Q14565; P51587: BRCA2; NbExp=12; IntAct=EBI-930865, EBI-79792; CC Q14565; Q14565: DMC1; NbExp=3; IntAct=EBI-930865, EBI-930865; CC Q14565; Q9H8Y8: GORASP2; NbExp=8; IntAct=EBI-930865, EBI-739467; CC Q14565; Q8N5Z5: KCTD17; NbExp=4; IntAct=EBI-930865, EBI-743960; CC Q14565; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-930865, EBI-739832; CC Q14565; Q9GZT8: NIF3L1; NbExp=9; IntAct=EBI-930865, EBI-740897; CC Q14565; O75928-2: PIAS2; NbExp=3; IntAct=EBI-930865, EBI-348567; CC Q14565; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-930865, EBI-79165; CC Q14565; P25788: PSMA3; NbExp=7; IntAct=EBI-930865, EBI-348380; CC Q14565; Q96B01-2: RAD51AP1; NbExp=3; IntAct=EBI-930865, EBI-1178743; CC Q14565; O00560: SDCBP; NbExp=7; IntAct=EBI-930865, EBI-727004; CC Q14565; Q9H190: SDCBP2; NbExp=3; IntAct=EBI-930865, EBI-742426; CC Q14565; P36406: TRIM23; NbExp=3; IntAct=EBI-930865, EBI-740098; CC Q14565; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-930865, EBI-10180829; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q61880}. CC Chromosome {ECO:0000250|UniProtKB:Q61880}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q14565-1; Sequence=Displayed; CC Name=2; CC IsoId=Q14565-2; Sequence=VSP_055357; CC -!- SIMILARITY: Belongs to the RecA family. DMC1 subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/dmc1/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D63882; BAA09932.1; -; mRNA. DR EMBL; D64108; BAA10970.1; -; mRNA. DR EMBL; CR456486; CAG30372.1; -; mRNA. DR EMBL; AK292617; BAF85306.1; -; mRNA. DR EMBL; AK297664; BAG60028.1; -; mRNA. DR EMBL; AY520538; AAR89915.1; -; Genomic_DNA. DR EMBL; AL022320; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC125163; AAI25164.1; -; mRNA. DR EMBL; BC125164; AAI25165.1; -; mRNA. DR CCDS; CCDS13973.1; -. [Q14565-1] DR CCDS; CCDS63477.1; -. [Q14565-2] DR PIR; S62354; S62354. DR RefSeq; NP_001265137.1; NM_001278208.1. [Q14565-2] DR RefSeq; NP_008999.2; NM_007068.3. [Q14565-1] DR RefSeq; XP_006724175.1; XM_006724112.2. DR PDB; 1V5W; X-ray; 3.20 A; A/B=1-340. DR PDB; 2ZJB; X-ray; 3.50 A; A/B=1-340. DR PDB; 4HYY; X-ray; 2.60 A; A/B/C/D=84-340. DR PDB; 6R3P; X-ray; 2.05 A; A/B/C/D=83-340. DR PDB; 7C98; EM; 3.47 A; A/B/C=1-340. DR PDB; 7C99; EM; 3.36 A; A/B/C=1-340. DR PDB; 7C9C; EM; 3.33 A; A/B/C=1-340. DR PDB; 7CGY; EM; 3.20 A; A/B/C=1-340. DR PDBsum; 1V5W; -. DR PDBsum; 2ZJB; -. DR PDBsum; 4HYY; -. DR PDBsum; 6R3P; -. DR PDBsum; 7C98; -. DR PDBsum; 7C99; -. DR PDBsum; 7C9C; -. DR PDBsum; 7CGY; -. DR AlphaFoldDB; Q14565; -. DR SMR; Q14565; -. DR BioGRID; 116316; 29. DR DIP; DIP-24192N; -. DR IntAct; Q14565; 22. DR MINT; Q14565; -. DR STRING; 9606.ENSP00000216024; -. DR DrugBank; DB03366; Imidazole. DR PhosphoSitePlus; Q14565; -. DR BioMuta; DMC1; -. DR DMDM; 13878923; -. DR MassIVE; Q14565; -. DR PaxDb; Q14565; -. DR PeptideAtlas; Q14565; -. DR PRIDE; Q14565; -. DR ProteomicsDB; 60046; -. [Q14565-1] DR Antibodypedia; 246; 415 antibodies from 34 providers. DR DNASU; 11144; -. DR Ensembl; ENST00000216024.7; ENSP00000216024.2; ENSG00000100206.11. DR Ensembl; ENST00000428462.6; ENSP00000412703.2; ENSG00000100206.11. [Q14565-2] DR GeneID; 11144; -. DR KEGG; hsa:11144; -. DR MANE-Select; ENST00000216024.7; ENSP00000216024.2; NM_007068.4; NP_008999.2. DR UCSC; uc003avz.3; human. [Q14565-1] DR CTD; 11144; -. DR DisGeNET; 11144; -. DR GeneCards; DMC1; -. DR HGNC; HGNC:2927; DMC1. DR HPA; ENSG00000100206; Tissue enhanced (testis). DR MIM; 602721; gene. DR neXtProt; NX_Q14565; -. DR OpenTargets; ENSG00000100206; -. DR Orphanet; 619; NON RARE IN EUROPE: Primary ovarian failure. DR PharmGKB; PA27377; -. DR VEuPathDB; HostDB:ENSG00000100206; -. DR eggNOG; KOG1434; Eukaryota. DR GeneTree; ENSGT00760000119398; -. DR HOGENOM; CLU_041732_0_0_1; -. DR InParanoid; Q14565; -. DR OMA; GGINDPD; -. DR OrthoDB; 877394at2759; -. DR PhylomeDB; Q14565; -. DR TreeFam; TF300698; -. DR PathwayCommons; Q14565; -. DR Reactome; R-HSA-912446; Meiotic recombination. DR SignaLink; Q14565; -. DR SIGNOR; Q14565; -. DR BioGRID-ORCS; 11144; 5 hits in 1081 CRISPR screens. DR ChiTaRS; DMC1; human. DR EvolutionaryTrace; Q14565; -. DR GeneWiki; DMC1_(gene); -. DR GenomeRNAi; 11144; -. DR Pharos; Q14565; Tbio. DR PRO; PR:Q14565; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; Q14565; protein. DR Bgee; ENSG00000100206; Expressed in buccal mucosa cell and 158 other tissues. DR ExpressionAtlas; Q14565; baseline and differential. DR Genevisible; Q14565; HS. DR GO; GO:0005694; C:chromosome; ISS:UniProtKB. DR GO; GO:0000781; C:chromosome, telomeric region; IEA:Ensembl. DR GO; GO:0000794; C:condensed nuclear chromosome; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; TAS:ProtInc. DR GO; GO:0008094; F:ATP-dependent activity, acting on DNA; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; TAS:ProtInc. DR GO; GO:0000150; F:DNA strand exchange activity; IBA:GO_Central. DR GO; GO:0003690; F:double-stranded DNA binding; IBA:GO_Central. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0003697; F:single-stranded DNA binding; IBA:GO_Central. DR GO; GO:0070192; P:chromosome organization involved in meiotic cell cycle; IBA:GO_Central. DR GO; GO:0000730; P:DNA recombinase assembly; IBA:GO_Central. DR GO; GO:0007292; P:female gamete generation; TAS:ProtInc. DR GO; GO:0007129; P:homologous chromosome pairing at meiosis; IEA:Ensembl. DR GO; GO:0007141; P:male meiosis I; IEA:Ensembl. DR GO; GO:0051321; P:meiotic cell cycle; TAS:ProtInc. DR GO; GO:0006312; P:mitotic recombination; IBA:GO_Central. DR GO; GO:0001556; P:oocyte maturation; IEA:Ensembl. DR GO; GO:0001541; P:ovarian follicle development; IEA:Ensembl. DR GO; GO:0007131; P:reciprocal meiotic recombination; IDA:UniProtKB. DR GO; GO:0007286; P:spermatid development; IEA:Ensembl. DR GO; GO:0007283; P:spermatogenesis; TAS:ProtInc. DR GO; GO:0042148; P:strand invasion; IBA:GO_Central. DR CDD; cd01123; Rad51_DMC1_radA; 1. DR DisProt; DP02746; -. DR Gene3D; 3.40.50.300; -; 1. DR IDEAL; IID00078; -. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR011940; Dmc1. DR InterPro; IPR013632; DNA_recomb/repair_Rad51_C. DR InterPro; IPR016467; DNA_recomb/repair_RecA-like. DR InterPro; IPR010995; DNA_repair_Rad51/TF_NusA_a-hlx. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR033925; Rad51_DMC1_RadA. DR InterPro; IPR020588; RecA_ATP-bd. DR InterPro; IPR020587; RecA_monomer-monomer_interface. DR Pfam; PF08423; Rad51; 1. DR PIRSF; PIRSF005856; Rad51; 1. DR SMART; SM00382; AAA; 1. DR SUPFAM; SSF47794; SSF47794; 1. DR SUPFAM; SSF52540; SSF52540; 1. DR TIGRFAMs; TIGR02238; recomb_DMC1; 1. DR PROSITE; PS50162; RECA_2; 1. DR PROSITE; PS50163; RECA_3; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cell cycle; Chromosome; KW DNA-binding; Meiosis; Nucleotide-binding; Nucleus; Reference proteome. FT CHAIN 1..340 FT /note="Meiotic recombination protein DMC1/LIM15 homolog" FT /id="PRO_0000122918" FT NP_BIND 126..133 FT /note="ATP" FT /evidence="ECO:0000305" FT BINDING 230 FT /note="dsDNA" FT /evidence="ECO:0000269|PubMed:15125839" FT BINDING 230 FT /note="ssDNA" FT /evidence="ECO:0000269|PubMed:15125839" FT BINDING 233 FT /note="ssDNA" FT /evidence="ECO:0000269|PubMed:15125839" FT BINDING 236 FT /note="dsDNA" FT /evidence="ECO:0000269|PubMed:15125839" FT BINDING 236 FT /note="ssDNA" FT /evidence="ECO:0000269|PubMed:15125839" FT BINDING 242 FT /note="dsDNA" FT /evidence="ECO:0000269|PubMed:15125839" FT BINDING 242 FT /note="ssDNA" FT /evidence="ECO:0000269|PubMed:15125839" FT BINDING 311 FT /note="ssDNA" FT /evidence="ECO:0000269|PubMed:15125839" FT VAR_SEQ 141..196 FT /note="VTAQLPGAGGYPGGKIIFIDTENTFRPDRLRDIADRFNVDHDAVLDNVLYAR FT AYTS -> G (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055357" FT VARIANT 150 FT /note="G -> D (in dbSNP:rs58396845)" FT /id="VAR_061757" FT VARIANT 200 FT /note="M -> V (in dbSNP:rs2227914)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_018960" FT MUTAGEN 230 FT /note="R->A: Abolishes binding to ssDNA or dsDNA." FT /evidence="ECO:0000269|PubMed:15125839" FT MUTAGEN 233 FT /note="F->A: Abolishes binding to ssDNA." FT /evidence="ECO:0000269|PubMed:15125839" FT MUTAGEN 236 FT /note="R->A: Abolishes binding to ssDNA or dsDNA." FT /evidence="ECO:0000269|PubMed:15125839" FT MUTAGEN 242 FT /note="R->A: Abolishes binding to ssDNA or dsDNA." FT /evidence="ECO:0000269|PubMed:15125839" FT MUTAGEN 258 FT /note="E->A,Q: Decreases octamer stability." FT /evidence="ECO:0000269|PubMed:15125839" FT MUTAGEN 311 FT /note="R->A: Abolishes binding to ssDNA." FT /evidence="ECO:0000269|PubMed:15125839" FT CONFLICT 37 FT /note="I -> N (in Ref. 2; BAA10970)" FT /evidence="ECO:0000305" FT CONFLICT 183 FT /note="A -> P (in Ref. 1; BAA09932)" FT /evidence="ECO:0000305" FT TURN 24..27 FT /evidence="ECO:0007829|PDB:7C99" FT TURN 28..31 FT /evidence="ECO:0007829|PDB:7CGY" FT HELIX 34..40 FT /evidence="ECO:0007829|PDB:7CGY" FT TURN 41..44 FT /evidence="ECO:0007829|PDB:7CGY" FT STRAND 47..54 FT /evidence="ECO:0007829|PDB:7CGY" FT HELIX 56..59 FT /evidence="ECO:0007829|PDB:7CGY" FT HELIX 67..70 FT /evidence="ECO:0007829|PDB:7CGY" FT HELIX 72..77 FT /evidence="ECO:0007829|PDB:7CGY" FT TURN 78..80 FT /evidence="ECO:0007829|PDB:7CGY" FT STRAND 85..87 FT /evidence="ECO:0007829|PDB:1V5W" FT HELIX 88..95 FT /evidence="ECO:0007829|PDB:6R3P" FT HELIX 106..112 FT /evidence="ECO:0007829|PDB:6R3P" FT STRAND 114..127 FT /evidence="ECO:0007829|PDB:6R3P" FT HELIX 132..142 FT /evidence="ECO:0007829|PDB:6R3P" FT HELIX 148..150 FT /evidence="ECO:0007829|PDB:6R3P" FT STRAND 155..163 FT /evidence="ECO:0007829|PDB:6R3P" FT HELIX 167..176 FT /evidence="ECO:0007829|PDB:6R3P" FT HELIX 181..186 FT /evidence="ECO:0007829|PDB:6R3P" FT STRAND 188..192 FT /evidence="ECO:0007829|PDB:6R3P" FT HELIX 196..212 FT /evidence="ECO:0007829|PDB:6R3P" FT STRAND 216..223 FT /evidence="ECO:0007829|PDB:6R3P" FT HELIX 227..232 FT /evidence="ECO:0007829|PDB:6R3P" FT HELIX 235..237 FT /evidence="ECO:0007829|PDB:1V5W" FT HELIX 239..259 FT /evidence="ECO:0007829|PDB:6R3P" FT STRAND 263..268 FT /evidence="ECO:0007829|PDB:6R3P" FT STRAND 270..272 FT /evidence="ECO:0007829|PDB:7C9C" FT STRAND 287..289 FT /evidence="ECO:0007829|PDB:4HYY" FT HELIX 290..296 FT /evidence="ECO:0007829|PDB:6R3P" FT STRAND 298..305 FT /evidence="ECO:0007829|PDB:6R3P" FT STRAND 310..315 FT /evidence="ECO:0007829|PDB:6R3P" FT STRAND 319..321 FT /evidence="ECO:0007829|PDB:7C99" FT HELIX 322..324 FT /evidence="ECO:0007829|PDB:6R3P" FT STRAND 325..331 FT /evidence="ECO:0007829|PDB:6R3P" FT STRAND 334..336 FT /evidence="ECO:0007829|PDB:6R3P" SQ SEQUENCE 340 AA; 37681 MW; 040A6E4CF1FEBFA2 CRC64; MKEDQVVAEE PGFQDEEESL FQDIDLLQKH GINVADIKKL KSVGICTIKG IQMTTRRALC NVKGLSEAKV DKIKEAANKL IEPGFLTAFE YSEKRKMVFH ITTGSQEFDK LLGGGIESMA ITEAFGEFRT GKTQLSHTLC VTAQLPGAGG YPGGKIIFID TENTFRPDRL RDIADRFNVD HDAVLDNVLY ARAYTSEHQM ELLDYVAAKF HEEAGIFKLL IIDSIMALFR VDFSGRGELA ERQQKLAQML SRLQKISEEY NVAVFVTNQM TADPGATMTF QADPKKPIGG HILAHASTTR ISLRKGRGEL RIAKIYDSPE MPENEATFAI TAGGIGDAKE // ID RA51B_HUMAN Reviewed; 384 AA. AC O15315; O60914; O75210; Q3Y4F8; Q6FHX8; Q86SY3; Q86SY4; Q86TR0; Q86U92; AC Q86U93; Q86U94; Q8N6H4; Q9UPL5; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 07-NOV-2003, sequence version 2. DT 25-MAY-2022, entry version 184. DE RecName: Full=DNA repair protein RAD51 homolog 2; DE Short=R51H2; DE AltName: Full=RAD51 homolog B; DE Short=Rad51B; DE AltName: Full=RAD51-like protein 1; GN Name=RAD51B; Synonyms=RAD51L1, REC2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=9207106; DOI=10.1073/pnas.94.14.7417; RA Rice M.C., Smith S.T., Bullrich F., Havre P., Kmiec E.B.; RT "Isolation of human and mouse genes based on homology to REC2, a RT recombinational repair gene from the fungus Ustilago maydis."; RL Proc. Natl. Acad. Sci. U.S.A. 94:7417-7422(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=9441753; DOI=10.1006/geno.1997.5062; RA Albala J.S., Thelen M.P., Prange C.K., Fan W., Christensen M., RA Thompson L.H., Lennon G.G.; RT "Identification of a novel human RAD51 homolog, RAD51B."; RL Genomics 46:476-479(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RX PubMed=9512535; DOI=10.1093/nar/26.7.1653; RA Cartwright R., Dunn A.M., Simpson P.J., Tambini C.E., Thacker J.; RT "Isolation of novel human and mouse genes of the recA/RAD51 recombination- RT repair gene family."; RL Nucleic Acids Res. 26:1653-1659(1998). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 4 AND 5). RC TISSUE=Neuroblastoma; RA Li W.B., Gruber C., Jessee J., Polayes D.; RT "Full-length cDNA libraries and normalization."; RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS MET-9; CYS-82; TRP-172; RP CYS-180; ARG-243 AND ALA-250. RG NIEHS SNPs program; RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12508121; DOI=10.1038/nature01348; RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., RA Waterston R., Hood L., Weissenbach J.; RT "The DNA sequence and analysis of human chromosome 14."; RL Nature 421:601-607(2003). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 253-310, AND CHROMOSOMAL TRANSLOCATION WITH RP HMGA2. RX PubMed=12649198; RA Quade B.J., Weremowicz S., Neskey D.M., Vanni R., Ladd C., Dal Cin P., RA Morton C.C.; RT "Fusion transcripts involving HMGA2 are not a common molecular mechanism in RT uterine leiomyomata with rearrangements in 12q15."; RL Cancer Res. 63:1351-1358(2003). RN [11] RP FUNCTION, AND IDENTIFICATION IN THE BCDX2 COMPLEX WITH RAD51C; RAD51D AND RP XRCC2. RX PubMed=11751635; DOI=10.1101/gad.947001; RA Masson J.Y., Tarsounas M.C., Stasiak A.Z., Stasiak A., Shah R., RA McIlwraith M.J., Benson F.E., West S.C.; RT "Identification and purification of two distinct complexes containing the RT five RAD51 paralogs."; RL Genes Dev. 15:3296-3307(2001). RN [12] RP FUNCTION, AND INTERACTION WITH RAD51C. RX PubMed=11751636; DOI=10.1101/gad.935501; RA Sigurdsson S., Van Komen S., Bussen W., Schild D., Albala J.S., Sung P.; RT "Mediator function of the human Rad51B-Rad51C complex in Rad51/RPA- RT catalyzed DNA strand exchange."; RL Genes Dev. 15:3308-3318(2001). RN [13] RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH RAD51C; RAD51D AND XRCC2. RX PubMed=11842113; DOI=10.1093/nar/30.4.1009; RA Liu N., Schild D., Thelen M.P., Thompson L.H.; RT "Involvement of Rad51C in two distinct protein complexes of Rad51 paralogs RT in human cells."; RL Nucleic Acids Res. 30:1009-1015(2002). RN [14] RP INTERACTION WITH RAD51C, AND SUBUNIT. RX PubMed=11744692; DOI=10.1074/jbc.m108306200; RA Miller K.A., Yoshikawa D.M., McConnell I.R., Clark R., Schild D., RA Albala J.S.; RT "RAD51C interacts with RAD51B and is central to a larger protein complex in RT vivo exclusive of RAD51."; RL J. Biol. Chem. 277:8406-8411(2002). RN [15] RP IDENTIFICATION IN A COMPLEX WITH RAD51C; RAD51D AND XRCC2. RX PubMed=11842112; DOI=10.1093/nar/30.4.1001; RA Wiese C., Collins D.W., Albala J.S., Thompson L.H., Kronenberg A., RA Schild D.; RT "Interactions involving the Rad51 paralogs Rad51C and XRCC3 in human RT cells."; RL Nucleic Acids Res. 30:1001-1008(2002). RN [16] RP INTERACTION WITH RAD51 AND RAD51C. RX PubMed=12427746; DOI=10.1074/jbc.m211038200; RA Lio Y.-C., Mazin A.V., Kowalczykowski S.C., Chen D.J.; RT "Complex formation by the human Rad51B and Rad51C DNA repair proteins and RT their activities in vitro."; RL J. Biol. Chem. 278:2469-2478(2003). RN [17] RP CHROMOSOMAL TRANSLOCATION WITH HMGA2. RX PubMed=9892177; RA Schoenmakers E.F.P.M., Huysmans C., Van de Ven W.J.M.; RT "Allelic knockout of novel splice variants of human recombination repair RT gene RAD51B in t(12;14) uterine leiomyomas."; RL Cancer Res. 59:19-23(1999). RN [18] RP CHROMOSOMAL TRANSLOCATION WITH HMGA1. RX PubMed=11978964; DOI=10.1159/000057011; RA Blank C., Schoenmakers E.F.P.M., Rogalla P., Huys E.H., van Rijk A.A., RA Drieschner N., Bullerdiek J.; RT "Intragenic breakpoint within RAD51L1 in a t(6;14)(p21.3;q24) of a RT pulmonary chondroid hamartoma."; RL Cytogenet. Cell Genet. 95:17-19(2001). RN [19] RP FUNCTION. RX PubMed=12441335; DOI=10.1074/jbc.m210899200; RA Yokoyama H., Kurumizaka H., Ikawa S., Yokoyama S., Shibata T.; RT "Holliday junction binding activity of the human Rad51B protein."; RL J. Biol. Chem. 278:2767-2772(2003). RN [20] RP INTERACTION WITH RAD51C. RX PubMed=14704354; DOI=10.1093/nar/gkg925; RA Miller K.A., Sawicka D., Barsky D., Albala J.S.; RT "Domain mapping of the Rad51 paralog protein complexes."; RL Nucleic Acids Res. 32:169-178(2004). RN [21] RP PHOSPHORYLATION BY BCR-ABL, AND MUTAGENESIS OF PRO-326. RX PubMed=19657362; DOI=10.1038/leu.2009.164; RA Slupianek A., Jozwiakowski S.K., Gurdek E., Skorski T.; RT "BCR/ABL kinase interacts with and phosphorylates the RAD51 paralog, RT RAD51B."; RL Leukemia 23:2308-2310(2009). RN [22] RP INTERACTION WITH SWSAP1. RX PubMed=21965664; DOI=10.1074/jbc.m111.271080; RA Liu T., Wan L., Wu Y., Chen J., Huang J.; RT "hSWS1.SWSAP1 is an evolutionarily conserved complex required for efficient RT homologous recombination repair."; RL J. Biol. Chem. 286:41758-41766(2011). RN [23] RP FUNCTION IN MITOTIC CELL PROGRESSION. RX PubMed=23108668; DOI=10.1242/jcs.114595; RA Rodrigue A., Coulombe Y., Jacquet K., Gagne J.P., Roques C., Gobeil S., RA Poirier G., Masson J.Y.; RT "The RAD51 paralogs ensure cellular protection against mitotic defects and RT aneuploidy."; RL J. Cell Sci. 126:348-359(2013). RN [24] RP FUNCTION OF THE BCDX2 COMPLEX. RX PubMed=23149936; DOI=10.1128/mcb.00465-12; RA Chun J., Buechelmaier E.S., Powell S.N.; RT "Rad51 paralog complexes BCDX2 and CX3 act at different stages in the RT BRCA1-BRCA2-dependent homologous recombination pathway."; RL Mol. Cell. Biol. 33:387-395(2013). RN [25] RP INTERACTION WITH HELQ. RX PubMed=24005041; DOI=10.1093/nar/gkt676; RA Luebben S.W., Kawabata T., Akre M.K., Lee W.L., Johnson C.S., RA O'Sullivan M.G., Shima N.; RT "Helq acts in parallel to Fancc to suppress replication-associated genome RT instability."; RL Nucleic Acids Res. 41:10283-10297(2013). RN [26] RP ELECTRON MICROSCOPY OF THE BCDX2 COMPLEX, AND DNA-BINDING OF THE BCDX2 RP COMPLEX. RX PubMed=20207730; DOI=10.1074/jbc.m109.074286; RA Compton S.A., Ozgur S., Griffith J.D.; RT "Ring-shaped Rad51 paralog protein complexes bind Holliday junctions and RT replication forks as visualized by electron microscopy."; RL J. Biol. Chem. 285:13349-13356(2010). CC -!- FUNCTION: Involved in the homologous recombination repair (HRR) pathway CC of double-stranded DNA breaks arising during DNA replication or induced CC by DNA-damaging agents. May promote the assembly of presynaptic RAD51 CC nucleoprotein filaments. Binds single-stranded DNA and double-stranded CC DNA and has DNA-dependent ATPase activity. Part of the RAD51 paralog CC protein complex BCDX2 which acts in the BRCA1-BRCA2-dependent HR CC pathway. Upon DNA damage, BCDX2 acts downstream of BRCA2 recruitment CC and upstream of RAD51 recruitment. BCDX2 binds predominantly to the CC intersection of the four duplex arms of the Holliday junction and to CC junction of replication forks. The BCDX2 complex was originally CC reported to bind single-stranded DNA, single-stranded gaps in duplex CC DNA and specifically to nicks in duplex DNA. The BCDX2 subcomplex CC RAD51B:RAD51C exhibits single-stranded DNA-dependent ATPase activity CC suggesting an involvement in early stages of the HR pathway. CC {ECO:0000269|PubMed:11751635, ECO:0000269|PubMed:11751636, CC ECO:0000269|PubMed:11842113, ECO:0000269|PubMed:12441335, CC ECO:0000269|PubMed:23108668, ECO:0000269|PubMed:23149936}. CC -!- SUBUNIT: Part of the BCDX2 complex consisting of RAD51B, RAD51C, RAD51D CC and XRCC2; the complex has a ring-like structure arranged into a flat CC disc around a central channel (PubMed:11744692, PubMed:11751635, CC PubMed:11751636, PubMed:11842112, PubMed:11842113, PubMed:12427746, CC PubMed:14704354). The BCDX2 subcomplex RAD51B:RAD51C interacts with CC RAD51 (PubMed:11744692, PubMed:11751635, PubMed:11751636, CC PubMed:11842112, PubMed:11842113, PubMed:12427746, PubMed:14704354). CC Interacts with SWSAP1; involved in homologous recombination repair CC (PubMed:21965664). Interacts with HELQ (PubMed:24005041). CC {ECO:0000269|PubMed:11744692, ECO:0000269|PubMed:11751635, CC ECO:0000269|PubMed:11751636, ECO:0000269|PubMed:11842112, CC ECO:0000269|PubMed:11842113, ECO:0000269|PubMed:12427746, CC ECO:0000269|PubMed:14704354, ECO:0000269|PubMed:21965664, CC ECO:0000269|PubMed:24005041}. CC -!- INTERACTION: CC O15315; Q8IZU0: FAM9B; NbExp=3; IntAct=EBI-2824089, EBI-10175124; CC O15315; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-2824089, EBI-16439278; CC O15315; O43502: RAD51C; NbExp=12; IntAct=EBI-2824089, EBI-2267048; CC O15315; O75771: RAD51D; NbExp=5; IntAct=EBI-2824089, EBI-1055693; CC O15315; Q86UA6: RPAIN; NbExp=3; IntAct=EBI-2824089, EBI-3907663; CC O15315; Q6NVH7: SWSAP1; NbExp=2; IntAct=EBI-2824089, EBI-5281637; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=O15315-3; Sequence=Displayed; CC Name=2; Synonyms=RAD51L1a; CC IsoId=O15315-1; Sequence=VSP_008819; CC Name=3; Synonyms=RAD51L1b; CC IsoId=O15315-2; Sequence=VSP_008818; CC Name=4; CC IsoId=O15315-4; Sequence=VSP_008820; CC Name=5; CC IsoId=O15315-5; Sequence=VSP_008817, VSP_008818; CC -!- TISSUE SPECIFICITY: Expressed in a wide range of tissues. CC -!- PTM: Phosphorylated on tyrosine residues by BCR-ABL. CC {ECO:0000269|PubMed:19657362}. CC -!- DISEASE: Note=A chromosomal aberration involving RAD51B is found in CC pulmonary chondroid hamartoma. Translocation t(6;14)(p21;q23-24) with CC HMGA1. {ECO:0000269|PubMed:11978964}. CC -!- DISEASE: Note=A chromosomal aberration involving RAD51B is found in CC uterine leiomyoma. Translocation t(12;14)(q15;q23-24) with HMGA2. CC {ECO:0000269|PubMed:12649198, ECO:0000269|PubMed:9892177}. CC -!- SIMILARITY: Belongs to the RecA family. RAD51 subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAD62357.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAD66573.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/rad51l1/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U92074; AAB63358.1; -; mRNA. DR EMBL; U84138; AAC39723.1; -; mRNA. DR EMBL; Y15571; CAA75680.1; -; mRNA. DR EMBL; BX161515; CAD61950.1; -; mRNA. DR EMBL; BX248061; CAD62357.1; ALT_INIT; mRNA. DR EMBL; BX248766; CAD66573.1; ALT_INIT; mRNA. DR EMBL; DQ160197; AAZ85144.1; -; Genomic_DNA. DR EMBL; AC004518; AAC32426.1; -; Genomic_DNA. DR EMBL; AC004518; AAC32425.1; -; Genomic_DNA. DR EMBL; CR536560; CAG38797.1; -; mRNA. DR EMBL; CH471061; EAW80957.1; -; Genomic_DNA. DR EMBL; BC030219; AAH30219.1; -; mRNA. DR EMBL; AY138857; AAN60542.1; -; mRNA. DR EMBL; AY138858; AAN60543.1; -; mRNA. DR EMBL; AY138859; AAN60544.1; -; mRNA. DR CCDS; CCDS9789.1; -. [O15315-3] DR CCDS; CCDS9790.1; -. [O15315-2] DR RefSeq; NP_001308746.1; NM_001321817.1. [O15315-5] DR RefSeq; NP_002868.1; NM_002877.5. [O15315-1] DR RefSeq; NP_598193.2; NM_133509.3. [O15315-3] DR RefSeq; NP_598194.1; NM_133510.3. [O15315-2] DR AlphaFoldDB; O15315; -. DR SMR; O15315; -. DR BioGRID; 111827; 41. DR CORUM; O15315; -. DR DIP; DIP-41246N; -. DR IntAct; O15315; 16. DR MINT; O15315; -. DR STRING; 9606.ENSP00000419471; -. DR iPTMnet; O15315; -. DR PhosphoSitePlus; O15315; -. DR BioMuta; RAD51B; -. DR EPD; O15315; -. DR jPOST; O15315; -. DR MassIVE; O15315; -. DR MaxQB; O15315; -. DR PaxDb; O15315; -. DR PeptideAtlas; O15315; -. DR PRIDE; O15315; -. DR ProteomicsDB; 48575; -. [O15315-3] DR ProteomicsDB; 48576; -. [O15315-1] DR ProteomicsDB; 48577; -. [O15315-2] DR ProteomicsDB; 48578; -. [O15315-4] DR ProteomicsDB; 48579; -. [O15315-5] DR TopDownProteomics; O15315-2; -. [O15315-2] DR Antibodypedia; 4257; 299 antibodies from 36 providers. DR DNASU; 5890; -. DR Ensembl; ENST00000471583.6; ENSP00000418859.1; ENSG00000182185.19. [O15315-2] DR Ensembl; ENST00000487270.5; ENSP00000419471.1; ENSG00000182185.19. DR Ensembl; ENST00000488612.5; ENSP00000420061.1; ENSG00000182185.19. [O15315-4] DR GeneID; 5890; -. DR KEGG; hsa:5890; -. DR MANE-Select; ENST00000471583.6; ENSP00000418859.1; NM_133510.4; NP_598194.1. [O15315-2] DR UCSC; uc001xkd.4; human. [O15315-3] DR CTD; 5890; -. DR DisGeNET; 5890; -. DR GeneCards; RAD51B; -. DR HGNC; HGNC:9822; RAD51B. DR HPA; ENSG00000182185; Low tissue specificity. DR MIM; 150699; phenotype. DR MIM; 602948; gene. DR neXtProt; NX_O15315; -. DR OpenTargets; ENSG00000182185; -. DR PharmGKB; PA34178; -. DR VEuPathDB; HostDB:ENSG00000182185; -. DR eggNOG; KOG1433; Eukaryota. DR GeneTree; ENSGT00940000160169; -. DR HOGENOM; CLU_013059_0_0_1; -. DR InParanoid; O15315; -. DR OMA; QLQGNMK; -. DR OrthoDB; 1345899at2759; -. DR PhylomeDB; O15315; -. DR TreeFam; TF101219; -. DR PathwayCommons; O15315; -. DR Reactome; R-HSA-5685942; HDR through Homologous Recombination (HRR). DR Reactome; R-HSA-5693554; Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA). DR Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates. DR Reactome; R-HSA-5693579; Homologous DNA Pairing and Strand Exchange. DR Reactome; R-HSA-5693616; Presynaptic phase of homologous DNA pairing and strand exchange. DR Reactome; R-HSA-9701192; Defective HDR through Homologous Recombination (HRR) due to BRCA1 loss-of-function. DR Reactome; R-HSA-9704331; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function. DR Reactome; R-HSA-9704646; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function. DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production. DR SignaLink; O15315; -. DR SIGNOR; O15315; -. DR BioGRID-ORCS; 5890; 102 hits in 1081 CRISPR screens. DR ChiTaRS; RAD51B; human. DR GeneWiki; RAD51L1; -. DR GenomeRNAi; 5890; -. DR Pharos; O15315; Tbio. DR PRO; PR:O15315; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; O15315; protein. DR Bgee; ENSG00000182185; Expressed in sural nerve and 171 other tissues. DR ExpressionAtlas; O15315; baseline and differential. DR Genevisible; O15315; HS. