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 12-SEP-2018, entry version 208. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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., RA Arason A., Gudmundsson J., Ficenec D., Kelsell D., Ford D., Tonin P., RA Bishop D.T., Spurr N.K., Ponder B.A.J., Eeles R., Peto J., Devilee P., RA Cornelisse C., Lynch H., Narod S., Lenoir G., Egilsson V., RA Barkadottir R.B., Easton D.F., Bentley D.R., Futreal P.A., RA 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., RA Dumont M., Frye C., Hattier T., Jammulapati S., Janecki T., Jiang P., RA Kehrer R., Leblanc J.-F., Mitchell J.T., McArthur-Morrison J., RA Nguyen K., Peng Y., Samson C., Schroeder M., Snyder S.C., Steele L., RA Stringfellow M., Stroup C., Swedlund B., Swensen J., Teng D., RA Thomas A., Tran T., Tran T., Tranchant M., Weaver-Feldhaus J., RA Wong A.K.C., Shizuya H., Eyfjord J.E., Cannon-Albright L., Labrie F., RA Skolnick M.H., Weber B., Kamb A., Goldar D.E.; RT "The complete BRCA2 gene and mutations in chromosome 13q-linked RT kindreds."; RL Nat. Genet. 12:333-337(1996). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-289; GLN-322; RP HIS-372; VAL-784; SER-929; PHE-976; ILE-987; ASP-991; ASN-1561; RP LYS-1880; MET-1915; PHE-2138; ARG-2162; ARG-2440; VAL-2466; THR-2490; RP PRO-2835; ALA-2856; 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., RA Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., RA Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T., RA Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., RA Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., RA 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., RA Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., RA Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., RA Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., RA Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., RA Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., RA Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., RA Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., RA King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., RA Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., RA 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., RA Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., RA Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., RA Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., RA Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., RA Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., RA Hubbard T., Sulston J.E., Beck S., Bentley D.R., 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 RT cancer 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 RT gene BRCA2 and DSS1, a protein functionally conserved from yeast to RT 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., RA Ashworth A., Jones N.J., Mathew C.G.; RT "Direct interaction of FANCD2 with BRCA2 in DNA damage response RT 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 RT in 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 RT cellular 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 RT in 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 RT homologous 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 RT human 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; RP CYS-31 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 RT partner, 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 RP 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, RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., RA Lerenthal Y., Shiloh Y., 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., RA Hoatlin M.E., Mathew C.G., Takata M., Thompson L.H., Kupfer G.M., RA Jones N.J.; RT "FANCG promotes formation of a newly identified protein complex RT containing 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., RA Hasty P.E., Stambrook P.J.; RT "The checkpoint kinases Chk1 and Chk2 regulate the functional RT associations 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 RP COMPLEX 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 RT homologous 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., RA Petronczki M., Griffith J.D., West S.C.; RT "The breast cancer tumor suppressor BRCA2 promotes the specific RT targeting 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 RP RAD51 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 RT a 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 RT are 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, RP MUTAGENESIS OF TRP-2725, NUCLEAR EXPORT SIGNAL, AND SUBCELLULAR RP 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 RT signals 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, RT which 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., RA Sung P., 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., RA Herrera-Moyano E., Aguilera A.; RT "BRCA2 prevents R-loop accumulation and associates with TREX-2 mRNA RT export 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., RA Burke K.A., Berman S.H., Blecua P., Riaz N., Huo Y., Ding Y.C., RA Neuhausen