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 12-OCT-2022, entry version 234. 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=26; 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; 241. 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; 57. 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; 332 antibodies from 40 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 OpenTargets; ENSG00000139618; -. 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 Orphanet; 618572; Selection of therapeutic option in ovarian cancer. DR PharmGKB; PA25412; -. DR VEuPathDB; HostDB:ENSG00000139618; -. DR eggNOG; KOG4751; Eukaryota. DR GeneTree; ENSGT00390000003602; -. 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-5685939; HDR through MMEJ (alt-NHEJ). 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-9709275; Impaired BRCA2 translocation to the nucleus. DR Reactome; R-HSA-9709570; Impaired BRCA2 binding to RAD51. DR Reactome; R-HSA-9709603; Impaired BRCA2 binding to PALB2. DR Reactome; R-HSA-9763198; Impaired BRCA2 binding to SEM1 (DSS1). 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 114 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:0071479; P:cellular response to ionizing radiation; IMP:ComplexPortal. DR GO; GO:0090398; P:cellular senescence; IEA:Ensembl. 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:0071425; P:hematopoietic stem cell proliferation; 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:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; IEA:Ensembl. 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 DNA-templated transcription; 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 12-OCT-2022, entry version 159. 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=26; IntAct=EBI-1222653, EBI-79792; CC Q86YC2; Q14145: KEAP1; NbExp=5; 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; 40. 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; 254 antibodies from 34 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 Reactome; R-HSA-9709603; Impaired BRCA2 binding to PALB2. 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 146 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:0006915; P:apoptotic process; 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 12-OCT-2022, entry version 168. 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; 118. 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; 161 antibodies from 27 providers. DR DNASU; 56647; -. DR Ensembl; ENST00000278100.11; ENSP00000278100.6; ENSG00000107949.17. [Q9P287-1] 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 ventricular zone and 198 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 12-OCT-2022, entry version 175. 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; 121. 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-GlcNAc 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; 182 antibodies from 26 providers. DR DNASU; 56946; -. DR Ensembl; ENST00000334736.7; ENSP00000334130.3; ENSG00000158636.17. [Q7Z589-1] DR Ensembl; ENST00000524767.5; ENSP00000433205.1; ENSG00000158636.17. [Q7Z589-7] DR Ensembl; ENST00000525038.5; ENSP00000436968.1; ENSG00000158636.17. [Q7Z589-4] DR Ensembl; ENST00000525919.5; ENSP00000432010.1; ENSG00000158636.17. [Q7Z589-5] DR Ensembl; ENST00000529032.5; ENSP00000432327.1; ENSG00000158636.17. [Q7Z589-1] DR Ensembl; ENST00000533248.5; ENSP00000433634.1; ENSG00000158636.17. [Q7Z589-6] DR Ensembl; ENST00000533988.5; ENSP00000434665.1; ENSG00000158636.17. [Q7Z589-3] DR Ensembl; ENST00000695367.1; ENSP00000511840.1; ENSG00000158636.17. [Q7Z589-7] DR GeneID; 56946; -. DR KEGG; hsa:56946; -. DR MANE-Select; ENST00000695367.1; ENSP00000511840.1; NM_001300942.2; NP_001287871.1. [Q7Z589-7] 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 ventricular zone and 174 other tissues. DR ExpressionAtlas; Q7Z589; baseline and differential. DR Genevisible; Q7Z589; HS. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. 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 DNA-templated transcription; 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 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 12-OCT-2022, entry version 159. 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; 140. 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; 152 antibodies from 27 providers. DR DNASU; 7979; -. DR Ensembl; ENST00000248566.4; ENSP00000248566.2; ENSG00000127922.10. [P60896-1] 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; ENSGT00940000162732; -. 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-5685942; HDR through Homologous Recombination (HRR). 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-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-68867; Assembly of the pre-replicative 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-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-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-9709275; Impaired BRCA2 translocation to the nucleus. DR Reactome; R-HSA-9709570; Impaired BRCA2 binding to RAD51. DR Reactome; R-HSA-9755511; KEAP1-NFE2L2 pathway. DR Reactome; R-HSA-9762114; GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2. DR Reactome; R-HSA-9763198; Impaired BRCA2 binding to SEM1 (DSS1). 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 calcaneal tendon and 202 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 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 12-OCT-2022, entry version 191. 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=14; 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=12; 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; 56. 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; 386 antibodies from 34 providers. DR CPTC; O43502; 2 antibodies. DR DNASU; 5889; -. DR Ensembl; ENST00000337432.9; ENSP00000336701.4; ENSG00000108384.15. [O43502-1] 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-9709603; Impaired BRCA2 binding to PALB2. 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 right testis and 198 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:0140664; F:ATP-dependent DNA damage sensor activity; 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 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 BINDING 125..132 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" 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 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 12-OCT-2022, entry version 142. 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 14 providers. DR DNASU; 116028; -. DR Ensembl; ENST00000312499.6; ENSP00000310356.5; ENSG00000175643.10. [Q96E14-1] 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 Reactome; R-HSA-9709570; Impaired BRCA2 binding to RAD51. DR Reactome; R-HSA-9709603; Impaired BRCA2 binding to PALB2. 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 127 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 // ID RMI1_HUMAN Reviewed; 625 AA. AC Q9H9A7; Q05BX1; Q05CW3; Q5SQG8; Q5SQG9; Q6P1Q4; Q6PI89; Q7Z6L6; DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot. DT 08-FEB-2011, sequence version 3. DT 12-OCT-2022, entry version 160. DE RecName: Full=RecQ-mediated genome instability protein 1; DE AltName: Full=BLM-associated protein of 75 kDa; DE Short=BLAP75; DE AltName: Full=FAAP75; GN Name=RMI1; Synonyms=C9orf76; 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], AND VARIANT SER-455. 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=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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS HIS-100 AND SER-455. RC TISSUE=Brain, Skin, Testis, 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 [4] RP FUNCTION, IDENTIFICATION IN COMPLEX WITH BLM AND TOP3A, AND SUBCELLULAR RP LOCATION. RX PubMed=15775963; DOI=10.1038/sj.emboj.7600622; RA Yin J., Sobeck A., Xu C., Meetei A.R., Hoatlin M., Li L., Wang W.; RT "BLAP75, an essential component of Bloom's syndrome protein complexes that RT maintain genome integrity."; RL EMBO J. 24:1465-1476(2005). RN [5] RP FUNCTION, AND INTERACTION WITH BLM AND TOP3A. RX PubMed=16595695; DOI=10.1074/jbc.c600051200; RA Raynard S., Bussen W., Sung P.; RT "A double Holliday junction dissolvasome comprising BLM, topoisomerase III RT alpha, and BLAP75."; RL J. Biol. Chem. 281:13861-13864(2006). RN [6] RP FUNCTION, BINDING TO DOUBLE HOLLIDAY JUNCTION, AND INTERACTION WITH TOP3A. RX PubMed=16537486; DOI=10.1073/pnas.0508295103; RA Wu L., Bachrati C.Z., Ou J., Xu C., Yin J., Chang M., Wang W., Li L., RA Brown G.W., Hickson I.D.; RT "BLAP75/RMI1 promotes the BLM-dependent dissolution of homologous RT recombination intermediates."; RL Proc. Natl. Acad. Sci. U.S.A. 103:4068-4073(2006). RN [7] RP IDENTIFICATION IN THE RMI COMPLEX, AND INTERACTION WITH RMI2. 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 [8] RP IDENTIFICATION IN THE RMI COMPLEX, AND INTERACTION WITH RMI2. 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 [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-225, 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 [10] 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 [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284 AND SER-292, AND RP 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 [12] RP INTERACTION WITH BLM. 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 [13] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-426, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25755297; DOI=10.1074/mcp.o114.044792; RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V., RA Vertegaal A.C.; RT "System-wide analysis of SUMOylation dynamics in response to replication RT stress reveals novel small ubiquitin-like modified target proteins and RT acceptor lysines relevant for genome stability."; RL Mol. Cell. Proteomics 14:1419-1434(2015). RN [14] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-334; LYS-387 AND LYS-426, AND RP IDENTIFICATION BY MASS 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: Essential component of the RMI complex, a complex that plays CC an important role in the processing of homologous recombination CC intermediates to limit DNA crossover formation in cells. Promotes TOP3A CC binding to double Holliday junctions (DHJ) and hence stimulates TOP3A- CC mediated dissolution. Required for BLM phosphorylation during mitosis. CC Within the BLM complex, required for BLM and TOP3A stability. CC {ECO:0000269|PubMed:15775963, ECO:0000269|PubMed:16537486, CC ECO:0000269|PubMed:16595695}. CC -!- SUBUNIT: Component of the RMI complex, containing at least TOP3A, RMI1 CC and RMI2. The RMI complex interacts with BLM. Directly interacts with CC RMI2 and TOP3A. May bind DHJ. Interacts (via N-terminal region) with CC BLM; the interaction is direct. {ECO:0000269|PubMed:15775963, CC ECO:0000269|PubMed:16537486, ECO:0000269|PubMed:16595695, CC ECO:0000269|PubMed:18923082, ECO:0000269|PubMed:18923083, CC ECO:0000269|PubMed:23509288}. CC -!- INTERACTION: CC Q9H9A7; P54132: BLM; NbExp=15; IntAct=EBI-621339, EBI-621372; CC Q9H9A7; Q96E14: RMI2; NbExp=4; IntAct=EBI-621339, EBI-2555534; CC Q9H9A7; Q96E14-1: RMI2; NbExp=13; IntAct=EBI-621339, EBI-15876491; CC Q9H9A7; Q13472: TOP3A; NbExp=10; IntAct=EBI-621339, EBI-621345; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15775963}. Note=Forms CC foci in response to DNA damage. CC -!- SIMILARITY: Belongs to the RMI1 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH20606.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; CC Sequence=AAH32494.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; CC Sequence=AAH39999.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAH53549.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; CC Sequence=AAH64937.1; 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; AK022950; BAB14325.1; -; mRNA. DR EMBL; AL732446; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC020606; AAH20606.1; ALT_SEQ; mRNA. DR EMBL; BC032494; AAH32494.1; ALT_SEQ; mRNA. DR EMBL; BC039999; AAH39999.1; ALT_FRAME; mRNA. DR EMBL; BC053549; AAH53549.1; ALT_SEQ; mRNA. DR EMBL; BC064937; AAH64937.1; ALT_FRAME; mRNA. DR CCDS; CCDS6669.1; -. DR RefSeq; NP_079221.2; NM_024945.2. DR RefSeq; XP_005252268.1; XM_005252211.2. DR RefSeq; XP_005252270.1; XM_005252213.2. DR RefSeq; XP_011517336.1; XM_011519034.2. DR RefSeq; XP_016870629.1; XM_017015140.1. DR PDB; 3MXN; X-ray; 1.55 A; A=473-625. DR PDB; 3NBH; X-ray; 2.00 A; A=475-625. DR PDB; 3NBI; X-ray; 2.00 A; A=2-213. DR PDB; 4CGY; X-ray; 2.85 A; B=1-219. DR PDB; 4CHT; X-ray; 3.25 A; B=1-219. DR PDB; 4DAY; X-ray; 3.30 A; A=473-625. DR PDBsum; 3MXN; -. DR PDBsum; 3NBH; -. DR PDBsum; 3NBI; -. DR PDBsum; 4CGY; -. DR PDBsum; 4CHT; -. DR PDBsum; 4DAY; -. DR AlphaFoldDB; Q9H9A7; -. DR SMR; Q9H9A7; -. DR BioGRID; 123066; 37. DR ComplexPortal; CPX-3301; BTR double Holliday Junction dissolution complex. DR CORUM; Q9H9A7; -. DR DIP; DIP-33324N; -. DR IntAct; Q9H9A7; 23. DR MINT; Q9H9A7; -. DR STRING; 9606.ENSP00000317039; -. DR iPTMnet; Q9H9A7; -. DR PhosphoSitePlus; Q9H9A7; -. DR BioMuta; RMI1; -. DR DMDM; 322510109; -. DR EPD; Q9H9A7; -. DR jPOST; Q9H9A7; -. DR MassIVE; Q9H9A7; -. DR MaxQB; Q9H9A7; -. DR PaxDb; Q9H9A7; -. DR PeptideAtlas; Q9H9A7; -. DR PRIDE; Q9H9A7; -. DR ProteomicsDB; 81306; -. DR Antibodypedia; 27643; 171 antibodies from 23 providers. DR DNASU; 80010; -. DR Ensembl; ENST00000325875.7; ENSP00000317039.3; ENSG00000178966.17. DR Ensembl; ENST00000445877.6; ENSP00000402433.2; ENSG00000178966.17. DR GeneID; 80010; -. DR KEGG; hsa:80010; -. DR MANE-Select; ENST00000445877.6; ENSP00000402433.2; NM_001358291.2; NP_001345220.1. DR UCSC; uc004anq.5; human. DR CTD; 80010; -. DR DisGeNET; 80010; -. DR GeneCards; RMI1; -. DR HGNC; HGNC:25764; RMI1. DR HPA; ENSG00000178966; Low tissue specificity. DR MIM; 610404; gene. DR neXtProt; NX_Q9H9A7; -. DR OpenTargets; ENSG00000178966; -. DR PharmGKB; PA134939007; -. DR VEuPathDB; HostDB:ENSG00000178966; -. DR eggNOG; KOG3683; Eukaryota. DR GeneTree; ENSGT00940000161055; -. DR InParanoid; Q9H9A7; -. DR OMA; STWHVKV; -. DR OrthoDB; 531291at2759; -. DR PhylomeDB; Q9H9A7; -. DR TreeFam; TF316491; -. DR PathwayCommons; Q9H9A7; -. 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 Reactome; R-HSA-9709570; Impaired BRCA2 binding to RAD51. DR Reactome; R-HSA-9709603; Impaired BRCA2 binding to PALB2. DR SignaLink; Q9H9A7; -. DR BioGRID-ORCS; 80010; 458 hits in 1082 CRISPR screens. DR GeneWiki; RMI1; -. DR GenomeRNAi; 80010; -. DR Pharos; Q9H9A7; Tbio. DR PRO; PR:Q9H9A7; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; Q9H9A7; protein. DR Bgee; ENSG00000178966; Expressed in oocyte and 191 other tissues. DR ExpressionAtlas; Q9H9A7; baseline and differential. DR Genevisible; Q9H9A7; HS. DR GO; GO:0016604; C:nuclear body; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IC:ComplexPortal. DR GO; GO:0031422; C:RecQ family helicase-topoisomerase III complex; IPI:ComplexPortal. DR GO; GO:0000166; F:nucleotide binding; IEA:InterPro. 