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; TAS:ProtInc. DR GO; GO:0033063; C:Rad51B-Rad51C-Rad51D-XRCC2 complex; IDA:UniProtKB. DR GO; GO:0005657; C:replication fork; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0008094; F:ATP-dependent activity, acting on DNA; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; TAS:ProtInc. DR GO; GO:0003690; F:double-stranded DNA binding; IDA:UniProtKB. DR GO; GO:0003697; F:single-stranded DNA binding; IDA:UniProtKB. DR GO; GO:0001832; P:blastocyst growth; IEA:Ensembl. DR GO; GO:0006310; P:DNA recombination; TAS:ProtInc. DR GO; GO:0006281; P:DNA repair; TAS:ProtInc. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IMP:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl. DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; IMP:UniProtKB. DR GO; GO:0007131; P:reciprocal meiotic recombination; TAS:ProtInc. DR GO; GO:0061053; P:somite development; IEA:Ensembl. DR CDD; cd01123; Rad51_DMC1_radA; 1. DR Gene3D; 3.40.50.300; -; 1. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR013632; DNA_recomb/repair_Rad51_C. DR InterPro; IPR016467; DNA_recomb/repair_RecA-like. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR033925; Rad51_DMC1_RadA. DR InterPro; IPR030548; RAD51B. DR InterPro; IPR020588; RecA_ATP-bd. DR PANTHER; PTHR46456; PTHR46456; 1. DR Pfam; PF08423; Rad51; 1. DR PIRSF; PIRSF005856; Rad51; 1. DR SMART; SM00382; AAA; 1. DR SUPFAM; SSF52540; SSF52540; 1. DR PROSITE; PS50162; RECA_2; 1. PE 1: Evidence at protein level; KW Alternative splicing; ATP-binding; Chromosomal rearrangement; DNA damage; KW DNA recombination; DNA repair; DNA-binding; Nucleotide-binding; Nucleus; KW Phosphoprotein; Reference proteome. FT CHAIN 1..384 FT /note="DNA repair protein RAD51 homolog 2" FT /id="PRO_0000122939" FT NP_BIND 108..115 FT /note="ATP" FT /evidence="ECO:0000255" FT REGION 1..75 FT /note="Interaction with RAD51C" FT SITE 252..253 FT /note="Breakpoint for translocation to form HMGA2-RAD51B" FT VAR_SEQ 1..119 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|Ref.4" FT /id="VSP_008817" FT VAR_SEQ 346..384 FT /note="ETTFCSVTQAELNWAPEILPPQPPEQLGLQMCHHTQLIF -> AYGNS (in FT isoform 2)" FT /evidence="ECO:0000303|PubMed:9207106, FT ECO:0000303|PubMed:9441753, ECO:0000303|Ref.6" FT /id="VSP_008819" FT VAR_SEQ 346..384 FT /note="ETTFCSVTQAELNWAPEILPPQPPEQLGLQMCHHTQLIF -> GQEKP (in FT isoform 3 and isoform 5)" FT /evidence="ECO:0000303|PubMed:9512535, ECO:0000303|Ref.4" FT /id="VSP_008818" FT VAR_SEQ 347..384 FT /note="TTFCSVTQAELNWAPEILPPQPPEQLGLQMCHHTQLIF -> FWHICISGFS FT IQNRLKENES (in isoform 4)" FT /evidence="ECO:0000303|Ref.4" FT /id="VSP_008820" FT VARIANT 9 FT /note="V -> M (in dbSNP:rs34583846)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_025243" FT VARIANT 82 FT /note="F -> C (in dbSNP:rs35282642)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_025244" FT VARIANT 172 FT /note="L -> W (in dbSNP:rs34094401)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_025245" FT VARIANT 180 FT /note="Y -> C (in dbSNP:rs28910275)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_025246" FT VARIANT 207 FT /note="V -> L (in dbSNP:rs28908168)" FT /id="VAR_035437" FT VARIANT 243 FT /note="K -> R (in dbSNP:rs34594234)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_025247" FT VARIANT 250 FT /note="S -> A (in dbSNP:rs33929366)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_025248" FT VARIANT 365 FT /note="P -> R (in dbSNP:rs28908468)" FT /id="VAR_051730" FT MUTAGEN 326 FT /note="P->L: Abolishes interaction with BCR-ABLSH3 domain." FT /evidence="ECO:0000269|PubMed:19657362" FT CONFLICT 281 FT /note="S -> P (in Ref. 9; AAN60542/AAN60543/AAN60544)" FT /evidence="ECO:0000305" SQ SEQUENCE 384 AA; 42196 MW; DB0B9AE82F44A52B CRC64; MGSKKLKRVG LSQELCDRLS RHQILTCQDF LCLSPLELMK VTGLSYRGVH ELLCMVSRAC APKMQTAYGI KAQRSADFSP AFLSTTLSAL DEALHGGVAC GSLTEITGPP GCGKTQFCIM MSILATLPTN MGGLEGAVVY IDTESAFSAE RLVEIAESRF PRYFNTEEKL LLTSSKVHLY RELTCDEVLQ RIESLEEEII SKGIKLVILD SVASVVRKEF DAQLQGNLKE RNKFLAREAS SLKYLAEEFS IPVILTNQIT THLSGALASQ ADLVSPADDL SLSEGTSGSS CVIAALGNTW SHSVNTRLIL QYLDSERRQI LIAKSPLAPF TSFVYTIKEE GLVLQETTFC SVTQAELNWA PEILPPQPPE QLGLQMCHHT QLIF // ID FANCG_HUMAN Reviewed; 622 AA. AC O15287; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 25-MAY-2022, entry version 205. DE RecName: Full=Fanconi anemia group G protein; DE Short=Protein FACG; DE AltName: Full=DNA repair protein XRCC9; GN Name=FANCG; Synonyms=XRCC9; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9256465; DOI=10.1073/pnas.94.17.9232; RA Liu N., Lamerdin J.E., Tucker J.D., Zhou Z.-Q., Walter C.A., Albala J.S., RA Busch D.B., Thompson L.H.; RT "The human XRCC9 gene corrects chromosomal instability and mutagen RT sensitivities in CHO UV40 cells."; RL Proc. Natl. Acad. Sci. U.S.A. 94:9232-9237(1997). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RX PubMed=9806548; DOI=10.1038/3093; RA De Winter J.P., Waisfisz Q., Rooimans M.A., Van Berkel C.G.M., RA Bosnoyan-Collins L., Alon N., Carreau M., Bender O., Demuth I., RA Schindler D., Pronk J.C., Arwert F., Hoehn H., Digweed M., Buchwald M., RA Joenje H.; RT "The Fanconi anaemia group G gene FANCG is identical with XRCC9."; RL Nat. Genet. 20:281-283(1998). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLU-294; ILE-297; SER-330; RP LEU-378; GLU-430; GLN-513 AND PHE-603. RG NIEHS SNPs program; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Kidney, and Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP CHARACTERIZATION. RX PubMed=10373536; DOI=10.1128/mcb.19.7.4866; RA Garcia-Higuera I., Kuang Y., Naf D., Wasik J., D'Andrea A.D.; RT "Fanconi anemia proteins FANCA, FANCC, and FANCG/XRCC9 interact in a RT functional nuclear complex."; RL Mol. Cell. Biol. 19:4866-4873(1999). RN [7] RP IDENTIFICATION IN A COMPLEX WITH FANCA; FANCC; FANCE; FANCF AND FANCL. RX PubMed=12724401; DOI=10.1128/mcb.23.10.3417-3426.2003; RA Meetei A.R., Sechi S., Wallisch M., Yang D., Young M.K., Joenje H., RA Hoatlin M.E., Wang W.; RT "A multiprotein nuclear complex connects Fanconi anemia and Bloom RT syndrome."; RL Mol. Cell. Biol. 23:3417-3426(2003). RN [8] RP IDENTIFICATION IN A COMPLEX WITH EIF2AK2; FANCA; FANCC AND HSP70. RX PubMed=15299030; DOI=10.1074/jbc.m403884200; RA Zhang X., Li J., Sejas D.P., Rathbun K.R., Bagby G.C., Pang Q.; RT "The Fanconi anemia proteins functionally interact with the protein kinase RT regulated by RNA (PKR)."; RL J. Biol. Chem. 279:43910-43919(2004). RN [9] RP IDENTIFICATION IN A COMPLEX WITH FANCA; FANCB; FANCC; FANCE; FANCF AND RP FANCL. RX PubMed=15502827; DOI=10.1038/ng1458; RA Meetei A.R., Levitus M., Xue Y., Medhurst A.L., Zwaan M., Ling C., RA Rooimans M.A., Bier P., Hoatlin M., Pals G., de Winter J.P., Wang W., RA Joenje H.; RT "X-linked inheritance of Fanconi anemia complementation group B."; RL Nat. Genet. 36:1219-1224(2004). RN [10] RP IDENTIFICATION IN A COMPLEX WITH FANCA; FANCB; FANCC; FANCE; FANCF; FANCL RP AND FANCM. RX PubMed=16116422; DOI=10.1038/ng1626; RA Meetei A.R., Medhurst A.L., Ling C., Xue Y., Singh T.R., Bier P., RA Steltenpool J., Stone S., Dokal I., Mathew C.G., Hoatlin M., Joenje H., RA de Winter J.P., Wang W.; RT "A human ortholog of archaeal DNA repair protein Hef is defective in RT Fanconi anemia complementation group M."; RL Nat. Genet. 37:958-963(2005). RN [11] RP INTERACTION WITH BRCA2; FANCD2 AND XRCC3, PHOSPHORYLATION AT SER-7, AND RP MUTAGENESIS OF SER-7; SER-383 AND SER-387. RX PubMed=18212739; DOI=10.1038/sj.onc.1211034; RA Wilson J.B., Yamamoto K., Marriott A.S., Hussain S., Sung P., Hoatlin M.E., RA Mathew C.G., Takata M., Thompson L.H., Kupfer G.M., Jones N.J.; RT "FANCG promotes formation of a newly identified protein complex containing RT BRCA2, FANCD2 and XRCC3."; RL Oncogene 27:3641-3652(2008). RN [12] RP IDENTIFICATION IN THE FA COMPLEX. RX PubMed=22343915; DOI=10.1182/blood-2011-10-385963; RA Ali A.M., Pradhan A., Singh T.R., Du C., Li J., Wahengbam K., Grassman E., RA Auerbach A.D., Pang Q., Meetei A.R.; RT "FAAP20: a novel ubiquitin-binding FA nuclear core-complex protein required RT for functional integrity of the FA-BRCA DNA repair pathway."; RL Blood 119:3285-3294(2012). RN [13] RP IDENTIFICATION IN THE FA COMPLEX. RX PubMed=22705371; DOI=10.1016/j.molcel.2012.05.026; RA Yan Z., Guo R., Paramasivam M., Shen W., Ling C., Fox D. III, Wang Y., RA Oostra A.B., Kuehl J., Lee D.Y., Takata M., Hoatlin M.E., Schindler D., RA Joenje H., de Winter J.P., Li L., Seidman M.M., Wang W.; RT "A ubiquitin-binding protein, FAAP20, links RNF8-mediated ubiquitination to RT the Fanconi anemia DNA repair network."; RL Mol. Cell 47:61-75(2012). RN [14] RP IDENTIFICATION IN THE FA COMPLEX. RX PubMed=22266823; DOI=10.1038/nsmb.2222; RA Kim H., Yang K., Dejsuphong D., D'Andrea A.D.; RT "Regulation of Rev1 by the Fanconi anemia core complex."; RL Nat. Struct. Mol. Biol. 19:164-170(2012). RN [15] RP VARIANT FANCG PRO-71. RX PubMed=11093276; DOI=10.1038/sj.ejhg.5200552; RA Demuth I., Wlodarski M., Tipping A.J., Morgan N.V., de Winter J.P., RA Thiel M., Grasl S., Schindler D., D'Andrea A.D., Altay C., Kayserili H., RA Zatterale A., Kunze J., Ebell W., Mathew C.G., Joenje H., Sperling K., RA Digweed M.; RT "Spectrum of mutations in the Fanconi anaemia group G gene, FANCG/XRCC9."; RL Eur. J. Hum. Genet. 8:861-868(2000). RN [16] RP VARIANT [LARGE SCALE ANALYSIS] THR-607. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [17] RP VARIANT FANCG PRO-71, INTERACTION WITH HES1, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF GLY-546. RX PubMed=18550849; DOI=10.1182/blood-2008-04-152710; RA Tremblay C.S., Huang F.F., Habi O., Huard C.C., Godin C., Levesque G., RA Carreau M.; RT "HES1 is a novel interactor of the Fanconi anemia core complex."; RL Blood 112:2062-2070(2008). CC -!- FUNCTION: DNA repair protein that may operate in a postreplication CC repair or a cell cycle checkpoint function. May be implicated in CC interstrand DNA cross-link repair and in the maintenance of normal CC chromosome stability. Candidate tumor suppressor gene. CC -!- SUBUNIT: Belongs to the multisubunit FA complex composed of FANCA, CC FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9 and FANCM. The complex is CC not found in FA patients. In complex with FANCF, FANCA and FANCL, but CC not with FANCC, nor FANCE, interacts with HES1; this interaction may be CC essential for the stability and nuclear localization of FA core complex CC proteins. The complex with FANCC and FANCG may also include EIF2AK2 and CC HSP70. When phosphorylated at Ser-7, forms a complex with BRCA2, FANCD2 CC and XRCC3. {ECO:0000269|PubMed:12724401, ECO:0000269|PubMed:15299030, CC ECO:0000269|PubMed:15502827, ECO:0000269|PubMed:16116422, CC ECO:0000269|PubMed:18212739, ECO:0000269|PubMed:18550849, CC ECO:0000269|PubMed:22266823, ECO:0000269|PubMed:22343915, CC ECO:0000269|PubMed:22705371}. CC -!- INTERACTION: CC O15287; Q92870-2: APBB2; NbExp=3; IntAct=EBI-81610, EBI-21535880; CC O15287; P54252: ATXN3; NbExp=3; IntAct=EBI-81610, EBI-946046; CC O15287; Q8TD31-3: CCHCR1; NbExp=3; IntAct=EBI-81610, EBI-10175300; CC O15287; P08684: CYP3A4; NbExp=3; IntAct=EBI-81610, EBI-3928618; CC O15287; G5E9A7: DMWD; NbExp=3; IntAct=EBI-81610, EBI-10976677; CC O15287; O15360: FANCA; NbExp=13; IntAct=EBI-81610, EBI-81570; CC O15287; O15360-3: FANCA; NbExp=5; IntAct=EBI-81610, EBI-21315382; CC O15287; Q9NPI8: FANCF; NbExp=4; IntAct=EBI-81610, EBI-81589; CC O15287; P14136: GFAP; NbExp=3; IntAct=EBI-81610, EBI-744302; CC O15287; Q53GS7: GLE1; NbExp=3; IntAct=EBI-81610, EBI-1955541; CC O15287; P04792: HSPB1; NbExp=3; IntAct=EBI-81610, EBI-352682; CC O15287; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-81610, EBI-1055254; CC O15287; O60333-2: KIF1B; NbExp=3; IntAct=EBI-81610, EBI-10975473; CC O15287; O14901: KLF11; NbExp=3; IntAct=EBI-81610, EBI-948266; CC O15287; P19404: NDUFV2; NbExp=3; IntAct=EBI-81610, EBI-713665; CC O15287; P29474: NOS3; NbExp=3; IntAct=EBI-81610, EBI-1391623; CC O15287; Q9BVL2: NUP58; NbExp=3; IntAct=EBI-81610, EBI-2811583; CC O15287; P16284: PECAM1; NbExp=3; IntAct=EBI-81610, EBI-716404; CC O15287; Q13393: PLD1; NbExp=3; IntAct=EBI-81610, EBI-2827556; CC O15287; Q99633: PRPF18; NbExp=3; IntAct=EBI-81610, EBI-2798416; CC O15287; P60891: PRPS1; NbExp=3; IntAct=EBI-81610, EBI-749195; CC O15287; P20339: RAB5A; NbExp=3; IntAct=EBI-81610, EBI-399437; CC O15287; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-81610, EBI-5235340; CC O15287; Q13813: SPTAN1; NbExp=4; IntAct=EBI-81610, EBI-351450; CC O15287; P51687: SUOX; NbExp=3; IntAct=EBI-81610, EBI-3921347; CC O15287; Q8N8B7-2: TCEANC; NbExp=3; IntAct=EBI-81610, EBI-11955057; CC O15287; Q8N7U7-2: TPRX1; NbExp=3; IntAct=EBI-81610, EBI-14115717; CC O15287; P08670: VIM; NbExp=3; IntAct=EBI-81610, EBI-353844; CC O15287; O76024: WFS1; NbExp=3; IntAct=EBI-81610, EBI-720609; CC O15287; Q86UD4: ZNF329; NbExp=3; IntAct=EBI-81610, EBI-7233259; CC O15287; P14079: tax; Xeno; NbExp=3; IntAct=EBI-81610, EBI-9675698; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18550849}. Cytoplasm CC {ECO:0000269|PubMed:18550849}. Note=The major form is nuclear. The CC minor form is cytoplasmic. CC -!- TISSUE SPECIFICITY: Highly expressed in testis and thymus. Found in CC lymphoblasts. CC -!- DISEASE: Fanconi anemia complementation group G (FANCG) [MIM:614082]: A CC disorder affecting all bone marrow elements and resulting in anemia, CC leukopenia and thrombopenia. It is associated with cardiac, renal and CC limb malformations, dermal pigmentary changes, and a predisposition to CC the development of malignancies. At the cellular level it is associated CC with hypersensitivity to DNA-damaging agents, chromosomal instability CC (increased chromosome breakage) and defective DNA repair. CC {ECO:0000269|PubMed:11093276, ECO:0000269|PubMed:18550849}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- WEB RESOURCE: Name=Fanconi Anemia Mutation Database; CC URL="https://www2.rockefeller.edu/fanconi/genes/jumpg"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/FANCGID295.html"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/fancg/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U70310; AAB80802.1; -; mRNA. DR EMBL; AJ007669; CAA07602.1; -; mRNA. DR EMBL; AY795970; AAV40841.1; -; Genomic_DNA. DR EMBL; AC004472; AAC07981.1; -; Genomic_DNA. DR EMBL; AL353795; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC000032; AAH00032.1; -; mRNA. DR EMBL; BC011623; AAH11623.1; -; mRNA. DR CCDS; CCDS6574.1; -. DR PIR; T02244; T02244. DR RefSeq; NP_004620.1; NM_004629.1. DR PDB; 7KZP; EM; 3.10 A; G/H=1-622. DR PDB; 7KZQ; EM; 4.20 A; G/H=1-622. DR PDB; 7KZR; EM; 4.20 A; G/H=1-622. DR PDB; 7KZS; EM; 4.20 A; G/H=1-622. DR PDB; 7KZT; EM; 4.20 A; G/H=1-622. DR PDB; 7KZV; EM; 4.20 A; G/H=1-622. DR PDBsum; 7KZP; -. DR PDBsum; 7KZQ; -. DR PDBsum; 7KZR; -. DR PDBsum; 7KZS; -. DR PDBsum; 7KZT; -. DR PDBsum; 7KZV; -. DR AlphaFoldDB; O15287; -. DR SMR; O15287; -. DR BioGRID; 108484; 106. DR ComplexPortal; CPX-6263; Fanconi anemia ubiquitin ligase complex. DR CORUM; O15287; -. DR IntAct; O15287; 81. DR MINT; O15287; -. DR STRING; 9606.ENSP00000367910; -. DR MoonDB; O15287; Predicted. DR iPTMnet; O15287; -. DR PhosphoSitePlus; O15287; -. DR BioMuta; FANCG; -. DR EPD; O15287; -. DR jPOST; O15287; -. DR MassIVE; O15287; -. DR PaxDb; O15287; -. DR PeptideAtlas; O15287; -. DR PRIDE; O15287; -. DR ProteomicsDB; 48561; -. DR Antibodypedia; 25694; 444 antibodies from 37 providers. DR DNASU; 2189; -. DR Ensembl; ENST00000378643.8; ENSP00000367910.4; ENSG00000221829.10. DR GeneID; 2189; -. DR KEGG; hsa:2189; -. DR MANE-Select; ENST00000378643.8; ENSP00000367910.4; NM_004629.2; NP_004620.1. DR CTD; 2189; -. DR DisGeNET; 2189; -. DR GeneCards; FANCG; -. DR GeneReviews; FANCG; -. DR HGNC; HGNC:3588; FANCG. DR HPA; ENSG00000221829; Low tissue specificity. DR MalaCards; FANCG; -. DR MIM; 602956; gene. DR MIM; 614082; phenotype. DR neXtProt; NX_O15287; -. DR OpenTargets; ENSG00000221829; -. DR Orphanet; 84; Fanconi anemia. DR PharmGKB; PA28002; -. DR VEuPathDB; HostDB:ENSG00000221829; -. DR eggNOG; ENOG502QVUI; Eukaryota. DR GeneTree; ENSGT00390000007195; -. DR HOGENOM; CLU_018870_0_0_1; -. DR InParanoid; O15287; -. DR OMA; GAASNCE; -. DR OrthoDB; 358660at2759; -. DR PhylomeDB; O15287; -. DR TreeFam; TF330722; -. DR PathwayCommons; O15287; -. DR Reactome; R-HSA-6783310; Fanconi Anemia Pathway. DR SignaLink; O15287; -. DR SIGNOR; O15287; -. DR BioGRID-ORCS; 2189; 68 hits in 1088 CRISPR screens. DR ChiTaRS; FANCG; human. DR GeneWiki; FANCG; -. DR GenomeRNAi; 2189; -. DR Pharos; O15287; Tbio. DR PRO; PR:O15287; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; O15287; protein. DR Bgee; ENSG00000221829; Expressed in subventricular zone (inner) (primate) and 116 other tissues. DR ExpressionAtlas; O15287; baseline and differential. DR Genevisible; O15287; HS. DR GO; GO:0000785; C:chromatin; IDA:ComplexPortal. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0043240; C:Fanconi anaemia nuclear complex; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0003684; F:damaged DNA binding; TAS:ProtInc. DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IBA:GO_Central. DR GO; GO:0006281; P:DNA repair; TAS:ProtInc. DR GO; GO:0036297; P:interstrand cross-link repair; IC:ComplexPortal. DR GO; GO:0007005; P:mitochondrion organization; IMP:UniProtKB. DR GO; GO:0001541; P:ovarian follicle development; IEA:Ensembl. DR GO; GO:0006513; P:protein monoubiquitination; IDA:ComplexPortal. DR GO; GO:0009314; P:response to radiation; IEA:Ensembl. DR GO; GO:0007286; P:spermatid development; IEA:Ensembl. DR Gene3D; 1.25.40.10; -; 1. DR InterPro; IPR039684; FANCG. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR InterPro; IPR019734; TPR_repeat. DR PANTHER; PTHR15254; PTHR15254; 1. DR SMART; SM00028; TPR; 3. DR SUPFAM; SSF48452; SSF48452; 2. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasm; Disease variant; DNA damage; DNA repair; KW Fanconi anemia; Nucleus; Phosphoprotein; Reference proteome; Repeat; KW TPR repeat. FT CHAIN 1..622 FT /note="Fanconi anemia group G protein" FT /id="PRO_0000106292" FT REPEAT 246..279 FT /note="TPR 1" FT REPEAT 344..377 FT /note="TPR 2" FT REPEAT 453..486 FT /note="TPR 3" FT REPEAT 514..547 FT /note="TPR 4" FT MOD_RES 7 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:18212739" FT VARIANT 71 FT /note="L -> P (in FANCG; associated with a mild clinical FT phenotype; disruption of HES1-binding; no effect on FT FANCA-binding)" FT /evidence="ECO:0000269|PubMed:11093276, FT ECO:0000269|PubMed:18550849" FT /id="VAR_017495" FT VARIANT 294 FT /note="G -> E (in dbSNP:rs17880082)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_021103" FT VARIANT 297 FT /note="T -> I (in dbSNP:rs2237857)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_020311" FT VARIANT 330 FT /note="P -> S (in dbSNP:rs4986940)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_021104" FT VARIANT 378 FT /note="S -> L (in dbSNP:rs4986939)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_021105" FT VARIANT 430 FT /note="K -> E (in dbSNP:rs17881054)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_021106" FT VARIANT 513 FT /note="R -> Q (in dbSNP:rs17885240)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_021107" FT VARIANT 603 FT /note="S -> F (in dbSNP:rs17878854)" FT /evidence="ECO:0000269|Ref.3" FT /id="VAR_021108" FT VARIANT 607 FT /note="A -> T (in a colorectal cancer sample; somatic FT mutation; dbSNP:rs758407400)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035864" FT MUTAGEN 7 FT /note="S->A: Loss of BRCA2-, FANCD2- and XRCC3-binding. No FT effect on complex formation with FANCA and FANCF." FT /evidence="ECO:0000269|PubMed:18212739" FT MUTAGEN 383 FT /note="S->A: No effect on BRCA2-, FANCA-, FANCF-, nor FT XRCC3-binding." FT /evidence="ECO:0000269|PubMed:18212739" FT MUTAGEN 387 FT /note="S->A: No effect on BRCA2-, FANCA-, FANCF-, nor FT XRCC3-binding." FT /evidence="ECO:0000269|PubMed:18212739" FT MUTAGEN 546 FT /note="G->R: No effect on HES1-, nor FANCA-binding." FT /evidence="ECO:0000269|PubMed:18550849" SQ SEQUENCE 622 AA; 68554 MW; 4BC7475472AC3C84 CRC64; MSRQTTSVGS SCLDLWREKN DRLVRQAKVA QNSGLTLRRQ QLAQDALEGL RGLLHSLQGL PAAVPVLPLE LTVTCNFIIL RASLAQGFTE DQAQDIQRSL ERVLETQEQQ GPRLEQGLRE LWDSVLRASC LLPELLSALH RLVGLQAALW LSADRLGDLA LLLETLNGSQ SGASKDLLLL LKTWSPPAEE LDAPLTLQDA QGLKDVLLTA FAYRQGLQEL ITGNPDKALS SLHEAASGLC PRPVLVQVYT ALGSCHRKMG NPQRALLYLV AALKEGSAWG PPLLEASRLY QQLGDTTAEL ESLELLVEAL NVPCSSKAPQ FLIEVELLLP PPDLASPLHC GTQSQTKHIL ASRCLQTGRA GDAAEHYLDL LALLLDSSEP RFSPPPSPPG PCMPEVFLEA AVALIQAGRA QDALTLCEEL LSRTSSLLPK MSRLWEDARK GTKELPYCPL WVSATHLLQG QAWVQLGAQK VAISEFSRCL ELLFRATPEE KEQGAAFNCE QGCKSDAALQ QLRAAALISR GLEWVASGQD TKALQDFLLS VQMCPGNRDT YFHLLQTLKR LDRRDEATAL WWRLEAQTKG SHEDALWSLP LYLESYLSWI RPSDRDAFLE EFRTSLPKSC DL // ID SPT22_HUMAN Reviewed; 363 AA. AC Q8NHS9; B4DXB1; D3DTI9; J3KN63; Q969H3; Q96JT4; DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 2. DT 25-MAY-2022, entry version 136. DE RecName: Full=Spermatogenesis-associated protein 22 {ECO:0000305}; DE AltName: Full=Testis development protein NYD-SP20; GN Name=SPATA22 {ECO:0000312|HGNC:HGNC:30705}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY. RC TISSUE=Testis; RX PubMed=15713825; DOI=10.1002/j.1939-4640.2005.tb01085.x; RA Huang X., Li J., Lu L., Xu M., Xiao J., Yin L., Zhu H., Zhou Z., Sha J.H.; RT "Novel development-related alternative splices in human testis identified RT by cDNA microarrays."; RL J. Androl. 26:189-196(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS MET-148 RP AND THR-160. RC TISSUE=Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). CC -!- FUNCTION: Meiosis-specific protein required for homologous CC recombination in meiosis I. {ECO:0000250|UniProtKB:Q5SV06}. CC -!- SUBUNIT: Component of a multiprotein complex with MEIOB and RPA2. CC Interacts with the complex BRME1:HSF2BP:BRCA2. CC {ECO:0000250|UniProtKB:Q5SV06}. CC -!- INTERACTION: CC Q8NHS9; Q9UBB4: ATXN10; NbExp=3; IntAct=EBI-7067260, EBI-702390; CC Q8NHS9; O75190: DNAJB6; NbExp=3; IntAct=EBI-7067260, EBI-1053164; CC Q8NHS9; Q01658: DR1; NbExp=3; IntAct=EBI-7067260, EBI-750300; CC Q8NHS9; P35637: FUS; NbExp=3; IntAct=EBI-7067260, EBI-400434; CC Q8NHS9; P14136: GFAP; NbExp=3; IntAct=EBI-7067260, EBI-744302; CC Q8NHS9; Q08379: GOLGA2; NbExp=3; IntAct=EBI-7067260, EBI-618309; CC Q8NHS9; Q00403: GTF2B; NbExp=3; IntAct=EBI-7067260, EBI-389564; CC Q8NHS9; Q9Y5Q9: GTF3C3; NbExp=3; IntAct=EBI-7067260, EBI-1054873; CC Q8NHS9; O75031: HSF2BP; NbExp=6; IntAct=EBI-7067260, EBI-7116203; CC Q8NHS9; P42858: HTT; NbExp=9; IntAct=EBI-7067260, EBI-466029; CC Q8NHS9; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-7067260, EBI-1055254; CC Q8NHS9; Q5S007: LRRK2; NbExp=3; IntAct=EBI-7067260, EBI-5323863; CC Q8NHS9; P19404: NDUFV2; NbExp=3; IntAct=EBI-7067260, EBI-713665; CC Q8NHS9; P35240-4: NF2; NbExp=3; IntAct=EBI-7067260, EBI-1014514; CC Q8NHS9; D3DTS7: PMP22; NbExp=3; IntAct=EBI-7067260, EBI-25882629; CC Q8NHS9; P37840: SNCA; NbExp=3; IntAct=EBI-7067260, EBI-985879; CC Q8NHS9; P00441: SOD1; NbExp=3; IntAct=EBI-7067260, EBI-990792; CC Q8NHS9; Q6NUL7: SPTLC1; NbExp=3; IntAct=EBI-7067260, EBI-25912847; CC Q8NHS9; Q13148: TARDBP; NbExp=6; IntAct=EBI-7067260, EBI-372899; CC -!- SUBCELLULAR LOCATION: Chromosome {ECO:0000250|UniProtKB:Q5SV06}. CC Note=Localizes on meiotic chromosome axes. Accumulates on resected DNA. CC Localization is dependent on MEIOB. {ECO:0000250|UniProtKB:Q5SV06}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=NYD-SP20C, NYD-SP20D; CC IsoId=Q8NHS9-1; Sequence=Displayed; CC Name=2; Synonyms=NYD-SP20B; CC IsoId=Q8NHS9-2; Sequence=VSP_020763; CC Name=3; CC IsoId=Q8NHS9-3; Sequence=VSP_044858; CC -!