ID BRCA2_HUMAN Reviewed; 3418 AA. AC P51587; O00183; O15008; Q13879; Q5TBJ7; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 11-NOV-2015, sequence version 3. DT 22-APR-2020, entry version 222. DE RecName: Full=Breast cancer type 2 susceptibility protein; DE AltName: Full=Fanconi anemia group D1 protein; GN Name=BRCA2; 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]. 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], AND VARIANTS HIS-372 AND PHE-599. 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; VAL-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]. 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 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 [31] 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 [32] 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 [33] RP VARIANT OVARIAN CANCER HIS-2787, AND VARIANTS HIS-372; MET-1915 AND RP VAL-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 [34] 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 [35] 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 [36] 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 [37] 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 [38] 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 [39] 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 [40] 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 [41] 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 [42] 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 [43] 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 [44] 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 [45] 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 [46] 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 [47] 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 [48] 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 [49] 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 [50] 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 [51] 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 [52] 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 [53] 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 [54] 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 [55] 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 [56] 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 [57] 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 [58] 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 [59] 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 [60] 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 [61] RP VARIANTS HIS-289; HIS-372; GLY-462; ASP-991; SER-1279; TYR-1420; ASP-1771 RP AND VAL-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 [62] 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 [63] 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 [64] 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 [65] 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 [66] 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 [67] 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 VAL-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 [68] 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 [69] 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 [70] 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 [71] 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 [72] 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 [73] 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 [74] 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 [75] 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 [76] 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 [77] 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; VAL-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 [78] 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). Interacts directly with PALB2 which may serve CC as a scaffold for a HR complex containing PALB2, BRCA2, RAD51C, RAD51 CC and XRCC3 (PubMed:19369211, PubMed:24141787, PubMed:28319063, CC PubMed:16793542, PubMed:19609323). Interacts with BRCA1 only in the CC presence of PALB2 which serves as the bridging protein CC (PubMed:19369211). Interacts with POLH; the interaction is direct CC (PubMed:24485656). Interacts with the TREX-2 complex subunits PCID2 and CC SEM1 (PubMed:24896180, PubMed:21719596). {ECO:0000269|PubMed:10373512, CC ECO:0000269|PubMed:12442171, ECO:0000269|PubMed:15115758, CC ECO:0000269|PubMed:15199141, ECO:0000269|PubMed:15314155, CC ECO:0000269|PubMed:15800615, ECO:0000269|PubMed:15967112, CC ECO:0000269|PubMed:16205630, ECO:0000269|PubMed:16793542, CC ECO:0000269|PubMed:18212739, ECO:0000269|PubMed:18317453, CC ECO:0000269|PubMed:19369211, ECO:0000269|PubMed:19609323, 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:24013206, CC ECO:0000269|PubMed:24141787, ECO:0000269|PubMed:24485656, CC ECO:0000269|PubMed:24896180, ECO:0000269|PubMed:28319063}. CC -!