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:0042593; P:glucose homeostasis; IEA:Ensembl. DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl. DR GO; GO:0002023; P:reduction of food intake in response to dietary excess; IEA:Ensembl. DR GO; GO:0000712; P:resolution of meiotic recombination intermediates; IBA:GO_Central. DR GO; GO:0071139; P:resolution of recombination intermediates; IDA:ComplexPortal. DR GO; GO:0009749; P:response to glucose; IEA:Ensembl. DR Gene3D; 1.10.8.1020; -; 1. DR Gene3D; 2.40.50.770; -; 1. DR IDEAL; IID00421; -. DR InterPro; IPR033472; RMI1-like_N_hel. DR InterPro; IPR032199; RMI1_C. DR InterPro; IPR013894; RMI1_N. DR InterPro; IPR042470; RMI1_N_C_sf. DR InterPro; IPR044881; RMI1_N_N_sf. DR Pfam; PF16099; RMI1_C; 1. DR Pfam; PF08585; RMI1_N; 1. DR SMART; SM01161; DUF1767; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; DNA replication; Isopeptide bond; Nucleus; KW Phosphoprotein; Reference proteome; Ubl conjugation. FT CHAIN 1..625 FT /note="RecQ-mediated genome instability protein 1" FT /id="PRO_0000227546" FT REGION 257..282 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22814378" FT MOD_RES 225 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 284 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 292 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CROSSLNK 334 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 387 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 426 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25755297, FT ECO:0007744|PubMed:28112733" FT VARIANT 100 FT /note="Y -> H (in dbSNP:rs17855932)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_025556" FT VARIANT 455 FT /note="N -> S (in dbSNP:rs1982151)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334" FT /id="VAR_025557" FT CONFLICT 11 FT /note="E -> G (in Ref. 1; BAB14325)" FT /evidence="ECO:0000305" FT CONFLICT 259 FT /note="A -> T (in Ref. 1; BAB14325)" FT /evidence="ECO:0000305" FT CONFLICT 318 FT /note="E -> D (in Ref. 3; AAH20606)" FT /evidence="ECO:0000305" FT CONFLICT 443 FT /note="L -> F (in Ref. 3; AAH39999)" FT /evidence="ECO:0000305" FT HELIX 3..18 FT /evidence="ECO:0007829|PDB:3NBI" FT HELIX 24..38 FT /evidence="ECO:0007829|PDB:3NBI" FT HELIX 45..57 FT /evidence="ECO:0007829|PDB:3NBI" FT HELIX 61..64 FT /evidence="ECO:0007829|PDB:3NBI" FT TURN 71..75 FT /evidence="ECO:0007829|PDB:3NBI" FT STRAND 77..95 FT /evidence="ECO:0007829|PDB:3NBI" FT HELIX 96..108 FT /evidence="ECO:0007829|PDB:3NBI" FT HELIX 113..115 FT /evidence="ECO:0007829|PDB:4CGY" FT HELIX 126..129 FT /evidence="ECO:0007829|PDB:4CHT" FT STRAND 135..143 FT /evidence="ECO:0007829|PDB:3NBI" FT STRAND 145..150 FT /evidence="ECO:0007829|PDB:3NBI" FT STRAND 166..176 FT /evidence="ECO:0007829|PDB:3NBI" FT STRAND 179..182 FT /evidence="ECO:0007829|PDB:3NBI" FT HELIX 184..186 FT /evidence="ECO:0007829|PDB:3NBI" FT STRAND 187..191 FT /evidence="ECO:0007829|PDB:3NBI" FT HELIX 195..201 FT /evidence="ECO:0007829|PDB:3NBI" FT HELIX 203..210 FT /evidence="ECO:0007829|PDB:4CGY" FT HELIX 480..482 FT /evidence="ECO:0007829|PDB:3MXN" FT HELIX 483..487 FT /evidence="ECO:0007829|PDB:3MXN" FT HELIX 494..499 FT /evidence="ECO:0007829|PDB:3MXN" FT STRAND 506..517 FT /evidence="ECO:0007829|PDB:3MXN" FT HELIX 524..526 FT /evidence="ECO:0007829|PDB:3MXN" FT STRAND 531..535 FT /evidence="ECO:0007829|PDB:3MXN" FT STRAND 540..545 FT /evidence="ECO:0007829|PDB:3MXN" FT HELIX 547..554 FT /evidence="ECO:0007829|PDB:3MXN" FT HELIX 558..564 FT /evidence="ECO:0007829|PDB:3MXN" FT HELIX 568..587 FT /evidence="ECO:0007829|PDB:3MXN" FT STRAND 589..597 FT /evidence="ECO:0007829|PDB:3MXN" FT TURN 598..601 FT /evidence="ECO:0007829|PDB:3MXN" FT STRAND 602..609 FT /evidence="ECO:0007829|PDB:3MXN" FT HELIX 613..622 FT /evidence="ECO:0007829|PDB:3MXN" SQ SEQUENCE 625 AA; 70144 MW; 2BB449363DBF76B7 CRC64; MNVTSIALRA ETWLLAAWHV KVPPMWLEAC INWIQEENNN VNLSQAQMNK QVFEQWLLTD LRDLEHPLLP DGILEIPKGE LNGFYALQIN SLVDVSQPAY SQIQKLRGKN TTNDLVTAEA QVTPKPWEAK PSRMLMLQLT DGIVQIQGME YQPIPILHSD LPPGTKILIY GNISFRLGVL LLKPENVKVL GGEVDALLEE YAQEKVLARL IGEPDLVVSV IPNNSNENIP RVTDVLDPAL GPSDEELLAS LDENDELTAN NDTSSERCFT TGSSSNTIPT RQSSFEPEFV ISPRPKEEPS NLSIHVMDGE LDDFSLEEAL LLEETVQKEQ METKELQPLT FNRNADRSIE RFSHNPNTTN NFSLTCKNGN NNWSEKNVSE QMTNEDKSFG CPSVRDQNRS IFSVHCNVPL AHDFTNKEKN LETDNKIKQT SSSDSHSLNN KILNREVVNY VQKRNSQISN ENDCNLQSCS LRSSENSINL SIAMDLYSPP FVYLSVLMAS KPKEVTTVKV KAFIVTLTGN LSSSGGIWSI TAKVSDGTAY LDVDFVDEIL TSLIGFSVPE MKQSKKDPLQ YQKFLEGLQK CQRDLIDLCC LMTISFNPSL SKAMVLALQD VNMEHLENLK KRLNK // 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 12-OCT-2022, entry version 175. 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; 75. 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; 309 antibodies from 33 providers. DR DNASU; 10362; -. DR Ensembl; ENST00000333651.11; ENSP00000328269.6; ENSG00000064961.19. [Q9P0W2-1] 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 178 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:0016925; P:protein sumoylation; 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 12-OCT-2022, entry version 184. 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=12; 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 may also 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; 175. 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; 607 antibodies from 34 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 mucosa of stomach and 95 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:0140664; F:ATP-dependent DNA damage sensor activity; 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 BINDING 107..114 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" 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 03-AUG-2022, entry version 127. 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; 43 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. [Q0VDD7-1] DR Ensembl; ENST00000672170.1; ENSP00000500215.1; ENSG00000288152.1. [Q0VDD7-1] 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 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 RNAct; Q0VDD7; protein. DR Bgee; ENSG00000132016; Expressed in right testis and 94 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 12-OCT-2022, entry version 234. 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 FUNCTION, INTERACTION WITH PALB2, AND IDENTIFICATION IN A PALB2-CONTAINING RP HR 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 SUBCELLULAR LOCATION, AND INTERACTION WITH MMS22L. RX PubMed=27797818; DOI=10.15252/embj.201593132; RA Piwko W., Mlejnkova L.J., Mutreja K., Ranjha L., Stafa D., Smirnov A., RA Brodersen M.M., Zellweger R., Sturzenegger A., Janscak P., Lopes M., RA Peter M., Cejka P.; RT "The MMS22L-TONSL heterodimer directly promotes RAD51-dependent RT recombination upon replication stress."; RL EMBO J. 35:2584-2601(2016). RN [49] 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 [50] 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 [51] RP FUNCTION, INTERACTION WITH ATAD5 RFC-LIKE COMPLEX; ATAD5 AND WDR48, AND RP SUBCELLULAR LOCATION. RX PubMed=31844045; DOI=10.1038/s41467-019-13667-4; RA Park S.H., Kang N., Song E., Wie M., Lee E.A., Hwang S., Lee D., Ra J.S., RA Park I.B., Park J., Kang S., Park J.H., Hohng S., Lee K.Y., Myung K.; RT "ATAD5 promotes replication restart by regulating RAD51 and PCNA in RT response to replication stress."; RL Nat. Commun. 10:5718-5718(2019). RN [52] 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 601:268-273(2022). RN [53] 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 [54] 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 [55] 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 [56] 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 [57] 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:18417535, PubMed:20348101, PubMed:12205100, PubMed:20231364, CC PubMed:23754376, PubMed:23509288, PubMed:28575658, PubMed:26681308). CC Binds to single-stranded DNA in an ATP-dependent manner to form CC nucleoprotein filaments which are essential for the homology search and CC strand exchange (PubMed:18417535, PubMed:20348101, PubMed:12205100, CC PubMed:20231364, PubMed:23754376, PubMed:23509288, PubMed:28575658, CC PubMed:26681308). Catalyzes the recognition of homology and strand CC exchange between homologous DNA partners to form a joint molecule CC between a processed DNA break and the repair template (PubMed:18417535, CC PubMed:20348101, PubMed:12205100, PubMed:20231364, PubMed:23754376, CC PubMed:23509288, PubMed:28575658, PubMed:26681308). Recruited to CC resolve stalled replication forks during replication stress CC (PubMed:27797818, PubMed:31844045). Part of a PALB2-scaffolded HR CC complex containing BRCA2 and RAD51C and which is thought to play a role CC in DNA repair by HR (PubMed:24141787, PubMed:12442171). Plays a role in CC regulating mitochondrial DNA copy number under conditions of oxidative CC stress in the presence of RAD51C and XRCC3 (PubMed:20413593). Also CC involved in interstrand cross-link repair (PubMed:26253028). CC {ECO:0000269|PubMed:12205100, ECO:0000269|PubMed:12442171, CC ECO:0000269|PubMed:18417535, ECO:0000269|PubMed:20231364, CC ECO:0000269|PubMed:20348101, ECO:0000269|PubMed:20413593, CC ECO:0000269|PubMed:23509288, ECO:0000269|PubMed:23754376, CC ECO:0000269|PubMed:24141787, ECO:0000269|PubMed:26253028, CC ECO:0000269|PubMed:26681308, ECO:0000269|PubMed:27797818, CC ECO:0000269|PubMed:28575658, ECO:0000269|PubMed:31844045}. 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). Interacts with MMS22L; the interaction is direct and CC promotes recruitment of RAD51 to sites of DNA damage (PubMed:27797818). CC Interacts with the ATAD5 RFC-like complex (PubMed:31844045). Within the CC ATAD5 RFC-like complex, interacts with ATAD5 (via N-terminus); the CC interaction is direct and enhanced under replication stress CC (PubMed:31844045). Interacts with WDR48; the interaction is enhanced CC under replication stress (PubMed:31844045). CC {ECO:0000250|UniProtKB:Q08297, ECO:0000269|PubMed:10851248, CC ECO:0000269|PubMed:11842113, ECO:0000269|PubMed:12427746, CC ECO:0000269|PubMed:12442171, ECO:0000269|PubMed:14580352, CC ECO:0000269|PubMed:15665856, ECO:0000269|PubMed:16990250, CC ECO:0000269|PubMed:18449195, ECO:0000269|PubMed:19995904, CC ECO:0000269|PubMed:20154705, ECO:0000269|PubMed:20231364, CC ECO:0000269|PubMed:20348101, ECO:0000269|PubMed:20705237, CC ECO:0000269|PubMed:20871615, ECO:0000269|PubMed:21252223, CC ECO:0000269|PubMed:21965664, ECO:0000269|PubMed:22153967, CC ECO:0000269|PubMed:23393192, ECO:0000269|PubMed:23401855, CC ECO:0000269|PubMed:23509288, ECO:0000269|PubMed:23754376, CC ECO:0000269|PubMed:24141787, ECO:0000269|PubMed:25642963, CC ECO:0000269|PubMed:26833090, ECO:0000269|PubMed:27797818, CC ECO:0000269|PubMed:28575658, ECO:0000269|PubMed:31844045, CC ECO:0000269|PubMed:34937945, ECO:0000269|PubMed:9192668, CC ECO:0000269|PubMed:9321665, ECO:0000269|PubMed:9396801, CC 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, ECO:0000269|PubMed:27797818, CC ECO:0000269|PubMed:31844045}. Cytoplasm, cytoskeleton, microtubule CC organizing center, centrosome {ECO:0000269|PubMed:21276791}. CC Note=Colocalizes with RAD51AP1 and RPA2 to multiple nuclear foci upon CC induction of DNA damage (PubMed:20154705). DNA damage induces an CC increase in nuclear levels (PubMed:20154705). Together with FIGNL1, CC redistributed in discrete nuclear DNA damage-induced foci after CC ionizing radiation (IR) or camptothecin (CPT) treatment CC (PubMed:23754376). Accumulated at sites of DNA damage in a SPIDR- CC dependent manner (PubMed:23509288). Recruited at sites of DNA damage in CC a MCM9-MCM8-dependent manner (PubMed:23401855). Colocalizes with CC ERCC5/XPG to nuclear foci in S phase (PubMed:26833090). Recruited to CC stalled replication forks during replication stress by the TONSL-MMS22L CC complex, as well as ATAD5 and WDR48 in an ATR-dependent manner CC (PubMed:27797818, PubMed:31844045). {ECO:0000269|PubMed:20154705, CC ECO:0000269|PubMed:23401855, ECO:0000269|PubMed:23509288, CC ECO:0000269|PubMed:23754376, ECO:0000269|PubMed:26833090, CC ECO:0000269|PubMed:27797818, ECO:0000269|PubMed:31844045}. 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 PDB; 7EJC; EM; 2.97 A; A/B/C=1-339. DR PDB; 7EJE; EM; 3.98 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 PDBsum; 7EJC; -. DR PDBsum; 7EJE; -. DR AlphaFoldDB; Q06609; -. DR BMRB; Q06609; -. DR SMR; Q06609; -. DR BioGRID; 111825; 238. 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; 969 antibodies from 44 providers. DR DNASU; 5888; -. DR Ensembl; ENST00000267868.8; ENSP00000267868.3; ENSG00000051180.17. [Q06609-1] 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. [Q06609-1] 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 Reactome; R-HSA-9709570; Impaired BRCA2 binding to RAD51. DR Reactome; R-HSA-9709603; Impaired BRCA2 binding to PALB2. 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 buccal mucosa cell and 129 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:0001673; C:male germ cell nucleus; IEA:Ensembl. 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:0140664; F:ATP-dependent DNA damage sensor activity; IEA:InterPro. 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; IDA:UniProtKB. 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:0003676; F:nucleic acid binding; IDA:DisProt. 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 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 BINDING 127..134 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" 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 TURN 25..32 FT /evidence="ECO:0007829|PDB:7EJC" FT HELIX 35..44 FT /evidence="ECO:0007829|PDB:7EJC" FT HELIX 49..53 FT /evidence="ECO:0007829|PDB:7EJC" FT STRAND 54..56 FT /evidence="ECO:0007829|PDB:1B22" FT HELIX 57..61 FT /evidence="ECO:0007829|PDB:7EJC" FT TURN 62..65 FT /evidence="ECO:0007829|PDB:1B22" FT HELIX 69..81 FT /evidence="ECO:0007829|PDB:7EJC" FT HELIX 89..97 FT /evidence="ECO:0007829|PDB:7EJC" 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..132 FT /evidence="ECO:0007829|PDB:7EJC" FT HELIX 133..143 FT /evidence="ECO:0007829|PDB:1N0W" FT STRAND 144..146 FT /evidence="ECO:0007829|PDB:7EJC" 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 STRAND 234..237 FT /evidence="ECO:0007829|PDB:7EJC" FT HELIX 238..259 FT /evidence="ECO:0007829|PDB:1N0W" FT STRAND 262..267 FT /evidence="ECO:0007829|PDB:1N0W" FT TURN 287..289 FT /evidence="ECO:0007829|PDB:7EJC" FT HELIX 290..295 FT /evidence="ECO:0007829|PDB:7EJC" 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:7EJC" 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 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 12-OCT-2022, entry version 186. 