- TISSUE SPECIFICITY: Highly expressed in adult testis. CC {ECO:0000269|PubMed:15713825}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF367472; AAK53408.1; -; mRNA. DR EMBL; AY032684; AAK51120.1; -; mRNA. DR EMBL; AY035867; AAK61373.1; -; mRNA. DR EMBL; AY035868; AAK61374.1; -; mRNA. DR EMBL; AK301892; BAG63323.1; -; mRNA. DR EMBL; AC025125; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471108; EAW90508.1; -; Genomic_DNA. DR EMBL; CH471108; EAW90509.1; -; Genomic_DNA. DR EMBL; CH471108; EAW90510.1; -; Genomic_DNA. DR EMBL; CH471108; EAW90511.1; -; Genomic_DNA. DR EMBL; BC029483; AAH29483.1; -; mRNA. DR CCDS; CCDS11027.1; -. [Q8NHS9-1] DR CCDS; CCDS54066.1; -. [Q8NHS9-2] DR CCDS; CCDS54067.1; -. [Q8NHS9-3] DR RefSeq; NP_001164166.1; NM_001170695.1. [Q8NHS9-1] DR RefSeq; NP_001164167.1; NM_001170696.1. [Q8NHS9-2] DR RefSeq; NP_001164168.1; NM_001170697.1. [Q8NHS9-1] DR RefSeq; NP_001164169.1; NM_001170698.1. [Q8NHS9-1] DR RefSeq; NP_001164170.1; NM_001170699.1. [Q8NHS9-3] DR RefSeq; NP_001308265.1; NM_001321336.1. DR RefSeq; NP_001308266.1; NM_001321337.1. [Q8NHS9-1] DR RefSeq; NP_115987.2; NM_032598.4. [Q8NHS9-1] DR AlphaFoldDB; Q8NHS9; -. DR BioGRID; 124205; 12. DR IntAct; Q8NHS9; 28. DR MINT; Q8NHS9; -. DR STRING; 9606.ENSP00000459580; -. DR iPTMnet; Q8NHS9; -. DR PhosphoSitePlus; Q8NHS9; -. DR BioMuta; SPATA22; -. DR DMDM; 296452914; -. DR MassIVE; Q8NHS9; -. DR PaxDb; Q8NHS9; -. DR PeptideAtlas; Q8NHS9; -. DR PRIDE; Q8NHS9; -. DR ProteomicsDB; 73750; -. [Q8NHS9-1] DR ProteomicsDB; 73751; -. [Q8NHS9-2] DR Antibodypedia; 42583; 92 antibodies from 20 providers. DR DNASU; 84690; -. DR Ensembl; ENST00000268981.9; ENSP00000268981.5; ENSG00000141255.13. [Q8NHS9-3] DR Ensembl; ENST00000355380.8; ENSP00000347541.4; ENSG00000141255.13. [Q8NHS9-2] DR Ensembl; ENST00000397168.7; ENSP00000380354.3; ENSG00000141255.13. DR Ensembl; ENST00000572969.6; ENSP00000460187.1; ENSG00000141255.13. DR Ensembl; ENST00000573128.5; ENSP00000459580.1; ENSG00000141255.13. DR Ensembl; ENST00000575375.5; ENSP00000459329.1; ENSG00000141255.13. DR GeneID; 84690; -. DR KEGG; hsa:84690; -. DR MANE-Select; ENST00000572969.6; ENSP00000460187.1; NM_001170698.2; NP_001164169.1. DR UCSC; uc002fvm.5; human. [Q8NHS9-1] DR CTD; 84690; -. DR DisGeNET; 84690; -. DR GeneCards; SPATA22; -. DR HGNC; HGNC:30705; SPATA22. DR HPA; ENSG00000141255; Tissue enriched (testis). DR MalaCards; SPATA22; -. DR MIM; 617673; gene. DR neXtProt; NX_Q8NHS9; -. DR OpenTargets; ENSG00000141255; -. DR PharmGKB; PA142670887; -. DR VEuPathDB; HostDB:ENSG00000141255; -. DR eggNOG; ENOG502RNNP; Eukaryota. DR GeneTree; ENSGT00390000018151; -. DR HOGENOM; CLU_050539_1_0_1; -. DR InParanoid; Q8NHS9; -. DR OMA; NIFRCVS; -. DR PhylomeDB; Q8NHS9; -. DR TreeFam; TF332549; -. DR PathwayCommons; Q8NHS9; -. DR SignaLink; Q8NHS9; -. DR BioGRID-ORCS; 84690; 10 hits in 1065 CRISPR screens. DR ChiTaRS; SPATA22; human. DR GenomeRNAi; 84690; -. DR Pharos; Q8NHS9; Tbio. DR PRO; PR:Q8NHS9; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q8NHS9; protein. DR Bgee; ENSG00000141255; Expressed in testis and 114 other tissues. DR ExpressionAtlas; Q8NHS9; baseline and differential. DR Genevisible; Q8NHS9; HS. DR GO; GO:0005694; C:chromosome; ISS:UniProtKB. DR GO; GO:0007276; P:gamete generation; IEA:InterPro. DR GO; GO:0007129; P:homologous chromosome pairing at meiosis; IEA:InterPro. DR GO; GO:0000711; P:meiotic DNA repair synthesis; IEA:InterPro. DR GO; GO:0051445; P:regulation of meiotic cell cycle; IBA:GO_Central. DR InterPro; IPR033536; Spata22. DR PANTHER; PTHR35258; PTHR35258; 1. PE 1: Evidence at protein level; KW Alternative splicing; Chromosome; Meiosis; Reference proteome. FT CHAIN 1..363 FT /note="Spermatogenesis-associated protein 22" FT /id="PRO_0000251605" FT REGION 1..51 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 98..127 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 140..170 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 26..51 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 140..162 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 15..57 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15713825" FT /id="VSP_020763" FT VAR_SEQ 268..363 FT /note="AVLDSAVTPGPYYSKTFLMRDGKNTLPCVFYEIDRELPRLIRGRVHRCVGNY FT DQKKNIFQCVSVRPASVSEQKTFQAFVKIADVEMQYYINVMNET -> GS (in FT isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_044858" FT VARIANT 112 FT /note="R -> T (in dbSNP:rs2291604)" FT /id="VAR_027693" FT VARIANT 148 FT /note="V -> M (in dbSNP:rs1488690)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_027694" FT VARIANT 155 FT /note="Q -> R (in dbSNP:rs11556563)" FT /id="VAR_027695" FT VARIANT 160 FT /note="I -> T (in dbSNP:rs1488689)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_027696" FT CONFLICT 6 FT /note="N -> S (in Ref. 1; FT AAK51120/AAK53408/AAK61373/AAK61374)" FT /evidence="ECO:0000305" FT CONFLICT 84 FT /note="V -> A (in Ref. 1; AAK53408/AAK61373/AAK61374)" FT /evidence="ECO:0000305" FT CONFLICT 106 FT /note="Q -> R (in Ref. 2; BAG63323)" FT /evidence="ECO:0000305" SQ SEQUENCE 363 AA; 41318 MW; 71E6C8E4BF2526B8 CRC64; MKRSLNENSA RSTAGCLPVP LFNQKKRNRQ PLTSNPLKDD SGISTPSDNY DFPPLPTDWA WEAVNPELAP VMKTVDTGQI PHSVSRPLRS QDSVFNSIQS NTGRSQGGWS YRDGNKNTSL KTWNKNDFKP QCKRTNLVAN DGKNSCPVSS GAQQQKQLRI PEPPNLSRNK ETELLRQTHS SKISGCTMRG LDKNSALQTL KPNFQQNQYK KQMLDDIPED NTLKETSLYQ LQFKEKASSL RIISAVIESM KYWREHAQKT VLLFEVLAVL DSAVTPGPYY SKTFLMRDGK NTLPCVFYEI DRELPRLIRG RVHRCVGNYD QKKNIFQCVS VRPASVSEQK TFQAFVKIAD VEMQYYINVM NET // ID MEIOB_HUMAN Reviewed; 442 AA. AC Q8N635; B1AK39; C9J0S1; Q96RY0; DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot. DT 05-MAY-2009, sequence version 3. DT 25-MAY-2022, entry version 132. DE RecName: Full=Meiosis-specific with OB domain-containing protein {ECO:0000305}; DE EC=3.1.-.-; GN Name=MEIOB {ECO:0000312|HGNC:HGNC:28569}; Synonyms=C16orf73; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11157797; DOI=10.1093/hmg/10.4.339; RA Daniels R.J., Peden J.F., Lloyd C., Horsley S.W., Clark K., Tufarelli C., RA Kearney L., Buckle V.J., Doggett N.A., Flint J., Higgs D.R.; RT "Sequence, structure and pathology of the fully annotated terminal 2 Mb of RT the short arm of human chromosome 16."; RL Hum. Mol. Genet. 10:339-352(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 95-442 (ISOFORM 1). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP TISSUE SPECIFICITY. RX PubMed=24068956; DOI=10.1371/journal.pgen.1003784; RA Souquet B., Abby E., Herve R., Finsterbusch F., Tourpin S., Le Bouffant R., RA Duquenne C., Messiaen S., Martini E., Bernardino-Sgherri J., Toth A., RA Habert R., Livera G.; RT "MEIOB targets single-strand DNA and is necessary for meiotic RT recombination."; RL PLoS Genet. 9:E1003784-E1003784(2013). RN [5] RP INVOLVEMENT IN SPGF22, VARIANT SPGF22 ILE-64, AND TISSUE SPECIFICITY. RX PubMed=28206990; DOI=10.1038/gim.2016.225; RA Gershoni M., Hauser R., Yogev L., Lehavi O., Azem F., Yavetz H., RA Pietrokovski S., Kleiman S.E.; RT "A familial study of azoospermic men identifies three novel causative RT mutations in three new human azoospermia genes."; RL Genet. Med. 19:998-1006(2017). CC -!- FUNCTION: Single-stranded DNA-binding protein required for homologous CC recombination in meiosis I. Required for double strand breaks (DSBs) CC repair and crossover formation and promotion of faithful and complete CC synapsis. Not required for the initial loading of recombinases but CC required to maintain a proper number of RAD51 and DMC1 foci after the CC zygotene stage. May act by ensuring the stabilization of recombinases, CC which is required for successful homology search and meiotic CC recombination. Displays Single-stranded DNA 3'-5' exonuclease activity CC in vitro. {ECO:0000250|UniProtKB:Q9D513}. CC -!- SUBUNIT: Component of a multiprotein complex with RPA2 and SPATA22. CC Interacts with the complex BRME1:HSF2BP:BRCA2. CC {ECO:0000250|UniProtKB:Q9D513}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9D513}. Nucleus CC {ECO:0000250|UniProtKB:Q9D513}. Chromosome CC {ECO:0000250|UniProtKB:Q9D513}. Note=Co-localizes with the RPA complex CC on meiotic chromosome axes. Accumulates on resected DNA. Localization CC is dependent on SPATA22. {ECO:0000250|UniProtKB:Q9D513}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q8N635-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8N635-2; Sequence=VSP_047664; CC -!- TISSUE SPECIFICITY: In fetal gonads, specifically expressed in the CC ovary starting at the 14th weeks post fertilization (PubMed:24068956). CC In the adult, restricted to testis (PubMed:28206990). CC {ECO:0000269|PubMed:24068956, ECO:0000269|PubMed:28206990}. CC -!- DISEASE: Spermatogenic failure 22 (SPGF22) [MIM:617706]: An infertility CC disorder caused by spermatogenesis defects that result in non- CC obstructive azoospermia. {ECO:0000269|PubMed:28206990}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the MEIOB family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH29829.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAK61296.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AE006639; AAK61296.1; ALT_SEQ; Genomic_DNA. DR EMBL; AL031722; CAM26474.1; -; Genomic_DNA. DR EMBL; AL499628; CAM26474.1; JOINED; Genomic_DNA. DR EMBL; AL499628; CAM28376.1; -; Genomic_DNA. DR EMBL; AL031722; CAM28376.1; JOINED; Genomic_DNA. DR EMBL; AL132823; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC029829; AAH29829.1; ALT_INIT; mRNA. DR CCDS; CCDS10449.2; -. [Q8N635-1] DR CCDS; CCDS53983.1; -. [Q8N635-2] DR RefSeq; NP_001157032.1; NM_001163560.2. [Q8N635-2] DR RefSeq; NP_689977.2; NM_152764.2. [Q8N635-1] DR AlphaFoldDB; Q8N635; -. DR SMR; Q8N635; -. DR BioGRID; 129038; 4. DR IntAct; Q8N635; 1. DR STRING; 9606.ENSP00000390778; -. DR iPTMnet; Q8N635; -. DR PhosphoSitePlus; Q8N635; -. DR BioMuta; MEIOB; -. DR DMDM; 229462984; -. DR MassIVE; Q8N635; -. DR PeptideAtlas; Q8N635; -. DR PRIDE; Q8N635; -. DR ProteomicsDB; 72128; -. [Q8N635-1] DR ProteomicsDB; 7972; -. DR Antibodypedia; 42506; 40 antibodies from 13 providers. DR DNASU; 254528; -. DR Ensembl; ENST00000325962.9; ENSP00000314484.3; ENSG00000162039.17. [Q8N635-2] DR Ensembl; ENST00000397344.7; ENSP00000380504.3; ENSG00000162039.17. DR GeneID; 254528; -. DR KEGG; hsa:254528; -. DR MANE-Select; ENST00000325962.9; ENSP00000314484.3; NM_001163560.3; NP_001157032.1. [Q8N635-2] DR UCSC; uc002cne.3; human. [Q8N635-1] DR CTD; 254528; -. DR DisGeNET; 254528; -. DR GeneCards; MEIOB; -. DR HGNC; HGNC:28569; MEIOB. DR HPA; ENSG00000162039; Tissue enriched (testis). DR MalaCards; MEIOB; -. DR MIM; 617670; gene. DR MIM; 617706; phenotype. DR neXtProt; NX_Q8N635; -. DR OpenTargets; ENSG00000162039; -. DR Orphanet; 399805; Male infertility with azoospermia or oligozoospermia due to single gene mutation. DR PharmGKB; PA145149601; -. DR VEuPathDB; HostDB:ENSG00000162039; -. DR eggNOG; KOG0851; Eukaryota. DR GeneTree; ENSGT00390000001723; -. DR HOGENOM; CLU_042457_2_0_1; -. DR InParanoid; Q8N635; -. DR OMA; SCTLIYE; -. DR OrthoDB; 615895at2759; -. DR PhylomeDB; Q8N635; -. DR TreeFam; TF323670; -. DR PathwayCommons; Q8N635; -. DR SignaLink; Q8N635; -. DR BioGRID-ORCS; 254528; 11 hits in 1080 CRISPR screens. DR ChiTaRS; MEIOB; human. DR GenomeRNAi; 254528; -. DR Pharos; Q8N635; Tdark. DR PRO; PR:Q8N635; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; Q8N635; protein. DR Bgee; ENSG00000162039; Expressed in right testis and 106 other tissues. DR ExpressionAtlas; Q8N635; baseline and differential. DR Genevisible; Q8N635; HS. DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB. DR GO; GO:0008310; F:single-stranded DNA 3'-5' exodeoxyribonuclease activity; ISS:UniProtKB. DR GO; GO:0003697; F:single-stranded DNA binding; ISS:UniProtKB. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; ISS:UniProtKB. DR GO; GO:0007144; P:female meiosis I; ISS:UniProtKB. DR GO; GO:0009566; P:fertilization; ISS:UniProtKB. DR GO; GO:0007129; P:homologous chromosome pairing at meiosis; ISS:UniProtKB. DR GO; GO:0007141; P:male meiosis I; IEA:Ensembl. DR GO; GO:0007140; P:male meiotic nuclear division; ISS:UniProtKB. DR GO; GO:0000712; P:resolution of meiotic recombination intermediates; ISS:UniProtKB. DR Gene3D; 2.40.50.140; -; 3. DR InterPro; IPR012340; NA-bd_OB-fold. DR SUPFAM; SSF50249; SSF50249; 2. PE 2: Evidence at transcript level; KW Alternative splicing; Chromosome; Cytoplasm; DNA-binding; Exonuclease; KW Hydrolase; Meiosis; Nuclease; Nucleus; Reference proteome. FT CHAIN 1..442 FT /note="Meiosis-specific with OB domain-containing protein" FT /id="PRO_0000337134" FT DNA_BIND 167..272 FT /note="OB" FT VAR_SEQ 406 FT /note="T -> TVHEFLAMTDEQKTALKWQFLLERSKIYLK (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_047664" FT VARIANT 18 FT /note="T -> P (in dbSNP:rs1742446)" FT /id="VAR_061619" FT VARIANT 64 FT /note="N -> I (in SPGF22; dbSNP:rs1555472691)" FT /evidence="ECO:0000269|PubMed:28206990" FT /id="VAR_080034" FT VARIANT 75 FT /note="K -> T (in dbSNP:rs1657125)" FT /id="VAR_059624" FT VARIANT 261 FT /note="I -> T (in dbSNP:rs9806945)" FT /id="VAR_043620" SQ SEQUENCE 442 AA; 49313 MW; 3418C8EB3672EE8F CRC64; MANSFAARIF TTLSDLQTNM ANLKVIGIVI GKTDVKGFPD RKNIGSERYT FSFTIRDSPA HFVNAASWGN EDYIKSLSDS FRVGDCVIIE NPLIQRKEIE REEKFSPATP SNCKLLLSEN HSTVKVCSSY EVDTKLLSLI HLPVKESHDY YSLGDIVANG HSLNGRIINV LAAVKSVGEP KYFTTSDRRK GQRCEVRLYD ETESSFAMTC WDNESILLAQ SWMPRETVIF ASDVRINFDK FRNCMTATVI SKTIITTNPD IPEANILLNF IRENKETNVL DDEIDSYFKE SINLSTIVDV YTVEQLKGKA LKNEGKADPS YGILYAYIST LNIDDETTKV VRNRCSSCGY IVNEASNMCT TCNKNSLDFK SVFLSFHVLI DLTDHTGTLH SCSLTGSVAE ETLGCTFVLS HRARSGLKIS VLSCKLADPT EASRNLSGQK HV // ID CFA52_HUMAN Reviewed; 620 AA. AC Q8N1V2; B2RDU7; Q5DX23; Q8TC73; Q8TCI3; DT 02-MAY-2006, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2007, sequence version 3. DT 25-MAY-2022, entry version 160. DE RecName: Full=Cilia- and flagella-associated protein 52 {ECO:0000312|HGNC:HGNC:16053}; DE AltName: Full=WD repeat-containing protein 16 {ECO:0000312|HGNC:HGNC:16053}; DE AltName: Full=WD40-repeat protein up-regulated in HCC {ECO:0000303|PubMed:15967112}; GN Name=CFAP52 {ECO:0000312|HGNC:HGNC:16053}; GN Synonyms=WDR16 {ECO:0000312|HGNC:HGNC:16053}, WDRPUH GN {ECO:0000303|PubMed:15967112}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH HSP70; RP CCT CHAPERONIN COMPLEX AND BRCA2, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=15967112; DOI=10.1593/neo.04544; RA Silva F.P., Hamamoto R., Nakamura Y., Furukawa Y.; RT "WDRPUH, a novel WD-repeat-containing protein, is highly expressed in human RT hepatocellular carcinoma and involved in cell proliferation."; RL Neoplasia 7:348-355(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), AND VARIANT RP LYS-336. RC TISSUE=Caudate nucleus, Lung, and Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LYS-336. RC TISSUE=Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP FUNCTION, INTERACTION WITH AK8; CFAP45 AND DNAI1, SUBCELLULAR LOCATION, RP TISSUE SPECIFICITY, INVOLVEMENT IN MOTILE CILIOPATHY, AND VARIANT MOTILE RP CILIOPATHY ARG-271. RX PubMed=33139725; DOI=10.1038/s41467-020-19113-0; RA Dougherty G.W., Mizuno K., Noethe-Menchen T., Ikawa Y., Boldt K., RA Ta-Shma A., Aprea I., Minegishi K., Pang Y.P., Pennekamp P., Loges N.T., RA Raidt J., Hjeij R., Wallmeier J., Mussaffi H., Perles Z., Elpeleg O., RA Rabert F., Shiratori H., Letteboer S.J., Horn N., Young S., Struenker T., RA Stumme F., Werner C., Olbrich H., Takaoka K., Ide T., Twan W.K., RA Biebach L., Grosse-Onnebrink J., Klinkenbusch J.A., Praveen K., RA Bracht D.C., Hoeben I.M., Junger K., Guetzlaff J., Cindric S., Aviram M., RA Kaiser T., Memari Y., Dzeja P.P., Dworniczak B., Ueffing M., Roepman R., RA Bartscherer K., Katsanis N., Davis E.E., Amirav I., Hamada H., Omran H.; RT "CFAP45 deficiency causes situs abnormalities and asthenospermia by RT disrupting an axonemal adenine nucleotide homeostasis module."; RL Nat. Commun. 11:5520-5520(2020). CC -!- FUNCTION: Important for proper ciliary and flagellar beating. May act CC in cooperation with CFAP45 and axonemal dynein subunit DNAH11 CC (PubMed:33139725). May play a role in cell growth and/or survival CC (PubMed:15967112). {ECO:0000269|PubMed:15967112, CC ECO:0000269|PubMed:33139725}. CC -!- SUBUNIT: Interacts with BRCA2 (PubMed:15967112). Interacts with the CCT CC chaperonin complex (PubMed:15967112). Interacts with HSP70 CC (PubMed:15967112). Interacts with AK8 (PubMed:33139725). Interacts with CC CFAP45 (PubMed:33139725). Interacts with DNAI1 (PubMed:33139725). CC Interacts with IQDC (By similarity). {ECO:0000250|UniProtKB:F1SS88, CC ECO:0000269|PubMed:15967112, ECO:0000269|PubMed:33139725}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15967112}. Cell CC projection, cilium, flagellum {ECO:0000250|UniProtKB:A8ILK1}. CC Cytoplasm, cytoskeleton, cilium axoneme {ECO:0000269|PubMed:33139725}. CC Note=Located in the proximal region of respiratory cilia. CC {ECO:0000269|PubMed:33139725}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q8N1V2-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8N1V2-2; Sequence=VSP_018067; CC Name=3; CC IsoId=Q8N1V2-3; Sequence=VSP_018068; CC -!- TISSUE SPECIFICITY: Expressed in respiratory cells and sperm (at CC protein level) (PubMed:33139725). Highly expressed in testis CC (PubMed:15967112). Up-regulated in hepatocellular carcinoma (HCC) CC (PubMed:15967112). {ECO:0000269|PubMed:15967112, CC ECO:0000269|PubMed:33139725}. CC -!- DISEASE: Note=Defects in CFAP52 may be the cause of autosomal recessive CC motile ciliopathy. Patients show left-right asymmetry abnormalities, CC including situs inversus totalis, and mild chronic upper respiratory CC symptoms. Male individuals are infertile. CC {ECO:0000269|PubMed:33139725}. CC -!- MISCELLANEOUS: May be a good candidate as a diagnostic marker for HCC CC as well as a potential molecular target for development of novel CC therapeutic drugs. CC -!- SIMILARITY: Belongs to the CFAP52 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAB85083.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB065281; BAB83743.1; -; mRNA. DR EMBL; AK074435; BAB85083.1; ALT_FRAME; mRNA. DR EMBL; AK094847; BAC04435.1; -; mRNA. DR EMBL; AK315679; BAG38044.1; -; mRNA. DR EMBL; AC087501; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC118755; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC025392; AAH25392.1; -; mRNA. DR CCDS; CCDS11149.2; -. [Q8N1V2-1] DR CCDS; CCDS42262.1; -. [Q8N1V2-3] DR RefSeq; NP_001074025.1; NM_001080556.1. [Q8N1V2-3] DR RefSeq; NP_659491.4; NM_145054.4. [Q8N1V2-1] DR AlphaFoldDB; Q8N1V2; -. DR SMR; Q8N1V2; -. DR BioGRID; 127014; 25. DR IntAct; Q8N1V2; 10. DR STRING; 9606.ENSP00000339449; -. DR iPTMnet; Q8N1V2; -. DR PhosphoSitePlus; Q8N1V2; -. DR BioMuta; CFAP52; -. DR DMDM; 146291099; -. DR MassIVE; Q8N1V2; -. DR PaxDb; Q8N1V2; -. DR PeptideAtlas; Q8N1V2; -. DR PRIDE; Q8N1V2; -. DR ProteomicsDB; 71634; -. [Q8N1V2-1] DR ProteomicsDB; 71635; -. [Q8N1V2-2] DR ProteomicsDB; 71636; -. [Q8N1V2-3] DR Antibodypedia; 12661; 101 antibodies from 20 providers. DR DNASU; 146845; -. DR Ensembl; ENST00000352665.10; ENSP00000339449.5; ENSG00000166596.15. DR Ensembl; ENST00000396219.7; ENSP00000379521.3; ENSG00000166596.15. [Q8N1V2-3] DR GeneID; 146845; -. DR KEGG; hsa:146845; -. DR MANE-Select; ENST00000352665.10; ENSP00000339449.5; NM_145054.5; NP_659491.4. DR UCSC; uc002gly.5; human. [Q8N1V2-1] DR CTD; 146845; -. DR DisGeNET; 146845; -. DR GeneCards; CFAP52; -. DR HGNC; HGNC:16053; CFAP52. DR HPA; ENSG00000166596; Tissue enhanced (choroid plexus, fallopian tube). DR MalaCards; CFAP52; -. DR MIM; 609804; gene. DR neXtProt; NX_Q8N1V2; -. DR OpenTargets; ENSG00000166596; -. DR Orphanet; 101063; Situs inversus totalis. DR PharmGKB; PA38084; -. DR VEuPathDB; HostDB:ENSG00000166596; -. DR eggNOG; KOG0266; Eukaryota. DR GeneTree; ENSGT00940000157016; -. DR HOGENOM; CLU_009244_2_0_1; -. DR InParanoid; Q8N1V2; -. DR OMA; LLRIMVY; -. DR OrthoDB; 185227at2759; -. DR PhylomeDB; Q8N1V2; -. DR TreeFam; TF323254; -. DR PathwayCommons; Q8N1V2; -. DR SignaLink; Q8N1V2; -. DR BioGRID-ORCS; 146845; 12 hits in 1069 CRISPR screens. DR ChiTaRS; CFAP52; human. DR GenomeRNAi; 146845; -. DR Pharos; Q8N1V2; Tbio. DR PRO; PR:Q8N1V2; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q8N1V2; protein. DR Bgee; ENSG00000166596; Expressed in bronchial epithelial cell and 128 other tissues. DR ExpressionAtlas; Q8N1V2; baseline and differential. DR Genevisible; Q8N1V2; HS. DR GO; GO:0097729; C:9+2 motile cilium; IMP:GO_Central. DR GO; GO:0005930; C:axoneme; IMP:GO_Central. DR GO; GO:0060271; P:cilium assembly; IBA:GO_Central. DR GO; GO:0061966; P:establishment of left/right asymmetry; IMP:GO_Central. DR GO; GO:0030317; P:flagellated sperm motility; IMP:GO_Central. DR Gene3D; 2.130.10.10; -; 3. DR InterPro; IPR033015; CFAP52. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR InterPro; IPR001680; WD40_repeat. DR InterPro; IPR019775; WD40_repeat_CS. DR InterPro; IPR036322; WD40_repeat_dom_sf. DR PANTHER; PTHR13720:SF14; PTHR13720:SF14; 1. DR Pfam; PF00400; WD40; 5. DR SMART; SM00320; WD40; 11. DR SUPFAM; SSF50978; SSF50978; 2. DR PROSITE; PS00678; WD_REPEATS_1; 2. DR PROSITE; PS50082; WD_REPEATS_2; 5. DR PROSITE; PS50294; WD_REPEATS_REGION; 2. PE 1: Evidence at protein level; KW Alternative splicing; Cell projection; Cilium; Cytoplasm; Cytoskeleton; KW Flagellum; Reference proteome; Repeat; WD repeat. FT CHAIN 1..620 FT /note="Cilia- and flagella-associated protein 52" FT /id="PRO_0000233153" FT REPEAT 62..106 FT /note="WD 1" FT /evidence="ECO:0000255" FT REPEAT 109..150 FT /note="WD 2" FT /evidence="ECO:0000255" FT REPEAT 156..195 FT /note="WD 3" FT /evidence="ECO:0000255" FT REPEAT 288..327 FT /note="WD 4" FT /evidence="ECO:0000255" FT REPEAT 330..369 FT /note="WD 5" FT /evidence="ECO:0000255" FT REPEAT 372..411 FT /note="WD 6" FT /evidence="ECO:0000255" FT REPEAT 415..454 FT /note="WD 7" FT /evidence="ECO:0000255" FT REPEAT 459..498 FT /note="WD 8" FT /evidence="ECO:0000255" FT REPEAT 500..539 FT /note="WD 9" FT /evidence="ECO:0000255" FT REPEAT 543..582 FT /note="WD 10" FT /evidence="ECO:0000255" FT REPEAT 585..620 FT /note="WD 11" FT /evidence="ECO:0000255" FT VAR_SEQ 1..23 FT /note="MDNKISPEAQVAELELDAVIGFN -> MEAVVLPWQIFGVRELPVERGVTMK FT GPRLFRAP (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_018067" FT VAR_SEQ 24..91 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_018068" FT VARIANT 271 FT /note="G -> R (found in a patient with a motile ciliopathy; FT unknown pathological significance; loss of panaxonemal FT expression in respiratory cilia; dbSNP:rs140921334)" FT /evidence="ECO:0000269|PubMed:33139725" FT /id="VAR_085332" FT VARIANT 336 FT /note="E -> K (in dbSNP:rs6503235)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334" FT /id="VAR_026057" FT CONFLICT 91 FT /note="A -> V (in Ref. 4; AAH25392)" FT /evidence="ECO:0000305" FT CONFLICT 199 FT /note="C -> S (in Ref. 4; AAH25392)" FT /evidence="ECO:0000305" FT CONFLICT 243 FT /note="G -> E (in Ref. 2; BAB85083)" FT /evidence="ECO:0000305" SQ SEQUENCE 620 AA; 68298 MW; DC2F5DC3994CD7DD CRC64; MDNKISPEAQ VAELELDAVI GFNGHVPTGL KCHPDQEHMI YPLGCTVLIQ AINTKEQNFL QGHGNNVSCL AISRSGEYIA SGQVTFMGFK ADIILWDYKN RELLARLSLH KGKIEALAFS PNDLYLVSLG GPDDGSVVVW SIAKRDAICG SPAAGLNVGN ATNVIFSRCR DEMFMTAGNG TIRVWELDLP NRKIWPTECQ TGQLKRIVMS IGVDDDDSFF YLGTTTGDIL KMNPRTKLLT DVGPAKDKFS LGVSAIRCLK MGGLLVGSGA GLLVFCKSPG YKPIKKIQLQ GGITSITLRG EGHQFLVGTE ESHIYRVSFT DFKETLIATC HFDAVEDIVF PFGTAELFAT CAKKDIRVWH TSSNRELLRI TVPNMTCHGI DFMRDGKSII SAWNDGKIRA FAPETGRLMY VINNAHRIGV TAIATTSDCK RVISGGGEGE VRVWQIGCQT QKLEEALKEH KSSVSCIRVK RNNEECVTAS TDGTCIIWDL VRLRRNQMIL ANTLFQCVCY HPEEFQIITS GTDRKIAYWE VFDGTVIREL EGSLSGSING MDITQEGVHF VTGGNDHLVK VWDYNEGEVT HVGVGHSGNI TRIRISPGNQ YIVSVSADGA ILRWKYPYTS // ID FIGL1_HUMAN Reviewed; 674 AA. AC Q6PIW4; D3DVM6; Q86V18; Q8ND59; Q9H8P1; Q9H917; DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot. DT 11-SEP-2007, sequence version 2. DT 25-MAY-2022, entry version 161. DE RecName: Full=Fidgetin-like protein 1; DE EC=3.6.4.-; GN Name=FIGNL1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Ovary; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Testis; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D., RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., RA Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT MET-137. RC TISSUE=Pancreas, and Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-339, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [12] RP FUNCTION, INTERACTION WITH RAD51 AND SPIDR, SUBCELLULAR LOCATION, RP MUTAGENESIS OF PHE-295; PHE-340; LYS-447 AND ASP-500, AND IDENTIFICATION BY RP MASS SPECTROMETRY. RX PubMed=23754376; DOI=10.1073/pnas.1220662110; RA Yuan J., Chen J.; RT "FIGNL1-containing protein complex is required for efficient homologous RT recombination repair."; RL Proc. Natl. Acad. Sci. U.S.A. 110:10640-10645(2013). RN [13] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-225, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [14] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 341-674 IN COMPLEX WITH ADP. RG Structural genomics consortium (SGC); RT "Human fidgetin-like protein 1."; RL Submitted (FEB-2009) to the PDB data bank. CC -!- FUNCTION: Involved in DNA double-strand break (DBS) repair via CC homologous recombination (HR). Recruited at DSB sites independently of CC BRCA2, RAD51 and RAD51 paralogs in a H2AX-dependent manner. May CC regulate osteoblast proliferation and differentiation CC (PubMed:23754376). May play a role in the control of male meiosis CC dynamic (By similarity). {ECO:0000250|UniProtKB:Q8BPY9, CC ECO:0000269|PubMed:23754376}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC -!- SUBUNIT: Hexamer (By similarity). Interacts (via N-terminal one-half CC region) with RAD51; the interaction is direct. Interacts (via N- CC terminal one-half region) with SPIDR (via the C-terminal region); the CC interaction is direct. {ECO:0000250, ECO:0000269|PubMed:23754376, CC ECO:0000269|Ref.14}. CC -!- INTERACTION: CC Q6PIW4; Q96CN9: GCC1; NbExp=3; IntAct=EBI-8468390, EBI-746252; CC Q6PIW4; O14713: ITGB1BP1; NbExp=3; IntAct=EBI-8468390, EBI-2127319; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23754376}. Cytoplasm CC {ECO:0000250|UniProtKB:Q8BPY9}. Cytoplasm, perinuclear region CC {ECO:0000250|UniProtKB:Q8BPY9}. Note=Together with RAD51 and a subset CC of H2A histone proteins, redistributed in discrete nuclear DNA damage- CC induced foci after ionizing radiation (IR) treatment (PubMed:23754376). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q6PIW4-1; Sequence=Displayed; CC Name=2; CC IsoId=Q6PIW4-2; Sequence=VSP_027937; CC -!- DOMAIN: The N-terminus is necessary for its recruitment to DNA damage CC sites. {ECO:0000269|PubMed:23754376}. CC -!- SIMILARITY: Belongs to the AAA ATPase family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAB14567.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK023142; BAB14426.1; -; mRNA. DR EMBL; AK023411; BAB14567.1; ALT_INIT; mRNA. DR EMBL; AL834387; CAD39050.1; -; mRNA. DR EMBL; AC018705; AAS01996.1; -; Genomic_DNA. DR EMBL; CH236955; EAL23899.1; -; Genomic_DNA. DR EMBL; CH471128; EAW60975.1; -; Genomic_DNA. DR EMBL; CH471128; EAW60976.1; -; Genomic_DNA. DR EMBL; BC051867; AAH51867.1; -; mRNA. DR CCDS; CCDS5510.1; -. [Q6PIW4-1] DR RefSeq; NP_001036227.1; NM_001042762.3. [Q6PIW4-1] DR RefSeq; NP_001274421.1; NM_001287492.2. [Q6PIW4-1] DR RefSeq; NP_001274422.1; NM_001287493.2. [Q6PIW4-1] DR RefSeq; NP_001274423.1; NM_001287494.2. [Q6PIW4-1] DR RefSeq; NP_001274424.1; NM_001287495.2. [Q6PIW4-1] DR RefSeq; NP_001274425.1; NM_001287496.2. [Q6PIW4-2] DR RefSeq; NP_001333487.1; NM_001346558.1. [Q6PIW4-2] DR RefSeq; NP_001333488.1; NM_001346559.1. [Q6PIW4-2] DR RefSeq; NP_001333489.1; NM_001346560.1. [Q6PIW4-1] DR RefSeq; NP_001333490.1; NM_001346561.1. [Q6PIW4-1] DR RefSeq; NP_001333491.1; NM_001346562.1. [Q6PIW4-1] DR RefSeq; NP_001333492.1; NM_001346563.1. [Q6PIW4-1] DR RefSeq; NP_001333493.1; NM_001346564.1. [Q6PIW4-1] DR RefSeq; NP_001333494.1; NM_001346565.1. [Q6PIW4-1] DR RefSeq; NP_071399.2; NM_022116.5. [Q6PIW4-1] DR RefSeq; XP_011513772.1; XM_011515470.2. [Q6PIW4-1] DR RefSeq; XP_016867990.1; XM_017012501.1. [Q6PIW4-1] DR PDB; 3D8B; X-ray; 2.00 A; A/B=341-674. DR PDBsum; 3D8B; -. DR AlphaFoldDB; Q6PIW4; -. DR SMR; Q6PIW4; -. DR BioGRID; 122026; 74. DR IntAct; Q6PIW4; 36. DR MINT; Q6PIW4; -. DR STRING; 9606.ENSP00000410811; -. DR GlyGen; Q6PIW4; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q6PIW4; -. DR MetOSite; Q6PIW4; -. DR PhosphoSitePlus; Q6PIW4; -. DR BioMuta; FIGNL1; -. DR DMDM; 158563967; -. DR CPTAC; CPTAC-1608; -. DR EPD; Q6PIW4; -. DR jPOST; Q6PIW4; -. DR MassIVE; Q6PIW4; -. DR MaxQB; Q6PIW4; -. DR PaxDb; Q6PIW4; -. DR PeptideAtlas; Q6PIW4; -. DR PRIDE; Q6PIW4; -. DR ProteomicsDB; 67182; -. [Q6PIW4-1] DR ProteomicsDB; 67183; -. [Q6PIW4-2] DR Antibodypedia; 27700; 143 antibodies from 26 providers. DR DNASU; 63979; -. DR Ensembl; ENST00000356889.8; ENSP00000349356.4; ENSG00000132436.12. DR Ensembl; ENST00000395556.6; ENSP00000378924.2; ENSG00000132436.12. DR Ensembl; ENST00000419119.1; ENSP00000410811.1; ENSG00000132436.12. DR Ensembl; ENST00000433017.6; ENSP00000399997.1; ENSG00000132436.12. DR Ensembl; ENST00000611938.4; ENSP00000484551.1; ENSG00000132436.12. DR Ensembl; ENST00000613602.3; ENSP00000481751.1; ENSG00000132436.12. DR Ensembl; ENST00000615084.4; ENSP00000483543.1; ENSG00000132436.12. DR Ensembl; ENST00000617389.4; ENSP00000483126.1; ENSG00000132436.12. DR GeneID; 63979; -. DR KEGG; hsa:63979; -. DR MANE-Select; ENST00000433017.6; ENSP00000399997.1; NM_001287492.4; NP_001274421.1. DR UCSC; uc003tpc.5; human. [Q6PIW4-1] DR CTD; 63979; -. DR DisGeNET; 63979; -. DR GeneCards; FIGNL1; -. DR HGNC; HGNC:13286; FIGNL1. DR HPA; ENSG00000132436; Low tissue specificity. DR MIM; 615383; gene. DR neXtProt; NX_Q6PIW4; -. DR OpenTargets; ENSG00000132436; -. DR PharmGKB; PA28148; -. DR VEuPathDB; HostDB:ENSG00000132436; -. DR eggNOG; KOG0740; Eukaryota. DR GeneTree; ENSGT00940000161552; -. DR HOGENOM; CLU_000688_21_10_1; -. DR InParanoid; Q6PIW4; -. DR OMA; YSDKWES; -. DR OrthoDB; 1176820at2759; -. DR PhylomeDB; Q6PIW4; -. DR TreeFam; TF105013; -. DR PathwayCommons; Q6PIW4; -. DR SignaLink; Q6PIW4; -. DR BioGRID-ORCS; 63979; 15 hits in 1079 CRISPR screens. DR EvolutionaryTrace; Q6PIW4; -. DR GenomeRNAi; 63979; -. DR Pharos; Q6PIW4; Tbio. DR PRO; PR:Q6PIW4; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; Q6PIW4; protein. DR Bgee; ENSG00000132436; Expressed in secondary oocyte and 203 other tissues. DR ExpressionAtlas; Q6PIW4; baseline and differential. DR Genevisible; Q6PIW4; HS. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0000228; C:nuclear chromosome; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro. DR GO; GO:0016787; F:hydrolase activity; ISS:UniProtKB. DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB. DR GO; GO:0008568; F:microtubule-severing ATPase activity; IBA:GO_Central. DR GO; GO:0046034; P:ATP metabolic process; ISS:UniProtKB. DR GO; GO:0071479; P:cellular response to ionizing radiation; IDA:UniProtKB. DR GO; GO:0007140; P:male meiotic nuclear division; ISS:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB. DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IEA:Ensembl. DR GO; GO:0001649; P:osteoblast differentiation; ISS:UniProtKB. DR GO; GO:0033687; P:osteoblast proliferation; ISS:UniProtKB. DR GO; GO:0051726; P:regulation of cell cycle; ISS:UniProtKB. DR GO; GO:0010569; P:regulation of double-strand break repair via homologous recombination; IDA:UniProtKB. DR Gene3D; 3.40.50.300; -; 1. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR003959; ATPase_AAA_core. DR InterPro; IPR003960; ATPase_AAA_CS. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR015415; Vps4_C. DR Pfam; PF00004; AAA; 1. DR Pfam; PF09336; Vps4_C; 1. DR SMART; SM00382; AAA; 1. DR SUPFAM; SSF52540; SSF52540; 1. DR PROSITE; PS00674; AAA; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Cytoplasm; KW Hydrolase; Isopeptide bond; Magnesium; Metal-binding; Nucleotide-binding; KW Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation. FT CHAIN 1..674 FT /note="Fidgetin-like protein 1" FT /id="PRO_0000302723" FT NP_BIND 444..449 FT /note="ATP" FT /evidence="ECO:0000305|Ref.14" FT REGION 157..179 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 295..344 FT /note="Necessary and sufficient for interaction with RAD51" FT /evidence="ECO:0000305|PubMed:23754376" FT COMPBIAS 164..178 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 404 FT /note="ATP; via amide nitrogen and carbonyl oxygen" FT /evidence="ECO:0000305|Ref.14" FT MOD_RES 259 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 339 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT CROSSLNK 225 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 1..111 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_027937" FT VARIANT 137 FT /note="V -> M (in dbSNP:rs10235371)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_034941" FT VARIANT 216 FT /note="H -> Y (in dbSNP:rs35929700)" FT /id="VAR_034942" FT MUTAGEN 295 FT /note="F->E: Reduces interaction with RAD51 and inhibits FT HR-mediated DNA repair. Strongly reduce, but does abolish, FT interaction with RAD51; when associated with E-340." FT /evidence="ECO:0000269|PubMed:23754376" FT MUTAGEN 340 FT /note="F->E: Reduces weakly interaction with RAD51. FT Strongly reduce, but does abolish, interaction with RAD51; FT when associated with E-295." FT /evidence="ECO:0000269|PubMed:23754376" FT MUTAGEN 447 FT /note="K->A: Inhibits HR-mediated DNA repair." FT /evidence="ECO:0000269|PubMed:23754376" FT MUTAGEN 500 FT /note="D->A: Inhibits HR-mediated DNA repair." FT /evidence="ECO:0000269|PubMed:23754376" FT CONFLICT 614 FT /note="E -> G (in Ref. 1; BAB14426)" FT /evidence="ECO:0000305" FT HELIX 381..390 FT /evidence="ECO:0007829|PDB:3D8B" FT HELIX 400..402 FT /evidence="ECO:0007829|PDB:3D8B" FT HELIX 407..416 FT /evidence="ECO:0007829|PDB:3D8B" FT HELIX 418..422 FT /evidence="ECO:0007829|PDB:3D8B" FT TURN 424..426 FT /evidence="ECO:0007829|PDB:3D8B" FT HELIX 429..431 FT /evidence="ECO:0007829|PDB:3D8B" FT STRAND 435..442 FT /evidence="ECO:0007829|PDB:3D8B" FT HELIX 447..457 FT /evidence="ECO:0007829|PDB:3D8B" FT STRAND 461..466 FT /evidence="ECO:0007829|PDB:3D8B" FT HELIX 467..470 FT /evidence="ECO:0007829|PDB:3D8B" FT HELIX 477..491 FT /evidence="ECO:0007829|PDB:3D8B" FT STRAND 494..500 FT /evidence="ECO:0007829|PDB:3D8B" FT HELIX 502..505 FT /evidence="ECO:0007829|PDB:3D8B" FT HELIX 516..529 FT /evidence="ECO:0007829|PDB:3D8B" FT STRAND 539..546 FT /evidence="ECO:0007829|PDB:3D8B" FT HELIX 548..550 FT /evidence="ECO:0007829|PDB:3D8B" FT HELIX 553..556 FT /evidence="ECO:0007829|PDB:3D8B" FT STRAND 561..564 FT /evidence="ECO:0007829|PDB:3D8B" FT HELIX 570..582 FT /evidence="ECO:0007829|PDB:3D8B" FT HELIX 590..599 FT /evidence="ECO:0007829|PDB:3D8B" FT TURN 600..602 FT /evidence="ECO:0007829|PDB:3D8B" FT HELIX 605..616 FT /evidence="ECO:0007829|PDB:3D8B" FT HELIX 618..622 FT /evidence="ECO:0007829|PDB:3D8B" FT HELIX 633..635 FT /evidence="ECO:0007829|PDB:3D8B" FT HELIX 641..651 FT /evidence="ECO:0007829|PDB:3D8B" FT HELIX 652..654 FT /evidence="ECO:0007829|PDB:3D8B" FT HELIX 660..670 FT /evidence="ECO:0007829|PDB:3D8B" SQ SEQUENCE 674 AA; 74077 MW; 2EB812B407495BF2 CRC64; MQTSSSRSVH LSEWQKNYFA ITSGICTGPK ADAYRAQILR IQYAWANSEI SQVCATKLFK KYAEKYSAII DSDNVESGLN NYAENILTLA GSQQTDSDKW QSGLSINNVF KMSSVQKMMQ AGKKFKDSLL EPALASVVIH KEATVFDLPK FSVCGSSQES DSLPNSAHDR DRTQDFPESN RLKLLQNAQP PMVTNTARTC PTFSAPVGES ATAKFHVTPL FGNVKKENHS SAKENIGLNV FLSNQSCFPA ACENPQRKSF YGSGTIDALS NPILNKACSK TEDNGPKEDS SLPTFKTAKE QLWVDQQKKY HQPQRASGSS YGGVKKSLGA SRSRGILGKF VPPIPKQDGG EQNGGMQCKP YGAGPTEPAH PVDERLKNLE PKMIELIMNE IMDHGPPVNW EDIAGVEFAK ATIKEIVVWP MLRPDIFTGL RGPPKGILLF GPPGTGKTLI GKCIASQSGA TFFSISASSL TSKWVGEGEK MVRALFAVAR CQQPAVIFID EIDSLLSQRG DGEHESSRRI KTEFLVQLDG ATTSSEDRIL VVGATNRPQE IDEAARRRLV KRLYIPLPEA SARKQIVINL MSKEQCCLSE EEIEQIVQQS DAFSGADMTQ LCREASLGPI RSLQTADIAT ITPDQVRPIA YIDFENAFRT VRPSVSPKDL ELYENWNKTF GCGK // ID PDS5B_HUMAN Reviewed; 1447 AA. AC Q9NTI5; Q5R3S3; Q5W0K8; Q6NSC3; Q8IXT6; Q9H5N8; Q9Y2I5; Q9Y451; DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 25-MAY-2022, entry version 176. DE RecName: Full=Sister chromatid cohesion protein PDS5 homolog B; DE AltName: Full=Androgen-induced proliferation inhibitor; DE AltName: Full=Androgen-induced prostate proliferative shutoff-associated protein AS3; GN Name=PDS5B; GN Synonyms=APRIN, AS3 {ECO:0000312|EMBL:AAD22134.2}, KIAA0979 GN {ECO:0000312|EMBL:BAA76823.2}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INDUCTION. RX PubMed=9459187; DOI=10.1016/s0960-0760(97)00122-2; RA Geck P., Szelei J., Jimenez J., Lin T.-M., Sonnenschein C., Soto A.M.; RT "Expression of novel genes linked to the androgen-induced, proliferative RT shutoff in prostate cancer cells."; RL J. Steroid Biochem. Mol. Biol. 63:211-218(1997). RN [2] {ECO:0000305, ECO:0000312|EMBL:AAD22134.2} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Prostate {ECO:0000312|EMBL:AAD22134.2}; RX PubMed=10215036; DOI=10.1016/s0960-0760(98)00165-4; RA Geck P., Szelei J., Jimenez J., Sonnenschein C., Soto A.M.; RT "Early gene expression during androgen-induced inhibition of proliferation RT of prostate cancer cells: a new suppressor candidate on chromosome 13, in RT the BRCA2-Rb1 locus."; RL J. Steroid Biochem. Mol. Biol. 68:41-50(1999). RN [3] {ECO:0000305, ECO:0000312|EMBL:BAA76823.2} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain {ECO:0000312|EMBL:BAA76823.2}; RX PubMed=10231032; DOI=10.1093/dnares/6.1.63; RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., RA Tanaka A., Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XIII. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 6:63-70(1999). RN [4] RP SEQUENCE REVISION. RX PubMed=12168954; DOI=10.1093/dnares/9.3.99; RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.; RT "Construction of expression-ready cDNA clones for KIAA genes: manual RT curation of 330 KIAA cDNA clones."; RL DNA Res. 9:99-106(2002). RN [5] {ECO:0000305, ECO:0000312|EMBL:BAB15584.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). RC TISSUE=Colon {ECO:0000312|EMBL:BAB15584.1}; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] {ECO:0000312|EMBL:CAB69911.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Rhodes S., Huckle E.; RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases. RN [7] {ECO:0000312|EMBL:CAB69911.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057823; DOI=10.1038/nature02379; RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L., RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., RA Frankish A.G., Frankland J., French L., Garner P., Garnett J., RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., RA Rogers J., Ross M.T.; RT "The DNA sequence and analysis of human chromosome 13."; RL Nature 428:522-528(2004). RN [8] {ECO:0000305, ECO:0000312|EMBL:AAH39256.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4). RC TISSUE=Prostate {ECO:0000312|EMBL:AAH70274.1}, and Testis RC {ECO:0000312|EMBL:AAH39256.1}; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] {ECO:0000305} RP FUNCTION. RX PubMed=10963680; DOI=10.1073/pnas.97.18.10185; RA Geck P., Maffini M.V., Szelei J., Sonnenschein C., Soto A.M.; RT "Androgen-induced proliferative quiescence in prostate cancer cells: the RT role of AS3 as its mediator."; RL Proc. Natl. Acad. Sci. U.S.A. 97:10185-10190(2000). RN [10] {ECO:0000305} RP FUNCTION, AND INTERACTION WITH COHESIN COMPLEX. RX PubMed=15855230; DOI=10.1242/jcs.02355; RA Losada A., Yokochi T., Hirano T.; RT "Functional contribution of Pds5 to cohesin-mediated cohesion in human RT cells and Xenopus egg extracts."; RL J. Cell Sci. 118:2133-2141(2005). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1358 AND THR-1370, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1367, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1358, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=T-cell; RX PubMed=19367720; DOI=10.1021/pr800500r; RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.; RT "Phosphorylation analysis of primary human T lymphocytes using sequential RT IMAC and titanium oxide enrichment."; RL J. Proteome Res. 7:5167-5176(2008). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1182; SER-1283 AND SER-1358, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1257 AND SER-1334, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [18] RP FUNCTION, AND INTERACTION WITH WAPL AND RAD21. RX PubMed=19696148; DOI=10.1101/gad.1844309; RA Shintomi K., Hirano T.; RT "Releasing cohesin from chromosome arms in early mitosis: opposing actions RT of Wapl-Pds5 and Sgo1."; RL Genes Dev. 23:2224-2236(2009). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1162; SER-1166; SER-1176; RP SER-1182; SER-1191; SER-1257; SER-1283; SER-1358 AND THR-1370, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [20] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-1136, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [21] RP INTERACTION WITH WAPL AND CDCA5. RX PubMed=21111234; DOI=10.1016/j.cell.2010.10.031; RA Nishiyama T., Ladurner R., Schmitz J., Kreidl E., Schleiffer A., RA Bhaskara V., Bando M., Shirahige K., Hyman A.A., Mechtler K., Peters J.M.; RT "Sororin mediates sister chromatid cohesion by antagonizing wapl."; RL Cell 143:737-749(2010). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1166; SER-1182; SER-1283 AND RP SER-1358, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [23] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1166; SER-1182; SER-1283; RP SER-1358; THR-1381 AND SER-1383, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1140; SER-1166; SER-1176; RP SER-1182; THR-1255; SER-1257; SER-1259; SER-1283; SER-1319; SER-1358 AND RP THR-1370, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1166, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). CC -!- FUNCTION: Regulator of sister chromatid cohesion in mitosis which may CC stabilize cohesin complex association with chromatin. May couple sister CC chromatid cohesion during mitosis to DNA replication. Cohesion ensures CC that chromosome partitioning is accurate in both meiotic and mitotic CC cells and plays an important role in DNA repair. Plays a role in CC androgen-induced proliferative arrest in prostate cells. CC {ECO:0000269|PubMed:10963680, ECO:0000269|PubMed:15855230, CC ECO:0000269|PubMed:19696148}. CC -!- SUBUNIT: Interacts with the cohesin complex. Interacts with RAD21; the CC interaction is direct. Interacts with WAPL (via FGF motifs) or CDCA5 CC (via the FGF motif); the interaction is direct, cohesin-dependent and CC competitive (Probable). {ECO:0000305|PubMed:15855230, CC ECO:0000305|PubMed:19696148, ECO:0000305|PubMed:21111234}. CC -!- INTERACTION: CC Q9NTI5; P51587: BRCA2; NbExp=26; IntAct=EBI-1175604, EBI-79792; CC Q9NTI5; O60216: RAD21; NbExp=4; IntAct=EBI-1175604, EBI-80739; CC Q9NTI5; Q9UQE7: SMC3; NbExp=7; IntAct=EBI-1175604, EBI-80718; CC Q9NTI5; Q8WVM7: STAG1; NbExp=4; IntAct=EBI-1175604, EBI-1175097; CC Q9NTI5; Q8N3U4: STAG2; NbExp=4; IntAct=EBI-1175604, EBI-1057252; CC Q9NTI5; Q7Z5K2: WAPL; NbExp=9; IntAct=EBI-1175604, EBI-1022242; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q6TRW4}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1 {ECO:0000269|PubMed:10231032}; CC IsoId=Q9NTI5-1; Sequence=Displayed; CC Name=2 {ECO:0000269|PubMed:10215036}; CC IsoId=Q9NTI5-2; Sequence=VSP_052402; CC Name=3 {ECO:0000269|PubMed:15489334}; CC IsoId=Q9NTI5-3; Sequence=VSP_052399, VSP_052400; CC Name=4 {ECO:0000269|PubMed:15489334}; CC IsoId=Q9NTI5-4; Sequence=VSP_052397, VSP_052398; CC Name=5 {ECO:0000269|PubMed:14702039}; CC IsoId=Q9NTI5-5; Sequence=VSP_052396, VSP_052401; CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:9459187}. CC -!- INDUCTION: By the synthetic androgen R1881 in prostate carcinoma cells CC undergoing proliferative arrest. Maximum levels occur 18-20 hours after CC androgen exposure. {ECO:0000269|PubMed:9459187}. CC -!- SIMILARITY: Belongs to the PDS5 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA76823.2; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U95825; AAD22134.2; -; mRNA. DR EMBL; AB023196; BAA76823.2; ALT_INIT; mRNA. DR EMBL; AK026889; BAB15584.1; -; mRNA. DR EMBL; AL137201; CAB69911.1; -; mRNA. DR EMBL; AL138820; CAH73160.2; -; Genomic_DNA. DR EMBL; Z75889; CAH73160.2; JOINED; Genomic_DNA. DR EMBL; Z75889; CAI10806.2; -; Genomic_DNA. DR EMBL; AL138820; CAI10806.2; JOINED; Genomic_DNA. DR EMBL; BC039256; AAH39256.1; -; mRNA. DR EMBL; BC070274; AAH70274.1; -; mRNA. DR CCDS; CCDS41878.1; -. [Q9NTI5-1] DR RefSeq; NP_055847.1; NM_015032.3. [Q9NTI5-1] DR RefSeq; XP_016875939.1; XM_017020450.1. [Q9NTI5-1] DR PDB; 5HDT; X-ray; 2.71 A; A/B=21-1120. DR PDBsum; 5HDT; -. DR AlphaFoldDB; Q9NTI5; -. DR SMR; Q9NTI5; -. DR BioGRID; 116685; 140. DR CORUM; Q9NTI5; -. DR DIP; DIP-35420N; -. DR IntAct; Q9NTI5; 50. DR MINT; Q9NTI5; -. DR STRING; 9606.ENSP00000313851; -. DR GlyGen; Q9NTI5; 1 site, 2 O-linked glycans (1 site). DR iPTMnet; Q9NTI5; -. DR MetOSite; Q9NTI5; -. DR PhosphoSitePlus; Q9NTI5; -. DR SwissPalm; Q9NTI5; -. DR BioMuta; PDS5B; -. DR DMDM; 74725312; -. DR EPD; Q9NTI5; -. DR jPOST; Q9NTI5; -. DR MassIVE; Q9NTI5; -. DR MaxQB; Q9NTI5; -. DR PaxDb; Q9NTI5; -. DR PeptideAtlas; Q9NTI5; -. DR PRIDE; Q9NTI5; -. DR ProteomicsDB; 82610; -. [Q9NTI5-1] DR ProteomicsDB; 82611; -. [Q9NTI5-2] DR ProteomicsDB; 82612; -. [Q9NTI5-3] DR ProteomicsDB; 82613; -. [Q9NTI5-4] DR ProteomicsDB; 82614; -. [Q9NTI5-5] DR Antibodypedia; 22916; 167 antibodies from 29 providers. DR DNASU; 23047; -. DR Ensembl; ENST00000315596.15; ENSP00000313851.10; ENSG00000083642.19. DR Ensembl; ENST00000450460.5; ENSP00000401619.1; ENSG00000083642.19. [Q9NTI5-2] DR GeneID; 23047; -. DR KEGG; hsa:23047; -. DR MANE-Select; ENST00000315596.15; ENSP00000313851.10; NM_015032.4; NP_055847.1. DR UCSC; uc010abf.4; human. [Q9NTI5-1] DR CTD; 23047; -. DR DisGeNET; 23047; -. DR GeneCards; PDS5B; -. DR HGNC; HGNC:20418; PDS5B. DR HPA; ENSG00000083642; Low tissue specificity. DR MIM; 605333; gene. DR neXtProt; NX_Q9NTI5; -. DR OpenTargets; ENSG00000083642; -. DR PharmGKB; PA162399098; -. DR VEuPathDB; HostDB:ENSG00000083642; -. DR eggNOG; KOG1525; Eukaryota. DR GeneTree; ENSGT00940000157257; -. DR HOGENOM; CLU_004041_0_0_1; -. DR InParanoid; Q9NTI5; -. DR OMA; CFDIVSG; -. DR OrthoDB; 69768at2759; -. DR PhylomeDB; Q9NTI5; -. DR TreeFam; TF106415; -. DR PathwayCommons; Q9NTI5; -. DR Reactome; R-HSA-2467813; Separation of Sister Chromatids. DR Reactome; R-HSA-2468052; Establishment of Sister Chromatid Cohesion. DR Reactome; R-HSA-2470946; Cohesin Loading onto Chromatin. DR Reactome; R-HSA-2500257; Resolution of Sister Chromatid Cohesion. DR SignaLink; Q9NTI5; -. DR BioGRID-ORCS; 23047; 63 hits in 1093 CRISPR screens. DR ChiTaRS; PDS5B; human. DR GeneWiki; PDS5B; -. DR GenomeRNAi; 23047; -. DR Pharos; Q9NTI5; Tbio. DR PRO; PR:Q9NTI5; -. DR Proteomes; UP000005640; Chromosome 13. DR RNAct; Q9NTI5; protein. DR Bgee; ENSG00000083642; Expressed in kidney and 234 other tissues. DR ExpressionAtlas; Q9NTI5; baseline and differential. DR Genevisible; Q9NTI5; HS. DR GO; GO:0000785; C:chromatin; IDA:UniProtKB. DR GO; GO:0005694; C:chromosome; TAS:Reactome. DR GO; GO:0000775; C:chromosome, centromeric region; TAS:Reactome. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0003677; F:DNA binding; IDA:MGI. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0008283; P:cell population proliferation; TAS:ProtInc. DR GO; GO:0006281; P:DNA repair; IBA:GO_Central. DR GO; GO:0007064; P:mitotic sister chromatid cohesion; IMP:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB. DR GO; GO:0042127; P:regulation of cell population proliferation; IDA:MGI. DR Gene3D; 1.25.10.10; -; 2. DR InterPro; IPR011989; ARM-like. DR InterPro; IPR016024; ARM-type_fold. DR InterPro; IPR039776; Pds5. DR PANTHER; PTHR12663; PTHR12663; 1. DR SUPFAM; SSF48371; SSF48371; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cell cycle; Cell division; KW Mitosis; Nucleus; Phosphoprotein; Reference proteome; Repeat. FT CHAIN 1..1447 FT /note="Sister chromatid cohesion protein PDS5 homolog B" FT /id="PRO_0000287424" FT REPEAT 383..419 FT /note="HEAT" FT /evidence="ECO:0000255" FT DNA_BIND 1249..1261 FT /note="A.T hook 1" FT /evidence="ECO:0000255" FT DNA_BIND 1287..1299 FT /note="A.T hook 2" FT /evidence="ECO:0000255" FT DNA_BIND 1372..1384 FT /note="A.T hook 3" FT /evidence="ECO:0000255" FT REGION 1117..1447 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1132..1170 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1195..1287 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1306..1325 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1355..1392 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 1136 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 1140 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1162 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 1166 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 1176 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 1182 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 1191 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT MOD_RES 1255 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1257 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163" FT MOD_RES 1259 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1283 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 1319 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1334 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 1358 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19367720, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 1366 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q4VA53" FT MOD_RES 1367 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:17525332" FT MOD_RES 1369 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q4VA53" FT MOD_RES 1370 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163" FT MOD_RES 1381 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 1383 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 1417 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q4VA53" FT VAR_SEQ 1..1230 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_052396" FT VAR_SEQ 105..122 FT /note="DIFMFITRQLKGLEDTKS -> ASTDLNNSKIDRYFDLSF (in isoform FT 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_052397" FT VAR_SEQ 123..1447 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_052398" FT VAR_SEQ 491..529 FT /note="ALNEMWKCQNLLRHQVKDLLDLIKQPKTDASVKAIFSKV -> YVSNIKFCS FT FHPLQYIGFYGKETTNTCILKCNLCSVNIV (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_052399" FT VAR_SEQ 530..1447 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_052400" FT VAR_SEQ 1356..1447 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_052401" FT VAR_SEQ 1392..1447 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10215036" FT /id="VSP_052402" FT CONFLICT 256 FT /note="F -> S (in Ref. 2; AAD22134)" FT /evidence="ECO:0000305" FT CONFLICT 326 FT /note="H -> N (in Ref. 8; AAH39256)" FT /evidence="ECO:0000305" FT CONFLICT 394 FT /note="R -> G (in Ref. 2; AAD22134)" FT /evidence="ECO:0000305" FT CONFLICT 535 FT /note="N -> S (in Ref. 2; AAD22134)" FT /evidence="ECO:0000305" FT CONFLICT 742 FT /note="T -> A (in Ref. 2; AAD22134)" FT /evidence="ECO:0000305" FT CONFLICT 1115 FT /note="E -> G (in Ref. 2; AAD22134)" FT /evidence="ECO:0000305" FT CONFLICT 1156 FT /note="S -> G (in Ref. 2; AAD22134)" FT /evidence="ECO:0000305" FT CONFLICT 1197 FT /note="K -> R (in Ref. 2; AAD22134)" FT /evidence="ECO:0000305" FT CONFLICT 1225 FT /note="Q -> R (in Ref. 2; AAD22134)" FT /evidence="ECO:0000305" FT CONFLICT 1242 FT /note="K -> R (in Ref. 2; AAD22134)" FT /evidence="ECO:0000305" FT CONFLICT 1359 FT /note="P -> S (in Ref. 2; AAD22134)" FT /evidence="ECO:0000305" FT STRAND 24..26 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 28..44 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 50..63 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 66..69 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 74..91 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 100..113 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 114..118 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 125..138 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 140..146 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 150..164 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 171..186 FT /evidence="ECO:0007829|PDB:5HDT" FT STRAND 187..189 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 193..200 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 201..203 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 205..210 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 212..224 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 226..240 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 252..254 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 255..265 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 267..270 FT /evidence="ECO:0007829|PDB:5HDT" FT TURN 271..273 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 274..280 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 286..301 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 307..310 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 312..319 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 320..323 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 327..343 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 345..350 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 352..358 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 364..380 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 382..384 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 387..396 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 402..419 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 427..432 FT /evidence="ECO:0007829|PDB:5HDT" FT TURN 433..435 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 436..442 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 443..445 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 449..461 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 470..481 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 486..514 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 519..533 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 539..555 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 557..567 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 573..585 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 596..608 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 615..629 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 634..638 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 642..659 