- INTERACTION: CC P51587; P51587; NbExp=3; IntAct=EBI-79792, EBI-79792; CC P51587; Q14565: DMC1; NbExp=12; IntAct=EBI-79792, EBI-930865; CC P51587; Q9BXW9: FANCD2; NbExp=16; IntAct=EBI-79792, EBI-359343; CC P51587; Q9BXW9-2: FANCD2; NbExp=3; IntAct=EBI-79792, EBI-596878; CC P51587; Q9P0W2: HMG20B; NbExp=8; IntAct=EBI-79792, EBI-713401; CC P51587; Q86YC2: PALB2; NbExp=25; IntAct=EBI-79792, EBI-1222653; CC P51587; Q9NTI5: PDS5B; NbExp=26; IntAct=EBI-79792, EBI-1175604; CC P51587; Q9Y253: POLH; NbExp=6; IntAct=EBI-79792, EBI-2827270; CC P51587; Q06609: RAD51; NbExp=45; 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:0000305|PubMed:21276791}. Cytoplasm, cytoskeleton, microtubule CC organizing center, centrosome {ECO:0000269|PubMed:21276791}. 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 variations 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 mutations 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 variations 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 mutations 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 mutations affecting the gene represented CC in this entry. CC -!- WEB RESOURCE: Name=Fanconi Anemia Mutation Database; CC URL="http://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 PDBsum; 1N0W; -. DR PDBsum; 3EU7; -. DR PDBsum; 6GY2; -. DR PDBsum; 6HQU; -. DR SMR; P51587; -. DR BioGrid; 107142; 200. DR ComplexPortal; CPX-955; BRCC ubiquitin ligase complex. DR CORUM; P51587; -. DR DIP; DIP-24214N; -. DR ELM; P51587; -. DR IntAct; P51587; 56. DR MINT; P51587; -. DR STRING; 9606.ENSP00000369497; -. DR BindingDB; P51587; -. DR iPTMnet; P51587; -. DR PhosphoSitePlus; P51587; -. DR BioMuta; BRCA2; -. DR DMDM; 14424438; -. DR CPTAC; CPTAC-3279; -. DR CPTAC; CPTAC-3280; -. DR EPD; P51587; -. DR jPOST; P51587; -. DR MassIVE; P51587; -. DR PaxDb; P51587; -. DR PeptideAtlas; P51587; -. DR PRIDE; P51587; -. DR ProteomicsDB; 56340; -. DR Antibodypedia; 7788; 292 antibodies. DR DNASU; 675; -. DR Ensembl; ENST00000380152; ENSP00000369497; ENSG00000139618. DR Ensembl; ENST00000544455; ENSP00000439902; ENSG00000139618. DR GeneID; 675; -. DR KEGG; hsa:675; -. 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 (lymphoid tissue, testis). DR MalaCards; BRCA2; -. DR MIM; 114480; phenotype. DR MIM; 600185; gene. DR MIM; 605724; phenotype. DR MIM; 612555; phenotype. DR MIM; 613029; phenotype. DR MIM; 613347; phenotype. DR neXtProt; NX_P51587; -. DR Orphanet; 1333; Familial pancreatic carcinoma. DR Orphanet; 1331; Familial prostate cancer. DR Orphanet; 84; Fanconi anemia. DR Orphanet; 145; Hereditary breast and ovarian cancer syndrome. DR Orphanet; 227535; Hereditary breast cancer. DR Orphanet; 213524; Hereditary site-specific ovarian cancer syndrome. DR Orphanet; 319462; Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations. DR Orphanet; 654; Nephroblastoma. DR PharmGKB; PA25412; -. DR eggNOG; KOG4751; Eukaryota. DR eggNOG; ENOG410Y06W; LUCA. DR HOGENOM; CLU_000344_0_0_1; -. DR InParanoid; P51587; -. DR KO; K08775; -. DR OrthoDB; 257485at2759; -. DR TreeFam; TF105041; -. 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 SignaLink; P51587; -. DR SIGNOR; P51587; -. 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 126 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:0005829; C:cytosol; IDA:HPA. DR GO; GO:0000800; C:lateral element; IDA:MGI. DR GO; GO:0000784; C:nuclear chromosome, telomeric region; IDA:BHF-UCL. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0030141; C:secretory granule; IDA:UniProtKB. DR GO; GO:0043015; F:gamma-tubulin binding; IPI:UniProtKB. DR GO; GO:0010484; F:H3 histone acetyltransferase activity; IDA:UniProtKB. DR GO; GO:0010485; F:H4 histone acetyltransferase activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0002020; F:protease binding; IPI:UniProtKB. DR GO; GO:0008022; F:protein C-terminus binding; IDA:MGI. DR GO; GO:0003697; F:single-stranded DNA binding; IDA:UniProtKB. DR GO; GO:0007420; P:brain development; IEA:Ensembl. DR GO; GO:0007569; P:cell aging; IEA:Ensembl. DR GO; GO:0051298; P:centrosome duplication; IMP:UniProtKB. DR GO; GO:0006978; P:DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; IEA:Ensembl. DR GO; GO:0006302; P:double-strand break repair; IMP:UniProtKB. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IDA:UniProtKB. DR GO; GO:0070200; P:establishment of protein localization to telomere; IDA:BHF-UCL. DR GO; GO:0008585; P:female gonad development; IEA:Ensembl. DR GO; GO:0030097; P:hemopoiesis; IEA:Ensembl. DR GO; GO:0043966; P:histone H3 acetylation; IDA:UniProtKB. DR GO; GO:0043967; P:histone H4 acetylation; IDA:UniProtKB. DR GO; GO:0001833; P:inner cell mass cell proliferation; IEA:Ensembl. DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IEA:Ensembl. DR GO; GO:0007141; P:male meiosis I; IEA:Ensembl. DR GO; GO:1990426; P:mitotic recombination-dependent replication fork processing; IMP:BHF-UCL. DR GO; GO:0033600; P:negative regulation of mammary gland epithelial cell proliferation; IDA:UniProtKB. DR GO; GO:0006289; P:nucleotide-excision repair; IMP:UniProtKB. DR GO; GO:0001556; P:oocyte maturation; IEA:Ensembl. DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0032465; P:regulation of cytokinesis; IEA:Ensembl. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central. DR GO; GO:0048478; P:replication fork protection; IEA:Ensembl. DR GO; GO:0010332; P:response to gamma radiation; IEA:Ensembl. DR GO; GO:0010225; P:response to UV-C; IEA:Ensembl. DR GO; GO:0010165; P:response to X-ray; IEA:Ensembl. DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl. DR GO; GO:0000722; P:telomere maintenance via recombination; IEA:Ensembl. DR CDD; cd04493; BRCA2DBD_OB1; 1. DR CDD; cd04495; BRCA2DBD_OB3; 1. DR DisProt; DP01869; -. DR 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; 4. 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; 8. 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 mutation; KW DNA damage; DNA recombination; DNA repair; DNA-binding; Fanconi anemia; KW Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; KW Tumor suppressor; 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 639..1000 FT /note="Interaction with NPM1" FT /evidence="ECO:0000269|PubMed:21084279" 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 2350..2545 FT /note="Interaction with FANCD2" FT REGION 2481..2832 FT /note="Interaction with SEM1" FT /evidence="ECO:0000269|PubMed:10373512, FT ECO:0000269|PubMed:16205630" FT MOTIF 2682..2698 FT /note="Nuclear export signal; masked by interaction with FT SEM1" FT /evidence="ECO:0000269|PubMed:24013206" FT MOD_RES 70 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:23186163" FT MOD_RES 445 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:23186163" FT MOD_RES 492 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:23186163" FT MOD_RES 755 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:17525332" FT MOD_RES 1970 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:23186163" FT MOD_RES 2035 FT /note="Phosphothreonine" FT /evidence="ECO:0000244|PubMed:23186163" FT MOD_RES 2095 FT /note="Phosphoserine" FT /evidence="ECO:0000244|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:0000244|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 (common polymorphism; was originally thought FT to be linked to ovarian cancer; 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 (common polymorphism; may be associated with FT an increased risk of breast cancer; 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 (common polymorphism; 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 (polymorphism; was originally thought to be FT linked to breast cancer; 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 (may be a rare polymorphism; somatic FT mutation; 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 (polymorphism; no effect on homology-directed FT 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="A -> V (polymorphism; was originally thought to be FT linked to ovarian cancer; no effect on homology-directed FT repair activity)" FT /evidence="ECO:0000269|PubMed:12552570, FT ECO:0000269|PubMed:15057823, ECO:0000269|PubMed:15172753, FT ECO:0000269|PubMed:23108138, 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 (polymorphism; 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 (could be associated with cancer FT susceptibility; major splicing aberration identified with FT this mutant; multifactorial likelihood analysis provides FT evidence for pathogenicity; 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 homology- FT 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 (polymorphism; was originally thought to be FT associated with breast cancer; 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:0000244|PDB:3EU7" FT STRAND 203..206 FT /evidence="ECO:0000244|PDB:6GY2" FT HELIX 1520..1522 FT /evidence="ECO:0000244|PDB:1N0W" FT HELIX 1536..1541 FT /evidence="ECO:0000244|PDB:1N0W" FT TURN 1542..1546 FT /evidence="ECO:0000244|PDB:1N0W" SQ SEQUENCE 3418 AA; 384202 MW; 6A0B3B7B332153EB 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 NSNQAAAVTF 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 //