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=14; IntAct=EBI-2824089, EBI-2267048; CC O15315; O75771: RAD51D; NbExp=6; 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 35 providers. DR DNASU; 5890; -. DR Ensembl; ENST00000471583.6; ENSP00000418859.1; ENSG00000182185.19. [O15315-2] DR Ensembl; ENST00000487270.5; ENSP00000419471.1; ENSG00000182185.19. [O15315-3] 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-9709603; Impaired BRCA2 binding to PALB2. 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 125 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:0140664; F:ATP-dependent DNA damage sensor activity; IEA:InterPro. 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 REGION 1..75 FT /note="Interaction with RAD51C" FT BINDING 108..115 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255" 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 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 12-OCT-2022, entry version 188. 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; P00533: EGFR; NbExp=2; IntAct=EBI-359343, EBI-297353; 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; 851. DR ComplexPortal; CPX-6264; Fanconi anemia ID complex. DR CORUM; Q9BXW9; -. DR DIP; DIP-27606N; -. DR DIP; DIP-29382N; -. DR IntAct; Q9BXW9; 69. 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; 652 antibodies from 38 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. [Q9BXW9-2] DR Ensembl; ENST00000431693.1; ENSP00000399354.1; ENSG00000144554.13. [Q9BXW9-4] DR Ensembl; ENST00000675286.1; ENSP00000502379.1; ENSG00000144554.13. [Q9BXW9-2] 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 ventricular zone and 130 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 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 12-OCT-2022, entry version 193. 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; 30. 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; 417 antibodies from 33 providers. DR DNASU; 11144; -. DR Ensembl; ENST00000216024.7; ENSP00000216024.2; ENSG00000100206.11. [Q14565-1] 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 MalaCards; DMC1; -. 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 129 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:0140664; F:ATP-dependent DNA damage sensor activity; IEA:InterPro. 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 BINDING 126..133 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000305" FT BINDING 230 FT /ligand="dsDNA" FT /ligand_id="ChEBI:CHEBI:4705" FT /evidence="ECO:0000269|PubMed:15125839" FT BINDING 230 FT /ligand="ssDNA" FT /ligand_id="ChEBI:CHEBI:9160" FT /evidence="ECO:0000269|PubMed:15125839" FT BINDING 233 FT /ligand="ssDNA" FT /ligand_id="ChEBI:CHEBI:9160" FT /evidence="ECO:0000269|PubMed:15125839" FT BINDING 236 FT /ligand="dsDNA" FT /ligand_id="ChEBI:CHEBI:4705" FT /evidence="ECO:0000269|PubMed:15125839" FT BINDING 236 FT /ligand="ssDNA" FT /ligand_id="ChEBI:CHEBI:9160" FT /evidence="ECO:0000269|PubMed:15125839" FT BINDING 242 FT /ligand="dsDNA" FT /ligand_id="ChEBI:CHEBI:4705" FT /evidence="ECO:0000269|PubMed:15125839" FT BINDING 242 FT /ligand="ssDNA" FT /ligand_id="ChEBI:CHEBI:9160" FT /evidence="ECO:0000269|PubMed:15125839" FT BINDING 311 FT /ligand="ssDNA" FT /ligand_id="ChEBI:CHEBI:9160" 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 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 12-OCT-2022, entry version 157. 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). Binds and stabilizes BRCA2 and is thus CC involved in the control of R-loop-associated DNA damage and CC transcription-associated genomic instability (PubMed:24896180). Blocks CC the activity of the SRCAP chromatin remodeling complex by interacting CC with SRCAP complex member ZNHIT1 and inhibiting its interaction with CC the complex (By similarity). This prevents the deposition of histone CC variant H2AZ1/H2A.Z at the nucleosomes of key lymphoid fate regulator CC genes which suppresses their expression and restricts lymphoid lineage CC commitment (By similarity). {ECO:0000250|UniProtKB:Q8BFV2, CC ECO:0000269|PubMed:22307388, ECO:0000269|PubMed:24896180, CC 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). Interacts with SRCAP chromatin CC remodeling complex component ZNHIT1; the interaction results in CC inhibition of SRCAP complex activity, preventing the deposition of CC histone variant H2AZ1/H2A.Z to lymphoid fate regulator genes and CC restricting lymphoid lineage commitment (By similarity). CC {ECO:0000250|UniProtKB:Q8BFV2, 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; 68. DR DIP; DIP-50497N; -. DR IntAct; Q5JVF3; 27. 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; 97 antibodies from 16 providers. DR DNASU; 55795; -. DR Ensembl; ENST00000246505.9; ENSP00000246505.5; ENSG00000126226.22. [Q5JVF3-4] DR Ensembl; ENST00000337344.9; ENSP00000337405.4; ENSG00000126226.22. [Q5JVF3-1] 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. [Q5JVF3-1] DR Ensembl; ENST00000375479.6; ENSP00000364628.2; ENSG00000126226.22. [Q5JVF3-1] 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 185 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:1905457; P:negative regulation of lymphoid progenitor cell differentiation; ISS:UniProtKB. 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:0045893; P:positive regulation of DNA-templated transcription; IMP:UniProtKB. DR GO; GO:0090267; P:positive regulation of mitotic cell cycle spindle assembly checkpoint; IMP:UniProtKB. DR GO; GO:0000973; P:post-transcriptional 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:1900049; P:regulation of histone exchange; ISS:UniProtKB. 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 by 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 FANCG_HUMAN Reviewed; 622 AA. AC O15287; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 12-OCT-2022, entry version 207. 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; 107. 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; 447 antibodies from 36 providers. DR DNASU; 2189; -. DR Ensembl; ENST00000378643.8; ENSP00000367910.4; ENSG00000221829.11. DR Ensembl; ENST00000448890.2; ENSP00000409607.2; ENSG00000221829.11. 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 ventricular zone and 158 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 TOP3A_HUMAN Reviewed; 1001 AA. AC Q13472; A8KA61; B4DK80; D3DXC7; Q13473; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 1. DT 12-OCT-2022, entry version 191. DE RecName: Full=DNA topoisomerase 3-alpha; DE EC=5.6.2.1 {ECO:0000255|PROSITE-ProRule:PRU10131, ECO:0000269|PubMed:20445207, ECO:0000269|PubMed:8622991}; DE AltName: Full=DNA topoisomerase III alpha; GN Name=TOP3A; Synonyms=TOP3; 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 LONG AND SHORT), FUNCTION, AND RP CATALYTIC ACTIVITY. RX PubMed=8622991; DOI=10.1073/pnas.93.8.3653; RA Hanai R., Caron P.R., Wang J.C.; RT "Human TOP3: a single-copy gene encoding DNA topoisomerase III."; RL Proc. Natl. Acad. Sci. U.S.A. 93:3653-3657(1996). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=20843780; DOI=10.1093/nar/gkq750; RA Wang W., Shen P., Thiyagarajan S., Lin S., Palm C., Horvath R., RA Klopstock T., Cutler D., Pique L., Schrijver I., Davis R.W., Mindrinos M., RA Speed T.P., Scharfe C.; RT "Identification of rare DNA variants in mitochondrial disorders with RT improved array-based sequencing."; RL Nucleic Acids Res. 39:44-58(2011). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS LONG AND 3). RC TISSUE=Thalamus, and Trachea; 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 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 [5] 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). 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 [7] RP IDENTIFICATION IN COMPLEX WITH BLM AND RMI1. RX PubMed=15775963; DOI=10.1038/sj.emboj.7600622; RA Yin J., Sobeck A., Xu C., Meetei A.R., Hoatlin M., Li L., Wang W.; RT "BLAP75, an essential component of Bloom's syndrome protein complexes that RT maintain genome integrity."; RL EMBO J. 24:1465-1476(2005). RN [8] RP IDENTIFICATION IN THE RMI COMPLEX. 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 [9] RP IDENTIFICATION IN THE RMI COMPLEX. 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 [10] 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 [11] RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, COFACTOR, AND INTERACTION WITH RMI1. RX PubMed=20445207; DOI=10.1074/jbc.m110.123216; RA Yang J., Bachrati C.Z., Ou J., Hickson I.D., Brown G.W.; RT "Human topoisomerase IIIalpha is a single-stranded DNA decatenase that is RT stimulated by BLM and RMI1."; RL J. Biol. Chem. 285:21426-21436(2010). RN [12] RP INTERACTION WITH BLM. 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 [13] RP FUNCTION, INVOLVEMENT IN MGRISCE2, AND VARIANT MGRISCE2 VAL-176. RX PubMed=30057030; DOI=10.1016/j.ajhg.2018.07.001; RG GOSgene; RA Martin C.A., Sarlos K., Logan C.V., Thakur R.S., Parry D.A., Bizard A.H., RA Leitch A., Cleal L., Ali N.S., Al-Owain M.A., Allen W., Altmueller J., RA Aza-Carmona M., Barakat B.A.Y., Barraza-Garcia J., Begtrup A., Bogliolo M., RA Cho M.T., Cruz-Rojo J., Dhahrabi H.A.M., Elcioglu N.H., Gorman G.S., RA Jobling R., Kesterton I., Kishita Y., Kohda M., Le Quesne Stabej P., RA Malallah A.J., Nuernberg P., Ohtake A., Okazaki Y., Pujol R., Ramirez M.J., RA Revah-Politi A., Shimura M., Stevens P., Taylor R.W., Turner L., RA Williams H., Wilson C., Yigit G., Zahavich L., Alkuraya F.S., Surralles J., RA Iglesias A., Murayama K., Wollnik B., Dattani M., Heath K.E., Hickson I.D., RA Jackson A.P.; RT "Mutations in TOP3A cause a Bloom syndrome-like disorder."; RL Am. J. Hum. Genet. 103:221-231(2018). RN [14] RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, INVOLVEMENT IN PEOB5, VARIANTS RP PEOB5 VAL-100 AND 135-ARG--ARG-1001 DEL, CHARACTERIZATION OF VARIANT PEOB5 RP VAL-100, AND MUTAGENESIS OF TYR-362. RX PubMed=29290614; DOI=10.1016/j.molcel.2017.11.033; RA Nicholls T.J., Nadalutti C.A., Motori E., Sommerville E.W., Gorman G.S., RA Basu S., Hoberg E., Turnbull D.M., Chinnery P.F., Larsson N.G., Larsson E., RA Falkenberg M., Taylor R.W., Griffith J.D., Gustafsson C.M.; RT "Topoisomerase 3alpha is required for decatenation and segregation of human RT mtDNA."; RL Mol. Cell 69:9-23(2018). CC -!- FUNCTION: Releases the supercoiling and torsional tension of DNA CC introduced during the DNA replication and transcription by transiently CC cleaving and rejoining one strand of the DNA duplex. Introduces a CC single-strand break via transesterification at a target site in duplex CC DNA. The scissile phosphodiester is attacked by the catalytic tyrosine CC of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)- CC enzyme intermediate and the expulsion of a 3'-OH DNA strand. The free CC DNA strand then undergoes passage around the unbroken strand thus CC removing DNA supercoils. Finally, in the religation step, the DNA 3'-OH CC attacks the covalent intermediate to expel the active-site tyrosine and CC restore the DNA phosphodiester backbone. As an essential component of CC the RMI complex it is involved in chromosome separation and the CC processing of homologous recombination intermediates to limit DNA CC crossover formation in cells. Has DNA decatenation activity CC (PubMed:30057030). It is required for mtDNA decatenation and CC segregation after completion of replication, in a process that does not CC require BLM, RMI1 and RMI2 (PubMed:29290614). CC {ECO:0000269|PubMed:20445207, ECO:0000269|PubMed:29290614, CC ECO:0000269|PubMed:30057030, ECO:0000269|PubMed:8622991}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP-independent breakage of single-stranded DNA, followed by CC passage and rejoining.; EC=5.6.2.1; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU10131, ECO:0000269|PubMed:20445207, CC ECO:0000269|PubMed:8622991}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:20445207}; CC -!- SUBUNIT: Binds ssDNA (PubMed:29290614). Interacts (via N-terminal CC region) with BLM; the interaction is direct. Directly interacts with CC RMI1. Component of the RMI complex, containing at least TOP3A, RMI1 and CC RMI2. The RMI complex interacts with BLM. {ECO:0000269|PubMed:15775963, CC ECO:0000269|PubMed:18923082, ECO:0000269|PubMed:18923083, CC ECO:0000269|PubMed:20445207, ECO:0000269|PubMed:23509288, CC ECO:0000269|PubMed:29290614}. CC -!- INTERACTION: CC Q13472; P54132: BLM; NbExp=9; IntAct=EBI-621345, EBI-621372; CC Q13472; Q9H9A7: RMI1; NbExp=10; IntAct=EBI-621345, EBI-621339; CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix CC {ECO:0000269|PubMed:29290614}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=Long; CC IsoId=Q13472-1; Sequence=Displayed; CC Name=Short; CC IsoId=Q13472-2; Sequence=VSP_006524; CC Name=3; CC IsoId=Q13472-3; Sequence=VSP_054189; CC -!- TISSUE SPECIFICITY: High expression is found in testis, heart, skeletal CC muscle and pancreas. CC -!