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 662..664 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 667..677 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 682..695 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 699..702 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 704..720 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 723..736 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 740..754 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 761..763 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 764..776 FT /evidence="ECO:0007829|PDB:5HDT" FT TURN 778..781 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 782..791 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 794..797 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 815..817 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 820..839 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 846..859 FT /evidence="ECO:0007829|PDB:5HDT" FT TURN 860..862 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 872..890 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 893..896 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 901..908 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 909..912 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 916..931 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 937..939 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 941..948 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 952..975 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 980..984 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 988..990 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 991..1000 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 1011..1028 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 1036..1047 FT /evidence="ECO:0007829|PDB:5HDT" FT STRAND 1053..1055 FT /evidence="ECO:0007829|PDB:5HDT" FT HELIX 1059..1079 FT /evidence="ECO:0007829|PDB:5HDT" FT STRAND 1081..1085 FT /evidence="ECO:0007829|PDB:5HDT" FT TURN 1095..1097 FT /evidence="ECO:0007829|PDB:5HDT" SQ SEQUENCE 1447 AA; 164667 MW; 145C30308EA3EFD5 CRC64; MAHSKTRTND GKITYPPGVK EISDKISKEE MVRRLKMVVK TFMDMDQDSE EEKELYLNLA LHLASDFFLK HPDKDVRLLV ACCLADIFRI YAPEAPYTSP DKLKDIFMFI TRQLKGLEDT KSPQFNRYFY LLENIAWVKS YNICFELEDS NEIFTQLYRT LFSVINNGHN QKVHMHMVDL MSSIICEGDT VSQELLDTVL VNLVPAHKNL NKQAYDLAKA LLKRTAQAIE PYITNFFNQV LMLGKTSISD LSEHVFDLIL ELYNIDSHLL LSVLPQLEFK LKSNDNEERL QVVKLLAKMF GAKDSELASQ NKPLWQCYLG RFNDIHVPIR LECVKFASHC LMNHPDLAKD LTEYLKVRSH DPEEAIRHDV IVSIVTAAKK DILLVNDHLL NFVRERTLDK RWRVRKEAMM GLAQIYKKYA LQSAAGKDAA KQIAWIKDKL LHIYYQNSID DRLLVERIFA QYMVPHNLET TERMKCLYYL YATLDLNAVK ALNEMWKCQN LLRHQVKDLL DLIKQPKTDA SVKAIFSKVM VITRNLPDPG KAQDFMKKFT QVLEDDEKIR KQLEVLVSPT CSCKQAEGCV REITKKLGNP KQPTNPFLEM IKFLLERIAP VHIDTESISA LIKQVNKSID GTADDEDEGV PTDQAIRAGL ELLKVLSFTH PISFHSAETF ESLLACLKMD DEKVAEAALQ IFKNTGSKIE EDFPHIRSAL LPVLHHKSKK GPPRQAKYAI HCIHAIFSSK ETQFAQIFEP LHKSLDPSNL EHLITPLVTI GHIALLAPDQ FAAPLKSLVA TFIVKDLLMN DRLPGKKTTK LWVPDEEVSP ETMVKIQAIK MMVRWLLGMK NNHSKSGTST LRLLTTILHS DGDLTEQGKI SKPDMSRLRL AAGSAIVKLA QEPCYHEIIT LEQYQLCALA INDECYQVRQ VFAQKLHKGL SRLRLPLEYM AICALCAKDP VKERRAHARQ CLVKNINVRR EYLKQHAAVS EKLLSLLPEY VVPYTIHLLA HDPDYVKVQD IEQLKDVKEC LWFVLEILMA KNENNSHAFI RKMVENIKQT KDAQGPDDAK MNEKLYTVCD VAMNIIMSKS TTYSLESPKD PVLPARFFTQ PDKNFSNTKN YLPPEMKSFF TPGKPKTTNV LGAVNKPLSS AGKQSQTKSS RMETVSNASS SSNPSSPGRI KGRLDSSEMD HSENEDYTMS SPLPGKKSDK RDDSDLVRSE LEKPRGRKKT PVTEQEEKLG MDDLTKLVQE QKPKGSQRSR KRGHTASESD EQQWPEEKRL KEDILENEDE QNSPPKKGKR GRPPKPLGGG TPKEEPTMKT SKKGSKKKSG PPAPEEEEEE ERQSGNTEQK SKSKQHRVSR RAQQRAESPE SSAIESTQST PQKGRGRPSK TPSPSQPKKN VRVGRSKQAA TKENDSSEEV DVFQGSSPVD DIPQEETEEE EVSTVNVRRR SAKRERR // ID ERCC5_HUMAN Reviewed; 1186 AA. AC P28715; A6NGT4; Q5JUS4; Q5JUS5; Q7Z2V3; Q8IZL6; Q8N1B7; Q9HD59; Q9HD60; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 02-SEP-2008, sequence version 3. DT 25-MAY-2022, entry version 231. DE RecName: Full=DNA excision repair protein ERCC-5 {ECO:0000305}; DE EC=3.1.-.- {ECO:0000269|PubMed:32522879, ECO:0000269|PubMed:32821917, ECO:0000269|PubMed:7651464, ECO:0000269|PubMed:8078765, ECO:0000269|PubMed:8090225, ECO:0000269|PubMed:8206890}; DE AltName: Full=DNA repair protein complementing XP-G cells; DE AltName: Full=Xeroderma pigmentosum group G-complementing protein; GN Name=ERCC5; Synonyms=ERCM2, XPG, XPGC; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ARG-1053; ARG-1080 AND RP HIS-1104. RX PubMed=8483504; DOI=10.1038/363182a0; RA Scherly D., Nouspikel T., Corlet J., Ucla C., Bairoch A., Clarkson S.G.; RT "Complementation of the DNA repair defect in Xeroderma pigmentosum group G RT cells by a human cDNA related to yeast RAD2."; RL Nature 363:182-185(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS VAL-254; ARG-1053 AND RP ARG-1080. RX PubMed=7510366; DOI=10.1016/0921-8777(94)90080-9; RA Shiomi T., Harada Y.-N., Saito T., Shiomi N., Okuno Y., Yamaizumi M.; RT "An ERCC5 gene with homology to yeast RAD2 is involved in group G Xeroderma RT pigmentosum."; RL Mutat. Res. 314:167-175(1994). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS VAL-254; ARG-1053 AND RP ARG-1080. RX PubMed=8413238; DOI=10.1128/mcb.13.10.6393-6402.1993; RA Macinnes M.A., Dickson J.A., Hernandez R.R., Learmonth D., Lin G.Y., RA Mudgett J.S., Park M.S., Schauer S., Reynolds R.J., Strniste G.F., Yu J.Y.; RT "Human ERCC5 cDNA-cosmid complementation for excision repair and bipartite RT amino acid domains conserved with RAD proteins of Saccharomyces cerevisiae RT and Schizosaccharomyces pombe."; RL Mol. Cell. Biol. 13:6393-6402(1993). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORMS 1 AND RP 3). RX PubMed=11266544; DOI=10.1093/nar/29.7.1443; RA Emmert S., Schneider T.D., Khan S.G., Kraemer K.H.; RT "The human XPG gene: gene architecture, alternative splicing and single RT nucleotide polymorphisms."; RL Nucleic Acids Res. 29:1443-1452(2001). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS VAL-254; RP ARG-1053 AND ARG-1080. RC TISSUE=Bone marrow; RA Zan Q., Guo J.H., Yu L.; RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-181; VAL-254; ARG-256; RP CYS-311; LYS-399; SER-529; ILE-590; LEU-597; SER-879; HIS-1009 AND RP ARG-1053; ARG-1080 AND GLN-1080. RG NIEHS SNPs program; RL Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057823; DOI=10.1038/nature02379; RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L., RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., RA Frankish A.G., Frankland J., French L., Garner P., Garnett J., RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., RA Rogers J., Ross M.T.; RT "The DNA sequence and analysis of human chromosome 13."; RL Nature 428:522-528(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS ARG-1053 RP AND ARG-1080. RC TISSUE=Eye; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-88. RX PubMed=8088806; DOI=10.1006/geno.1994.1261; RA Samec S., Jones T.A., Corlet J., Scherly D., Sheer D., Wood R.D., RA Clarkson S.G.; RT "The human gene for Xeroderma pigmentosum complementation group G (XPG) RT maps to 13q33 by fluorescence in situ hybridization."; RL Genomics 21:283-285(1994). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=8206890; DOI=10.1016/s0021-9258(17)33956-x; RA O'Donovan A., Scherly D., Clarkson S.G., Wood R.D.; RT "Isolation of active recombinant XPG protein, a human DNA repair RT endonuclease."; RL J. Biol. Chem. 269:15965-15968(1994). RN [11] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=8090225; DOI=10.1038/371432a0; RA O'Donovan A., Davies A.A., Moggs J.G., West S.C., Wood R.D.; RT "XPG endonuclease makes the 3' incision in human DNA nucleotide excision RT repair."; RL Nature 371:432-435(1994). RN [12] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=8078765; DOI=10.1093/nar/22.16.3312; RA Habraken Y., Sung P., Prakash L., Prakash S.; RT "Human Xeroderma pigmentosum group G gene encodes a DNA endonuclease."; RL Nucleic Acids Res. 22:3312-3316(1994). RN [13] RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=7651464; DOI=10.1016/0165-7992(95)90070-5; RA Cloud K.G., Shen B., Strniste G.F., Park M.S.; RT "XPG protein has a structure-specific endonuclease activity."; RL Mutat. Res. 347:55-60(1995). RN [14] RP INTERACTION WITH PCNA. RX PubMed=9305916; DOI=10.1074/jbc.272.39.24522; RA Gary R., Ludwig D.L., Cornelius H.L., MacInnes M.A., Park M.S.; RT "The DNA repair endonuclease XPG binds to proliferating cell nuclear RT antigen (PCNA) and shares sequence elements with the PCNA-binding regions RT of FEN-1 and cyclin-dependent kinase inhibitor p21."; RL J. Biol. Chem. 272:24522-24529(1997). RN [15] RP FUNCTION, AND INTERACTION WITH NTHL1. RX PubMed=9927729; DOI=10.1093/nar/27.4.979; RA Bessho T.; RT "Nucleotide excision repair 3' endonuclease XPG stimulates the activity of RT base excision repair enzyme thymine glycol DNA glycosylase."; RL Nucleic Acids Res. 27:979-983(1999). RN [16] RP REVIEW. RX PubMed=14726017; DOI=10.1016/j.biochi.2003.10.014; RA Clarkson S.G.; RT "The XPG story."; RL Biochimie 85:1113-1121(2003). RN [17] RP REVIEW ON VARIANTS XP-G. RX PubMed=10447254; RX DOI=10.1002/(sici)1098-1004(1999)14:1<9::aid-humu2>3.0.co;2-6; RA Cleaver J.E., Thompson L.H., Richardson A.S., States J.C.; RT "A summary of mutations in the UV-sensitive disorders: xeroderma RT pigmentosum, Cockayne syndrome, and trichothiodystrophy."; RL Hum. Mutat. 14:9-22(1999). RN [18] RP FUNCTION, INTERACTION WITH ERCC6 AND RNA POLYMERASE II, SUBCELLULAR RP LOCATION, AND DOMAIN. RX PubMed=16246722; DOI=10.1016/j.molcel.2005.09.022; RA Sarker A.H., Tsutakawa S.E., Kostek S., Ng C., Shin D.S., Peris M., RA Campeau E., Tainer J.A., Nogales E., Cooper P.K.; RT "Recognition of RNA polymerase II and transcription bubbles by XPG, CSB, RT and TFIIH: insights for transcription-coupled repair and Cockayne RT Syndrome."; RL Mol. Cell 20:187-198(2005). RN [19] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-8, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [21] RP FUNCTION, IDENTIFICATION IN THE HR COMPLEX, INTERACTION WITH BRCA1; BRCA2 RP AND PALB2, SUBCELLULAR LOCATION, AND INDUCTION. RX PubMed=26833090; DOI=10.1016/j.molcel.2015.12.026; RA Trego K.S., Groesser T., Davalos A.R., Parplys A.C., Zhao W., Nelson M.R., RA Hlaing A., Shih B., Rydberg B., Pluth J.M., Tsai M.S., Hoeijmakers J.H.J., RA Sung P., Wiese C., Campisi J., Cooper P.K.; RT "Non-catalytic Roles for XPG with BRCA1 and BRCA2 in Homologous RT Recombination and Genome Stability."; RL Mol. Cell 61:535-546(2016). RN [22] {ECO:0007744|PDB:5EKF, ECO:0007744|PDB:5EKG} RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 1054-1077 AND OF 1168-1186 IN RP COMPLEX WITH MOUSE KPNA2, AND NUCLEAR LOCALIZATION SIGNAL. RX PubMed=26812207; DOI=10.1016/j.jmb.2016.01.019; RA Barros A.C., Takeda A.A., Dreyer T.R., Velazquez-Campoy A., Kobe B., RA Fontes M.R.; RT "Structural and Calorimetric Studies Demonstrate that Xeroderma Pigmentosum RT Type G (XPG) Can Be Imported to the Nucleus by a Classical Nuclear Import RT Pathway via a Monopartite NLS Sequence."; RL J. Mol. Biol. 428:2120-2131(2016). RN [23] {ECO:0007744|PDB:6TUR, ECO:0007744|PDB:6TUS, ECO:0007744|PDB:6TUW, ECO:0007744|PDB:6TUX} RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 1-747 AND 750-990; OF MUTANT RP ALA-812; OF APO FORM AND IN COMPLEX WITH DNA, FUNCTION, CATALYTIC ACTIVITY, RP DOMAIN, AND DNA BINDING. RX PubMed=32821917; DOI=10.1093/nar/gkaa688; RA Gonzalez-Corrochano R., Ruiz F.M., Taylor N.M.I., Huecas S., Drakulic S., RA Spinola-Amilibia M., Fernandez-Tornero C.; RT "The crystal structure of human XPG, the xeroderma pigmentosum group G RT endonuclease, provides insight into nucleotide excision DNA repair."; RL Nucleic Acids Res. 48:9943-9958(2020). RN [24] {ECO:0007744|PDB:6VBH} RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 766-987, FUNCTION, CATALYTIC RP ACTIVITY, SUBUNIT, DOMAIN, AND MUTAGENESIS OF 67-PHE--PHE-68; RP 955-LEU-ASP-956; PHE-978 AND LEU-981. RX PubMed=32522879; DOI=10.1073/pnas.1921311117; RA Tsutakawa S.E., Sarker A.H., Ng C., Arvai A.S., Shin D.S., Shih B., RA Jiang S., Thwin A.C., Tsai M.S., Willcox A., Her M.Z., Trego K.S., RA Raetz A.G., Rosenberg D., Bacolla A., Hammel M., Griffith J.D., RA Cooper P.K., Tainer J.A.; RT "Human XPG nuclease structure, assembly, and activities with insights for RT neurodegeneration and cancer from pathogenic mutations."; RL Proc. Natl. Acad. Sci. U.S.A. 117:14127-14138(2020). RN [25] RP INVOLVEMENT IN COFS3. RX PubMed=24700531; DOI=10.1002/ajmg.a.36506; RA Drury S., Boustred C., Tekman M., Stanescu H., Kleta R., Lench N., RA Chitty L.S., Scott R.H.; RT "A novel homozygous ERCC5 truncating mutation in a family with prenatal RT arthrogryposis--further evidence of genotype-phenotype correlation."; RL Am. J. Med. Genet. A 164A:1777-1783(2014). RN [26] RP VARIANT XP-G VAL-792. RX PubMed=7951246; DOI=10.1093/hmg/3.6.963; RA Nouspikel T., Clarkson S.G.; RT "Mutations that disable the DNA repair gene XPG in a Xeroderma pigmentosum RT group G patient."; RL Hum. Mol. Genet. 3:963-967(1994). RN [27] RP RETRACTED PAPER. RX PubMed=9096355; DOI=10.1073/pnas.94.7.3116; RA Nouspikel T., Lalle P., Leadon S.A., Cooper P.K., Clarkson S.G.; RT "A common mutational pattern in Cockayne syndrome patients from Xeroderma RT pigmentosum group G: implications for a second XPG function."; RL Proc. Natl. Acad. Sci. U.S.A. 94:3116-3121(1997). RN [28] RP RETRACTION NOTICE OF PUBMED:9096355. RX PubMed=17179216; DOI=10.1073/pnas.0609759103; RA Nouspikel T., Lalle P., Leadon S.A., Cooper P.K., Clarkson S.G.; RL Proc. Natl. Acad. Sci. U.S.A. 103:19606-19606(2006). RN [29] RP VARIANT XP-G HIS-72. RX PubMed=11228268; DOI=10.1203/00006450-200103000-00016; RA Zafeiriou D.I., Thorel F., Andreou A., Kleijer W.J., Raams A., RA Garritsen V.H., Gombakis N., Jaspers N.G.J., Clarkson S.G.; RT "Xeroderma pigmentosum group G with severe neurological involvement and RT features of Cockayne syndrome in infancy."; RL Pediatr. Res. 49:407-412(2001). RN [30] RP VARIANT XP-G PRO-858. RX PubMed=11841555; DOI=10.1046/j.0022-202x.2001.01673.x; RA Lalle P., Nouspikel T., Constantinou A., Thorel F., Clarkson S.G.; RT "The founding members of xeroderma pigmentosum group G produce XPG protein RT with severely impaired endonuclease activity."; RL J. Invest. Dermatol. 118:344-351(2002). RN [31] RP VARIANT XP-G THR-874. RX PubMed=12060391; DOI=10.1046/j.1523-1747.2002.01782.x; RA Emmert S., Slor H., Busch D.B., Batko S., Albert R.B., Coleman D., RA Khan S.G., Abu-Libdeh B., DiGiovanna J.J., Cunningham B.B., Lee M.M., RA Crollick J., Inui H., Ueda T., Hedayati M., Grossman L., Shahlavi T., RA Cleaver J.E., Kraemer K.H.; RT "Relationship of neurologic degeneration to genotype in three xeroderma RT pigmentosum group G patients."; RL J. Invest. Dermatol. 118:972-982(2002). RN [32] RP VARIANTS XP-G ASP-28 AND CYS-968, AND CHARACTERIZATION OF VARIANTS XP-G RP ASP-28 AND CYS-968. RX PubMed=23255472; DOI=10.1002/humu.22259; RA Soltys D.T., Rocha C.R., Lerner L.K., de Souza T.A., Munford V., Cabral F., RA Nardo T., Stefanini M., Sarasin A., Cabral-Neto J.B., Menck C.F.; RT "Novel XPG (ERCC5) mutations affect DNA repair and cell survival after RT ultraviolet but not oxidative stress."; RL Hum. Mutat. 34:481-489(2013). RN [33] RP VARIANT ALA-1078. RX PubMed=30533531; DOI=10.1212/nxg.0000000000000285; RA Reinthaler E.M., Graf E., Zrzavy T., Wieland T., Hotzy C., Kopecky C., RA Pferschy S., Schmied C., Leutmezer F., Keilani M., Lill C.M., Hoffjan S., RA Epplen J.T., Zettl U.K., Hecker M., Deutschlaender A., Meuth S.G., RA Ahram M., Mustafa B., El-Khateeb M., Vilarino-Gueell C., Sadovnick A.D., RA Zimprich F., Tomkinson B., Strom T., Kristoferitsch W., Lassmann H., RA Zimprich A.; RT "TPP2 mutation associated with sterile brain inflammation mimicking MS."; RL Neurol. Genet. 4:e285-e285(2018). CC -!- FUNCTION: Single-stranded structure-specific DNA endonuclease involved CC in DNA excision repair (PubMed:8206890, PubMed:8090225, PubMed:8078765, CC PubMed:7651464, PubMed:32821917, PubMed:32522879). Makes the 3'incision CC in DNA nucleotide excision repair (NER) (PubMed:8090225, CC PubMed:8078765, PubMed:32821917, PubMed:32522879). Binds and bends DNA CC repair bubble substrate and breaks base stacking at the single- CC strand/double-strand DNA junction of the DNA bubble (PubMed:32522879). CC Plays a role in base excision repair (BER) by promoting the binding of CC DNA glycosylase NTHL1 to its substrate and increasing NTHL1 catalytic CC activity that removes oxidized pyrimidines from DNA (PubMed:9927729). CC Involved in transcription-coupled nucleotide excision repair (TCR) CC which allows RNA polymerase II-blocking lesions to be rapidly removed CC from the transcribed strand of active genes (PubMed:16246722). CC Functions during the initial step of TCR in cooperation with ERCC6/CSB CC to recognized stalled RNA polymerase II (PubMed:16246722). Also, CC stimulates ERCC6/CSB binding to the DNA repair bubble and ERCC6/CSB CC ATPase activity (PubMed:16246722). Required for DNA replication fork CC maintenance and preservation of genomic stability (PubMed:26833090, CC PubMed:32522879). Involved in homologous recombination repair (HRR) CC induced by DNA replication stress by recruiting RAD51, BRCA2, and PALB2 CC to the damaged DNA site (PubMed:26833090). During HRR, binds to the CC replication fork with high specificity and stabilizes it CC (PubMed:32522879). Also, acts upstream of HRR, to promote the release CC of BRCA1 from DNA (PubMed:26833090). {ECO:0000269|PubMed:16246722, CC ECO:0000269|PubMed:26833090, ECO:0000269|PubMed:32522879, CC ECO:0000269|PubMed:32821917, ECO:0000269|PubMed:7651464, CC ECO:0000269|PubMed:8078765, ECO:0000269|PubMed:8090225, CC ECO:0000269|PubMed:8206890, ECO:0000269|PubMed:9927729}. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:8206890}; CC Note=Binds 2 magnesium ions per subunit. They probably participate in CC the reaction catalyzed by the enzyme. May bind an additional third CC magnesium ion after substrate binding. {ECO:0000250}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC pH dependence: CC Optimum pH is 6.5-7. {ECO:0000269|PubMed:8206890}; CC -!- SUBUNIT: Monomer (PubMed:32522879). Homodimer (PubMed:32522879). CC Component of the homologous recombination repair (HR) complex composed CC of ERCC5/XPG, BRCA2, PALB2, DSS1 and RAD51 (PubMed:26833090). Within CC the complex, interacts with BRCA2 and PALB2 (PubMed:26833090). CC Interacts with RNA polymerase II (PubMed:16246722). Interacts (via C- CC terminus) with ERCC6/CSB; the interaction stimulates ERCC6/CSB binding CC to the DNA repair bubble and ERCC6/CSB ATPase activity CC (PubMed:16246722). May form a complex composed of RNA polymerase II, CC ERCC6/CSB and ERCC5/XPG which associates with the DNA repair bubble CC during transcription-coupled nucleotide excision repair CC (PubMed:16246722). Interacts with BRCA1; the interaction promotes the CC release of BRCA1 from DNA (PubMed:26833090). Interacts with PCNA CC (PubMed:9305916). Interacts with NTHL1; the interaction stimulates CC NTHL1 activity and NTHL1 binding to its DNA substrate (PubMed:9927729). CC {ECO:0000269|PubMed:16246722, ECO:0000269|PubMed:26833090, CC ECO:0000269|PubMed:32522879, ECO:0000269|PubMed:9305916, CC ECO:0000269|PubMed:9927729}. CC -!- INTERACTION: CC P28715; P24522: GADD45A; NbExp=2; IntAct=EBI-765885, EBI-448167; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16246722, CC ECO:0000269|PubMed:26833090, ECO:0000269|PubMed:7651464}. Chromosome CC {ECO:0000269|PubMed:26833090}. Note=Colocalizes with RAD51 to nuclear CC foci in S phase (PubMed:26833090). Localizes to DNA double-strand CC breaks (DBS) during replication stress (PubMed:26833090). Colocalizes CC with BRCA2 to nuclear foci following DNA replication stress CC (PubMed:26833090). {ECO:0000269|PubMed:26833090}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P28715-1; Sequence=Displayed; CC Name=2; CC IsoId=P28715-2; Sequence=VSP_035380; CC Name=3; CC IsoId=P28715-3; Sequence=VSP_053828, VSP_053829; CC -!- INDUCTION: Induced by replication stress caused by DNA double-strand CC breaks (DBS). {ECO:0000269|PubMed:26833090}. CC -!- DOMAIN: Both nuclear localization signals 1 and 2 act as a monopartite CC signal which binds to the high affinity site on KPNA2/importin-alpha. CC {ECO:0000269|PubMed:26812207}. CC -!- DOMAIN: Both the spacer region (also known as the recognition (R) CC domain) and C-terminal domain are required for stable binding to the CC DNA repair bubble (PubMed:16246722). However, both domains are CC dispensable for incision of DNA bubble structures (PubMed:16246722, CC PubMed:32821917, PubMed:32522879). {ECO:0000269|PubMed:16246722, CC ECO:0000269|PubMed:32522879, ECO:0000269|PubMed:32821917}. CC -!- DISEASE: Xeroderma pigmentosum complementation group G (XP-G) CC [MIM:278780]: An autosomal recessive pigmentary skin disorder CC characterized by solar hypersensitivity of the skin, high CC predisposition for developing cancers on areas exposed to sunlight and, CC in some cases, neurological abnormalities. The skin develops marked CC freckling and other pigmentation abnormalities. Some XP-G patients CC present features of Cockayne syndrome, cachectic dwarfism, pigmentary CC retinopathy, ataxia, decreased nerve conduction velocities. The CC phenotype combining xeroderma pigmentosum and Cockayne syndrome traits CC is referred to as XP-CS complex. {ECO:0000269|PubMed:10447254, CC ECO:0000269|PubMed:11228268, ECO:0000269|PubMed:11841555, CC ECO:0000269|PubMed:12060391, ECO:0000269|PubMed:23255472, CC ECO:0000269|PubMed:7951246}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Cerebro-oculo-facio-skeletal syndrome 3 (COFS3) [MIM:616570]: CC A disorder of prenatal onset characterized by microcephaly, congenital CC cataracts, facial dysmorphism, neurogenic arthrogryposis, growth CC failure and severe psychomotor retardation. COFS is considered to be CC part of the nucleotide-excision repair disorders spectrum that include CC also xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome. CC {ECO:0000269|PubMed:24700531}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 3]: Includes a cryptic exon found in intron 6. CC {ECO:0000305}. CC -!- SIMILARITY: Belongs to the XPG/RAD2 endonuclease family. XPG subfamily. CC {ECO:0000305}. CC -!- CAUTION: A paper describing an additional role for this protein in a CC base excision repair pathway that is not coupled to transcription has CC been retracted, because some of the experimental data were incorrect. CC {ECO:0000269|PubMed:9096355, ECO:0000305|PubMed:17179216}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/XPGID300.html"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/ercc5/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X69978; CAA49598.1; -; mRNA. DR EMBL; D16305; BAA03812.1; -; mRNA. DR EMBL; L20046; AAC37533.1; -; mRNA. DR EMBL; AF255436; AAF89178.1; -; Genomic_DNA. DR EMBL; AF255431; AAF89178.1; JOINED; Genomic_DNA. DR EMBL; AF255433; AAF89178.1; JOINED; Genomic_DNA. DR EMBL; AF255434; AAF89178.1; JOINED; Genomic_DNA. DR EMBL; AF255435; AAF89178.1; JOINED; Genomic_DNA. DR EMBL; AF255442; AAF89179.1; -; Genomic_DNA. DR EMBL; AF255431; AAF89179.1; JOINED; Genomic_DNA. DR EMBL; AF255433; AAF89179.1; JOINED; Genomic_DNA. DR EMBL; AF255434; AAF89179.1; JOINED; Genomic_DNA. DR EMBL; AF255435; AAF89179.1; JOINED; Genomic_DNA. DR EMBL; AF255436; AAF89179.1; JOINED; Genomic_DNA. DR EMBL; AF255437; AAF89179.1; JOINED; Genomic_DNA. DR EMBL; AF255438; AAF89179.1; JOINED; Genomic_DNA. DR EMBL; AF255439; AAF89179.1; JOINED; Genomic_DNA. DR EMBL; AF255440; AAF89179.1; JOINED; Genomic_DNA. DR EMBL; AF255441; AAF89179.1; JOINED; Genomic_DNA. DR EMBL; AF462447; AAP97715.1; -; mRNA. DR EMBL; AF550128; AAN46091.1; -; Genomic_DNA. DR EMBL; AL157769; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC031522; AAH31522.1; -; mRNA. DR EMBL; X71341; CAA50481.1; -; Genomic_DNA. DR EMBL; X71342; CAA50481.1; JOINED; Genomic_DNA. DR CCDS; CCDS32004.1; -. [P28715-1] DR PIR; I58009; I58009. DR PIR; S35993; S35993. DR RefSeq; NP_000114.2; NM_000123.3. [P28715-1] DR PDB; 5EKF; X-ray; 2.00 A; B/C=1054-1077. DR PDB; 5EKG; X-ray; 2.80 A; B/C=1168-1186. DR PDB; 6TUR; X-ray; 2.90 A; AAA/BBB/CCC/DDD=1-747, AAA/BBB/CCC/DDD=750-990. DR PDB; 6TUS; X-ray; 2.50 A; A/B=1-747, A/B=750-990. DR PDB; 6TUW; X-ray; 3.50 A; A=1-747, A=750-990. DR PDB; 6TUX; X-ray; 3.10 A; A/B=1-747, A/B=750-986. DR PDB; 6VBH; X-ray; 2.00 A; A=766-987. DR PDBsum; 5EKF; -. DR PDBsum; 5EKG; -. DR PDBsum; 6TUR; -. DR PDBsum; 6TUS; -. DR PDBsum; 6TUW; -. DR PDBsum; 6TUX; -. DR PDBsum; 6VBH; -. DR AlphaFoldDB; P28715; -. DR SMR; P28715; -. DR BioGRID; 108385; 42. DR DIP; DIP-750N; -. DR ELM; P28715; -. DR IntAct; P28715; 14. DR STRING; 9606.ENSP00000347978; -. DR BindingDB; P28715; -. DR ChEMBL; CHEMBL4736; -. DR GlyGen; P28715; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; P28715; -. DR PhosphoSitePlus; P28715; -. DR BioMuta; ERCC5; -. DR DMDM; 205371791; -. DR EPD; P28715; -. DR jPOST; P28715; -. DR MassIVE; P28715; -. DR MaxQB; P28715; -. DR PaxDb; P28715; -. DR PeptideAtlas; P28715; -. DR PRIDE; P28715; -. DR ProteomicsDB; 54495; -. [P28715-1] DR ProteomicsDB; 54496; -. [P28715-2] DR ProteomicsDB; 81837; -. DR Antibodypedia; 11224; 376 antibodies from 30 providers. DR DNASU; 2073; -. DR Ensembl; ENST00000652225.2; ENSP00000498881.2; ENSG00000134899.24. DR GeneID; 2073; -. DR KEGG; hsa:2073; -. DR MANE-Select; ENST00000652225.2; ENSP00000498881.2; NM_000123.4; NP_000114.3. DR UCSC; uc001vpw.4; human. [P28715-1] DR CTD; 2073; -. DR DisGeNET; 2073; -. DR GeneCards; ERCC5; -. DR GeneReviews; ERCC5; -. DR HGNC; HGNC:3437; ERCC5. DR HPA; ENSG00000134899; Low tissue specificity. DR MalaCards; ERCC5; -. DR MIM; 133530; gene. DR MIM; 278780; phenotype. DR MIM; 616570; phenotype. DR neXtProt; NX_P28715; -. DR OpenTargets; ENSG00000134899; -. DR Orphanet; 1466; COFS syndrome. DR Orphanet; 910; Xeroderma pigmentosum. DR Orphanet; 220295; Xeroderma pigmentosum-Cockayne syndrome complex. DR PharmGKB; PA27851; -. DR VEuPathDB; HostDB:ENSG00000134899; -. DR eggNOG; KOG2520; Eukaryota. DR GeneTree; ENSGT00510000048601; -. DR HOGENOM; CLU_003018_2_0_1; -. DR InParanoid; P28715; -. DR OMA; EDSTCEN; -. DR OrthoDB; 1094524at2759; -. DR PhylomeDB; P28715; -. DR TreeFam; TF101235; -. DR PathwayCommons; P28715; -. DR Reactome; R-HSA-5696395; Formation of Incision Complex in GG-NER. DR Reactome; R-HSA-5696400; Dual Incision in GG-NER. DR Reactome; R-HSA-6782135; Dual incision in TC-NER. DR SignaLink; P28715; -. DR SIGNOR; P28715; -. DR BioGRID-ORCS; 2073; 25 hits in 1076 CRISPR screens. DR GeneWiki; ERCC5; -. DR GenomeRNAi; 2073; -. DR Pharos; P28715; Tchem. DR PRO; PR:P28715; -. DR Proteomes; UP000005640; Chromosome 13. DR RNAct; P28715; protein. DR Bgee; ENSG00000134899; Expressed in tendon of biceps brachii and 237 other tissues. DR ExpressionAtlas; P28715; baseline and differential. DR Genevisible; P28715; HS. DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0000109; C:nucleotide-excision repair complex; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0000405; F:bubble DNA binding; IDA:UniProtKB. DR GO; GO:0003684; F:damaged DNA binding; IDA:UniProtKB. DR GO; GO:0003690; F:double-stranded DNA binding; IDA:UniProtKB. DR GO; GO:0004520; F:endodeoxyribonuclease activity; IDA:UniProtKB. DR GO; GO:0004519; F:endonuclease activity; IDA:UniProtKB. DR GO; GO:0008047; F:enzyme activator activity; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB. DR GO; GO:0047485; F:protein N-terminus binding; IPI:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; IDA:UniProtKB. DR GO; GO:0000993; F:RNA polymerase II complex binding; IDA:UniProtKB. DR GO; GO:0003697; F:single-stranded DNA binding; IDA:UniProtKB. DR GO; GO:0006285; P:base-excision repair, AP site formation; IDA:UniProtKB. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IMP:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:0006289; P:nucleotide-excision repair; IDA:UniProtKB. DR GO; GO:0006295; P:nucleotide-excision repair, DNA incision, 3'-to lesion; IDA:UniProtKB. DR GO; GO:0006296; P:nucleotide-excision repair, DNA incision, 5'-to lesion; TAS:Reactome. DR GO; GO:0050790; P:regulation of catalytic activity; IDA:UniProtKB. DR GO; GO:0009411; P:response to UV; IDA:UniProtKB. DR GO; GO:0010225; P:response to UV-C; IMP:UniProtKB. DR GO; GO:0006283; P:transcription-coupled nucleotide-excision repair; IMP:UniProtKB. DR GO; GO:0009650; P:UV protection; IGI:MGI. DR InterPro; IPR036279; 5-3_exonuclease_C_sf. DR InterPro; IPR008918; HhH2. DR InterPro; IPR029060; PIN-like_dom_sf. DR InterPro; IPR006086; XPG-I_dom. DR InterPro; IPR006084; XPG/Rad2. DR InterPro; IPR001044; XPG/Rad2_eukaryotes. DR InterPro; IPR019974; XPG_CS. DR InterPro; IPR006085; XPG_DNA_repair_N. DR Pfam; PF00867; XPG_I; 1. DR Pfam; PF00752; XPG_N; 1. DR PRINTS; PR00853; XPGRADSUPER. DR PRINTS; PR00066; XRODRMPGMNTG. DR SMART; SM00279; HhH2; 1. DR SMART; SM00484; XPGI; 1. DR SMART; SM00485; XPGN; 1. DR SUPFAM; SSF47807; SSF47807; 1. DR SUPFAM; SSF88723; SSF88723; 1. DR TIGRFAMs; TIGR00600; rad2; 1. DR PROSITE; PS00841; XPG_1; 1. DR PROSITE; PS00842; XPG_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Chromosome; KW Cockayne syndrome; Deafness; Disease variant; DNA damage; DNA repair; KW DNA-binding; Dwarfism; Endonuclease; Hydrolase; Magnesium; Metal-binding; KW Nuclease; Nucleus; Phosphoprotein; Reference proteome; KW Xeroderma pigmentosum. FT CHAIN 1..1186 FT /note="DNA excision repair protein ERCC-5" FT /id="PRO_0000154031" FT REGION 1..78 FT /note="N-domain" FT /evidence="ECO:0000305|PubMed:32522879" FT REGION 31..67 FT /note="DNA-binding; may bind to the undamaged single-strand FT DNA of the DNA repair bubble" FT /evidence="ECO:0000269|PubMed:32821917, FT ECO:0000312|PDB:6TUW, ECO:0007744|PDB:6TUX" FT REGION 79..785 FT /note="Spacer region" FT /evidence="ECO:0000269|PubMed:16246722" FT REGION 306..342 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 354..385 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 404..473 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 510..533 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 667..724 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 786..881 FT /note="I-domain" FT /evidence="ECO:0000305|PubMed:32522879" FT REGION 820..836 FT /note="DNA-binding; may bind to the undamaged single-strand FT DNA of the DNA repair bubble" FT /evidence="ECO:0000269|PubMed:32821917, FT ECO:0000312|PDB:6TUW, ECO:0007744|PDB:6TUX" FT REGION 848..880 FT /note="DNA-binding; H2TH (helix-2turn-helix) motif which FT binds double-stranded DNA" FT /evidence="ECO:0000269|PubMed:32821917, FT ECO:0000312|PDB:6TUW, ECO:0007744|PDB:6TUX" FT REGION 912..918 FT /note="DNA-binding; may bind double-stranded DNA" FT /evidence="ECO:0000269|PubMed:32821917, FT ECO:0000312|PDB:6TUW, ECO:0007744|PDB:6TUX" FT REGION 981..1009 FT /note="Interaction with PCNA" FT /evidence="ECO:0000269|PubMed:9305916" FT REGION 1011..1186 FT /note="Interaction with ERCC6/CSB" FT /evidence="ECO:0000269|PubMed:16246722" FT REGION 1056..1081 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1095..1186 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 1057..1074 FT /note="Nuclear localization signal 1" FT /evidence="ECO:0000305|PubMed:26812207" FT MOTIF 1169..1186 FT /note="Nuclear localization signal 2" FT /evidence="ECO:0000305|PubMed:26812207" FT COMPBIAS 443..458 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 676..724 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1095..1150 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1168..1186 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT METAL 30 FT /note="Magnesium 1" FT /evidence="ECO:0000250|UniProtKB:P39748" FT METAL 77 FT /note="Magnesium 1" FT /evidence="ECO:0000250|UniProtKB:P39748" FT METAL 789 FT /note="Magnesium 1" FT /evidence="ECO:0000250|UniProtKB:P39748" FT METAL 791 FT /note="Magnesium 1" FT /evidence="ECO:0000250|UniProtKB:P39748" FT METAL 810 FT /note="Magnesium 2" FT /evidence="ECO:0000250|UniProtKB:P39748" FT METAL 812 FT /note="Magnesium 2" FT /evidence="ECO:0000250|UniProtKB:P39748" FT METAL 861 FT /note="Magnesium 2" FT /evidence="ECO:0000250|UniProtKB:P39748" FT MOD_RES 8 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 384 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P35689" FT MOD_RES 705 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P35689" FT VAR_SEQ 1..767 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_035380" FT VAR_SEQ 225..232 FT /note="ESDDFSQY -> VYLPLLQP (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_053828" FT VAR_SEQ 233..1186 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_053829" FT VARIANT 28 FT /note="A -> D (in XP-G; patient cells show a strong DNA FT repair defect in response to UV light but not in response FT to oxidative stress; decreased nucleotide-excision repair FT activity; dbSNP:rs267607281)" FT /evidence="ECO:0000269|PubMed:23255472" FT /id="VAR_075773" FT VARIANT 72 FT /note="P -> H (in XP-G; combined with features of Cockayne FT syndrome; dbSNP:rs121434574)" FT /evidence="ECO:0000269|PubMed:11228268" FT /id="VAR_015280" FT VARIANT 145 FT /note="V -> I (in dbSNP:rs4987063)" FT /id="VAR_020431" FT VARIANT 181 FT /note="H -> R (in dbSNP:rs4150295)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_023120" FT VARIANT 254 FT /note="M -> V (in dbSNP:rs1047769)" FT /evidence="ECO:0000269|PubMed:7510366, FT ECO:0000269|PubMed:8413238, ECO:0000269|Ref.5, FT ECO:0000269|Ref.6" FT /id="VAR_007732" FT VARIANT 256 FT /note="Q -> R (in dbSNP:rs4150313)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_020432" FT VARIANT 311 FT /note="S -> C (in dbSNP:rs2307491)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_014829" FT VARIANT 399 FT /note="E -> K (in dbSNP:rs4150315)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_023121" FT VARIANT 529 FT /note="C -> S (in dbSNP:rs2227869)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_020433" FT VARIANT 590 FT /note="V -> I (in dbSNP:rs4150318)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_023122" FT VARIANT 597 FT /note="V -> L (in dbSNP:rs4150319)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_023123" FT VARIANT 670 FT /note="F -> L (in dbSNP:rs1803542)" FT /id="VAR_046373" FT VARIANT 680 FT /note="Q -> R (in dbSNP:rs4987168)" FT /id="VAR_020434" FT VARIANT 792 FT /note="A -> V (in XP-G; mild form; dbSNP:rs121434571)" FT /evidence="ECO:0000269|PubMed:7951246" FT /id="VAR_007733" FT VARIANT 858 FT /note="L -> P (in XP-G; reduced stability and greatly FT impaired endonuclease activity; dbSNP:rs121434575)" FT /evidence="ECO:0000269|PubMed:11841555" FT /id="VAR_017097" FT VARIANT 874 FT /note="A -> T (in XP-G; mild form; residual activity; FT dbSNP:rs121434576)" FT /evidence="ECO:0000269|PubMed:12060391" FT /id="VAR_017096" FT VARIANT 879 FT /note="N -> S (in dbSNP:rs4150342)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_020435" FT VARIANT 968 FT /note="W -> C (in XP-G; patient cells show a strong DNA FT repair defect in response to UV light but not in response FT to oxidative stress; decreased nucleotide-excision repair FT activity; dbSNP:rs267607280)" FT /evidence="ECO:0000269|PubMed:23255472" FT /id="VAR_075774" FT VARIANT 1009 FT /note="R -> H (in dbSNP:rs4150387)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_023124" FT VARIANT 1053 FT /note="G -> R (in dbSNP:rs9514066)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:7510366, ECO:0000269|PubMed:8413238, FT ECO:0000269|PubMed:8483504, ECO:0000269|Ref.5, FT ECO:0000269|Ref.6" FT /id="VAR_046374" FT VARIANT 1078 FT /note="S -> A (found in a patient diagnosed with multiple FT sclerosis; unknown pathological significance; FT dbSNP:rs760347832)" FT /evidence="ECO:0000269|PubMed:30533531" FT /id="VAR_085644" FT VARIANT 1080 FT /note="G -> Q (requires 2 nucleotide substitutions; FT dbSNP:rs587778291)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_023125" FT VARIANT 1080 FT /note="G -> R (in dbSNP:rs9514067)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:7510366, ECO:0000269|PubMed:8413238, FT ECO:0000269|PubMed:8483504, ECO:0000269|Ref.5, FT ECO:0000269|Ref.6" FT /id="VAR_046375" FT VARIANT 1104 FT /note="D -> H (in dbSNP:rs17655)" FT /evidence="ECO:0000269|PubMed:8483504" FT /id="VAR_007734" FT VARIANT 1119 FT /note="A -> V (in dbSNP:rs2227871)" FT /id="VAR_020436" FT MUTAGEN 67..68 FT /note="FF->AA: Slight reduction in endonuclease activity. FT Increased affinity for bubble DNA." FT /evidence="ECO:0000269|PubMed:32522879" FT MUTAGEN 955..956 FT /note="LD->AA: Reduced protein stability, two-fold decrease FT in 15-nt bubble DNA incision activity and smaller decrease FT in YDNA incision activity; when associated with A-978 and FT A-981." FT /evidence="ECO:0000269|PubMed:32522879" FT MUTAGEN 978 FT /note="F->A: Reduced protein stability, two-fold decrease FT in 15-nt bubble DNA incision activity and smaller decrease FT in YDNA incision activity; when associated with 955-A-A-956 FT and A-981." FT /evidence="ECO:0000269|PubMed:32522879" FT MUTAGEN 981 FT /note="L->A: Reduced protein stability, two-fold decrease FT in 15-nt bubble DNA incision activity and smaller decrease FT in YDNA incision activity; when associated with 955-A-A-956 FT and A-978." FT /evidence="ECO:0000269|PubMed:32522879" FT CONFLICT 55 FT /note="L -> P (in Ref. 2; BAA03812)" FT /evidence="ECO:0000305" FT CONFLICT 120..122 FT /note="KTA -> QTS (in Ref. 2; BAA03812)" FT /evidence="ECO:0000305" FT CONFLICT 126 FT /note="K -> Q (in Ref. 2; BAA03812)" FT /evidence="ECO:0000305" FT CONFLICT 264..266 FT /note="RQY -> SSH (in Ref. 2; BAA03812)" FT /evidence="ECO:0000305" FT CONFLICT 760 FT /note="I -> F (in Ref. 2; BAA03812)" FT /evidence="ECO:0000305" FT CONFLICT 796 FT /note="I -> V (in Ref. 2; BAA03812)" FT /evidence="ECO:0000305" FT CONFLICT 864..872 FT /note="EGIPTVGCV -> GNTNCGLC (in Ref. 2; BAA03812)" FT /evidence="ECO:0000305" FT CONFLICT 959 FT /note="R -> S (in Ref. 2; BAA03812)" FT /evidence="ECO:0000305" FT STRAND 3..5 FT /evidence="ECO:0007829|PDB:6TUX" FT HELIX 6..10 FT /evidence="ECO:0007829|PDB:6TUS" FT HELIX 11..13 FT /evidence="ECO:0007829|PDB:6TUS" FT STRAND 15..17 FT /evidence="ECO:0007829|PDB:6TUS" FT HELIX 19..22 FT /evidence="ECO:0007829|PDB:6TUS" FT STRAND 26..30 FT /evidence="ECO:0007829|PDB:6TUS" FT HELIX 31..40 FT /evidence="ECO:0007829|PDB:6TUS" FT STRAND 45..48 FT /evidence="ECO:0007829|PDB:6TUX" FT HELIX 53..67 FT /evidence="ECO:0007829|PDB:6TUS" FT STRAND 71..76 FT /evidence="ECO:0007829|PDB:6TUS" FT STRAND 713..715 FT /evidence="ECO:0007829|PDB:6TUS" FT HELIX 716..724 FT /evidence="ECO:0007829|PDB:6TUX" FT TURN 755..757 FT /evidence="ECO:0007829|PDB:6TUX" FT HELIX 766..779 FT /evidence="ECO:0007829|PDB:6VBH" FT STRAND 783..785 FT /evidence="ECO:0007829|PDB:6VBH" FT HELIX 790..799 FT /evidence="ECO:0007829|PDB:6VBH" FT STRAND 802..804 FT /evidence="ECO:0007829|PDB:6VBH" FT HELIX 812..815 FT /evidence="ECO:0007829|PDB:6VBH" FT STRAND 820..823 FT /evidence="ECO:0007829|PDB:6VBH" FT STRAND 830..836 FT /evidence="ECO:0007829|PDB:6VBH" FT HELIX 837..844 FT /evidence="ECO:0007829|PDB:6VBH" FT HELIX 848..858 FT /evidence="ECO:0007829|PDB:6VBH" FT HELIX 871..880 FT /evidence="ECO:0007829|PDB:6VBH" FT HELIX 887..901 FT /evidence="ECO:0007829|PDB:6VBH" FT HELIX 913..919 FT /evidence="ECO:0007829|PDB:6VBH" FT HELIX 930..937 FT /evidence="ECO:0007829|PDB:6VBH" FT HELIX 955..966 FT /evidence="ECO:0007829|PDB:6VBH" FT HELIX 970..985 FT /evidence="ECO:0007829|PDB:6VBH" SQ SEQUENCE 1186 AA; 133108 MW; B0A844D617C53F2E CRC64; MGVQGLWKLL ECSGRQVSPE ALEGKILAVD ISIWLNQALK GVRDRHGNSI ENPHLLTLFH RLCKLLFFRI RPIFVFDGDA PLLKKQTLVK RRQRKDLASS DSRKTTEKLL KTFLKRQAIK TAFRSKRDEA LPSLTQVRRE NDLYVLPPLQ EEEKHSSEEE DEKEWQERMN QKQALQEEFF HNPQAIDIES EDFSSLPPEV KHEILTDMKE FTKRRRTLFE AMPEESDDFS QYQLKGLLKK NYLNQHIEHV QKEMNQQHSG HIRRQYEDEG GFLKEVESRR VVSEDTSHYI LIKGIQAKTV AEVDSESLPS SSKMHGMSFD VKSSPCEKLK TEKEPDATPP SPRTLLAMQA ALLGSSSEEE LESENRRQAR GRNAPAAVDE GSISPRTLSA IKRALDDDED VKVCAGDDVQ TGGPGAEEMR INSSTENSDE GLKVRDGKGI PFTATLASSS VNSAEEHVAS TNEGREPTDS VPKEQMSLVH VGTEAFPISD ESMIKDRKDR LPLESAVVRH SDAPGLPNGR ELTPASPTCT NSVSKNETHA EVLEQQNELC PYESKFDSSL LSSDDETKCK PNSASEVIGP VSLQETSSIV SVPSEAVDNV ENVVSFNAKE HENFLETIQE QQTTESAGQD LISIPKAVEP MEIDSEESES DGSFIEVQSV ISDEELQAEF PETSKPPSEQ GEEELVGTRE GEAPAESESL LRDNSERDDV DGEPQEAEKD AEDSLHEWQD INLEELETLE SNLLAQQNSL KAQKQQQERI AATVTGQMFL ESQELLRLFG IPYIQAPMEA EAQCAILDLT DQTSGTITDD SDIWLFGARH VYRNFFNKNK FVEYYQYVDF HNQLGLDRNK LINLAYLLGS DYTEGIPTVG CVTAMEILNE FPGHGLEPLL KFSEWWHEAQ KNPKIRPNPH DTKVKKKLRT LQLTPGFPNP AVAEAYLKPV VDDSKGSFLW GKPDLDKIRE FCQRYFGWNR TKTDESLFPV LKQLDAQQTQ LRIDSFFRLA QQEKEDAKRI KSQRLNRAVT CMLRKEKEAA ASEIEAVSVA MEKEFELLDK AKGKTQKRGI TNTLEESSSL KRKRLSDSKG KNTCGGFLGE TCLSESSDGS SSEDAESSSL MNVQRRTAAK EPKTSASDSQ NSVKEAPVKN GGATTSSSSD SDDDGGKEKM VLVTARSVFG KKRRKLRRAR GRKRKT // ID N42L2_HUMAN Reviewed; 583 AA. AC Q92802; A3KME8; DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1997, sequence version 1. DT 25-MAY-2022, entry version 168. DE RecName: Full=NEDD4-binding protein 2-like 2; DE AltName: Full=Phosphonoformate immuno-associated protein 5; GN Name=N4BP2L2; Synonyms=CG005, PFAAP5; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=8812419; DOI=10.1006/geno.1996.0428; RA Couch F.J., Rommens J.M., Neuhausen S.L., Belanger C., Dumont M., RA Kenneth A., Bell R., Berry S., Bogden R., Cannon-Albright L., Farid L., RA Frye C., Hattier T., Janecki T., Jiang P., Kehrer R., Leblanc J.F., RA McArthur-Morrison J., McSweeney D., Miki Y., Peng Y., Samson C., RA Schroeder M., Snyder S.C., Stringfellow M., Stroup C., Swedlund B., RA Swensen J., Teng D., Thakur S., Tran T., Tranchant M., Welver-Feldhaus J., RA Wong A.K.C., Shizuya H., Labrie F., Skolnick M.H., Goldgar D.E., Kamb A., RA Weber B.L., Tavtigian S.V., Simard J.; RT "Generation of an integrated transcription map of the BRCA2 region on RT chromosome 13q12-q13."; RL Genomics 36:86-99(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Liu Y., Cheng J., Lu Y.; RT "Screening and cloning of a new immuno-associated gene regulated by RT phosphonoformate."; RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Rhodes S.; RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057823; DOI=10.1038/nature02379; RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L., RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., RA Frankish A.G., Frankland J., French L., Garner P., Garnett J., RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., RA Rogers J., Ross M.T.; RT "The DNA sequence and analysis of human chromosome 13."; RL Nature 428:522-528(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 434-583 (ISOFORM 2). RC TISSUE=Colon; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RX PubMed=16344560; DOI=10.1101/gr.4039406; RA Kimura K., Wakamatsu A., Suzuki Y., Ota T., Nishikawa T., Yamashita R., RA Yamamoto J., Sekine M., Tsuritani K., Wakaguri H., Ishii S., Sugiyama T., RA Saito K., Isono Y., Irie R., Kushida N., Yoneyama T., Otsuka R., Kanda K., RA Yokoi T., Kondo H., Wagatsuma M., Murakawa K., Ishida S., Ishibashi T., RA Takahashi-Fujii A., Tanase T., Nagai K., Kikuchi H., Nakai K., Isogai T., RA Sugano S.; RT "Diversification of transcriptional modulation: large-scale identification RT and characterization of putative alternative promoters of human genes."; RL Genome Res. 16:55-65(2006). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). CC -!- INTERACTION: CC Q92802; P49639: HOXA1; NbExp=3; IntAct=EBI-2514973, EBI-740785; CC Q92802; P25791: LMO2; NbExp=3; IntAct=EBI-2514973, EBI-739696; CC Q92802; Q9BRA0: NAA38; NbExp=3; IntAct=EBI-2514973, EBI-9106509; CC Q92802; O43447: PPIH; NbExp=10; IntAct=EBI-2514973, EBI-1055615; CC Q92802; Q9Y3C6: PPIL1; NbExp=3; IntAct=EBI-2514973, EBI-2557649; CC Q92802; P09022: Hoxa1; Xeno; NbExp=3; IntAct=EBI-2514973, EBI-3957603; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q92802-1; Sequence=Displayed; CC Name=2; CC IsoId=Q92802-2; Sequence=VSP_027518; CC Name=3; CC IsoId=Q92802-3; Sequence=VSP_041337, VSP_041338, VSP_041339; CC -!- SEQUENCE CAUTION: CC Sequence=AAI31632.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305}; CC Sequence=BP361938; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U50532; AAC50875.1; -; mRNA. DR EMBL; AF530063; AAQ09947.1; -; mRNA. DR EMBL; AL049783; CAB42441.1; -; mRNA. DR EMBL; BT007172; AAP35836.1; -; mRNA. DR EMBL; AL353665; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471075; EAX08514.1; -; Genomic_DNA. DR EMBL; BC010643; AAH10643.1; -; mRNA. DR EMBL; BC131631; AAI31632.1; ALT_SEQ; mRNA. DR EMBL; BP361938; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS45024.1; -. [Q92802-3] DR CCDS; CCDS9346.1; -. [Q92802-1] DR RefSeq; NP_055702.1; NM_014887.2. [Q92802-1] DR RefSeq; XP_016875836.1; XM_017020347.1. [Q92802-1] DR RefSeq; XP_016875837.1; XM_017020348.1. [Q92802-1] DR RefSeq; XP_016875838.1; XM_017020349.1. [Q92802-1] DR AlphaFoldDB; Q92802; -. DR BioGRID; 115708; 78. DR IntAct; Q92802; 50. DR MINT; Q92802; -. DR STRING; 9606.ENSP00000382328; -. DR iPTMnet; Q92802; -. DR PhosphoSitePlus; Q92802; -. DR BioMuta; N4BP2L2; -. DR DMDM; 74751659; -. DR EPD; Q92802; -. DR jPOST; Q92802; -. DR MassIVE; Q92802; -. DR MaxQB; Q92802; -. DR PaxDb; Q92802; -. DR PeptideAtlas; Q92802; -. DR PRIDE; Q92802; -. DR ProteomicsDB; 75485; -. [Q92802-1] DR ProteomicsDB; 75486; -. [Q92802-2] DR ProteomicsDB; 75487; -. [Q92802-3] DR Antibodypedia; 42083; 219 antibodies from 21 providers. DR DNASU; 10443; -. DR Ensembl; ENST00000267068.5; ENSP00000267068.3; ENSG00000244754.9. DR Ensembl; ENST00000399396.7; ENSP00000382328.3; ENSG00000244754.9. [Q92802-3] DR Ensembl; ENST00000446957.6; ENSP00000394239.2; ENSG00000244754.9. [Q92802-2] DR Ensembl; ENST00000674349.1; ENSP00000501516.1; ENSG00000244754.9. DR Ensembl; ENST00000674421.1; ENSP00000501518.1; ENSG00000244754.9. DR Ensembl; ENST00000674465.1; ENSP00000501416.1; ENSG00000244754.9. DR Ensembl; ENST00000674484.1; ENSP00000501537.1; ENSG00000244754.9. DR GeneID; 10443; -. DR KEGG; hsa:10443; -. DR UCSC; uc001uuk.5; human. [Q92802-1] DR CTD; 10443; -. DR DisGeNET; 10443; -. DR GeneCards; N4BP2L2; -. DR HGNC; HGNC:26916; N4BP2L2. DR HPA; ENSG00000244754; Low tissue specificity. DR MIM; 615788; gene. DR neXtProt; NX_Q92802; -. DR OpenTargets; ENSG00000244754; -. DR PharmGKB; PA162396632; -. DR VEuPathDB; HostDB:ENSG00000244754; -. DR eggNOG; KOG2401; Eukaryota. DR GeneTree; ENSGT00940000161440; -. DR HOGENOM; CLU_006655_0_0_1; -. DR InParanoid; Q92802; -. DR OMA; LNIGGQC; -. DR OrthoDB; 76267at2759; -. DR PhylomeDB; Q92802; -. DR TreeFam; TF336975; -. DR PathwayCommons; Q92802; -. DR SignaLink; Q92802; -. DR BioGRID-ORCS; 10443; 11 hits in 1075 CRISPR screens. DR ChiTaRS; N4BP2L2; human. DR GenomeRNAi; 10443; -. DR Pharos; Q92802; Tbio. DR PRO; PR:Q92802; -. DR Proteomes; UP000005640; Chromosome 13. DR RNAct; Q92802; protein. DR Bgee; ENSG00000244754; Expressed in calcaneal tendon and 245 other tissues. DR ExpressionAtlas; Q92802; baseline and differential. DR Genevisible; Q92802; HS. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0017053; C:transcription repressor complex; IDA:UniProtKB. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0003714; F:transcription corepressor activity; ISS:UniProtKB. DR GO; GO:0001824; P:blastocyst development; IEA:Ensembl. DR GO; GO:1902037; P:negative regulation of hematopoietic stem cell differentiation; IMP:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:CAFA. DR GO; GO:1902035; P:positive regulation of hematopoietic stem cell proliferation; IMP:UniProtKB. DR Gene3D; 3.40.50.300; -; 1. DR InterPro; IPR026568; NEDD4-bind_pro_2-like_2. DR InterPro; IPR026302; NEDD4_b_p2. DR InterPro; IPR027417; P-loop_NTPase. DR PANTHER; PTHR13308; PTHR13308; 1. DR PANTHER; PTHR13308:SF23; PTHR13308:SF23; 1. DR SUPFAM; SSF52540; SSF52540; 1. PE 1: Evidence at protein level; KW Alternative splicing; Coiled coil; Reference proteome. FT CHAIN 1..583 FT /note="NEDD4-binding protein 2-like 2" FT /id="PRO_0000299026" FT REGION 549..575 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 162..197 FT /evidence="ECO:0000255" FT VAR_SEQ 8..32 FT /note="GKFLGPREEVTSEPRCKKLKSTTES -> EFCLVRIVMALCSALMTIFTIKM FT GT (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_041337" FT VAR_SEQ 33..461 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_041338" FT VAR_SEQ 566..583 FT /note="RWGGSLGSHNRVCVTNNH -> RERVLKKTGHRLSKTKQKRNRKRNKKQNSQ FT NRIMEENSLEFLSDLTPGDQDPSQSEEEDIEKTRRESEYPFIDGLQNEVGDFVTGYKEK FT RWKNKDPKDSFQNVMSIVELDNTPKNYLSKEGDNLFVSLLLRPNEISVTCPILTQNLSC FT VTTDDCSGMKVEKHIRNRHTIALDTQDLSAETSCLFMKKREIVDKNLSHEPILCHQHGI FT RMSDKVLREEQVYTTKINHWAFFTTNLSDEDLQLGSDRQPYFGSWPAGPHKFICEQRPK FT KDRACKLAGPDSRGQWIQMIFTSVAASEPGNNPEILTDKLLIGNEDFSPPPETMDSFIE FT TNLFRSCLPQPDIPKNALESTKNKKRRKKRIFNLVPNFDLLGQSRIGVKEREKCDLLTK FT NHGLKITLGEEKDRISERNSEEENKQKLMTFDHHPLWFYLDIIKATPLNIDGQRYSHCL FT SFNRLRCSASLYKNYIPSFVLHNLSSIWKPSFTNKKLFLTFESQTRVGNKLNDAGFISP FT EILHSHPDTSCSLGVTSDFHFLNERFDRKLKRWEEPKELPAEDSQDLTSTDYRSLELPL FT SQGFAFQLVKLFGSPGVPMESLLPDDYVVPLDWKTLKMIYLQWKMSVEKRQKKIG (in FT isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_041339" FT VAR_SEQ 567..583 FT /note="WGGSLGSHNRVCVTNNH -> FDRKLKRWEEPKELPAEDSQDLTSTDYRSLE FT LPLSQGFAFQLVKLFGSPGVPMESLLPDDYVVPLDWKTLKMIYLQWKMSVEKRQKKIG FT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_027518" FT VARIANT 272 FT /note="Y -> H (in dbSNP:rs34062461)" FT /id="VAR_034765" SQ SEQUENCE 583 AA; 67459 MW; 318DC4D81CD0FF2A CRC64; MSYGEIEGKF LGPREEVTSE PRCKKLKSTT ESYVFHNHSN ADFHRIQEKT GNDWVPVTII DVRGHSYLQE NKIKTTDLHR PLHDEMPGNR PDVIESIDSQ VLQEARPPLV SADDEIYSTS KAFIGPIYKP PEKKKRNEGR NEAHVLNGIN DRGGQKEKQK FNSEKSEIDN ELFQFYKEIE ELEKEKDGFE NSCKESEPSQ EQFVPFYEGH NNGLLKPDEE KKDLSNKAMP SHCDYQQNLG NEPDKYPCNG QVIPTFCDTS FTSFRPEWQS VYPFIVPYGP PLPSLNYHLN IQRFSGPPNP PSNIFQAQDD SQIQNGYYVN NCHVNWNCMT FDQNNEYTDC SENRSSVHPS GNGCSMQDRY VSNGFCEVRE RCWKDHCMDK HNGTDRFVNQ QFQEEKLNKL QKLLILLRGL PGSGKTTLSR ILLGQNRDGI VFSTDDYFHH QDGYRYNVNQ LGDAHDWNQN RAKQAIDQGR SPVIIDNTNI QAWEMKPYVE VAIGKGYRVE FHEPETWWKF DPEELEKRNK HGVSRKKIAQ MLDRYEYQMS ISIVMNSVEP SHKSTQRPPP PQGRQRWGGS LGSHNRVCVT NNH // ID BABA2_HUMAN Reviewed; 383 AA. AC Q9NXR7; A8K4X1; D6W562; D6W563; Q13880; Q4ZFX8; Q53SD0; Q969X9; Q96P06; DT 21-FEB-2006, integrated into UniProtKB/Swiss-Prot. DT 05-MAY-2009, sequence version 2. DT 25-MAY-2022, entry version 163. DE RecName: Full=BRISC and BRCA1-A complex member 2 {ECO:0000312|HGNC:HGNC:1106}; DE AltName: Full=BRCA1-A complex subunit BRE; DE AltName: Full=BRCA1/BRCA2-containing complex subunit 45 {ECO:0000303|PubMed:14636569}; DE AltName: Full=Brain and reproductive organ-expressed protein {ECO:0000303|PubMed:7826398}; GN Name=BABAM2 {ECO:0000312|HGNC:HGNC:1106}; Synonyms=BRCC45, BRE; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] {ECO:0000305, ECO:0000312|EMBL:AAA64231.1} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND INDUCTION. RX PubMed=7826398; DOI=10.1006/bbrc.1995.1108; RA Li L., Yoo H., Becker F.F., Ali-Osman F., Chan J.Y.-H.; RT "Identification of a brain- and reproductive-organs-specific gene RT responsive to DNA damage and retinoic acid."; RL Biochem. Biophys. Res. Commun. 206:764-774(1995). RN [2] {ECO:0000305, ECO:0000312|EMBL:AAL17818.1} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4), TISSUE SPECIFICITY, AND RP INDUCTION. RC TISSUE=Monocyte {ECO:0000269|PubMed:11676476}; RX PubMed=11676476; DOI=10.1006/bbrc.2001.5801; RA Ching A.K.K., Li P.S., Li Q., Chan B.C.L., Chan J.Y.-H., Lim P.L., RA Pang J.C.S., Chui Y.L.; RT "Expression of human BRE in multiple isoforms."; RL Biochem. Biophys. Res. Commun. 288:535-545(2001). RN [3] {ECO:0000305, ECO:0000312|EMBL:AAR30499.1} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, AND IDENTIFICATION IN RP BRCC COMPLEX. RX PubMed=14636569; DOI=10.1016/s1097-2765(03)00424-6; RA Dong Y., Hakimi M.-A., Chen X., Kumaraswamy E., Cooch N.S., Godwin A.K., RA Shiekhattar R.; RT "Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a RT signalosome-like subunit and its role in DNA repair."; RL Mol. Cell 12:1087-1099(2003). RN [4] {ECO:0000305, ECO:0000312|EMBL:AAB69387.1} RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RA Keeton K.R., Miles W.M.; RL Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases. RN [5] {ECO:0000305, ECO:0000312|EMBL:BAA90943.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Colon {ECO:0000312|EMBL:BAA90943.1}, and Teratocarcinoma; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [7] {ECO:0000305, ECO:0000312|EMBL:AAB69387.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] {ECO:0000305, ECO:0000312|EMBL:AAH01251.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Cervix {ECO:0000312|EMBL:AAH01251.1}; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] {ECO:0000305} RP FUNCTION, INTERACTION WITH FAS AND TNFRSF1A, AND SUBCELLULAR LOCATION. RX PubMed=15465831; DOI=10.1074/jbc.m408678200; RA Li Q., Ching A.K.-K., Chan B.C.-L., Chow S.K.-Y., Lim P.-L., Ho T.C.-Y., RA Ip W.-K., Wong C.-K., Lam C.W.-K., Lee K.K.-H., Chan J.Y.-H., Chui Y.-L.; RT "A death receptor-associated anti-apoptotic protein, BRE, inhibits RT mitochondrial apoptotic pathway."; RL J. Biol. Chem. 279:52106-52116(2004). RN [10] RP IDENTIFICATION IN THE BRCA1-A COMPLEX. RX PubMed=17525341; DOI=10.1126/science.1139516; RA Sobhian B., Shao G., Lilli D.R., Culhane A.C., Moreau L.A., Xia B., RA Livingston D.M., Greenberg R.A.; RT "RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage RT sites."; RL Science 316:1198-1202(2007). RN [11] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [12] RP IDENTIFICATION IN THE BRISC COMPLEX. RX PubMed=19214193; DOI=10.1038/emboj.2009.27; RA Cooper E.M., Cutcliffe C., Kristiansen T.Z., Pandey A., Pickart C.M., RA Cohen R.E.; RT "K63-specific deubiquitination by two JAMM/MPN+ complexes: BRISC-associated RT Brcc36 and proteasomal Poh1."; RL EMBO J. 28:621-631(2009). RN [13] RP IDENTIFICATION IN THE BRCA1-A COMPLEX. RX PubMed=19261746; DOI=10.1101/gad.1739609; RA Shao G., Patterson-Fortin J., Messick T.E., Feng D., Shanbhag N., Wang Y., RA Greenberg R.A.; RT "MERIT40 controls BRCA1-Rap80 complex integrity and recruitment to DNA RT double-strand breaks."; RL Genes Dev. 23:740-754(2009). RN [14] RP FUNCTION, IDENTIFICATION IN THE BRCA1-A COMPLEX, DOMAIN UEV-LIKE, RP UBIQUITIN-BINDING, AND INTERACTION WITH ABRAXAS1. RX PubMed=19261749; DOI=10.1101/gad.1770309; RA Wang B., Hurov K., Hofmann K., Elledge S.J.; RT "NBA1, a new player in the Brca1 A complex, is required for DNA damage RT resistance and checkpoint control."; RL Genes Dev. 23:729-739(2009). RN [15] RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE RP BRCA1-A COMPLEX, SUBCELLULAR LOCATION, AND INTERACTION WITH ABRAXAS1; RP BABAM1 AND BRCC3. RX PubMed=19261748; DOI=10.1101/gad.1770609; RA Feng L., Huang J., Chen J.; RT "MERIT40 facilitates BRCA1 localization and DNA damage repair."; RL Genes Dev. 23:719-728(2009). RN [16] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT SER-2, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [18] RP IDENTIFICATION IN ARISC COMPLEX, IDENTIFICATION IN BRISC COMPLEX, AND RP INTERACTION WITH BABAM1. RX PubMed=21282113; DOI=10.1074/jbc.m110.200857; RA Hu X., Kim J.A., Castillo A., Huang M., Liu J., Wang B.; RT "NBA1/MERIT40 and BRE interaction is required for the integrity of two RT distinct deubiquitinating enzyme BRCC36-containing complexes."; RL J. Biol. Chem. 286:11734-11745(2011). RN [19] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [21] RP FUNCTION, IDENTIFICATION IN THE BRISC COMPLEX, IDENTIFICATION BY MASS RP SPECTROMETRY, IDENTIFICATION IN THE ARISC COMPLEX, AND SUBCELLULAR RP LOCATION. RX PubMed=24075985; DOI=10.1016/j.celrep.2013.08.025; RA Zheng H., Gupta V., Patterson-Fortin J., Bhattacharya S., Katlinski K., RA Wu J., Varghese B., Carbone C.J., Aressy B., Fuchs S.Y., Greenberg R.A.; RT "A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates interferon RT responses."; RL Cell Rep. 5:180-193(2013). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [23] RP IDENTIFICATION IN THE BRISC COMPLEX. RX PubMed=25283148; DOI=10.1038/ncomms6059; RA Zhang J., Cao M., Dong J., Li C., Xu W., Zhan Y., Wang X., Yu M., Ge C., RA Ge Z., Yang X.; RT "ABRO1 suppresses tumourigenesis and regulates the DNA damage response by RT stabilizing p53."; RL Nat. Commun. 5:5059-5059(2014). RN [24] RP FUNCTION OF THE BRISC COMPLEX. RX PubMed=26195665; DOI=10.1083/jcb.201503039; RA Yan K., Li L., Wang X., Hong R., Zhang Y., Yang H., Lin M., Zhang S., RA He Q., Zheng D., Tang J., Yin Y., Shao G.; RT "The deubiquitinating enzyme complex BRISC is required for proper mitotic RT spindle assembly in mammalian cells."; RL J. Cell Biol. 210:209-224(2015). CC -!- FUNCTION: Component of the BRCA1-A complex, a complex that specifically CC recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA CC lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites CC of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also CC possesses deubiquitinase activity that specifically removes 'Lys-63'- CC linked ubiquitin on histones H2A and H2AX (PubMed:17525341, CC PubMed:19261746, PubMed:19261749, PubMed:19261748). In the BRCA1-A CC complex, it acts as an adapter that bridges the interaction between CC BABAM1/NBA1 and the rest of the complex, thereby being required for the CC complex integrity and modulating the E3 ubiquitin ligase activity of CC the BRCA1-BARD1 heterodimer (PubMed:21282113, PubMed:19261748). CC Component of the BRISC complex, a multiprotein complex that CC specifically cleaves 'Lys-63'-linked ubiquitin in various substrates CC (PubMed:19214193, PubMed:24075985, PubMed:25283148, PubMed:26195665). CC Within the BRISC complex, acts as an adapter that bridges the CC interaction between BABAM1/NBA1 and the rest of the complex, thereby CC being required for the complex integrity (PubMed:21282113). The BRISC CC complex is required for normal mitotic spindle assembly and microtubule CC attachment to kinetochores via its role in deubiquitinating NUMA1 CC (PubMed:26195665). The BRISC complex plays a role in interferon CC signaling via its role in the deubiquitination of the interferon CC receptor IFNAR1; deubiquitination increases IFNAR1 activity by CC enhancing its stability and cell surface expression (PubMed:24075985). CC Down-regulates the response to bacterial lipopolysaccharide (LPS) via CC its role in IFNAR1 deubiquitination (PubMed:24075985). May play a role CC in homeostasis or cellular differentiation in cells of neural, CC epithelial and germline origins. May also act as a death receptor- CC associated anti-apoptotic protein, which inhibits the mitochondrial CC apoptotic pathway. May regulate TNF-alpha signaling through its CC interactions with TNFRSF1A; however these effects may be indirect CC (PubMed:15465831). {ECO:0000269|PubMed:14636569, CC ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19261749, CC ECO:0000269|PubMed:24075985, ECO:0000269|PubMed:26195665, CC ECO:0000305|PubMed:15465831}. CC -!- SUBUNIT: Component of the ARISC complex, at least composed of CC UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1 CC (PubMed:21282113, PubMed:24075985). Component of the BRCA1-A complex, CC at least composed of BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, CC BABAM2 and BABAM1/NBA1. In the BRCA1-A complex, interacts directly with CC ABRAXAS1, BRCC3/BRCC36 and BABAM1/NBA1. Binds polyubiquitin. Component CC of the BRISC complex, at least composed of ABRAXAS2, BRCC3/BRCC36, CC BABAM2 and BABAM1/NBA1 (PubMed:19214193, PubMed:21282113, CC PubMed:24075985, PubMed:25283148). Identified in a complex with SHMT2 CC and the other subunits of the BRISC complex (PubMed:24075985). CC Component of the BRCA1/BRCA2 containing complex (BRCC), which also CC contains BRCA1, BRCA2, BARD1, BRCC3/BRCC36 and RAD51. BRCC is a CC ubiquitin E3 ligase complex that enhances cellular survival following CC DNA damage. May interact with FAS and TNFRSF1A (PubMed:15465831). CC {ECO:0000269|PubMed:14636569, ECO:0000269|PubMed:17525341, CC ECO:0000269|PubMed:19214193, ECO:0000269|PubMed:19261746, CC ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19261749, CC ECO:0000269|PubMed:24075985, ECO:0000269|PubMed:25283148, CC ECO:0000305|PubMed:15465831}. CC -!- INTERACTION: CC Q9NXR7; Q9NWV8: BABAM1; NbExp=6; IntAct=EBI-949389, EBI-745725; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15465831, CC ECO:0000269|PubMed:24075985}. Nucleus {ECO:0000269|PubMed:15465831, CC ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:24075985}. CC Note=Localizes at sites of DNA damage at double-strand breaks (DSBs). CC {ECO:0000269|PubMed:19261748}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Comment=Additional isoforms may exist. {ECO:0000305}; CC Name=2 {ECO:0000269|PubMed:14636569}; CC IsoId=Q9NXR7-2; Sequence=Displayed; CC Name=1 {ECO:0000305}; CC IsoId=Q9NXR7-1; Sequence=VSP_051956; CC Name=3 {ECO:0000269|PubMed:11676476}; Synonyms=Alpha a'; CC IsoId=Q9NXR7-3; Sequence=VSP_051957; CC Name=4; CC IsoId=Q9NXR7-4; Sequence=VSP_037261; CC -!- TISSUE SPECIFICITY: Expressed in all cell lines examined. Highly CC expressed in placenta. {ECO:0000269|PubMed:11676476}. CC -!- INDUCTION: Down-regulated by DNA-damaging agents in fibroblasts, by CC retinoic acid in brain glioma U-251MG and promyelocytic HL-60 cell CC lines, and by bacterial lipopolysaccharides (LPS) in peripheral blood CC mononuclear cells (PBMC). {ECO:0000269|PubMed:11676476, CC ECO:0000269|PubMed:7826398}. CC -!- DOMAIN: Contains 2 ubiquitin-conjugating enzyme family-like (UEV-like) CC regions. These regions lack the critical Cys residues required for CC ubiquitination but retain the ability to bind ubiquitin. CC {ECO:0000269|PubMed:19261749}. CC -!- SIMILARITY: Belongs to the BABAM2 family. {ECO:0000255}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/BREID839ch2p23.html"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L38616; AAA64231.1; -; mRNA. DR EMBL; AF420605; AAL17818.1; -; mRNA. DR EMBL; AY438031; AAR30499.1; -; mRNA. DR EMBL; AF015767; AAB69387.1; -; mRNA. DR EMBL; AF420602; AAL17814.1; -; mRNA. DR EMBL; AF420603; AAL17816.1; -; mRNA. DR EMBL; AK000097; BAA90943.1; -; mRNA. DR EMBL; AK291086; BAF83775.1; -; mRNA. DR EMBL; AC021171; AAY24156.1; -; Genomic_DNA. DR EMBL; AC093690; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC096552; AAX88935.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00545.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00546.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00547.1; -; Genomic_DNA. DR EMBL; CH471053; EAX00548.1; -; Genomic_DNA. DR EMBL; BC001251; AAH01251.1; -; mRNA. DR CCDS; CCDS1763.1; -. [Q9NXR7-2] DR CCDS; CCDS1764.1; -. [Q9NXR7-1] DR CCDS; CCDS1765.1; -. [Q9NXR7-4] DR PIR; JC2472; JC2472. DR RefSeq; NP_001248769.1; NM_001261840.1. [Q9NXR7-3] DR RefSeq; NP_001316041.1; NM_001329112.1. [Q9NXR7-2] DR RefSeq; NP_001316042.1; NM_001329113.1. [Q9NXR7-1] DR RefSeq; NP_004890.2; NM_004899.4. [Q9NXR7-1] DR RefSeq; NP_954661.1; NM_199191.2. [Q9NXR7-2] DR RefSeq; NP_954662.1; NM_199192.2. [Q9NXR7-4] DR RefSeq; NP_954663.1; NM_199193.2. [Q9NXR7-4] DR RefSeq; NP_954664.1; NM_199194.2. [Q9NXR7-2] DR PDB; 6H3C; EM; 3.90 A; C/H=1-383. DR PDB; 6R8F; EM; 3.80 A; E/G=1-133. DR PDBsum; 6H3C; -. DR PDBsum; 6R8F; -. DR AlphaFoldDB; Q9NXR7; -. DR SMR; Q9NXR7; -. DR BioGRID; 114946; 74. DR ComplexPortal; CPX-4425; BRCA1-A complex. DR ComplexPortal; CPX-955; BRCC ubiquitin ligase complex. DR CORUM; Q9NXR7; -. DR IntAct; Q9NXR7; 33. DR MINT; Q9NXR7; -. DR STRING; 9606.ENSP00000343412; -. DR BindingDB; Q9NXR7; -. DR iPTMnet; Q9NXR7; -. DR PhosphoSitePlus; Q9NXR7; -. DR BioMuta; BABAM2; -. DR DMDM; 229462810; -. DR EPD; Q9NXR7; -. DR jPOST; Q9NXR7; -. DR MassIVE; Q9NXR7; -. DR MaxQB; Q9NXR7; -. DR PaxDb; Q9NXR7; -. DR PeptideAtlas; Q9NXR7; -. DR PRIDE; Q9NXR7; -. DR ProteomicsDB; 83124; -. [Q9NXR7-2] DR ProteomicsDB; 83125; -. [Q9NXR7-1] DR ProteomicsDB; 83126; -. [Q9NXR7-3] DR ProteomicsDB; 83127; -. [Q9NXR7-4] DR Antibodypedia; 13903; 257 antibodies from 35 providers. DR DNASU; 9577; -. DR Ensembl; ENST00000342045.6; ENSP00000339371.2; ENSG00000158019.21. DR Ensembl; ENST00000344773.6; ENSP00000343412.2; ENSG00000158019.21. [Q9NXR7-1] DR Ensembl; ENST00000361704.6; ENSP00000354699.2; ENSG00000158019.21. [Q9NXR7-4] DR Ensembl; ENST00000379624.6; ENSP00000368945.1; ENSG00000158019.21. DR Ensembl; ENST00000379632.6; ENSP00000368953.2; ENSG00000158019.21. [Q9NXR7-4] DR GeneID; 9577; -. DR KEGG; hsa:9577; -. DR MANE-Select; ENST00000379624.6; ENSP00000368945.1; NM_199191.3; NP_954661.1. DR UCSC; uc002rlq.4; human. [Q9NXR7-2] DR CTD; 9577; -. DR DisGeNET; 9577; -. DR GeneCards; BABAM2; -. DR HGNC; HGNC:1106; BABAM2. DR HPA; ENSG00000158019; Tissue enriched (adrenal). DR MIM; 610497; gene. DR neXtProt; NX_Q9NXR7; -. DR OpenTargets; ENSG00000158019; -. DR PharmGKB; PA25419; -. DR VEuPathDB; HostDB:ENSG00000158019; -. DR eggNOG; ENOG502QUU0; Eukaryota. DR GeneTree; ENSGT00390000004208; -. DR HOGENOM; CLU_057019_0_0_1; -. DR InParanoid; Q9NXR7; -. DR OMA; KPTEARF; -. DR PhylomeDB; Q9NXR7; -. DR TreeFam; TF328507; -. DR PathwayCommons; Q9NXR7; -. DR Reactome; R-HSA-5689901; Metalloprotease DUBs. DR Reactome; R-HSA-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks. DR Reactome; R-HSA-5693571; Nonhomologous End-Joining (NHEJ). DR Reactome; R-HSA-5693607; Processing of DNA double-strand break ends. DR Reactome; R-HSA-69473; G2/M DNA damage checkpoint. DR SignaLink; Q9NXR7; -. DR SIGNOR; Q9NXR7; -. DR BioGRID-ORCS; 9577; 18 hits in 1089 CRISPR screens. DR ChiTaRS; BRE; human. DR GeneWiki; BRE_(gene); -. DR GenomeRNAi; 9577; -. DR Pharos; Q9NXR7; Tbio. DR PRO; PR:Q9NXR7; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q9NXR7; protein. DR Bgee; ENSG00000158019; Expressed in right adrenal gland and 235 other tissues. DR ExpressionAtlas; Q9NXR7; baseline and differential. DR Genevisible; Q9NXR7; HS. DR GO; GO:0070531; C:BRCA1-A complex; IDA:UniProtKB. DR GO; GO:0070552; C:BRISC complex; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0000152; C:nuclear ubiquitin ligase complex; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0000268; F:peroxisome targeting sequence binding; TAS:UniProtKB. DR GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; IDA:UniProtKB. DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IDA:UniProtKB. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IEP:UniProtKB. DR GO; GO:0071479; P:cellular response to ionizing radiation; IMP:ComplexPortal. DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW. DR GO; GO:0006302; P:double-strand break repair; IMP:UniProtKB. DR GO; GO:0070537; P:histone H2A K63-linked deubiquitination; IC:ComplexPortal. DR GO; GO:0035518; P:histone H2A monoubiquitination; IC:ComplexPortal. DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; IMP:UniProtKB. DR GO; GO:0044818; P:mitotic G2/M transition checkpoint; IC:ComplexPortal. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0045739; P:positive regulation of DNA repair; IMP:UniProtKB. DR GO; GO:0051865; P:protein autoubiquitination; IC:ComplexPortal. DR GO; GO:0070536; P:protein K63-linked deubiquitination; IC:UniProtKB. DR GO; GO:2000001; P:regulation of DNA damage checkpoint; IC:ComplexPortal. DR GO; GO:0006282; P:regulation of DNA repair; IC:ComplexPortal. DR GO; GO:0010212; P:response to ionizing radiation; IMP:UniProtKB. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR InterPro; IPR010358; BRE. DR PANTHER; PTHR15189; PTHR15189; 1. DR Pfam; PF06113; BRE; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; Cell cycle; KW Cell division; Chromatin regulator; Cytoplasm; DNA damage; DNA repair; KW Mitosis; Nucleus; Phosphoprotein; Reference proteome; Repeat; KW Ubl conjugation pathway. FT CHAIN 1..383 FT /note="BRISC and BRCA1-A complex member 2" FT /id="PRO_0000224189" FT REGION 30..147 FT /note="UEV-like 1" FT REGION 275..364 FT /note="UEV-like 2" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:22223895" FT MOD_RES 2 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT VAR_SEQ 363..383 FT /note="KAYFKTFVPQFQEAAFANGKL -> NSRRQHLPMESSRKHQS (in FT isoform 3)" FT /evidence="ECO:0000303|PubMed:11676476" FT /id="VSP_051957" FT VAR_SEQ 364..383 FT /note="AYFKTFVPQFQEAAFANGKL -> GCQGSRDACSPWEQVLAFAVAKTGCKLL FT QPQRNWPSSRGPPWRASEGERTAQ (in isoform 1)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_051956" FT VAR_SEQ 364..383 FT /note="AYFKTFVPQFQEAAFANGKL -> RESNRDGEESSSA (in isoform FT 4)" FT /evidence="ECO:0000303|PubMed:11676476" FT /id="VSP_037261" FT CONFLICT 192 FT /note="V -> L (in Ref. 5; BAF83775)" FT /evidence="ECO:0000305" SQ SEQUENCE 383 AA; 43552 MW; D830226E2B8F2C4B CRC64; MSPEVALNRI SPMLSPFISS VVRNGKVGLD ATNCLRITDL KSGCTSLTPG PNCDRFKLHI PYAGETLKWD IIFNAQYPEL PPDFIFGEDA EFLPDPSALQ NLASWNPSNP ECLLLVVKEL VQQYHQFQCS RLRESSRLMF EYQTLLEEPQ YGENMEIYAG KKNNWTGEFS ARFLLKLPVD FSNIPTYLLK DVNEDPGEDV ALLSVSFEDT EATQVYPKLY LSPRIEHALG GSSALHIPAF PGGGCLIDYV PQVCHLLTNK VQYVIQGYHK RREYIAAFLS HFGTGVVEYD AEGFTKLTLL LMWKDFCFLV HIDLPLFFPR DQPTLTFQSV YHFTNSGQLY SQAQKNYPYS PRWDGNEMAK RAKAYFKTFV PQFQEAAFAN GKL // ID XRCC2_HUMAN Reviewed; 280 AA. AC O43543; B2R925; DT 03-APR-2002, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1998, sequence version 1. DT 25-MAY-2022, entry version 171. DE RecName: Full=DNA repair protein XRCC2; DE AltName: Full=X-ray repair cross-complementing protein 2; GN Name=XRCC2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RC TISSUE=Cervix carcinoma; RX PubMed=9660962; DOI=10.1016/s1097-2765(00)80078-7; RA Liu N., Lamerdin J.E., Tebbs R.S., Schild D., Tucker J.D., Shen M.R., RA Brookman K.W., Siciliano M.J., Walter C.A., Fan W., Narayana L.S., RA Zhou Z.-Q., Adamson A.W., Sorensen K.J., Chen D.J., Jones N.J., RA Thompson L.H.; RT "XRCC2 and XRCC3, new human Rad51-family members, promote chromosome RT stability and protect against DNA cross-links and other damages."; RL Mol. Cell 1:783-793(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9126486; DOI=10.1006/geno.1997.4636; RA Tambini C.E., George A.M., Rommens J.M., Tsui L.-C., Scherer S.W., RA Thacker J.; RT "The XRCC2 DNA repair gene: identification of a positional candidate."; RL Genomics 41:84-92(1997). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RC TISSUE=Cervix carcinoma; RX PubMed=9628903; DOI=10.1093/nar/26.13.3084; RA Cartwright R., Tambini C.E., Simpson P.J., Thacker J.; RT "The XRCC2 DNA repair gene from human and mouse encodes a novel member of RT the recA/RAD51 family."; RL Nucleic Acids Res. 26:3084-3089(1998). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-188 AND THR-221. RG NIEHS SNPs program; RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP FUNCTION, AND IDENTIFICATION IN THE BCDX2 COMPLEX WITH RAD51C; RAD51D AND RP XRCC2. RX PubMed=11751635; DOI=10.1101/gad.947001; RA Masson J.Y., Tarsounas M.C., Stasiak A.Z., Stasiak A., Shah R., RA McIlwraith M.J., Benson F.E., West S.C.; RT "Identification and purification of two distinct complexes containing the RT five RAD51 paralogs."; RL Genes Dev. 15:3296-3307(2001). RN [9] RP SUBUNIT. RX PubMed=11744692; DOI=10.1074/jbc.m108306200; RA Miller K.A., Yoshikawa D.M., McConnell I.R., Clark R., Schild D., RA Albala J.S.; RT "RAD51C interacts with RAD51B and is central to a larger protein complex in RT vivo exclusive of RAD51."; RL J. Biol. Chem. 277:8406-8411(2002). RN [10] RP FUNCTION, AND SUBUNIT. RX PubMed=11834724; DOI=10.1074/jbc.m105719200; RA Kurumizaka H., Ikawa S., Nakada M., Enomoto R., Kagawa W., Kinebuchi T., RA Yamazoe M., Yokoyama S., Shibata T.; RT "Homologous pairing and ring and filament structure formation activities of RT the human Xrcc2*Rad51D complex."; RL J. Biol. Chem. 277:14315-14320(2002). RN [11] RP IDENTIFICATION IN A COMPLEX WITH RAD51B; RAD51C AND RAD51D. RX PubMed=11842112; DOI=10.1093/nar/30.4.1001; RA Wiese C., Collins D.W., Albala J.S., Thompson L.H., Kronenberg A., RA Schild D.; RT "Interactions involving the Rad51 paralogs Rad51C and XRCC3 in human RT cells."; RL Nucleic Acids Res. 30:1001-1008(2002). RN [12] RP IDENTIFICATION IN A COMPLEX WITH RAD51B; RAD51C AND RAD51D. RX PubMed=11842113; DOI=10.1093/nar/30.4.1009; RA Liu N., Schild D., Thelen M.P., Thompson L.H.; RT "Involvement of Rad51C in two distinct protein complexes of Rad51 paralogs RT in human cells."; RL Nucleic Acids Res. 30:1009-1015(2002). RN [13] RP INTERACTION WITH RAD51D. RX PubMed=14704354; DOI=10.1093/nar/gkg925; RA Miller K.A., Sawicka D., Barsky D., Albala J.S.; RT "Domain mapping of the Rad51 paralog protein complexes."; RL Nucleic Acids Res. 32:169-178(2004). RN [14] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=21276791; DOI=10.1016/j.yexcr.2011.01.021; RA Cappelli E., Townsend S., Griffin C., Thacker J.; RT "Homologous recombination proteins are associated with centrosomes and are RT required for mitotic stability."; RL Exp. Cell Res. 317:1203-1213(2011). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [16] RP FUNCTION OF THE BCDX2 COMPLEX. RX PubMed=23149936; DOI=10.1128/mcb.00465-12; RA Chun J., Buechelmaier E.S., Powell S.N.; RT "Rad51 paralog complexes BCDX2 and CX3 act at different stages in the RT BRCA1-BRCA2-dependent homologous recombination pathway."; RL Mol. Cell. Biol. 33:387-395(2013). RN [17] RP ELECTRON MICROSCOPY OF THE BCDX2 COMPLEX, AND DNA-BINDING OF THE BCDX2 RP COMPLEX. RX PubMed=20207730; DOI=10.1074/jbc.m109.074286; RA Compton S.A., Ozgur S., Griffith J.D.; RT "Ring-shaped Rad51 paralog protein complexes bind Holliday junctions and RT replication forks as visualized by electron microscopy."; RL J. Biol. Chem. 285:13349-13356(2010). RN [18] RP VARIANTS SER-16; ILE-61; TRP-91; VAL-95; CYS-231 AND VAL-270. RX PubMed=22464251; DOI=10.1016/j.ajhg.2012.02.027; RG Breast Cancer Family Registry; RG Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer; RA Park D.J., Lesueur F., Nguyen-Dumont T., Pertesi M., Odefrey F., Hammet F., RA Neuhausen S.L., John E.M., Andrulis I.L., Terry M.B., Daly M., Buys S., RA Le Calvez-Kelm F., Lonie A., Pope B.J., Tsimiklis H., Voegele C., RA Hilbers F.M., Hoogerbrugge N., Barroso A., Osorio A., Giles G.G., RA Devilee P., Benitez J., Hopper J.L., Tavtigian S.V., Goldgar D.E., RA Southey M.C.; RT "Rare mutations in XRCC2 increase the risk of breast cancer."; RL Am. J. Hum. Genet. 90:734-739(2012). RN [19] RP INVOLVEMENT IN FANCU. RX PubMed=22232082; DOI=10.1136/jmedgenet-2011-100585; RA Shamseldin H.E., Elfaki M., Alkuraya F.S.; RT "Exome sequencing reveals a novel Fanconi group defined by XRCC2 RT mutation."; RL J. Med. Genet. 49:184-186(2012). RN [20] RP VARIANTS ARG-47; GLN-75; VAL-95; ALA-118; TYR-120; PRO-133; GLN-164; RP ALA-170; CYS-188; MET-194; LEU-199; GLY-207; VAL-220; SER-238; GLU-248; RP CYS-258 AND VAL-270. RX PubMed=23054243; DOI=10.1136/jmedgenet-2012-101191; RA Hilbers F.S., Wijnen J.T., Hoogerbrugge N., Oosterwijk J.C., Collee M.J., RA Peterlongo P., Radice P., Manoukian S., Feroce I., Capra F., Couch F.J., RA Wang X., Guidugli L., Offit K., Shah S., Campbell I.G., Thompson E.R., RA James P.A., Trainer A.H., Gracia J., Benitez J., van Asperen C.J., RA Devilee P.; RT "Rare variants in XRCC2 as breast cancer susceptibility alleles."; RL J. Med. Genet. 49:618-620(2012). RN [21] RP VARIANTS SER-16; ARG-47; ILE-61; GLN-75; TRP-91; VAL-95; ALA-118; TYR-120; RP PRO-133; GLN-164; ALA-170; CYS-188; HIS-188; MET-194; LEU-199; GLY-207; RP VAL-220; CYS-231; SER-238; GLU-248; CYS-258 AND VAL-270, FUNCTION, AND RP CHARACTERIZATION OF VARIANTS SER-16; ARG-47; ILE-61; GLN-75; TRP-91; RP VAL-95; ALA-118; TYR-120; PRO-133; GLN-164; ALA-170; CYS-188; HIS-188; RP MET-194; LEU-199; GLY-207; VAL-220; CYS-231; SER-238; GLU-248; CYS-258 AND RP VAL-270. RX PubMed=27233470; DOI=10.1002/humu.23019; RA Hilbers F.S., Luijsterburg M.S., Wiegant W.W., Meijers C.M., RA Voelker-Albert M., Boonen R.A., van Asperen C.J., Devilee P., RA van Attikum H.; RT "Functional analysis of missense variants in the putative breast cancer RT susceptibility gene XRCC2."; RL Hum. Mutat. 37:914-925(2016). RN [22] RP VARIANT SPGF50 PRO-14, AND INVOLVEMENT IN SPGF50. RX PubMed=30042186; DOI=10.1136/jmedgenet-2017-105145; RA Yang Y., Guo J., Dai L., Zhu Y., Hu H., Tan L., Chen W., Liang D., He J., RA Tu M., Wang K., Wu L.; RT "XRCC2 mutation causes meiotic arrest, azoospermia and infertility."; RL J. Med. Genet. 55:628-636(2018). RN [23] RP VARIANT POF17 PRO-14, AND INVOLVEMENT IN POF17. RX PubMed=30489636; DOI=10.1111/cge.13475; RA Zhang Y.X., Li H.Y., He W.B., Tu C., Du J., Li W., Lu G.X., Lin G., RA Yang Y., Tan Y.Q.; RT "XRCC2 mutation causes premature ovarian insufficiency as well as non- RT obstructive azoospermia in humans."; RL Clin. Genet. 95:442-443(2019). RN [24] RP VARIANT 215-ARG--CYS-280 DEL. RX PubMed=30237576; DOI=10.1038/s41436-018-0138-x; RA Maddirevula S., Alzahrani F., Al-Owain M., Al Muhaizea M.A., Kayyali H.R., RA AlHashem A., Rahbeeni Z., Al-Otaibi M., Alzaidan H.I., Balobaid A., RA El Khashab H.Y., Bubshait D.K., Faden M., Yamani S.A., Dabbagh O., RA Al-Mureikhi M., Jasser A.A., Alsaif H.S., Alluhaydan I., Seidahmed M.Z., RA Alabbasi B.H., Almogarri I., Kurdi W., Akleh H., Qari A., Al Tala S.M., RA Alhomaidi S., Kentab A.Y., Salih M.A., Chedrawi A., Alameer S., Tabarki B., RA Shamseldin H.E., Patel N., Ibrahim N., Abdulwahab F., Samira M., Goljan E., RA Abouelhoda M., Meyer B.F., Hashem M., Shaheen R., AlShahwan S., RA Alfadhel M., Ben-Omran T., Al-Qattan M.M., Monies D., Alkuraya F.S.; RT "Autozygome and high throughput confirmation of disease genes candidacy."; RL Genet. Med. 21:736-742(2019). CC -!- FUNCTION: Involved in the homologous recombination repair (HRR) pathway CC of double-stranded DNA, thought to repair chromosomal fragmentation, CC translocations and deletions. Part of the RAD51 paralog protein complex CC BCDX2 which acts in the BRCA1-BRCA2-dependent HR pathway. Upon DNA CC damage, BCDX2 acts downstream of BRCA2 recruitment and upstream of CC RAD51 recruitment. BCDX2 binds predominantly to the intersection of the CC four duplex arms of the Holliday junction and to junction of CC replication forks. The BCDX2 complex was originally reported to bind CC single-stranded DNA, single-stranded gaps in duplex DNA and CC specifically to nicks in duplex DNA. {ECO:0000269|PubMed:11751635, CC ECO:0000269|PubMed:11834724, ECO:0000269|PubMed:21276791, CC ECO:0000269|PubMed:23149936, ECO:0000269|PubMed:27233470}. CC -!