- DISEASE: Microcephaly, growth restriction, and increased sister CC chromatid exchange 2 (MGRISCE2) [MIM:618097]: An autosomal recessive CC disorder characterized by intrauterine growth restriction, poor CC postnatal growth with short stature and microcephaly, and increased CC sister chromatid exchange on cell studies. CC {ECO:0000269|PubMed:30057030}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Progressive external ophthalmoplegia with mitochondrial DNA CC deletions, autosomal recessive 5 (PEOB5) [MIM:618098]: A form of CC progressive external ophthalmoplegia, a mitochondrial myopathy CC characterized by progressive paralysis of the levator palpebrae, CC orbicularis oculi, and extraocular muscles. PEOB5 features include CC slowly progressive ptosis, intermittent double vision, cardiac CC arrhythmias, exercise intolerance, proximal limb and neck muscle CC weakness, and cerebellar ataxia. Patients skeletal muscle biopsy show CC numerous COX-deficient ragged-red fibers, increased mtDNA deletions, CC and extensive variable mtDNA rearrangements. CC {ECO:0000269|PubMed:29290614}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the type IA topoisomerase 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; U43431; AAB03694.1; -; mRNA. DR EMBL; U43431; AAB03695.1; -; mRNA. DR EMBL; HQ205026; ADP90454.1; -; Genomic_DNA. DR EMBL; HQ205027; ADP90455.1; -; Genomic_DNA. DR EMBL; HQ205028; ADP90456.1; -; Genomic_DNA. DR EMBL; HQ205029; ADP90457.1; -; Genomic_DNA. DR EMBL; HQ205030; ADP90458.1; -; Genomic_DNA. DR EMBL; HQ205031; ADP90459.1; -; Genomic_DNA. DR EMBL; HQ205032; ADP90460.1; -; Genomic_DNA. DR EMBL; HQ205033; ADP90461.1; -; Genomic_DNA. DR EMBL; HQ205034; ADP90462.1; -; Genomic_DNA. DR EMBL; HQ205035; ADP90463.1; -; Genomic_DNA. DR EMBL; HQ205036; ADP90464.1; -; Genomic_DNA. DR EMBL; HQ205037; ADP90465.1; -; Genomic_DNA. DR EMBL; HQ205038; ADP90466.1; -; Genomic_DNA. DR EMBL; HQ205039; ADP90467.1; -; Genomic_DNA. DR EMBL; HQ205040; ADP90468.1; -; Genomic_DNA. DR EMBL; HQ205041; ADP90469.1; -; Genomic_DNA. DR EMBL; HQ205042; ADP90470.1; -; Genomic_DNA. DR EMBL; HQ205043; ADP90471.1; -; Genomic_DNA. DR EMBL; HQ205044; ADP90472.1; -; Genomic_DNA. DR EMBL; HQ205045; ADP90473.1; -; Genomic_DNA. DR EMBL; HQ205046; ADP90474.1; -; Genomic_DNA. DR EMBL; HQ205047; ADP90475.1; -; Genomic_DNA. DR EMBL; HQ205048; ADP90476.1; -; Genomic_DNA. DR EMBL; HQ205049; ADP90477.1; -; Genomic_DNA. DR EMBL; HQ205050; ADP90478.1; -; Genomic_DNA. DR EMBL; HQ205051; ADP90479.1; -; Genomic_DNA. DR EMBL; HQ205052; ADP90480.1; -; Genomic_DNA. DR EMBL; HQ205053; ADP90481.1; -; Genomic_DNA. DR EMBL; HQ205054; ADP90482.1; -; Genomic_DNA. DR EMBL; HQ205055; ADP90483.1; -; Genomic_DNA. DR EMBL; HQ205056; ADP90484.1; -; Genomic_DNA. DR EMBL; HQ205057; ADP90485.1; -; Genomic_DNA. DR EMBL; HQ205058; ADP90486.1; -; Genomic_DNA. DR EMBL; HQ205059; ADP90487.1; -; Genomic_DNA. DR EMBL; HQ205060; ADP90488.1; -; Genomic_DNA. DR EMBL; HQ205061; ADP90489.1; -; Genomic_DNA. DR EMBL; HQ205062; ADP90490.1; -; Genomic_DNA. DR EMBL; HQ205063; ADP90491.1; -; Genomic_DNA. DR EMBL; HQ205064; ADP90492.1; -; Genomic_DNA. DR EMBL; HQ205065; ADP90493.1; -; Genomic_DNA. DR EMBL; AK292926; BAF85615.1; -; mRNA. DR EMBL; AK296437; BAG59092.1; -; mRNA. DR EMBL; AC127537; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471196; EAW55646.1; -; Genomic_DNA. DR EMBL; CH471196; EAW55648.1; -; Genomic_DNA. DR EMBL; CH471196; EAW55649.1; -; Genomic_DNA. DR EMBL; BC051748; AAH51748.1; -; mRNA. DR CCDS; CCDS11194.1; -. [Q13472-1] DR RefSeq; NP_001307688.1; NM_001320759.1. [Q13472-3] DR RefSeq; NP_004609.1; NM_004618.4. [Q13472-1] DR PDB; 4CGY; X-ray; 2.85 A; A=2-753. DR PDB; 4CHT; X-ray; 3.25 A; A=2-753. DR PDBsum; 4CGY; -. DR PDBsum; 4CHT; -. DR AlphaFoldDB; Q13472; -. DR SMR; Q13472; -. DR BioGRID; 113009; 102. DR ComplexPortal; CPX-3301; BTR double Holliday Junction dissolution complex. DR CORUM; Q13472; -. DR DIP; DIP-33323N; -. DR IntAct; Q13472; 39. DR MINT; Q13472; -. DR STRING; 9606.ENSP00000442336; -. DR iPTMnet; Q13472; -. DR PhosphoSitePlus; Q13472; -. DR BioMuta; TOP3A; -. DR DMDM; 2501242; -. DR EPD; Q13472; -. DR jPOST; Q13472; -. DR MassIVE; Q13472; -. DR MaxQB; Q13472; -. DR PaxDb; Q13472; -. DR PeptideAtlas; Q13472; -. DR PRIDE; Q13472; -. DR ProteomicsDB; 4437; -. DR ProteomicsDB; 59469; -. [Q13472-1] DR ProteomicsDB; 59470; -. [Q13472-2] DR Antibodypedia; 43348; 83 antibodies from 19 providers. DR DNASU; 7156; -. DR Ensembl; ENST00000321105.10; ENSP00000321636.5; ENSG00000177302.15. [Q13472-1] DR Ensembl; ENST00000542570.5; ENSP00000442336.2; ENSG00000177302.15. [Q13472-1] DR Ensembl; ENST00000580095.5; ENSP00000462790.1; ENSG00000177302.15. [Q13472-2] DR Ensembl; ENST00000638894.1; ENSP00000492229.1; ENSG00000284238.2. [Q13472-1] DR Ensembl; ENST00000639065.1; ENSP00000491260.1; ENSG00000284238.2. [Q13472-2] DR Ensembl; ENST00000640743.2; ENSP00000491689.1; ENSG00000284238.2. [Q13472-1] DR GeneID; 7156; -. DR KEGG; hsa:7156; -. DR MANE-Select; ENST00000321105.10; ENSP00000321636.5; NM_004618.5; NP_004609.1. DR UCSC; uc002gsx.1; human. [Q13472-1] DR CTD; 7156; -. DR DisGeNET; 7156; -. DR GeneCards; TOP3A; -. DR HGNC; HGNC:11992; TOP3A. DR HPA; ENSG00000177302; Low tissue specificity. DR MalaCards; TOP3A; -. DR MIM; 601243; gene. DR MIM; 618097; phenotype. DR MIM; 618098; phenotype. DR neXtProt; NX_Q13472; -. DR OpenTargets; ENSG00000177302; -. DR Orphanet; 508512; Intrauterine growth restriction-congenital multiple cafe-au-lait macules-increased sister chromatid exchange syndrome. DR PharmGKB; PA36673; -. DR VEuPathDB; HostDB:ENSG00000177302; -. DR eggNOG; KOG1956; Eukaryota. DR GeneTree; ENSGT00940000156701; -. DR HOGENOM; CLU_002929_1_2_1; -. DR InParanoid; Q13472; -. DR OMA; EHICFEV; -. DR OrthoDB; 373433at2759; -. DR PhylomeDB; Q13472; -. DR TreeFam; TF105287; -. DR PathwayCommons; Q13472; -. 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-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-9709570; Impaired BRCA2 binding to RAD51. DR Reactome; R-HSA-9709603; Impaired BRCA2 binding to PALB2. DR SignaLink; Q13472; -. DR BioGRID-ORCS; 7156; 726 hits in 1090 CRISPR screens. DR ChiTaRS; TOP3A; human. DR GeneWiki; TOP3A; -. DR GenomeRNAi; 7156; -. DR Pharos; Q13472; Tbio. DR PRO; PR:Q13472; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; Q13472; protein. DR Bgee; ENSG00000177302; Expressed in blood and 107 other tissues. DR ExpressionAtlas; Q13472; baseline and differential. DR Genevisible; Q13472; HS. DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0016605; C:PML body; IDA:UniProtKB. DR GO; GO:0031422; C:RecQ family helicase-topoisomerase III complex; IPI:ComplexPortal. DR GO; GO:0003677; F:DNA binding; TAS:ProtInc. DR GO; GO:0003916; F:DNA topoisomerase activity; IBA:GO_Central. DR GO; GO:0003917; F:DNA topoisomerase type I (single strand cut, ATP-independent) activity; IDA:UniProtKB. DR GO; GO:0003697; F:single-stranded DNA binding; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0051304; P:chromosome separation; IMP:UniProtKB. DR GO; GO:0006265; P:DNA topological change; IDA:UniProtKB. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IDA:ComplexPortal. DR GO; GO:0051321; P:meiotic cell cycle; TAS:ProtInc. DR GO; GO:0032042; P:mitochondrial DNA metabolic process; IMP:UniProtKB. DR GO; GO:0071139; P:resolution of recombination intermediates; IDA:ComplexPortal. DR CDD; cd00186; TOP1Ac; 1. DR CDD; cd03362; TOPRIM_TopoIA_TopoIII; 1. DR Gene3D; 1.10.290.10; -; 1. DR Gene3D; 1.10.460.10; -; 1. DR Gene3D; 2.70.20.10; -; 1. DR InterPro; IPR000380; Topo_IA. DR InterPro; IPR003601; Topo_IA_2. DR InterPro; IPR023406; Topo_IA_AS. DR InterPro; IPR013497; Topo_IA_cen. DR InterPro; IPR013824; Topo_IA_cen_sub1. DR InterPro; IPR013825; Topo_IA_cen_sub2. DR InterPro; IPR013826; Topo_IA_cen_sub3. DR InterPro; IPR023405; Topo_IA_core_domain. DR InterPro; IPR003602; Topo_IA_DNA-bd_dom. DR InterPro; IPR013498; Topo_IA_Znf. DR InterPro; IPR006171; TOPRIM_domain. DR InterPro; IPR034144; TOPRIM_TopoIII. DR InterPro; IPR010666; Znf_GRF. DR PANTHER; PTHR11390; PTHR11390; 1. DR Pfam; PF01131; Topoisom_bac; 1. DR Pfam; PF01751; Toprim; 1. DR Pfam; PF01396; zf-C4_Topoisom; 1. DR Pfam; PF06839; zf-GRF; 2. DR PRINTS; PR00417; PRTPISMRASEI. DR SMART; SM00437; TOP1Ac; 1. DR SMART; SM00436; TOP1Bc; 1. DR SMART; SM00493; TOPRIM; 1. DR SUPFAM; SSF56712; SSF56712; 1. DR PROSITE; PS00396; TOPOISOMERASE_I_PROK; 1. DR PROSITE; PS50880; TOPRIM; 1. DR PROSITE; PS51999; ZF_GRF; 2. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Disease variant; DNA-binding; Dwarfism; KW Isomerase; Magnesium; Metal-binding; Mitochondrion; KW Primary mitochondrial disease; Progressive external ophthalmoplegia; KW Reference proteome; Repeat; Topoisomerase; Zinc; Zinc-finger. FT CHAIN 1..1001 FT /note="DNA topoisomerase 3-alpha" FT /id="PRO_0000145190" FT DOMAIN 35..179 FT /note="Toprim" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995" FT ZN_FING 658..685 FT /note="C4-type" FT /evidence="ECO:0000255" FT ZN_FING 813..852 FT /note="GRF-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01343" FT ZN_FING 897..939 FT /note="GRF-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01343" FT REGION 400..424 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 774..810 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 937..1001 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 937..951 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 362 FT /note="O-(5'-phospho-DNA)-tyrosine intermediate" FT /evidence="ECO:0000250" FT BINDING 813 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01343" FT BINDING 815 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01343" FT BINDING 838 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01343" FT BINDING 843 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01343" FT BINDING 897 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01343" FT BINDING 899 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01343" FT BINDING 922 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01343" FT BINDING 930 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01343" FT VAR_SEQ 1..105 FT /note="MIFPVARYALRWLRRPEDRAFSRAAMEMALRGVRKVLCVAEKNDAAKGIADL FT LSNGRMRRREGLSKFNKIYEFDYHLYGQNVTMVMTSVSGHLLAHDFQMQFRKW -> MN FT LIIICMAR (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054189" FT VAR_SEQ 1..25 FT /note="Missing (in isoform Short)" FT /evidence="ECO:0000303|PubMed:8622991" FT /id="VSP_006524" FT VARIANT 100 FT /note="M -> V (in PEOB5; results in decreased DNA FT decatenation; dbSNP:rs376902371)" FT /evidence="ECO:0000269|PubMed:29290614" FT /id="VAR_081105" FT VARIANT 135..1001 FT /note="Missing (in PEOB5)" FT /evidence="ECO:0000269|PubMed:29290614" FT /id="VAR_081106" FT VARIANT 176 FT /note="A -> V (in MGRISCE2)" FT /evidence="ECO:0000269|PubMed:30057030" FT /id="VAR_081107" FT VARIANT 459 FT /note="D -> N (in dbSNP:rs28671051)" FT /id="VAR_052588" FT VARIANT 596 FT /note="C -> Y" FT /id="VAR_007529" FT VARIANT 742 FT /note="D -> N (in dbSNP:rs9909732)" FT /id="VAR_052589" FT VARIANT 773 FT /note="N -> D (in dbSNP:rs9911283)" FT /id="VAR_052590" FT MUTAGEN 362 FT /note="Y->F: Decreased DNA decatenation." FT /evidence="ECO:0000269|PubMed:29290614" FT HELIX 23..30 FT /evidence="ECO:0007829|PDB:4CGY" FT STRAND 35..42 FT /evidence="ECO:0007829|PDB:4CGY" FT HELIX 43..54 FT /evidence="ECO:0007829|PDB:4CGY" FT STRAND 59..61 FT /evidence="ECO:0007829|PDB:4CGY" FT STRAND 70..77 FT /evidence="ECO:0007829|PDB:4CGY" FT STRAND 80..88 FT /evidence="ECO:0007829|PDB:4CGY" FT STRAND 95..98 FT /evidence="ECO:0007829|PDB:4CGY" FT HELIX 100..103 FT /evidence="ECO:0007829|PDB:4CGY" FT HELIX 105..107 FT /evidence="ECO:0007829|PDB:4CGY" FT HELIX 110..114 FT /evidence="ECO:0007829|PDB:4CGY" FT STRAND 118..121 FT /evidence="ECO:0007829|PDB:4CGY" FT HELIX 124..126 FT /evidence="ECO:0007829|PDB:4CGY" FT HELIX 127..139 FT /evidence="ECO:0007829|PDB:4CGY" FT STRAND 141..147 FT /evidence="ECO:0007829|PDB:4CGY" FT HELIX 151..165 FT /evidence="ECO:0007829|PDB:4CGY" FT STRAND 172..175 FT /evidence="ECO:0007829|PDB:4CGY" FT HELIX 183..191 FT /evidence="ECO:0007829|PDB:4CGY" FT HELIX 198..229 FT /evidence="ECO:0007829|PDB:4CGY" FT HELIX 231..234 FT /evidence="ECO:0007829|PDB:4CGY" FT HELIX 245..261 FT /evidence="ECO:0007829|PDB:4CGY" FT STRAND 266..276 FT /evidence="ECO:0007829|PDB:4CGY" FT STRAND 279..285 FT /evidence="ECO:0007829|PDB:4CGY" FT HELIX 293..304 FT /evidence="ECO:0007829|PDB:4CGY" FT STRAND 309..321 FT /evidence="ECO:0007829|PDB:4CGY" FT HELIX 329..338 FT /evidence="ECO:0007829|PDB:4CGY" FT HELIX 344..356 FT /evidence="ECO:0007829|PDB:4CGY" FT HELIX 376..381 FT /evidence="ECO:0007829|PDB:4CGY" FT TURN 382..385 FT /evidence="ECO:0007829|PDB:4CGY" FT TURN 387..389 FT /evidence="ECO:0007829|PDB:4CGY" FT HELIX 390..398 FT /evidence="ECO:0007829|PDB:4CGY" FT HELIX 428..444 FT /evidence="ECO:0007829|PDB:4CGY" FT STRAND 449..460 FT /evidence="ECO:0007829|PDB:4CGY" FT STRAND 463..474 FT /evidence="ECO:0007829|PDB:4CGY" FT HELIX 476..479 FT /evidence="ECO:0007829|PDB:4CGY" FT STRAND 503..511 FT /evidence="ECO:0007829|PDB:4CGY" FT HELIX 520..530 FT /evidence="ECO:0007829|PDB:4CGY" FT TURN 534..537 FT /evidence="ECO:0007829|PDB:4CGY" FT HELIX 538..547 FT /evidence="ECO:0007829|PDB:4CGY" FT STRAND 550..553 FT /evidence="ECO:0007829|PDB:4CGY" FT STRAND 559..561 FT /evidence="ECO:0007829|PDB:4CGY" FT HELIX 563..573 FT /evidence="ECO:0007829|PDB:4CGY" FT HELIX 583..596 FT /evidence="ECO:0007829|PDB:4CGY" FT HELIX 602..622 FT /evidence="ECO:0007829|PDB:4CGY" FT HELIX 625..635 FT /evidence="ECO:0007829|PDB:4CGY" SQ SEQUENCE 1001 AA; 112372 MW; 06558C749569E0C2 CRC64; MIFPVARYAL RWLRRPEDRA FSRAAMEMAL RGVRKVLCVA EKNDAAKGIA DLLSNGRMRR REGLSKFNKI YEFDYHLYGQ NVTMVMTSVS GHLLAHDFQM QFRKWQSCNP LVLFEAEIEK YCPENFVDIK KTLERETRQC QALVIWTDCD REGENIGFEI IHVCKAVKPN LQVLRARFSE ITPHAVRTAC ENLTEPDQRV SDAVDVRQEL DLRIGAAFTR FQTLRLQRIF PEVLAEQLIS YGSCQFPTLG FVVERFKAIQ AFVPEIFHRI KVTHDHKDGI VEFNWKRHRL FNHTACLVLY QLCVEDPMAT VVEVRSKPKS KWRPQALDTV ELEKLASRKL RINAKETMRI AEKLYTQGYI SYPRTETNIF PRDLNLTVLV EQQTPDPRWG AFAQSILERG GPTPRNGNKS DQAHPPIHPT KYTNNLQGDE QRLYEFIVRH FLACCSQDAQ GQETTVEIDI AQERFVAHGL MILARNYLDV YPYDHWSDKI LPVYEQGSHF QPSTVEMVDG ETSPPKLLTE ADLIALMEKH GIGTDATHAE HIETIKARMY VGLTPDKRFL PGHLGMGLVE GYDSMGYEMS KPDLRAELEA DLKLICDGKK DKFVVLRQQV QKYKQVFIEA VAKAKKLDEA LAQYFGNGTE LAQQEDIYPA MPEPIRKCPQ CNKDMVLKTK KNGGFYLSCM GFPECRSAVW LPDSVLEASR DSSVCPVCQP HPVYRLKLKF KRGSLPPTMP LEFVCCIGGC DDTLREILDL RFSGGPPRAS QPSGRLQANQ SLNRMDNSQH PQPADSRQTG SSKALAQTLP PPTAAGESNS VTCNCGQEAV LLTVRKEGPN RGRQFFKCNG GSCNFFLWAD SPNPGAGGPP ALAYRPLGAS LGCPPGPGIH LGGFGNPGDG SGSGTSCLCS QPSVTRTVQK DGPNKGRQFH TCAKPREQQC GFFQWVDENT APGTSGAPSW TGDRGRTLES EARSKRPRAS SSDMGSTAKK PRKCSLCHQP GHTRPFCPQN R // ID DNA2_HUMAN Reviewed; 1060 AA. AC P51530; Q2NKM1; Q5TC49; Q5TC50; Q6P455; Q6PI80; Q7Z6H9; Q8N346; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 12-DEC-2006, sequence version 3. DT 12-OCT-2022, entry version 174. DE RecName: Full=DNA replication ATP-dependent helicase/nuclease DNA2; DE Short=hDNA2; DE AltName: Full=DNA replication ATP-dependent helicase-like homolog; DE Includes: DE RecName: Full=DNA replication nuclease DNA2; DE EC=3.1.-.-; DE Includes: DE RecName: Full=DNA replication ATP-dependent helicase DNA2; DE EC=3.6.4.12; GN Name=DNA2; Synonyms=DNA2L, KIAA0083; 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=Bone marrow; RX PubMed=7788527; DOI=10.1093/dnares/2.1.37; RA Nagase T., Miyajima N., Tanaka A., Sazuka T., Seki N., Sato S., Tabata S., RA Ishikawa K., Kawarabayasi Y., Kotani H., Nomura N.; RT "Prediction of the coding sequences of unidentified human genes. III. The RT coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of RT cDNA clones from human cell line KG-1."; RL DNA Res. 2:37-43(1995). RN [2] 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 680-1060 (ISOFORM 4), AND NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 567-1060 (ISOFORM 1). RC TISSUE=Colon, Duodenum, and Lymph; 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=16595799; DOI=10.1093/nar/gkl102; RA Kim J.H., Kim H.D., Ryu G.H., Kim D.H., Hurwitz J., Seo Y.S.; RT "Isolation of human Dna2 endonuclease and characterization of its enzymatic RT properties."; RL Nucleic Acids Res. 34:1854-1864(2006). RN [5] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASP-277 AND LYS-654. RX PubMed=16595800; DOI=10.1093/nar/gkl070; RA Masuda-Sasa T., Imamura O., Campbell J.L.; RT "Biochemical analysis of human Dna2."; RL Nucleic Acids Res. 34:1865-1875(2006). RN [6] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=18995831; DOI=10.1016/j.molcel.2008.09.024; RA Zheng L., Zhou M., Guo Z., Lu H., Qian L., Dai H., Qiu J., Yakubovskaya E., RA Bogenhagen D.F., Demple B., Shen B.; RT "Human DNA2 is a mitochondrial nuclease/helicase for efficient processing RT of DNA replication and repair intermediates."; RL Mol. Cell 32:325-336(2008). RN [7] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=19487465; DOI=10.1128/mcb.01834-08; RA Duxin J.P., Dao B., Martinsson P., Rajala N., Guittat L., Campbell J.L., RA Spelbrink J.N., Stewart S.A.; RT "Human Dna2 is a nuclear and mitochondrial DNA maintenance protein."; RL Mol. Cell. Biol. 29:4274-4282(2009). RN [8] RP ACETYLATION. RX PubMed=20019387; DOI=10.1074/jbc.m109.086397; RA Balakrishnan L., Stewart J., Polaczek P., Campbell J.L., Bambara R.A.; RT "Acetylation of Dna2 endonuclease/helicase and flap endonuclease 1 by p300 RT promotes DNA stability by creating long flap intermediates."; RL J. Biol. Chem. 285:4398-4404(2010). RN [9] RP FUNCTION, INTERACTION WITH BLM, AND MUTAGENESIS OF ASP-277 AND LYS-654. RX PubMed=21325134; DOI=10.1101/gad.2003811; RA Nimonkar A.V., Genschel J., Kinoshita E., Polaczek P., Campbell J.L., RA Wyman C., Modrich P., Kowalczykowski S.C.; RT "BLM-DNA2-RPA-MRN and EXO1-BLM-RPA-MRN constitute two DNA end resection RT machineries for human DNA break repair."; RL Genes Dev. 25:350-362(2011). RN [10] RP FUNCTION, DNA-BINDING, AND MUTAGENESIS OF LYS-654. RX PubMed=21572043; DOI=10.1074/jbc.m111.243071; RA Fortini B.K., Pokharel S., Polaczek P., Balakrishnan L., Bambara R.A., RA Campbell J.L.; RT "Characterization of the endonuclease and ATP-dependent flap RT endo/exonuclease of Dna2."; RL J. Biol. Chem. 286:23763-23770(2011). RN [11] RP FUNCTION, DNA-BINDING, INTERACTION WITH WDHD1, AND MUTAGENESIS OF ASP-277 RP AND LYS-654. RX PubMed=22570476; DOI=10.1074/jbc.m112.359018; RA Duxin J.P., Moore H.R., Sidorova J., Karanja K., Honaker Y., Dao B., RA Piwnica-Worms H., Campbell J.L., Monnat R.J. Jr., Stewart S.A.; RT "Okazaki fragment processing-independent role for human Dna2 enzyme during RT DNA replication."; RL J. Biol. Chem. 287:21980-21991(2012). RN [12] RP FUNCTION, AND DNA-BINDING. RX PubMed=22570407; DOI=10.1093/nar/gks388; RA Gloor J.W., Balakrishnan L., Campbell J.L., Bambara R.A.; RT "Biochemical analyses indicate that binding and cleavage specificities RT define the ordered processing of human Okazaki fragments by Dna2 and RT FEN1."; RL Nucleic Acids Res. 40:6774-6786(2012). RN [13] RP INVOLVEMENT IN SCKL8. RX PubMed=24389050; DOI=10.1101/gr.160572.113; RA Shaheen R., Faqeih E., Ansari S., Abdel-Salam G., Al-Hassnan Z.N., RA Al-Shidi T., Alomar R., Sogaty S., Alkuraya F.S.; RT "Genomic analysis of primordial dwarfism reveals novel disease genes."; RL Genome Res. 24:291-299(2014). RN [14] RP VARIANTS PEOA6 HIS-198; GLU-227 AND ILE-637, AND CHARACTERIZATION OF RP VARIANTS PEOA6 HHIS-198; GLU-227 AND ILE-637. RX PubMed=23352259; DOI=10.1016/j.ajhg.2012.12.014; RA Ronchi D., Di Fonzo A., Lin W., Bordoni A., Liu C., Fassone E., RA Pagliarani S., Rizzuti M., Zheng L., Filosto M., Ferro M.T., Ranieri M., RA Magri F., Peverelli L., Li H., Yuan Y.C., Corti S., Sciacco M., Moggio M., RA Bresolin N., Shen B., Comi G.P.; RT "Mutations in DNA2 link progressive myopathy to mitochondrial DNA RT instability."; RL Am. J. Hum. Genet. 92:293-300(2013). CC -!- FUNCTION: Key enzyme involved in DNA replication and DNA repair in CC nucleus and mitochondrion. Involved in Okazaki fragments processing by CC cleaving long flaps that escape FEN1: flaps that are longer than 27 CC nucleotides are coated by replication protein A complex (RPA), leading CC to recruit DNA2 which cleaves the flap until it is too short to bind CC RPA and becomes a substrate for FEN1. Also involved in 5'-end resection CC of DNA during double-strand break (DSB) repair: recruited by BLM and CC mediates the cleavage of 5'-ssDNA, while the 3'-ssDNA cleavage is CC prevented by the presence of RPA. Also involved in DNA replication CC checkpoint independently of Okazaki fragments processing. Possesses CC different enzymatic activities, such as single-stranded DNA (ssDNA)- CC dependent ATPase, 5'-3' helicase and endonuclease activities. While the CC ATPase and endonuclease activities are well-defined and play a key role CC in Okazaki fragments processing and DSB repair, the 5'-3' DNA helicase CC activity is subject to debate. According to various reports, the CC helicase activity is weak and its function remains largely unclear. CC Helicase activity may promote the motion of DNA2 on the flap, helping CC the nuclease function. {ECO:0000269|PubMed:16595799, CC ECO:0000269|PubMed:16595800, ECO:0000269|PubMed:18995831, CC ECO:0000269|PubMed:19487465, ECO:0000269|PubMed:21325134, CC ECO:0000269|PubMed:21572043, ECO:0000269|PubMed:22570407, CC ECO:0000269|PubMed:22570476}. 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; EC=3.6.4.12; CC Evidence={ECO:0000269|PubMed:16595800}; CC -!- COFACTOR: CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; Evidence={ECO:0000250}; CC Note=Binds 1 [4Fe-4S] cluster. {ECO:0000250}; CC -!- SUBUNIT: Interacts with BLM and WDHD1. {ECO:0000269|PubMed:21325134, CC ECO:0000269|PubMed:22570476}. CC -!- SUBCELLULAR LOCATION: Nucleus. Mitochondrion. Note=Was initially CC reported to be exclusively mitochondrial (PubMed:18995831). However, it CC was later shown to localize both in mitochondrion and nucleus CC (PubMed:19487465). {ECO:0000269|PubMed:18995831, CC ECO:0000269|PubMed:19487465}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=P51530-1; Sequence=Displayed; CC Name=2; CC IsoId=P51530-2; Sequence=VSP_021870, VSP_021871; CC Name=3; CC IsoId=P51530-3; Sequence=VSP_021869; CC Name=4; CC IsoId=P51530-4; Sequence=VSP_044185; CC -!- PTM: Acetylated by EP300, leading to stimulate the 5'-3' endonuclease, CC the 5'-3' helicase and DNA-dependent ATPase activities, possibly by CC increasing DNA substrate affinity. {ECO:0000269|PubMed:20019387}. CC -!- DISEASE: Progressive external ophthalmoplegia with mitochondrial DNA CC deletions, autosomal dominant, 6 (PEOA6) [MIM:615156]: A disorder CC characterized by muscle weakness, mainly affecting the lower limbs, CC external ophthalmoplegia, exercise intolerance, and mitochondrial DNA CC deletions on muscle biopsy. Symptoms may appear in childhood or CC adulthood and show slow progression. {ECO:0000269|PubMed:23352259}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- DISEASE: Seckel syndrome 8 (SCKL8) [MIM:615807]: A rare autosomal CC recessive disorder characterized by proportionate dwarfism of prenatal CC onset associated with low birth weight, growth retardation, severe CC microcephaly with a bird-headed like appearance, and intellectual CC disability. {ECO:0000269|PubMed:24389050}. Note=The disease is caused CC by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the DNA2/NAM7 helicase family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH28188.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAH63664.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAA07647.1; Type=Erroneous initiation; Note=Extended N-terminus.; 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; D42046; BAA07647.1; ALT_INIT; mRNA. DR EMBL; AL136233; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC041115; AAH41115.1; -; mRNA. DR EMBL; BC053574; AAH53574.1; -; mRNA. DR EMBL; BC063664; AAH63664.1; ALT_INIT; mRNA. DR EMBL; BC111740; AAI11741.1; -; mRNA. DR EMBL; BC028188; AAH28188.1; ALT_INIT; mRNA. DR CCDS; CCDS44415.2; -. [P51530-1] DR PIR; T50697; T50697. DR RefSeq; NP_001073918.2; NM_001080449.2. [P51530-1] DR PDB; 5EAY; X-ray; 1.55 A; E/F/G/H=5-17. DR PDBsum; 5EAY; -. DR AlphaFoldDB; P51530; -. DR SMR; P51530; -. DR BioGRID; 108103; 79. DR IntAct; P51530; 25. DR STRING; 9606.ENSP00000351185; -. DR ChEMBL; CHEMBL4523236; -. DR iPTMnet; P51530; -. DR PhosphoSitePlus; P51530; -. DR BioMuta; DNA2; -. DR EPD; P51530; -. DR jPOST; P51530; -. DR MassIVE; P51530; -. DR MaxQB; P51530; -. DR PaxDb; P51530; -. DR PeptideAtlas; P51530; -. DR PRIDE; P51530; -. DR ProteomicsDB; 56322; -. [P51530-1] DR ProteomicsDB; 56323; -. [P51530-2] DR ProteomicsDB; 56324; -. [P51530-3] DR Antibodypedia; 28503; 152 antibodies from 25 providers. DR DNASU; 1763; -. DR Ensembl; ENST00000358410.8; ENSP00000351185.3; ENSG00000138346.15. [P51530-1] DR Ensembl; ENST00000399179.6; ENSP00000382132.3; ENSG00000138346.15. [P51530-2] DR Ensembl; ENST00000399180.3; ENSP00000382133.3; ENSG00000138346.15. [P51530-2] DR GeneID; 1763; -. DR KEGG; hsa:1763; -. DR MANE-Select; ENST00000358410.8; ENSP00000351185.3; NM_001080449.3; NP_001073918.2. DR UCSC; uc057tqx.1; human. [P51530-1] DR CTD; 1763; -. DR DisGeNET; 1763; -. DR GeneCards; DNA2; -. DR HGNC; HGNC:2939; DNA2. DR HPA; ENSG00000138346; Tissue enhanced (lymphoid). DR MalaCards; DNA2; -. DR MIM; 601810; gene. DR MIM; 615156; phenotype. DR MIM; 615807; phenotype. DR neXtProt; NX_P51530; -. DR OpenTargets; ENSG00000138346; -. DR Orphanet; 352470; DNA2-related mitochondrial DNA deletion syndrome. DR VEuPathDB; HostDB:ENSG00000138346; -. DR eggNOG; KOG1805; Eukaryota. DR GeneTree; ENSGT00780000122010; -. DR HOGENOM; CLU_001666_2_0_1; -. DR InParanoid; P51530; -. DR OMA; NYCEAAI; -. DR OrthoDB; 633768at2759; -. DR PhylomeDB; P51530; -. DR PathwayCommons; P51530; -. DR Reactome; R-HSA-174437; Removal of the Flap Intermediate from the C-strand. 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-69166; Removal of the Flap Intermediate. 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 Reactome; R-HSA-9709570; Impaired BRCA2 binding to RAD51. DR Reactome; R-HSA-9709603; Impaired BRCA2 binding to PALB2. DR SignaLink; P51530; -. DR BioGRID-ORCS; 1763; 40 hits in 232 CRISPR screens. DR ChiTaRS; DNA2; human. DR GeneWiki; DNA2L; -. DR GenomeRNAi; 1763; -. DR Pharos; P51530; Tbio. DR PRO; PR:P51530; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; P51530; protein. DR Bgee; ENSG00000138346; Expressed in secondary oocyte and 115 other tissues. DR ExpressionAtlas; P51530; baseline and differential. DR Genevisible; P51530; HS. DR GO; GO:0000781; C:chromosome, telomeric region; ISS:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0042645; C:mitochondrial nucleoid; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW. DR GO; GO:0043139; F:5'-3' DNA helicase activity; IDA:UniProtKB. DR GO; GO:0017108; F:5'-flap endonuclease activity; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATP hydrolysis activity; TAS:UniProtKB. DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB. DR GO; GO:0003678; F:DNA helicase activity; IDA:UniProtKB. DR GO; GO:0004386; F:helicase activity; TAS:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004518; F:nuclease activity; IDA:UniProtKB. DR GO; GO:0003723; F:RNA binding; IBA:GO_Central. DR GO; GO:0017116; F:single-stranded DNA helicase activity; IDA:UniProtKB. DR GO; GO:0016890; F:site-specific endodeoxyribonuclease activity, specific for altered base; IDA:UniProtKB. DR GO; GO:0006284; P:base-excision repair; IDA:UniProtKB. DR GO; GO:0000729; P:DNA double-strand break processing; IDA:UniProtKB. DR GO; GO:0006260; P:DNA replication; IMP:UniProtKB. DR GO; GO:0000076; P:DNA replication checkpoint signaling; IMP:UniProtKB. DR GO; GO:0033567; P:DNA replication, Okazaki fragment processing; IDA:UniProtKB. DR GO; GO:0043137; P:DNA replication, removal of RNA primer; IDA:UniProtKB. DR GO; GO:0044806; P:G-quadruplex DNA unwinding; TAS:BHF-UCL. DR GO; GO:0043504; P:mitochondrial DNA repair; IDA:UniProtKB. DR GO; GO:0006264; P:mitochondrial DNA replication; IDA:UniProtKB. DR GO; GO:1902990; P:mitotic telomere maintenance via semi-conservative replication; ISS:BHF-UCL. DR GO; GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; ISS:BHF-UCL. DR GO; GO:0045740; P:positive regulation of DNA replication; IDA:UniProtKB. DR GO; GO:0071932; P:replication fork reversal; IBA:GO_Central. DR GO; GO:0090656; P:t-circle formation; TAS:BHF-UCL. DR GO; GO:0000723; P:telomere maintenance; ISS:BHF-UCL. DR GO; GO:0032201; P:telomere maintenance via semi-conservative replication; TAS:Reactome. DR CDD; cd18808; SF1_C_Upf1; 1. DR Gene3D; 3.40.50.300; -; 2. DR Gene3D; 3.90.320.10; -; 1. DR InterPro; IPR026851; Dna2. DR InterPro; IPR045055; DNA2/NAM7-like. DR InterPro; IPR041679; DNA2/NAM7-like_C. DR InterPro; IPR041677; DNA2/NAM7_AAA_11. DR InterPro; IPR014808; DNA_replication_fac_Dna2_N. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR011604; PDDEXK-like_dom_sf. DR PANTHER; PTHR10887; PTHR10887; 1. DR PANTHER; PTHR10887:SF433; PTHR10887:SF433; 1. DR Pfam; PF13086; AAA_11; 2. DR Pfam; PF13087; AAA_12; 1. DR Pfam; PF08696; Dna2; 1. DR SUPFAM; SSF52540; SSF52540; 1. PE 1: Evidence at protein level; KW 3D-structure; 4Fe-4S; Acetylation; Alternative splicing; ATP-binding; KW Disease variant; DNA damage; DNA repair; DNA replication; DNA-binding; KW Dwarfism; Endonuclease; Helicase; Hydrolase; Intellectual disability; Iron; KW Iron-sulfur; Metal-binding; Mitochondrion; Multifunctional enzyme; KW Nuclease; Nucleotide-binding; Nucleus; Primary mitochondrial disease; KW Progressive external ophthalmoplegia; Reference proteome. FT CHAIN 1..1060 FT /note="DNA replication ATP-dependent helicase/nuclease FT DNA2" FT /id="PRO_0000080712" FT REGION 81..519 FT /note="Nuclease activity" FT /evidence="ECO:0000250" FT REGION 520..1060 FT /note="Helicase activity" FT /evidence="ECO:0000250" FT BINDING 136 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000250" FT BINDING 393 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000250" FT BINDING 396 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000250" FT BINDING 402 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000250" FT BINDING 648..655 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255" FT VAR_SEQ 663..900 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_021869" FT VAR_SEQ 664..687 FT /note="ILYACGFSVLLTSYTHSAVDNILL -> FRRFIQLSSNLQSKKFADQSPLNP FT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_021870" FT VAR_SEQ 688..1060 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_021871" FT VAR_SEQ 1040..1060 FT /note="IDLPSREHESLCHILGDFQRE -> SFFFCIWSHLIAL (in isoform FT 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_044185" FT VARIANT 198 FT /note="R -> H (in PEOA6; the mutant protein has a complete FT loss of nuclease activity and severely impaired helicase FT activity; consistent with a loss of function mutation; FT dbSNP:rs1272393477)" FT /evidence="ECO:0000269|PubMed:23352259" FT /id="VAR_069905" FT VARIANT 227 FT /note="K -> E (in PEOA6; the mutant protein has FT significantly reduced nuclease and helicase activity; FT consistent with a loss of function mutation; FT dbSNP:rs760412883)" FT /evidence="ECO:0000269|PubMed:23352259" FT /id="VAR_069906" FT VARIANT 637 FT /note="V -> I (in PEOA6; the mutant protein has decreased FT nuclease activity (30% of wild-type) and enhanced helicase FT activity; consistent with a loss of function mutation; FT dbSNP:rs746522359)" FT /evidence="ECO:0000269|PubMed:23352259" FT /id="VAR_069907" FT MUTAGEN 277 FT /note="D->A: Abolishes ability to resect DNA in present of FT BLM." FT /evidence="ECO:0000269|PubMed:16595800, FT ECO:0000269|PubMed:21325134, ECO:0000269|PubMed:22570476" FT MUTAGEN 654 FT /note="K->E: Abolishes ability to unwind DNA, while it does FT not affect ability to resect DNA." FT /evidence="ECO:0000269|PubMed:16595800, FT ECO:0000269|PubMed:21325134, ECO:0000269|PubMed:21572043, FT ECO:0000269|PubMed:22570476" FT CONFLICT 986 FT /note="K -> N (in Ref. 3; AAH28188)" FT /evidence="ECO:0000305" FT HELIX 7..10 FT /evidence="ECO:0007829|PDB:5EAY" SQ SEQUENCE 1060 AA; 120415 MW; 727D4B268FD75C5A CRC64; MEQLNELELL MEKSFWEEAE LPAELFQKKV VASFPRTVLS TGMDNRYLVL AVNTVQNKEG NCEKRLVITA SQSLENKELC ILRNDWCSVP VEPGDIIHLE GDCTSDTWII DKDFGYLILY PDMLISGTSI ASSIRCMRRA VLSETFRSSD PATRQMLIGT VLHEVFQKAI NNSFAPEKLQ ELAFQTIQEI RHLKEMYRLN LSQDEIKQEV EDYLPSFCKW AGDFMHKNTS TDFPQMQLSL PSDNSKDNST CNIEVVKPMD IEESIWSPRF GLKGKIDVTV GVKIHRGYKT KYKIMPLELK TGKESNSIEH RSQVVLYTLL SQERRADPEA GLLLYLKTGQ MYPVPANHLD KRELLKLRNQ MAFSLFHRIS KSATRQKTQL ASLPQIIEEE KTCKYCSQIG NCALYSRAVE QQMDCSSVPI VMLPKIEEET QHLKQTHLEY FSLWCLMLTL ESQSKDNKKN HQNIWLMPAS EMEKSGSCIG NLIRMEHVKI VCDGQYLHNF QCKHGAIPVT NLMAGDRVIV SGEERSLFAL SRGYVKEINM TTVTCLLDRN LSVLPESTLF RLDQEEKNCD IDTPLGNLSK LMENTFVSKK LRDLIIDFRE PQFISYLSSV LPHDAKDTVA CILKGLNKPQ RQAMKKVLLS KDYTLIVGMP GTGKTTTICT LVRILYACGF SVLLTSYTHS AVDNILLKLA KFKIGFLRLG QIQKVHPAIQ QFTEQEICRS KSIKSLALLE ELYNSQLIVA TTCMGINHPI FSRKIFDFCI VDEASQISQP ICLGPLFFSR RFVLVGDHQQ LPPLVLNREA RALGMSESLF KRLEQNKSAV VQLTVQYRMN SKIMSLSNKL TYEGKLECGS DKVANAVINL RHFKDVKLEL EFYADYSDNP WLMGVFEPNN PVCFLNTDKV PAPEQVEKGG VSNVTEAKLI VFLTSIFVKA GCSPSDIGII APYRQQLKII NDLLARSIGM VEVNTVDKYQ GRDKSIVLVS FVRSNKDGTV GELLKDWRRL NVAITRAKHK LILLGCVPSL NCYPPLEKLL NHLNSEKLII DLPSREHESL CHILGDFQRE // 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 03-AUG-2022, entry version 133. 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. [Q8N635-1] 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 98 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: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 RHNO1_HUMAN Reviewed; 238 AA. AC Q9BSD3; B7Z989; DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 1. DT 12-OCT-2022, entry version 138. DE RecName: Full=RAD9, HUS1, RAD1-interacting nuclear orphan protein 1; DE AltName: Full=RAD9, RAD1, HUS1-interacting nuclear orphan protein; GN Name=RHNO1; Synonyms=C12orf32, RHINO; ORFNames=HKMT1188; 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=Hepatoblastoma; RX PubMed=15221005; DOI=10.1038/sj.onc.1207782; RA Yamada S., Ohira M., Horie H., Ando K., Takayasu H., Suzuki Y., Sugano S., RA Hirata T., Goto T., Matsunaga T., Hiyama E., Hayashi Y., Ando H., Suita S., RA Kaneko M., Sasaki F., Hashizume K., Ohnuma N., Nakagawara A.; RT "Expression profiling and differential screening between hepatoblastomas RT and the corresponding normal livers: identification of high expression of RT the PLK1 oncogene as a poor-prognostic indicator of hepatoblastomas."; RL Oncogene 23:5901-5911(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Uterus; 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=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Pancreas; 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 INDUCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND IDENTIFICATION BY RP MASS SPECTROMETRY. RX PubMed=20811708; RA Kim J.W., Fukukawa C., Ueda K., Nishidate T., Katagiri T., Nakamura Y.; RT "Involvement of C12orf32 overexpression in breast carcinogenesis."; RL Int. J. Oncol. 37:861-867(2010). RN [6] RP FUNCTION, INTERACTION WITH RAD9A; RAD18; TOPBP1 AND UBE2N, MUTAGENESIS OF RP 55-SER--PHE-61, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=21659603; DOI=10.1126/science.1203430; RA Cotta-Ramusino C., McDonald E.R. III, Hurov K., Sowa M.E., Harper J.W., RA Elledge S.J.; RT "A DNA damage response screen identifies RHINO, a 9-1-1 and TopBP1 RT interacting protein required for ATR signaling."; RL Science 332:1313-1317(2011). CC -!- FUNCTION: Plays a role in DNA damage response (DDR) signaling upon CC genotoxic stresses such as ionizing radiation (IR) during the S phase. CC Recruited to sites of DNA damage through interaction with the 9-1-1 CC cell-cycle checkpoint response complex and TOPBP1 in a ATR-dependent CC manner. Required for the progression of the G1 to S phase transition. CC Plays a role in the stimulation of CHEK1 phosphorylation. CC {ECO:0000269|PubMed:21659603}. CC -!- SUBUNIT: Interacts with RAD9A, RAD18, TOPBP1 and UBE2N. CC {ECO:0000269|PubMed:21659603}. CC -!- INTERACTION: CC Q9BSD3; Q9Y5Z0: BACE2; NbExp=3; IntAct=EBI-9658624, EBI-11282723; CC Q9BSD3; Q8N9N5-2: BANP; NbExp=3; IntAct=EBI-9658624, EBI-11524452; CC Q9BSD3; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-9658624, EBI-3867333; CC Q9BSD3; Q08379: GOLGA2; NbExp=3; IntAct=EBI-9658624, EBI-618309; CC Q9BSD3; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-9658624, EBI-10171774; CC Q9BSD3; P60411: KRTAP10-9; NbExp=3; IntAct=EBI-9658624, EBI-10172052; CC Q9BSD3; Q9BRK4: LZTS2; NbExp=3; IntAct=EBI-9658624, EBI-741037; CC Q9BSD3; Q9UBB9: TFIP11; NbExp=6; IntAct=EBI-9658624, EBI-1105213; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20811708}. Chromosome CC {ECO:0000269|PubMed:20811708}. Note=Localizes to sites of DNA damage in CC a H2AX-independent manner. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9BSD3-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9BSD3-2; Sequence=VSP_045307; CC -!- TISSUE SPECIFICITY: Weakly expressed in testis, prostate, ovary, thymus CC and small intestine. Expressed strongly in breast cancer cells. CC {ECO:0000269|PubMed:20811708}. CC -!- INDUCTION: Up-regulated in breast cancer cells. CC {ECO:0000269|PubMed:20811708}. 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; AB073599; BAD38639.1; -; mRNA. DR EMBL; AK304613; BAH14225.1; -; mRNA. DR EMBL; AC005911; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC005106; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS58199.1; -. [Q9BSD3-2] DR CCDS; CCDS8518.1; -. [Q9BSD3-1] DR RefSeq; NP_001239428.1; NM_001252499.2. [Q9BSD3-1] DR RefSeq; NP_001239429.1; NM_001252500.2. [Q9BSD3-2] DR RefSeq; NP_001244026.1; NM_001257097.1. [Q9BSD3-1] DR RefSeq; NP_001244027.1; NM_001257098.1. [Q9BSD3-1] DR PDB; 6J8Y; X-ray; 2.40 A; D=45-64. DR PDBsum; 6J8Y; -. DR AlphaFoldDB; Q9BSD3; -. DR SMR; Q9BSD3; -. DR BioGRID; 123729; 23. DR CORUM; Q9BSD3; -. DR IntAct; Q9BSD3; 13. DR STRING; 9606.ENSP00000479598; -. DR iPTMnet; Q9BSD3; -. DR PhosphoSitePlus; Q9BSD3; -. DR BioMuta; RHNO1; -. DR DMDM; 74739410; -. DR MassIVE; Q9BSD3; -. DR MaxQB; Q9BSD3; -. DR PaxDb; Q9BSD3; -. DR PeptideAtlas; Q9BSD3; -. DR PRIDE; Q9BSD3; -. DR Antibodypedia; 48896; 8 antibodies from 4 providers. DR DNASU; 83695; -. DR Ensembl; ENST00000461997.5; ENSP00000438828.1; ENSG00000171792.11. [Q9BSD3-2] DR Ensembl; ENST00000489288.7; ENSP00000438590.1; ENSG00000171792.11. [Q9BSD3-1] DR Ensembl; ENST00000618250.4; ENSP00000479598.1; ENSG00000171792.11. [Q9BSD3-1] DR GeneID; 83695; -. DR KEGG; hsa:83695; -. DR MANE-Select; ENST00000489288.7; ENSP00000438590.1; NM_001252499.3; NP_001239428.1. DR UCSC; uc001qlh.5; human. [Q9BSD3-1] DR CTD; 83695; -. DR DisGeNET; 83695; -. DR GeneCards; RHNO1; -. DR HGNC; HGNC:28206; RHNO1. DR HPA; ENSG00000171792; Low tissue specificity. DR MIM; 614085; gene. DR neXtProt; NX_Q9BSD3; -. DR OpenTargets; ENSG00000171792; -. DR VEuPathDB; HostDB:ENSG00000171792; -. DR eggNOG; ENOG502S7M3; Eukaryota. DR GeneTree; ENSGT00390000003219; -. DR HOGENOM; CLU_075584_0_0_1; -. DR InParanoid; Q9BSD3; -. DR OMA; VCPQFET; -. DR OrthoDB; 1140824at2759; -. DR PhylomeDB; Q9BSD3; -. DR TreeFam; TF336053; -. DR PathwayCommons; Q9BSD3; -. DR Reactome; R-HSA-5685938; HDR through Single Strand Annealing (SSA). 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-9709570; Impaired BRCA2 binding to RAD51. DR SignaLink; Q9BSD3; -. DR BioGRID-ORCS; 83695; 18 hits in 1067 CRISPR screens. DR ChiTaRS; RHNO1; human. DR GenomeRNAi; 83695; -. DR Pharos; Q9BSD3; Tbio. DR PRO; PR:Q9BSD3; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q9BSD3; protein. DR Bgee; ENSG00000171792; Expressed in ventricular zone and 166 other tissues. DR ExpressionAtlas; Q9BSD3; baseline and differential. DR Genevisible; Q9BSD3; HS. DR GO; GO:0005694; C:chromosome; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:0071479; P:cellular response to ionizing radiation; IDA:UniProtKB. DR GO; GO:0034644; P:cellular response to UV; IDA:UniProtKB. DR GO; GO:0000077; P:DNA damage checkpoint signaling; IMP:UniProtKB. DR GO; GO:0070318; P:positive regulation of G0 to G1 transition; IMP:UniProtKB. DR GO; GO:0000725; P:recombinational repair; IMP:UniProtKB. DR InterPro; IPR029293; RHNO1. DR PANTHER; PTHR35541; PTHR35541; 1. DR Pfam; PF15319; RHINO; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell cycle; Chromosome; DNA damage; KW Nucleus; Reference proteome. FT CHAIN 1..238 FT /note="RAD9, HUS1, RAD1-interacting nuclear orphan protein FT 1" FT /id="PRO_0000263105" FT REGION 1..31 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 74..105 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 88..105 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 43..56 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045307" FT MUTAGEN 55..61 FT /note="SWVSPDF->AAAAAAA: Inhibits binding to the 9-1-1 FT complex. Does not inhibit interaction with TOPBP1. Inhibits FT localizion to sites of DNA damage." FT /evidence="ECO:0000269|PubMed:21659603" SQ SEQUENCE 238 AA; 26709 MW; C405083C6F6E4CAD CRC64; MPPRKKRRQP SQKAPLLFHQ QPLEGPKHSC ASTQLPITHT RQVPSKPIDH STITSWVSPD FDTAAGSLFP AYQKHQNRAR HSSRKPTTSK FPHLTFESPQ SSSSETLGIP LIRECPSESE KDVSRRPLVP VLSPQSCGNM SVQALQSLPY VFIPPDIQTP ESSSVKEELI PQDQKENSLL SCTLHTGTPN SPEPGPVLVK DTPEDKYGIK VTWRRRQHLL AYLRERGKLS RSQFLVKS // 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 03-AUG-2022, entry version 137. 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; 100 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. [Q8NHS9-1] DR Ensembl; ENST00000572969.6; ENSP00000460187.1; ENSG00000141255.13. [Q8NHS9-1] DR Ensembl; ENST00000573128.5; ENSP00000459580.1; ENSG00000141255.13. [Q8NHS9-1] DR Ensembl; ENST00000575375.5; ENSP00000459329.1; ENSG00000141255.13. [Q8NHS9-1] 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 sperm and 101 other tissues. DR ExpressionAtlas; Q8NHS9; baseline and differential. DR Genevisible; Q8NHS9; HS. DR GO; GO:0005694; C:chromosome; ISS:UniProtKB. DR GO; GO:0009566; P:fertilization; IEA:Ensembl. DR GO; GO:0007276; P:gamete generation; IEA:Ensembl. DR GO; GO:0007129; P:homologous chromosome pairing at meiosis; IEA:Ensembl. DR GO; GO:0000711; P:meiotic DNA repair synthesis; IEA:Ensembl. DR GO; GO:0051445; P:regulation of meiotic cell cycle; IBA:GO_Central. DR GO; GO:0061458; P:reproductive system development; IEA:Ensembl. 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 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 12-OCT-2022, entry version 173. 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=39; 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; 378 antibodies from 35 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 Reactome; R-HSA-9709603; Impaired BRCA2 binding to PALB2. 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 206 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:0140664; F:ATP-dependent DNA damage sensor activity; 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:0022008; P:neurogenesis; 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; dbSNP:rs757140620)" 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 RA51D_HUMAN Reviewed; 328 AA. AC O75771; B4DJU7; E1P637; O43537; O60355; O75196; O75847; O75848; O76073; AC O76085; O94908; Q9UFU5; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 1. DT 12-OCT-2022, entry version 202. DE RecName: Full=DNA repair protein RAD51 homolog 4; DE AltName: Full=R51H3; DE AltName: Full=RAD51 homolog D; DE AltName: Full=RAD51-like protein 3; DE AltName: Full=TRAD; GN Name=RAD51D; Synonyms=RAD51L3; 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=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 [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=9570954; DOI=10.1006/geno.1998.5226; RA Pittman D.L., Weinberg L.R., Schimenti J.C.; RT "Identification, characterization, and genetic mapping of Rad51d, a new RT mouse and human RAD51/RecA-related gene."; RL Genomics 49:103-111(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE SPLICING (ISOFORMS 2; 3; 4; 5; RP 6 AND 7). RC TISSUE=Brain; RX PubMed=10092526; DOI=10.1006/bbrc.1999.0413; RA Kawabata M., Saeki K.; RT "Multiple alternative transcripts of the human homologue of the mouse RT TRAD/R51H3/RAD51D gene, a member of the recA/RAD51 gene family."; RL Biochem. Biophys. Res. Commun. 257:156-162(1999). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-24; GLN-165; THR-225; RP GLN-232 AND GLY-233. RG NIEHS SNPs program; RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 8). RC TISSUE=Thalamus; 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=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 [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=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 [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 156-328. RC TISSUE=Uterus; 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 [10] RP FUNCTION, AND INTERACTION WITH XRCC2. RX PubMed=10871607; DOI=10.1074/jbc.m002075200; RA Braybrooke J.P., Spink K.G., Thacker J., Hickson I.D.; RT "The RAD51 family member, RAD51L3, is a DNA-stimulated ATPase that forms a RT complex with XRCC2."; RL J. Biol. Chem. 275:29100-29106(2000). RN [11] RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH RAD51C; RAD51D AND 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 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 [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 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 FUNCTION OF THE BCDX2 COMPLEX, AND INTERACTION WITH BLM AND XRCC2. RX PubMed=12975363; DOI=10.1074/jbc.m308838200; RA Braybrooke J.P., Li J.L., Wu L., Caple F., Benson F.E., Hickson I.D.; RT "Functional interaction between the Bloom's syndrome helicase and the RAD51 RT paralog, RAD51L3 (RAD51D)."; RL J. Biol. Chem. 278:48357-48366(2003). RN [17] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=15109494; DOI=10.1016/s0092-8674(04)00337-x; RA Tarsounas M., Munoz P., Claas A., Smiraldo P.G., Pittman D.L., Blasco M.A., RA West S.C.; RT "Telomere maintenance requires the RAD51D recombination/repair protein."; RL Cell 117:337-347(2004). RN [18] RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S). RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8; RA Hillman R.T., Green R.E., Brenner S.E.; RT "An unappreciated role for RNA surveillance."; RL Genome Biol. 5:R8.1-R8.16(2004). RN [19] RP INTERACTION WITH ZSWIM7 AND XRCC2. RX PubMed=16710300; DOI=10.1038/sj.emboj.7601141; RA Martin V., Chahwan C., Gao H., Blais V., Wohlschlegel J., Yates J.R. III, RA McGowan C.H., Russell P.; RT "Sws1 is a conserved regulator of homologous recombination in eukaryotic RT cells."; RL EMBO J. 25:2564-2574(2006). RN [20] 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 [21] 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 [22] RP INVOLVEMENT IN BROVCA4. RX PubMed=21822267; DOI=10.1038/ng.893; RA Loveday C., Turnbull C., Ramsay E., Hughes D., Ruark E., Frankum J.R., RA Bowden G., Kalmyrzaev B., Warren-Perry M., Snape K., Adlard J.W., RA Barwell J., Berg J., Brady A.F., Brewer C., Brice G., Chapman C., Cook J., RA Davidson R., Donaldson A., Douglas F., Greenhalgh L., Henderson A., RA Izatt L., Kumar A., Lalloo F., Miedzybrodzka Z., Morrison P.J., RA Paterson J., Porteous M., Rogers M.T., Shanley S., Walker L., Eccles D., RA Evans D.G., Renwick A., Seal S., Lord C.J., Ashworth A., Reis-Filho J.S., RA Antoniou A.C., Rahman N.; RT "Germline mutations in RAD51D confer susceptibility to ovarian cancer."; RL Nat. Genet. 43:879-882(2011). RN [23] 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 [24] RP STRUCTURE BY NMR OF 1-83, AND DNA-BINDING. RX PubMed=21111057; DOI=10.1016/j.biocel.2010.11.014; RA Kim Y.M., Choi B.S.; RT "Structural and functional characterization of the N-terminal domain of RT human Rad51D."; RL Int. J. Biochem. Cell Biol. 43:416-422(2011). RN [25] RP VARIANT SER-9. RX PubMed=27932480; DOI=10.1681/asn.2016040387; RG NephroS; RG UK study of Nephrotic Syndrome; RA Bierzynska A., Soderquest K., Dean P., Colby E., Rollason R., Jones C., RA Inward C.D., McCarthy H.J., Simpson M.A., Lord G.M., Williams M., RA Welsh G.I., Koziell A.B., Saleem M.A.; RT "MAGI2 mutations cause congenital nephrotic syndrome."; RL J. Am. Soc. Nephrol. 28:1614-1621(2017). 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. Bind to single-stranded DNA (ssDNA) and has CC DNA-dependent ATPase activity. Part of the RAD51 paralog protein CC complex BCDX2 which acts in the BRCA1-BRCA2-dependent HR pathway. Upon CC DNA 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. Involved in telomere maintenance. CC The BCDX2 subcomplex XRCC2:RAD51D can stimulate Holliday junction CC resolution by BLM. {ECO:0000269|PubMed:10871607, CC ECO:0000269|PubMed:11751635, ECO:0000269|PubMed:11834724, CC ECO:0000269|PubMed:11842113, ECO:0000269|PubMed:12975363, CC ECO:0000269|PubMed:15109494, 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. In the absence of DNA, the BCDX2 CC subcomplex XRCC2:RAD51D formed a multimeric ring structure; in the CC presence of single-stranded DNA it formed a filamentous structure with CC the ssDNA. Interacts with SWSAP1 and ZSWIM7; involved in homologous CC recombination repair. Interacts with BLM; required for stimulation of CC BLM activity by the BCDX2 subcomplex XRCC2:RAD51D. CC {ECO:0000269|PubMed:10871607, 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:12975363, ECO:0000269|PubMed:16710300, CC ECO:0000269|PubMed:21965664}. CC -!- INTERACTION: CC O75771; Q9Y2J4: AMOTL2; NbExp=8; IntAct=EBI-1055693, EBI-746752; CC O75771; Q9Y2J4-4: AMOTL2; NbExp=3; IntAct=EBI-1055693, EBI-10187270; CC O75771; P54132: BLM; NbExp=4; IntAct=EBI-1055693, EBI-621372; CC O75771; Q6P1W5: C1orf94; NbExp=6; IntAct=EBI-1055693, EBI-946029; CC O75771; Q8N5R6: CCDC33; NbExp=3; IntAct=EBI-1055693, EBI-740841; CC O75771; Q9UK58: CCNL1; NbExp=3; IntAct=EBI-1055693, EBI-2836773; CC O75771; Q6P2R3: CEP57L1; NbExp=3; IntAct=EBI-1055693, EBI-12696312; CC O75771; Q8IYX8-2: CEP57L1; NbExp=3; IntAct=EBI-1055693, EBI-10181988; CC O75771; Q5JST6: EFHC2; NbExp=3; IntAct=EBI-1055693, EBI-2349927; CC O75771; P57678: GEMIN4; NbExp=3; IntAct=EBI-1055693, EBI-356700; CC O75771; O75031: HSF2BP; NbExp=3; IntAct=EBI-1055693, EBI-7116203; CC O75771; Q8IYA8: IHO1; NbExp=6; IntAct=EBI-1055693, EBI-8638439; CC O75771; Q13422: IKZF1; NbExp=5; IntAct=EBI-1055693, EBI-745305; CC O75771; Q13422-7: IKZF1; NbExp=3; IntAct=EBI-1055693, EBI-11522367; CC O75771; Q9UKT9: IKZF3; NbExp=11; IntAct=EBI-1055693, EBI-747204; CC O75771; Q9H079: KATNBL1; NbExp=3; IntAct=EBI-1055693, EBI-715394; CC O75771; F5H3M2: KIFC3; NbExp=3; IntAct=EBI-1055693, EBI-11953930; CC O75771; Q9BVG8: KIFC3; NbExp=4; IntAct=EBI-1055693, EBI-2125614; CC O75771; Q9BVG8-5: KIFC3; NbExp=3; IntAct=EBI-1055693, EBI-14069005; CC O75771; P19012: KRT15; NbExp=7; IntAct=EBI-1055693, EBI-739566; CC O75771; P48059-3: LIMS1; NbExp=3; IntAct=EBI-1055693, EBI-12864460; CC O75771; Q8TBB1: LNX1; NbExp=6; IntAct=EBI-1055693, EBI-739832; CC O75771; Q9BRK4: LZTS2; NbExp=9; IntAct=EBI-1055693, EBI-741037; CC O75771; Q9UPT6: MAPK8IP3; NbExp=3; IntAct=EBI-1055693, EBI-717887; CC O75771; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-1055693, EBI-16439278; CC O75771; Q8NI38: NFKBID; NbExp=3; IntAct=EBI-1055693, EBI-10271199; CC O75771; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-1055693, EBI-79165; CC O75771; Q8ND90: PNMA1; NbExp=3; IntAct=EBI-1055693, EBI-302345; CC O75771; Q8WUT1: POLDIP3; NbExp=3; IntAct=EBI-1055693, EBI-10276663; CC O75771; Q9GZV8: PRDM14; NbExp=3; IntAct=EBI-1055693, EBI-3957793; CC O75771; Q9NQX0: PRDM6; NbExp=3; IntAct=EBI-1055693, EBI-11320284; CC O75771; O15315: RAD51B; NbExp=6; IntAct=EBI-1055693, EBI-2824089; CC O75771; O43502: RAD51C; NbExp=6; IntAct=EBI-1055693, EBI-2267048; CC O75771; Q5RL73: RBM48; NbExp=3; IntAct=EBI-1055693, EBI-473821; CC O75771; Q04864-2: REL; NbExp=3; IntAct=EBI-1055693, EBI-10829018; CC O75771; O60504: SORBS3; NbExp=3; IntAct=EBI-1055693, EBI-741237; CC O75771; Q9H0A9-2: SPATC1L; NbExp=3; IntAct=EBI-1055693, EBI-11995806; CC O75771; O75558: STX11; NbExp=3; IntAct=EBI-1055693, EBI-714135; CC O75771; Q6NVH7: SWSAP1; NbExp=2; IntAct=EBI-1055693, EBI-5281637; CC O75771; P15884-3: TCF4; NbExp=3; IntAct=EBI-1055693, EBI-13636688; CC O75771; Q96N21: TEPSIN; NbExp=3; IntAct=EBI-1055693, EBI-11139477; CC O75771; Q08117-2: TLE5; NbExp=3; IntAct=EBI-1055693, EBI-11741437; CC O75771; Q14142: TRIM14; NbExp=3; IntAct=EBI-1055693, EBI-2820256; CC O75771; Q5W5X9-3: TTC23; NbExp=3; IntAct=EBI-1055693, EBI-9090990; CC O75771; Q9Y2B5: VPS9D1; NbExp=3; IntAct=EBI-1055693, EBI-9031083; CC O75771; O43543: XRCC2; NbExp=39; IntAct=EBI-1055693, EBI-3918457; CC O75771; B2RXF5: ZBTB42; NbExp=3; IntAct=EBI-1055693, EBI-12287587; CC O75771; Q53FD0-2: ZC2HC1C; NbExp=3; IntAct=EBI-1055693, EBI-14104088; CC O75771; Q6P1L6: ZNF343; NbExp=3; IntAct=EBI-1055693, EBI-10252492; CC O75771; Q6NX45: ZNF774; NbExp=3; IntAct=EBI-1055693, EBI-10251462; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. Cytoplasm, cytoskeleton, CC microtubule organizing center, centrosome. Chromosome, telomere. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=8; CC Name=1; Synonyms=TRAD; CC IsoId=O75771-1; Sequence=Displayed; CC Name=2; Synonyms=TRAD-D1, D2; CC IsoId=O75771-2; Sequence=VSP_005558, VSP_005559; CC Name=3; Synonyms=TRAD-D3; CC IsoId=O75771-3; Sequence=VSP_005560; CC Name=4; Synonyms=TRAD-D4; CC IsoId=O75771-4; Sequence=VSP_005561; CC Name=5; Synonyms=TRAD-D5; CC IsoId=O75771-5; Sequence=VSP_005562; CC Name=6; Synonyms=TRAD-D6, D7; CC IsoId=O75771-6; Sequence=VSP_005563, VSP_005564; CC Name=7; Synonyms=TRAD-D8; CC IsoId=O75771-7; Sequence=VSP_005565, VSP_005566; CC Name=8; CC IsoId=O75771-8; Sequence=VSP_043658; CC -!- TISSUE SPECIFICITY: Expressed in colon, prostate, spleen, testis, CC ovary, thymus and small intestine. Weakly expressed in leukocytes. CC -!- DISEASE: Breast-ovarian cancer, familial, 4 (BROVCA4) [MIM:614291]: 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:21822267}. Note=Disease CC susceptibility is associated with variants affecting the gene CC represented in this entry. CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA CC decay. {ECO:0000305}. 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/rad51l3/"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/RAD51L3ID347ch17q12.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; Y15572; CAA75681.1; -; mRNA. DR EMBL; AF034956; AAC39719.1; -; mRNA. DR EMBL; AB013341; BAA25914.1; -; mRNA. DR EMBL; AB016223; BAA31747.1; -; mRNA. DR EMBL; AB016224; BAA31748.1; -; mRNA. DR EMBL; AB016225; BAA31749.1; -; mRNA. DR EMBL; AB018360; BAA33779.1; -; mRNA. DR EMBL; AB018361; BAA33780.1; -; mRNA. DR EMBL; AB018362; BAA33781.1; -; mRNA. DR EMBL; AB018363; BAA33782.1; -; mRNA. DR EMBL; AB020412; BAA34690.1; -; mRNA. DR EMBL; AY623116; AAT38112.1; -; Genomic_DNA. DR EMBL; AK296241; BAG58959.1; -; mRNA. DR EMBL; AC022916; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471147; EAW80181.1; -; Genomic_DNA. DR EMBL; CH471147; EAW80184.1; -; Genomic_DNA. DR EMBL; CH471147; EAW80196.1; -; Genomic_DNA. DR EMBL; BC014422; AAH14422.1; -; mRNA. DR EMBL; AL117459; CAB55937.1; -; mRNA. DR CCDS; CCDS11287.1; -. [O75771-1] DR CCDS; CCDS11288.1; -. [O75771-3] DR CCDS; CCDS45646.1; -. [O75771-8] DR PIR; T17247; T17247. DR RefSeq; NP_001136043.1; NM_001142571.1. [O75771-8] DR RefSeq; NP_002869.3; NM_002878.3. [O75771-1] DR RefSeq; NP_598332.1; NM_133629.2. [O75771-3] DR PDB; 2KZ3; NMR; -; A=1-83. DR PDBsum; 2KZ3; -. DR AlphaFoldDB; O75771; -. DR BMRB; O75771; -. DR SMR; O75771; -. DR BioGRID; 111829; 91. DR CORUM; O75771; -. DR DIP; DIP-24265N; -. DR IntAct; O75771; 78. DR MINT; O75771; -. DR iPTMnet; O75771; -. DR PhosphoSitePlus; O75771; -. DR BioMuta; RAD51D; -. DR EPD; O75771; -. DR jPOST; O75771; -. DR MassIVE; O75771; -. DR MaxQB; O75771; -. DR PaxDb; O75771; -. DR PeptideAtlas; O75771; -. DR PRIDE; O75771; -. DR ProteomicsDB; 50183; -. [O75771-1] DR ProteomicsDB; 50184; -. [O75771-2] DR ProteomicsDB; 50185; -. [O75771-3] DR ProteomicsDB; 50186; -. [O75771-4] DR ProteomicsDB; 50187; -. [O75771-5] DR ProteomicsDB; 50188; -. [O75771-6] DR ProteomicsDB; 50189; -. [O75771-7] DR ProteomicsDB; 50190; -. [O75771-8] DR Antibodypedia; 15549; 374 antibodies from 32 providers. DR DNASU; 5892; -. DR Ensembl; ENST00000335858.11; ENSP00000338408.6; ENSG00000185379.21. [O75771-3] DR Ensembl; ENST00000345365.11; ENSP00000338790.6; ENSG00000185379.21. [O75771-1] DR Ensembl; ENST00000394589.8; ENSP00000378090.4; ENSG00000185379.21. [O75771-1] DR Ensembl; ENST00000586044.5; ENSP00000465584.1; ENSG00000185379.21. [O75771-2] DR Ensembl; ENST00000587977.5; ENSP00000466587.1; ENSG00000185379.21. [O75771-6] DR Ensembl; ENST00000588594.5; ENSP00000465366.1; ENSG00000185379.21. [O75771-2] DR Ensembl; ENST00000590016.5; ENSP00000466399.1; ENSG00000185379.21. [O75771-8] DR GeneID; 5892; -. DR KEGG; hsa:5892; -. DR MANE-Select; ENST00000345365.11; ENSP00000338790.6; NM_002878.4; NP_002869.3. DR UCSC; uc002hir.4; human. [O75771-1] DR CTD; 5892; -. DR DisGeNET; 5892; -. DR GeneCards; RAD51D; -. DR HGNC; HGNC:9823; RAD51D. DR HPA; ENSG00000185379; Low tissue specificity. DR MalaCards; RAD51D; -. DR MIM; 602954; gene. DR MIM; 614291; phenotype. DR neXtProt; NX_O75771; -. DR OpenTargets; ENSG00000185379; -. DR Orphanet; 1331; Familial prostate cancer. DR Orphanet; 145; Hereditary breast and ovarian cancer syndrome. DR PharmGKB; PA34179; -. DR VEuPathDB; HostDB:ENSG00000185379; -. DR eggNOG; KOG1433; Eukaryota. DR eggNOG; KOG4275; Eukaryota. DR GeneTree; ENSGT00940000159095; -. DR HOGENOM; CLU_058452_0_0_1; -. DR InParanoid; O75771; -. DR OMA; QRIHTFR; -. DR OrthoDB; 1214879at2759; -. DR PhylomeDB; O75771; -. DR PathwayCommons; O75771; -. 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-6796648; TP53 Regulates Transcription of DNA Repair Genes. 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-9709603; Impaired BRCA2 binding to PALB2. DR SignaLink; O75771; -. DR BioGRID-ORCS; 5892; 464 hits in 1094 CRISPR screens. DR GeneWiki; RAD51L3; -. DR GenomeRNAi; 5892; -. DR Pharos; O75771; Tbio. DR PRO; PR:O75771; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; O75771; protein. DR Bgee; ENSG00000185379; Expressed in sperm and 112 other tissues. DR ExpressionAtlas; O75771; baseline and differential. DR Genevisible; O75771; HS. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0000781; C:chromosome, telomeric region; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW. 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:0140664; F:ATP-dependent DNA damage sensor activity; IMP:FlyBase. DR GO; GO:0003677; F:DNA binding; TAS:ProtInc. DR GO; GO:0043015; F:gamma-tubulin binding; IDA:UniProtKB. DR GO; GO:0003697; F:single-stranded DNA binding; IDA:UniProtKB. 