- SUBUNIT: Interacts with RAD51D. Part of the BCDX2 complex consisting of CC RAD51B, RAD51C, RAD51D and XRCC2; the complex has a ring-like structure CC arranged into a flat disk around a central channel. In the absence of CC DNA, the BCDX2 subcomplex XRCC2:RAD51D formed a multimeric ring CC structure; in the presence of single-stranded DNA it formed a CC filamentous structure with the ssDNA. {ECO:0000269|PubMed:11744692, CC ECO:0000269|PubMed:11751635, ECO:0000269|PubMed:11834724, CC ECO:0000269|PubMed:11842112, ECO:0000269|PubMed:11842113, CC ECO:0000269|PubMed:14704354}. CC -!- INTERACTION: CC O43543; P50222: MEOX2; NbExp=3; IntAct=EBI-3918457, EBI-748397; CC O43543; O43502: RAD51C; NbExp=3; IntAct=EBI-3918457, EBI-2267048; CC O43543; O75771: RAD51D; NbExp=38; IntAct=EBI-3918457, EBI-1055693; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21276791}. Cytoplasm, CC cytoskeleton, microtubule organizing center, centrosome CC {ECO:0000269|PubMed:21276791}. CC -!- DISEASE: Fanconi anemia, complementation group U (FANCU) [MIM:617247]: CC A disorder affecting all bone marrow elements and resulting in anemia, CC leukopenia and thrombopenia. It is associated with cardiac, renal and CC limb malformations, dermal pigmentary changes, and a predisposition to CC the development of malignancies. At the cellular level it is associated CC with hypersensitivity to DNA-damaging agents, chromosomal instability CC (increased chromosome breakage) and defective DNA repair. CC {ECO:0000269|PubMed:22232082}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Spermatogenic failure 50 (SPGF50) [MIM:619145]: An autosomal CC recessive infertility disorder characterized by azoospermia due to CC meiotic arrest at the zygotene stage of prophase I. CC {ECO:0000269|PubMed:30042186}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Premature ovarian failure 17 (POF17) [MIM:619146]: A form of CC premature ovarian failure, an ovarian disorder defined as the cessation CC of ovarian function under the age of 40 years. It is characterized by CC oligomenorrhea or amenorrhea, in the presence of elevated levels of CC serum gonadotropins and low estradiol. POF17 transmission pattern is CC consistent with autosomal recessive inheritance. CC {ECO:0000269|PubMed:30489636}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the RecA family. RAD51 subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/xrcc2/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF035587; AAC05369.1; -; mRNA. DR EMBL; AC003109; AAC05802.1; -; Genomic_DNA. DR EMBL; Y08837; CAA70065.1; -; mRNA. DR EMBL; Y17033; CAA76597.1; -; Genomic_DNA. DR EMBL; AF520762; AAM55241.1; -; Genomic_DNA. DR EMBL; AK313607; BAG36372.1; -; mRNA. DR EMBL; CH471173; EAW53968.1; -; Genomic_DNA. DR EMBL; BC042137; AAH42137.1; -; mRNA. DR CCDS; CCDS5933.1; -. DR RefSeq; NP_005422.1; NM_005431.1. DR AlphaFoldDB; O43543; -. DR SMR; O43543; -. DR BioGRID; 113350; 26. DR CORUM; O43543; -. DR DIP; DIP-24242N; -. DR IntAct; O43543; 14. DR MINT; O43543; -. DR STRING; 9606.ENSP00000352271; -. DR iPTMnet; O43543; -. DR PhosphoSitePlus; O43543; -. DR BioMuta; XRCC2; -. DR EPD; O43543; -. DR jPOST; O43543; -. DR MassIVE; O43543; -. DR MaxQB; O43543; -. DR PaxDb; O43543; -. DR PeptideAtlas; O43543; -. DR PRIDE; O43543; -. DR ProteomicsDB; 49042; -. DR Antibodypedia; 18833; 374 antibodies from 36 providers. DR DNASU; 7516; -. DR Ensembl; ENST00000359321.2; ENSP00000352271.1; ENSG00000196584.3. DR GeneID; 7516; -. DR KEGG; hsa:7516; -. DR MANE-Select; ENST00000359321.2; ENSP00000352271.1; NM_005431.2; NP_005422.1. DR UCSC; uc003wld.4; human. DR CTD; 7516; -. DR DisGeNET; 7516; -. DR GeneCards; XRCC2; -. DR GeneReviews; XRCC2; -. DR HGNC; HGNC:12829; XRCC2. DR HPA; ENSG00000196584; Tissue enhanced (bone). DR MalaCards; XRCC2; -. DR MIM; 600375; gene. DR MIM; 617247; phenotype. DR MIM; 619145; phenotype. DR MIM; 619146; phenotype. DR neXtProt; NX_O43543; -. DR OpenTargets; ENSG00000196584; -. DR Orphanet; 84; Fanconi anemia. DR Orphanet; 227535; Hereditary breast cancer. DR Orphanet; 399805; Male infertility with azoospermia or oligozoospermia due to single gene mutation. DR PharmGKB; PA37421; -. DR VEuPathDB; HostDB:ENSG00000196584; -. DR eggNOG; KOG2859; Eukaryota. DR GeneTree; ENSGT00390000020445; -. DR HOGENOM; CLU_059815_1_0_1; -. DR InParanoid; O43543; -. DR OMA; KHCLGRL; -. DR OrthoDB; 1522846at2759; -. DR PhylomeDB; O43543; -. DR TreeFam; TF101202; -. DR PathwayCommons; O43543; -. DR Reactome; R-HSA-5685942; HDR through Homologous Recombination (HRR). DR Reactome; R-HSA-5693554; Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA). DR Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates. DR Reactome; R-HSA-5693579; Homologous DNA Pairing and Strand Exchange. DR Reactome; R-HSA-5693616; Presynaptic phase of homologous DNA pairing and strand exchange. DR Reactome; R-HSA-9701192; Defective HDR through Homologous Recombination (HRR) due to BRCA1 loss-of-function. DR Reactome; R-HSA-9704331; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function. DR Reactome; R-HSA-9704646; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function. DR SignaLink; O43543; -. DR BioGRID-ORCS; 7516; 391 hits in 1090 CRISPR screens. DR ChiTaRS; XRCC2; human. DR GeneWiki; XRCC2; -. DR GenomeRNAi; 7516; -. DR Pharos; O43543; Tbio. DR PRO; PR:O43543; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; O43543; protein. DR Bgee; ENSG00000196584; Expressed in buccal mucosa cell and 234 other tissues. DR ExpressionAtlas; O43543; baseline and differential. DR Genevisible; O43543; HS. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0033063; C:Rad51B-Rad51C-Rad51D-XRCC2 complex; IDA:UniProtKB. DR GO; GO:0005657; C:replication fork; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. DR GO; GO:0008094; F:ATP-dependent activity, acting on DNA; IEA:InterPro. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0007098; P:centrosome cycle; IMP:UniProtKB. DR GO; GO:0006281; P:DNA repair; IGI:BHF-UCL. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IMP:UniProtKB. DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:0051321; P:meiotic cell cycle; TAS:ProtInc. DR GO; GO:0000278; P:mitotic cell cycle; IMP:UniProtKB. DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:0050769; P:positive regulation of neurogenesis; IEA:Ensembl. DR GO; GO:2000269; P:regulation of fibroblast apoptotic process; IEA:Ensembl. DR GO; GO:0010332; P:response to gamma radiation; IEA:Ensembl. DR GO; GO:0010165; P:response to X-ray; IEA:Ensembl. DR GO; GO:0001756; P:somitogenesis; IEA:Ensembl. DR GO; GO:0042148; P:strand invasion; IDA:UniProtKB. DR Gene3D; 3.40.50.300; -; 1. DR InterPro; IPR013632; DNA_recomb/repair_Rad51_C. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR020588; RecA_ATP-bd. DR InterPro; IPR030547; XRCC2. DR PANTHER; PTHR46644; PTHR46644; 1. DR Pfam; PF08423; Rad51; 1. DR SUPFAM; SSF52540; SSF52540; 1. DR PROSITE; PS50162; RECA_2; 1. PE 1: Evidence at protein level; KW Cytoplasm; Cytoskeleton; Disease variant; DNA damage; DNA recombination; KW DNA repair; DNA-binding; Fanconi anemia; Nucleus; Phosphoprotein; KW Premature ovarian failure; Reference proteome. FT CHAIN 1..280 FT /note="DNA repair protein XRCC2" FT /id="PRO_0000122948" FT MOD_RES 10 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VARIANT 14 FT /note="L -> P (in SPGF50 and POF17; due to a nucleotide FT substitution that causes partial exon 2 skipping; patient FT cells contain both normally spliced transcripts and FT transcripts lacking exon 2)" FT /evidence="ECO:0000269|PubMed:30042186, FT ECO:0000269|PubMed:30489636" FT /id="VAR_085247" FT VARIANT 16 FT /note="A -> S (does not affect function in double-strand FT break repair via homologous recombination as shown in FT rescue assays of XRCC2-deficient cells; dbSNP:rs4987090)" FT /evidence="ECO:0000269|PubMed:22464251, FT ECO:0000269|PubMed:27233470" FT /id="VAR_020403" FT VARIANT 47 FT /note="H -> R (does not affect function in double-strand FT break repair via homologous recombination as shown in FT rescue assays of XRCC2-deficient cells; dbSNP:rs587780126)" FT /evidence="ECO:0000269|PubMed:23054243, FT ECO:0000269|PubMed:27233470" FT /id="VAR_077167" FT VARIANT 61 FT /note="L -> I (does not affect function in double-strand FT break repair via homologous recombination as shown in FT rescue assays of XRCC2-deficient cells; dbSNP:rs569810249)" FT /evidence="ECO:0000269|PubMed:22464251, FT ECO:0000269|PubMed:27233470" FT /id="VAR_077168" FT VARIANT 75 FT /note="E -> Q (does not affect function in double-strand FT break repair via homologous recombination as shown in FT rescue assays of XRCC2-deficient cells; FT dbSNP:rs1327414828)" FT /evidence="ECO:0000269|PubMed:23054243, FT ECO:0000269|PubMed:27233470" FT /id="VAR_077169" FT VARIANT 91 FT /note="R -> W (rare variant; found in breast cancer; FT unknown pathological significance; moderately decreased FT function in double-strand break repair via homologous FT recombination as shown in rescue assays of XRCC2-deficient FT cells; dbSNP:rs730882043)" FT /evidence="ECO:0000269|PubMed:22464251, FT ECO:0000269|PubMed:27233470" FT /id="VAR_077170" FT VARIANT 95 FT /note="I -> V (does not affect function in double-strand FT break repair via homologous recombination as shown in FT rescue assays of XRCC2-deficient cells; dbSNP:rs140214637)" FT /evidence="ECO:0000269|PubMed:22464251, FT ECO:0000269|PubMed:23054243, ECO:0000269|PubMed:27233470" FT /id="VAR_077171" FT VARIANT 118 FT /note="V -> A (does not affect function in double-strand FT break repair via homologous recombination as shown in FT rescue assays of XRCC2-deficient cells; dbSNP:rs185815454)" FT /evidence="ECO:0000269|PubMed:23054243, FT ECO:0000269|PubMed:27233470" FT /id="VAR_077172" FT VARIANT 120 FT /note="C -> Y (rare variant; found in breast cancer; FT unknown pathological significance; moderately decreased FT function in double-strand break repair via homologous FT recombination as shown in rescue assays of XRCC2-deficient FT cells; dbSNP:rs1432878196)" FT /evidence="ECO:0000269|PubMed:23054243, FT ECO:0000269|PubMed:27233470" FT /id="VAR_077173" FT VARIANT 133 FT /note="L -> P (rare variant; found in breast cancer; FT unknown pathological significance; moderately decreased FT function in double-strand break repair via homologous FT recombination as shown in rescue assays of XRCC2-deficient FT cells; dbSNP:rs765276614)" FT /evidence="ECO:0000269|PubMed:23054243, FT ECO:0000269|PubMed:27233470" FT /id="VAR_077174" FT VARIANT 164 FT /note="E -> Q (does not affect function in double-strand FT break repair via homologous recombination as shown in FT rescue assays of XRCC2-deficient cells; FT dbSNP:rs1215678098)" FT /evidence="ECO:0000269|PubMed:23054243, FT ECO:0000269|PubMed:27233470" FT /id="VAR_077175" FT VARIANT 170 FT /note="E -> A (does not affect function in double-strand FT break repair via homologous recombination as shown in FT rescue assays of XRCC2-deficient cells; dbSNP:rs778143946)" FT /evidence="ECO:0000269|PubMed:23054243, FT ECO:0000269|PubMed:27233470" FT /id="VAR_077176" FT VARIANT 188 FT /note="R -> C (does not affect function in double-strand FT break repair via homologous recombination as shown in FT rescue assays of XRCC2-deficient cells; dbSNP:rs139219364)" FT /evidence="ECO:0000269|PubMed:23054243, FT ECO:0000269|PubMed:27233470" FT /id="VAR_077177" FT VARIANT 188 FT /note="R -> H (does not affect function in double-strand FT break repair via homologous recombination as shown in FT rescue assays of XRCC2-deficient cells; dbSNP:rs3218536)" FT /evidence="ECO:0000269|PubMed:27233470, ECO:0000269|Ref.4" FT /id="VAR_020404" FT VARIANT 194 FT /note="T -> M (does not affect function in double-strand FT break repair via homologous recombination as shown in FT rescue assays of XRCC2-deficient cells; dbSNP:rs775565256)" FT /evidence="ECO:0000269|PubMed:23054243, FT ECO:0000269|PubMed:27233470" FT /id="VAR_077178" FT VARIANT 199 FT /note="M -> L (likely benign variant; does not affect FT function in double-strand break repair via homologous FT recombination as shown in rescue assays of XRCC2-deficient FT cells)" FT /evidence="ECO:0000269|PubMed:23054243, FT ECO:0000269|PubMed:27233470" FT /id="VAR_077179" FT VARIANT 207 FT /note="E -> G (does not affect function in double-strand FT break repair via homologous recombination as shown in FT rescue assays of XRCC2-deficient cells; dbSNP:rs61762969)" FT /evidence="ECO:0000269|PubMed:23054243, FT ECO:0000269|PubMed:27233470" FT /id="VAR_077180" FT VARIANT 215..280 FT /note="Missing (found in a patient with borderline FT microcephaly, bilateral hypoplastic thumb, multiple cafe FT late spots, strabismus and dysmorphic facial features; FT unknown pathological significance)" FT /evidence="ECO:0000269|PubMed:30237576" FT /id="VAR_082157" FT VARIANT 220 FT /note="D -> V (does not affect function in double-strand FT break repair via homologous recombination as shown in FT rescue assays of XRCC2-deficient cells; dbSNP:rs765021741)" FT /evidence="ECO:0000269|PubMed:23054243, FT ECO:0000269|PubMed:27233470" FT /id="VAR_077181" FT VARIANT 221 FT /note="I -> T (in dbSNP:rs3218537)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_029294" FT VARIANT 231 FT /note="W -> C (does not affect function in double-strand FT break repair via homologous recombination as shown in FT rescue assays of XRCC2-deficient cells; FT dbSNP:rs1267462913)" FT /evidence="ECO:0000269|PubMed:22464251, FT ECO:0000269|PubMed:27233470" FT /id="VAR_077182" FT VARIANT 238 FT /note="R -> S (does not affect function in double-strand FT break repair via homologous recombination as shown in FT rescue assays of XRCC2-deficient cells; dbSNP:rs534746330)" FT /evidence="ECO:0000269|PubMed:23054243, FT ECO:0000269|PubMed:27233470" FT /id="VAR_077183" FT VARIANT 248 FT /note="Q -> E (does not affect function in double-strand FT break repair via homologous recombination as shown in FT rescue assays of XRCC2-deficient cells; dbSNP:rs190900560)" FT /evidence="ECO:0000269|PubMed:23054243, FT ECO:0000269|PubMed:27233470" FT /id="VAR_077184" FT VARIANT 258 FT /note="R -> C (does not affect function in double-strand FT break repair via homologous recombination as shown in FT rescue assays of XRCC2-deficient cells; dbSNP:rs759300252)" FT /evidence="ECO:0000269|PubMed:23054243, FT ECO:0000269|PubMed:27233470" FT /id="VAR_077185" FT VARIANT 270 FT /note="F -> V (does not affect function in double-strand FT break repair via homologous recombination as shown in FT rescue assays of XRCC2-deficient cells; dbSNP:rs145085742)" FT /evidence="ECO:0000269|PubMed:22464251, FT ECO:0000269|PubMed:23054243, ECO:0000269|PubMed:27233470" FT /id="VAR_077186" SQ SEQUENCE 280 AA; 31956 MW; 5656277E74C06074 CRC64; MCSAFHRAES GTELLARLEG RSSLKEIEPN LFADEDSPVH GDILEFHGPE GTGKTEMLYH LTARCILPKS EGGLEVEVLF IDTDYHFDML RLVTILEHRL SQSSEEIIKY CLGRFFLVYC SSSTHLLLTL YSLESMFCSH PSLCLLILDS LSAFYWIDRV NGGESVNLQE STLRKCSQCL EKLVNDYRLV LFATTQTIMQ KASSSSEEPS HASRRLCDVD IDYRPYLCKA WQQLVKHRMF FSKQDDSQSS NQFSLVSRCL KSNSLKKHFF IIGESGVEFC // ID RMI2_HUMAN Reviewed; 147 AA. AC Q96E14; B3KVZ6; Q49AE2; Q8TBL0; DT 21-AUG-2007, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2004, sequence version 2. DT 25-MAY-2022, entry version 140. DE RecName: Full=RecQ-mediated genome instability protein 2; DE Short=hRMI2; DE AltName: Full=BLM-associated protein of 18 kDa; DE Short=BLAP18; GN Name=RMI2; Synonyms=C16orf75; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Lung, Lymph, Skin, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP FUNCTION, IDENTIFICATION IN THE RMI COMPLEX, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF LYS-121. RX PubMed=18923082; DOI=10.1101/gad.1708608; RA Xu D., Guo R., Sobeck A., Bachrati C.Z., Yang J., Enomoto T., Brown G.W., RA Hoatlin M.E., Hickson I.D., Wang W.; RT "RMI, a new OB-fold complex essential for Bloom syndrome protein to RT maintain genome stability."; RL Genes Dev. 22:2843-2855(2008). RN [6] RP FUNCTION, IDENTIFICATION IN THE RMI COMPLEX, IDENTIFICATION BY MASS RP SPECTROMETRY, PHOSPHORYLATION, AND MUTAGENESIS OF LYS-24; TRP-59; LYS-100; RP LYS-121 AND TRP-135. RX PubMed=18923083; DOI=10.1101/gad.1725108; RA Singh T.R., Ali A.M., Busygina V., Raynard S., Fan Q., Du C.-H., RA Andreassen P.R., Sung P., Meetei A.R.; RT "BLAP18/RMI2, a novel OB-fold-containing protein, is an essential component RT of the Bloom helicase-double Holliday junction dissolvasome."; RL Genes Dev. 22:2856-2868(2008). RN [7] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE RP ANALYSIS] AT SER-7, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE RP ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [8] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [10] RP FUNCTION, AND PROBABLE INVOLVEMENT IN BLOOM-LIKE SYNDROME. RX PubMed=27977684; DOI=10.1371/journal.pgen.1006483; RA Hudson D.F., Amor D.J., Boys A., Butler K., Williams L., Zhang T., RA Kalitsis P.; RT "Loss of RMI2 increases genome instability and causes a Bloom-like RT syndrome."; RL PLoS Genet. 12:E1006483-E1006483(2016). CC -!- FUNCTION: Essential component of the RMI complex, a complex that plays CC an important role in the processing of homologous recombination CC intermediates. It is required to regulate sister chromatid segregation CC and to limit DNA crossover. Essential for the stability, localization, CC and function of BLM, TOP3A, and complexes containing BLM. In the RMI CC complex, it is required to target BLM to chromatin and stress-induced CC nuclear foci and mitotic phosphorylation of BLM. CC {ECO:0000269|PubMed:18923082, ECO:0000269|PubMed:18923083, CC ECO:0000269|PubMed:27977684}. CC -!- SUBUNIT: Component of the RMI complex, containing at least TOP3A, RMI1 CC and RMI2. The RMI complex interacts with BLM. CC {ECO:0000269|PubMed:18923082, ECO:0000269|PubMed:18923083}. CC -!- INTERACTION: CC Q96E14; Q9H9A7: RMI1; NbExp=4; IntAct=EBI-2555534, EBI-621339; CC Q96E14-1; Q9H9A7: RMI1; NbExp=13; IntAct=EBI-15876491, EBI-621339; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18923082}. CC Note=Colocalizes with BLM at nuclear DNA repair foci. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q96E14-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96E14-2; Sequence=VSP_027287; CC -!- PTM: Phosphorylated during mitosis. {ECO:0000269|PubMed:18923083}. CC -!- DISEASE: Note=A homozygous deletion of RMI2 has been found in a family CC with a Bloom-like syndrome and is probable responsible for the CC phenotype. Patients manifest depigmented skin lesions, multiple cafe- CC au-lait macules, and growth deficiency. Cells from affected individuals CC show a high rate of sister chromatid exchange and increased chromosomal CC breaks. {ECO:0000269|PubMed:27977684}. CC -!- SIMILARITY: Belongs to the RMI2 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK123764; BAG53958.1; -; mRNA. DR EMBL; AC009121; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471112; EAW85155.1; -; Genomic_DNA. DR EMBL; BC013040; AAH13040.2; -; mRNA. DR EMBL; BC022427; AAH22427.1; -; mRNA. DR EMBL; BC031016; AAH31016.1; -; mRNA. DR EMBL; BC039361; AAH39361.1; -; mRNA. DR CCDS; CCDS10548.1; -. [Q96E14-1] DR RefSeq; NP_689521.1; NM_152308.2. [Q96E14-1] DR PDB; 3MXN; X-ray; 1.55 A; B=1-147. DR PDB; 3NBH; X-ray; 2.00 A; B=6-147. DR PDB; 4DAY; X-ray; 3.30 A; B=1-147. DR PDBsum; 3MXN; -. DR PDBsum; 3NBH; -. DR PDBsum; 4DAY; -. DR AlphaFoldDB; Q96E14; -. DR SMR; Q96E14; -. DR BioGRID; 125466; 28. DR ComplexPortal; CPX-3301; BTR double Holliday Junction dissolution complex. DR DIP; DIP-56480N; -. DR IntAct; Q96E14; 12. DR MINT; Q96E14; -. DR STRING; 9606.ENSP00000310356; -. DR iPTMnet; Q96E14; -. DR PhosphoSitePlus; Q96E14; -. DR BioMuta; RMI2; -. DR DMDM; 74731517; -. DR EPD; Q96E14; -. DR jPOST; Q96E14; -. DR MassIVE; Q96E14; -. DR MaxQB; Q96E14; -. DR PaxDb; Q96E14; -. DR PeptideAtlas; Q96E14; -. DR PRIDE; Q96E14; -. DR ProteomicsDB; 76362; -. [Q96E14-1] DR ProteomicsDB; 76363; -. [Q96E14-2] DR Antibodypedia; 52376; 39 antibodies from 15 providers. DR DNASU; 116028; -. DR Ensembl; ENST00000312499.6; ENSP00000310356.5; ENSG00000175643.10. DR Ensembl; ENST00000572173.1; ENSP00000461206.1; ENSG00000175643.10. [Q96E14-2] DR GeneID; 116028; -. DR KEGG; hsa:116028; -. DR MANE-Select; ENST00000312499.6; ENSP00000310356.5; NM_152308.3; NP_689521.1. DR UCSC; uc002daw.2; human. [Q96E14-1] DR CTD; 116028; -. DR DisGeNET; 116028; -. DR GeneCards; RMI2; -. DR HGNC; HGNC:28349; RMI2. DR HPA; ENSG00000175643; Tissue enhanced (lymphoid). DR MalaCards; RMI2; -. DR MIM; 612426; gene. DR neXtProt; NX_Q96E14; -. DR OpenTargets; ENSG00000175643; -. DR Orphanet; 508512; Intrauterine growth restriction-congenital multiple cafe-au-lait macules-increased sister chromatid exchange syndrome. DR PharmGKB; PA145149635; -. DR VEuPathDB; HostDB:ENSG00000175643; -. DR eggNOG; ENOG502S4AN; Eukaryota. DR GeneTree; ENSGT00390000001653; -. DR HOGENOM; CLU_2526905_0_0_1; -. DR InParanoid; Q96E14; -. DR OMA; RVSLVWM; -. DR OrthoDB; 1604165at2759; -. DR PhylomeDB; Q96E14; -. DR TreeFam; TF332971; -. DR PathwayCommons; Q96E14; -. DR Reactome; R-HSA-5685938; HDR through Single Strand Annealing (SSA). DR Reactome; R-HSA-5685942; HDR through Homologous Recombination (HRR). DR Reactome; R-HSA-5693554; Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA). DR Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates. DR Reactome; R-HSA-5693579; Homologous DNA Pairing and Strand Exchange. DR Reactome; R-HSA-5693607; Processing of DNA double-strand break ends. DR Reactome; R-HSA-5693616; Presynaptic phase of homologous DNA pairing and strand exchange. DR Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation. DR Reactome; R-HSA-69473; G2/M DNA damage checkpoint. DR Reactome; R-HSA-9701192; Defective HDR through Homologous Recombination (HRR) due to BRCA1 loss-of-function. DR Reactome; R-HSA-9704331; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function. DR Reactome; R-HSA-9704646; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function. DR SignaLink; Q96E14; -. DR BioGRID-ORCS; 116028; 70 hits in 1086 CRISPR screens. DR GenomeRNAi; 116028; -. DR Pharos; Q96E14; Tbio. DR PRO; PR:Q96E14; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; Q96E14; protein. DR Bgee; ENSG00000175643; Expressed in ventricular zone and 161 other tissues. DR ExpressionAtlas; Q96E14; baseline and differential. DR Genevisible; Q96E14; HS. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0016607; C:nuclear speck; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IC:ComplexPortal. DR GO; GO:0031422; C:RecQ family helicase-topoisomerase III complex; IPI:ComplexPortal. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0006281; P:DNA repair; IBA:GO_Central. DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IDA:ComplexPortal. DR GO; GO:0043007; P:maintenance of rDNA; IBA:GO_Central. DR GO; GO:2000042; P:negative regulation of double-strand break repair via homologous recombination; IBA:GO_Central. DR GO; GO:0033045; P:regulation of sister chromatid segregation; IMP:UniProtKB. DR GO; GO:0071139; P:resolution of recombination intermediates; IDA:ComplexPortal. DR DisProt; DP02895; -. DR Gene3D; 2.40.50.140; -; 1. DR IDEAL; IID00419; -. DR InterPro; IPR012340; NA-bd_OB-fold. DR InterPro; IPR032245; RMI2. DR PANTHER; PTHR33962; PTHR33962; 1. DR Pfam; PF16100; RMI2; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; DNA replication; KW DNA-binding; Nucleus; Phosphoprotein; Reference proteome. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:22814378" FT CHAIN 2..147 FT /note="RecQ-mediated genome instability protein 2" FT /id="PRO_0000297577" FT DNA_BIND 44..114 FT /note="OB" FT REGION 1..20 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:22814378" FT MOD_RES 7 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..98 FT /note="MAAAADSFSGGPAGVRLPRSPPLKVLAEQLRRDAEGGPGAWRLSRAAAGRGP FT LDLAAVWMQGRVVMADRGEARLRDPSGDFSVRGLERVPRGRPCLVP -> MKQTQVGSL FT FSLGIRNPEPGPVSGTAVPRQLAWKS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_027287" FT MUTAGEN 24 FT /note="K->A: Abolishes interaction with RMI1, TOP3A and FT BLM." FT /evidence="ECO:0000269|PubMed:18923083" FT MUTAGEN 59 FT /note="W->A: According to PubMed:18923083, abolishes FT interaction with RMI1, TOP3A and BLM. According to FT PubMed:18923082, does not affects interaction with RMI1 and FT TOP3A." FT /evidence="ECO:0000269|PubMed:18923083" FT MUTAGEN 100 FT /note="K->A: Does not affect interaction with RMI1, TOP3A FT and BLM." FT /evidence="ECO:0000269|PubMed:18923083" FT MUTAGEN 121 FT /note="K->A: According to PubMed:18923083, does not affect FT interaction with RMI1, TOP3A and BLM. According to FT PubMed:18923082, affects interaction with BLM and the BMI FT complex." FT /evidence="ECO:0000269|PubMed:18923082, FT ECO:0000269|PubMed:18923083" FT MUTAGEN 135 FT /note="W->A: Abolishes interaction with RMI1, TOP3A and FT BLM." FT /evidence="ECO:0000269|PubMed:18923083" FT HELIX 27..33 FT /evidence="ECO:0007829|PDB:3MXN" FT STRAND 34..36 FT /evidence="ECO:0007829|PDB:3MXN" FT STRAND 40..43 FT /evidence="ECO:0007829|PDB:3NBH" FT TURN 46..49 FT /evidence="ECO:0007829|PDB:3MXN" FT STRAND 56..68 FT /evidence="ECO:0007829|PDB:3MXN" FT STRAND 71..76 FT /evidence="ECO:0007829|PDB:3MXN" FT STRAND 79..84 FT /evidence="ECO:0007829|PDB:3MXN" FT HELIX 86..88 FT /evidence="ECO:0007829|PDB:3MXN" FT STRAND 92..94 FT /evidence="ECO:0007829|PDB:4DAY" FT STRAND 101..110 FT /evidence="ECO:0007829|PDB:3MXN" FT STRAND 112..114 FT /evidence="ECO:0007829|PDB:3MXN" FT STRAND 116..124 FT /evidence="ECO:0007829|PDB:3MXN" FT HELIX 130..143 FT /evidence="ECO:0007829|PDB:3MXN" SQ SEQUENCE 147 AA; 15865 MW; C385825F9AB4439E CRC64; MAAAADSFSG GPAGVRLPRS PPLKVLAEQL RRDAEGGPGA WRLSRAAAGR GPLDLAAVWM QGRVVMADRG EARLRDPSGD FSVRGLERVP RGRPCLVPGK YVMVMGVVQA CSPEPCLQAV KMTDLSDNPI HESMWELEVE DLHRNIP //