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:0036297; P:interstrand cross-link repair; IEA:Ensembl. DR GO; GO:0007131; P:reciprocal meiotic recombination; IBA:GO_Central. DR GO; GO:0051726; P:regulation of cell cycle; IEA:Ensembl. DR GO; GO:0042148; P:strand invasion; IDA:UniProtKB. DR GO; GO:0000723; P:telomere maintenance; IMP:UniProtKB. DR GO; GO:0000722; P:telomere maintenance via recombination; IMP:BHF-UCL. 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; IPR020588; RecA_ATP-bd. 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 3D-structure; Alternative splicing; ATP-binding; Chromosome; Cytoplasm; KW Cytoskeleton; DNA damage; DNA recombination; DNA repair; DNA-binding; KW Nucleotide-binding; Nucleus; Reference proteome; Telomere. FT CHAIN 1..328 FT /note="DNA repair protein RAD51 homolog 4" FT /id="PRO_0000122942" FT REGION 1..83 FT /note="preferentially binds ssDNA" FT BINDING 107..114 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255" FT VAR_SEQ 49..88 FT /note="ALVALRRVLLAQFSAFPVNGADLYEELKTSTAILSTGIGS -> TWRAHSSG FT NLGGLQLPQVPAGRSWSGVRNALKKAGLGHGGTDGLSLNAFDERGTAVSTSR (in FT isoform 8)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043658" FT VAR_SEQ 49 FT /note="A -> S (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_005558" FT VAR_SEQ 50..328 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_005559" FT VAR_SEQ 50..161 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_005560" FT VAR_SEQ 88..118 FT /note="SLDKLLDAGLYTGEVTEIVGGPGSGKTQVCL -> RHGGRTQVGTWEDCSCL FT RSPQGDRGVGSGML (in isoform 6)" FT /evidence="ECO:0000305" FT /id="VSP_005563" FT VAR_SEQ 88..101 FT /note="SLDKLLDAGLYTGE -> RQKLSGGSRWCMHL (in isoform 5)" FT /evidence="ECO:0000305" FT /id="VSP_005562" FT VAR_SEQ 116..160 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000305" FT /id="VSP_005561" FT VAR_SEQ 119..328 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000305" FT /id="VSP_005564" FT VAR_SEQ 193..212 FT /note="VTGSSGTVKVVVVDSVTAVV -> DGIPEHLNHIPHCLHVHLPC (in FT isoform 7)" FT /evidence="ECO:0000305" FT /id="VSP_005565" FT VAR_SEQ 213..328 FT /note="Missing (in isoform 7)" FT /evidence="ECO:0000305" FT /id="VSP_005566" FT VARIANT 9 FT /note="C -> S (in dbSNP:rs140825795)" FT /evidence="ECO:0000269|PubMed:27932480" FT /id="VAR_079271" FT VARIANT 24 FT /note="R -> S (in dbSNP:rs28363257)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_020560" FT VARIANT 165 FT /note="R -> Q (in dbSNP:rs4796033)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_020561" FT VARIANT 225 FT /note="A -> T (in dbSNP:rs28363282)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_020562" FT VARIANT 232 FT /note="R -> Q (in dbSNP:rs28363283)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_020563" FT VARIANT 233 FT /note="E -> G (in dbSNP:rs28363284)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_020564" FT CONFLICT 231 FT /note="A -> V (in Ref. 9; CAB55937)" FT /evidence="ECO:0000305" FT HELIX 14..22 FT /evidence="ECO:0007829|PDB:2KZ3" FT HELIX 28..31 FT /evidence="ECO:0007829|PDB:2KZ3" FT HELIX 36..43 FT /evidence="ECO:0007829|PDB:2KZ3" FT HELIX 47..61 FT /evidence="ECO:0007829|PDB:2KZ3" SQ SEQUENCE 328 AA; 35049 MW; 6038DA9356DF354A CRC64; MGVLRVGLCP GLTEEMIQLL RSHRIKTVVD LVSADLEEVA QKCGLSYKAL VALRRVLLAQ FSAFPVNGAD LYEELKTSTA ILSTGIGSLD KLLDAGLYTG EVTEIVGGPG SGKTQVCLCM AANVAHGLQQ NVLYVDSNGG LTASRLLQLL QAKTQDEEEQ AEALRRIQVV HAFDIFQMLD VLQELRGTVA QQVTGSSGTV KVVVVDSVTA VVSPLLGGQQ REGLALMMQL ARELKTLARD LGMAVVVTNH ITRDRDSGRL KPALGRSWSF VPSTRILLDT IEGAGASGGR RMACLAKSSR QPTGFQEMVD IGTWGTSEQS ATLQGDQT // ID RFC3_HUMAN Reviewed; 356 AA. AC P40938; C9JU95; O15252; Q5W0E8; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 15-DEC-1998, sequence version 2. DT 12-OCT-2022, entry version 195. DE RecName: Full=Replication factor C subunit 3; DE AltName: Full=Activator 1 38 kDa subunit; DE Short=A1 38 kDa subunit; DE AltName: Full=Activator 1 subunit 3; DE AltName: Full=Replication factor C 38 kDa subunit; DE Short=RF-C 38 kDa subunit; DE Short=RFC38; GN Name=RFC3; 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=8441605; DOI=10.1093/nar/21.1.1; RA O'Donnell M., Onrust R., Dean F.B., Chen M., Hurwitz J.; RT "Homology in accessory proteins of replicative polymerases -- E. coli to RT humans."; RL Nucleic Acids Res. 21:1-3(1993). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-16. RG NIEHS SNPs program; RL Submitted (FEB-2002) 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 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 51-305 (ISOFORM 2). RC TISSUE=Embryonic stem cell, 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 [6] RP INTERACTION WITH RAD17. RX PubMed=10884395; DOI=10.1074/jbc.m005782200; RA Rauen M., Burtelow M.A., Dufault V.M., Karnitz L.M.; RT "The human checkpoint protein hRad17 interacts with the PCNA-like proteins RT hRad1, hHus1, and hRad9."; RL J. Biol. Chem. 275:29767-29771(2000). RN [7] RP INTERACTION WITH RAD17. RX PubMed=11572977; DOI=10.1073/pnas.201373498; RA Lindsey-Boltz L.A., Bermudez V.P., Hurwitz J., Sancar A.; RT "Purification and characterization of human DNA damage checkpoint Rad RT complexes."; RL Proc. Natl. Acad. Sci. U.S.A. 98:11236-11241(2001). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125, 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 [9] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-20, 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 [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 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). CC -!- FUNCTION: The elongation of primed DNA templates by DNA polymerase CC delta and epsilon requires the action of the accessory proteins CC proliferating cell nuclear antigen (PCNA) and activator 1. CC -!- SUBUNIT: Heterotetramer of subunits RFC2, RFC3, RFC4 and RFC5 that can CC form a complex either with RFC1 or with RAD17. The former interacts CC with PCNA in the presence of ATP, while the latter has ATPase activity CC but is not stimulated by PCNA. Interacts with CNTD1; this interaction CC facilitates crossover formation (By similarity). CC {ECO:0000250|UniProtKB:Q8R323, ECO:0000269|PubMed:10884395, CC ECO:0000269|PubMed:11572977}. CC -!- INTERACTION: CC P40938; Q6AI12: ANKRD40; NbExp=3; IntAct=EBI-1055010, EBI-2838246; CC P40938; Q0VD86: INCA1; NbExp=3; IntAct=EBI-1055010, EBI-6509505; CC P40938; Q5VWX1: KHDRBS2; NbExp=3; IntAct=EBI-1055010, EBI-742808; CC P40938; O75525: KHDRBS3; NbExp=3; IntAct=EBI-1055010, EBI-722504; CC P40938; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-1055010, EBI-79165; CC P40938; P35249: RFC4; NbExp=11; IntAct=EBI-1055010, EBI-476655; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P40938-1; Sequence=Displayed; CC Name=2; CC IsoId=P40938-2; Sequence=VSP_044920; CC -!- SIMILARITY: Belongs to the activator 1 small subunits family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/rfc3/"; 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; L07541; AAB07268.1; -; mRNA. DR EMBL; AF484446; AAL82505.1; -; Genomic_DNA. DR EMBL; AL139081; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL160394; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL161891; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471075; EAX08537.1; -; Genomic_DNA. DR EMBL; BC000149; AAH00149.1; -; mRNA. DR EMBL; CX786577; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS45025.1; -. [P40938-2] DR CCDS; CCDS9352.1; -. [P40938-1] DR PIR; T09573; T09573. DR RefSeq; NP_002906.1; NM_002915.3. [P40938-1] DR RefSeq; NP_853536.2; NM_181558.2. [P40938-2] DR PDB; 6VVO; EM; 3.40 A; E=1-356. DR PDBsum; 6VVO; -. DR AlphaFoldDB; P40938; -. DR SMR; P40938; -. DR BioGRID; 111915; 167. DR ComplexPortal; CPX-415; DNA replication factor C complex. DR CORUM; P40938; -. DR DIP; DIP-36432N; -. DR IntAct; P40938; 55. DR MINT; P40938; -. DR STRING; 9606.ENSP00000369411; -. DR GlyGen; P40938; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P40938; -. DR MetOSite; P40938; -. DR PhosphoSitePlus; P40938; -. DR SwissPalm; P40938; -. DR BioMuta; RFC3; -. DR DMDM; 3915601; -. DR EPD; P40938; -. DR jPOST; P40938; -. DR MassIVE; P40938; -. DR MaxQB; P40938; -. DR PaxDb; P40938; -. DR PeptideAtlas; P40938; -. DR PRIDE; P40938; -. DR ProteomicsDB; 11702; -. DR ProteomicsDB; 55391; -. [P40938-1] DR Antibodypedia; 7909; 253 antibodies from 31 providers. DR DNASU; 5983; -. DR Ensembl; ENST00000380071.8; ENSP00000369411.3; ENSG00000133119.13. [P40938-1] DR Ensembl; ENST00000434425.5; ENSP00000401001.1; ENSG00000133119.13. [P40938-2] DR GeneID; 5983; -. DR KEGG; hsa:5983; -. DR MANE-Select; ENST00000380071.8; ENSP00000369411.3; NM_002915.4; NP_002906.1. DR UCSC; uc001uuz.4; human. [P40938-1] DR CTD; 5983; -. DR DisGeNET; 5983; -. DR GeneCards; RFC3; -. DR HGNC; HGNC:9971; RFC3. DR HPA; ENSG00000133119; Low tissue specificity. DR MalaCards; RFC3; -. DR MIM; 600405; gene. DR neXtProt; NX_P40938; -. DR OpenTargets; ENSG00000133119; -. DR PharmGKB; PA34340; -. DR VEuPathDB; HostDB:ENSG00000133119; -. DR eggNOG; KOG2035; Eukaryota. DR GeneTree; ENSGT00550000075006; -. DR HOGENOM; CLU_042324_5_0_1; -. DR InParanoid; P40938; -. DR OMA; LMCEACK; -. DR PhylomeDB; P40938; -. DR TreeFam; TF105724; -. DR BRENDA; 3.6.4.B8; 2681. DR PathwayCommons; P40938; -. DR Reactome; R-HSA-110312; Translesion synthesis by REV1. DR Reactome; R-HSA-110314; Recognition of DNA damage by PCNA-containing replication complex. DR Reactome; R-HSA-110320; Translesion Synthesis by POLH. DR Reactome; R-HSA-174411; Polymerase switching on the C-strand of the telomere. DR Reactome; R-HSA-176187; Activation of ATR in response to replication stress. DR Reactome; R-HSA-5651801; PCNA-Dependent Long Patch Base Excision Repair. DR Reactome; R-HSA-5655862; Translesion synthesis by POLK. DR Reactome; R-HSA-5656121; Translesion synthesis by POLI. DR Reactome; R-HSA-5656169; Termination of translesion DNA synthesis. 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-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-5696397; Gap-filling DNA repair synthesis and ligation in GG-NER. DR Reactome; R-HSA-5696400; Dual Incision in GG-NER. DR Reactome; R-HSA-6782135; Dual incision in TC-NER. DR Reactome; R-HSA-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER. DR Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation. DR Reactome; R-HSA-69091; Polymerase switching. DR Reactome; R-HSA-69473; G2/M DNA damage checkpoint. DR Reactome; R-HSA-9709570; Impaired BRCA2 binding to RAD51. DR SignaLink; P40938; -. DR SIGNOR; P40938; -. DR BioGRID-ORCS; 5983; 768 hits in 1089 CRISPR screens. DR ChiTaRS; RFC3; human. DR GeneWiki; RFC3; -. DR GenomeRNAi; 5983; -. DR Pharos; P40938; Tbio. DR PRO; PR:P40938; -. DR Proteomes; UP000005640; Chromosome 13. DR RNAct; P40938; protein. DR Bgee; ENSG00000133119; Expressed in ventricular zone and 189 other tissues. DR ExpressionAtlas; P40938; baseline and differential. DR Genevisible; P40938; HS. DR GO; GO:0031390; C:Ctf18 RFC-like complex; IDA:UniProtKB. DR GO; GO:0005663; C:DNA replication factor C complex; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0008094; F:ATP-dependent activity, acting on DNA; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0003689; F:DNA clamp loader activity; TAS:UniProtKB. DR GO; GO:0032508; P:DNA duplex unwinding; IEA:GOC. DR GO; GO:0006281; P:DNA repair; IBA:GO_Central. DR GO; GO:0006260; P:DNA replication; IDA:UniProtKB. DR GO; GO:0006271; P:DNA strand elongation involved in DNA replication; TAS:ProtInc. DR GO; GO:0000731; P:DNA synthesis involved in DNA repair; TAS:UniProtKB. DR GO; GO:0006261; P:DNA-templated DNA replication; IBA:GO_Central. DR GO; GO:1900264; P:positive regulation of DNA-directed DNA polymerase activity; IDA:UniProtKB. DR GO; GO:0046683; P:response to organophosphorus; IEP:UniProtKB. DR Gene3D; 3.40.50.300; -; 1. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR008921; DNA_pol3_clamp-load_cplx_C. DR InterPro; IPR027417; P-loop_NTPase. DR SMART; SM00382; AAA; 1. DR SUPFAM; SSF48019; SSF48019; 1. DR SUPFAM; SSF52540; SSF52540; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; DNA replication; KW DNA-binding; Nucleus; Phosphoprotein; Reference proteome. FT CHAIN 1..356 FT /note="Replication factor C subunit 3" FT /id="PRO_0000121761" FT MOD_RES 20 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 125 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17525332" FT VAR_SEQ 294..356 FT /note="GLLSELLHNCDGQLKGEVAQMAAYYEHRLQLGSKAIYHLEAFVAKFMALYKK FT FMEDGLEGMMF -> ACKEESRSCDIF (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_044920" FT VARIANT 16 FT /note="L -> V (in dbSNP:rs3135533)" FT /evidence="ECO:0000269|Ref.2" FT /id="VAR_018750" FT TURN 5..7 FT /evidence="ECO:0007829|PDB:6VVO" FT HELIX 13..15 FT /evidence="ECO:0007829|PDB:6VVO" FT HELIX 20..31 FT /evidence="ECO:0007829|PDB:6VVO" FT STRAND 32..34 FT /evidence="ECO:0007829|PDB:6VVO" FT STRAND 38..41 FT /evidence="ECO:0007829|PDB:6VVO" FT HELIX 48..59 FT /evidence="ECO:0007829|PDB:6VVO" FT HELIX 62..64 FT /evidence="ECO:0007829|PDB:6VVO" FT STRAND 68..75 FT /evidence="ECO:0007829|PDB:6VVO" FT STRAND 77..79 FT /evidence="ECO:0007829|PDB:6VVO" FT STRAND 81..88 FT /evidence="ECO:0007829|PDB:6VVO" FT STRAND 90..95 FT /evidence="ECO:0007829|PDB:6VVO" FT STRAND 99..102 FT /evidence="ECO:0007829|PDB:6VVO" FT HELIX 104..119 FT /evidence="ECO:0007829|PDB:6VVO" FT TURN 120..122 FT /evidence="ECO:0007829|PDB:6VVO" FT STRAND 130..136 FT /evidence="ECO:0007829|PDB:6VVO" FT HELIX 142..154 FT /evidence="ECO:0007829|PDB:6VVO" FT TURN 155..158 FT /evidence="ECO:0007829|PDB:6VVO" FT STRAND 159..164 FT /evidence="ECO:0007829|PDB:6VVO" FT HELIX 168..170 FT /evidence="ECO:0007829|PDB:6VVO" FT HELIX 173..176 FT /evidence="ECO:0007829|PDB:6VVO" FT STRAND 178..183 FT /evidence="ECO:0007829|PDB:6VVO" FT HELIX 189..203 FT /evidence="ECO:0007829|PDB:6VVO" FT HELIX 211..219 FT /evidence="ECO:0007829|PDB:6VVO" FT HELIX 223..232 FT /evidence="ECO:0007829|PDB:6VVO" FT TURN 233..236 FT /evidence="ECO:0007829|PDB:6VVO" FT HELIX 250..264 FT /evidence="ECO:0007829|PDB:6VVO" FT HELIX 268..283 FT /evidence="ECO:0007829|PDB:6VVO" FT HELIX 288..300 FT /evidence="ECO:0007829|PDB:6VVO" FT TURN 305..307 FT /evidence="ECO:0007829|PDB:6VVO" FT HELIX 308..322 FT /evidence="ECO:0007829|PDB:6VVO" FT HELIX 328..348 FT /evidence="ECO:0007829|PDB:6VVO" SQ SEQUENCE 356 AA; 40556 MW; 820C11675A2C63A5 CRC64; MSLWVDKYRP CSLGRLDYHK EQAAQLRNLV QCGDFPHLLV YGPSGAGKKT RIMCILRELY GVGVEKLRIE HQTITTPSKK KIEISTIASN YHLEVNPSDA GNSDRVVIQE MLKTVAQSQQ LETNSQRDFK VVLLTEVDKL TKDAQHALRR TMEKYMSTCR LILCCNSTSK VIPPIRSRCL AVRVPAPSIE DICHVLSTVC KKEGLNLPSQ LAHRLAEKSC RNLRKALLMC EACRVQQYPF TADQEIPETD WEVYLRETAN AIVSQQTPQR LLEVRGRLYE LLTHCIPPEI IMKGLLSELL HNCDGQLKGE VAQMAAYYEH RLQLGSKAIY HLEAFVAKFM ALYKKFMEDG LEGMMF //