S.L., 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 RP 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., RA Couch F.J., Weber B.L., LiVolsi V.A., Furusato M., Rebane B.A., RA Cardonick A., Benjamin I., Morgan M.A., King S.A., Mikuta J.J., RA 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., RA Shattuck-Eidens D., Godwin A.K., Daly M., Radford D.M., Sedlacek S., RA Rommens J., Simard J., Garber J., Merajver S., Weber B.L.; RT "BRCA2 germline mutations in male breast cancer cases and breast RT cancer 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., RA Gumbs C., Seal S., Barfoot R., Collins N., Bignell G., Patel S., RA Hamoudi R., Larsson C., Wiseman R.W., Berchuck A., Iglehart J.D., RA Marks J.R., 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 RT 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 RT 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 RT breast 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 RP 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., RA Morishita Y., Iino Y., Karino T., Ayabe H., Hara S., Kajiwara T., RA Houga S., Shimizu T., Toda M., Yamazaki Y., Uchida T., Kunitomo K., RA Sonoo H., Kurebayashi J., 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 RT ovarian cancer: no evidence for other ovarian cancer-susceptibility RT 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., RA Huang H.-W., Chen L.-M., Kao H.-W., Chen J.H., Tseng J.-N., Chen A., RA Hou M.-F., Huang T.-J., Chang H.-T., Mok K.-T., Tsai J.-H.; RT "Molecular characterization of germline mutations in the BRCA1 and RT BRCA2 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., RA Underhill P., Mountain J., Stierer M., Zielinski C., Oefner P.; RT "Global sequence diversity of BRCA2: analysis of 71 breast cancer RT families 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., RA Pharoah P.D.P., Luben R.N., Easton D.F., Ponder B.A.J.; RT "A common variant in BRCA2 is associated with both breast cancer risk RT and 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; RP HIS-372; 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; RX DOI=10.1002/1098-1004(2001)17:1<73::AID-HUMU12>3.3.CO;2-F; RA Kwiatkowska E., Teresiak M., Lamperska K.M., Karczewska A., RA Breborowicz D., Stawicka M., Godlewski D., Krzyzosiak W.J., RA 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 RP 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 RT for screening BRCA2 mutations-fluorescent mutation detection (F-MD)."; RL Hum. Mutat. 17:220-232(2001). RN [49] 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 [50] RP ERRATUM. RA Fackenthal J.D., Cartegni L., Krainer A.R., Olopade O.I.; RL Am. J. Hum. Genet. 73:1477-1477(2002). RN [51] 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 RT stomach cancers."; RL Br. J. Cancer 87:888-891(2002). RN [52] 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 RT familial pancreatic cancer: deleterious BRCA2 mutations in 17%."; RL Cancer Res. 62:3789-3793(2002). RN [53] 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., RA Roth M.J., Dawsey S.M., Huang J., Wang Q.-H., Ding T., Giffen C., RA Taylor P.R., 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 [54] 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 [55] 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., RA Lenoir G., Goldgar D.E., Bhatanager D.; RT "BRCA1 and BRCA2 in Indian breast cancer patients."; RL Hum. Mutat. 20:473-474(2002). RN [56] 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 RT families."; RL Hum. Mutat. 20:474-474(2002). RN [57] RP VARIANTS BC CYS-42; ARG-613; LEU-2118; LEU-2293 AND ARG-2793, AND RP VARIANT ILE-3374. RX PubMed=12442275; DOI=10.1002/humu.9084; RA Ruiz-Flores P., Sinilnikova O.M., Badzioch M., RA Calderon-Garciduenas A.L., Chopin S., Fabrice O., RA Gonzalez-Guerrero J.F., Szabo C., Lenoir G., Goldgar D.E., RA 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 [58] 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 RT loss of BRCA2 in sporadic male breast cancer."; RL Int. J. Cancer 98:943-945(2002). RN [59] 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., RA Ikeda H., Fox E.A., D'Andrea A.D.; RT "Biallelic inactivation of BRCA2 in Fanconi anemia."; RL Science 297:606-609(2002). RN [60] RP VARIANTS HIS-289; HIS-372; GLY-462; ASP-991; SER-1279; TYR-1420; RP ASP-1771 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 RT breast/ovarian cancer."; RL Hum. Mutat. 21:171-171(2003). RN [61] 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 RT and/or ovarian cancer families in Southern Germany."; RL Hum. Mutat. 22:259-259(2003). RN [62] 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., RA Kudo T., Abe R., Ohuchi N., Takenoshita S., Kanamaru R., Ishioka C.; RT "Evaluation of the diagnostic accuracy of the stop codon (SC) assay RT for identifying protein-truncating mutations in the BRCA1and RT BRCA2genes in familial breast cancer."; RL J. Hum. Genet. 48:130-137(2003). RN [63] RP VARIANTS CYS-2034 AND 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., RA Gruetzmann R., Rehder H., Rothmund M., Schmiegel W., Neoptolemos J.P., RA Bartsch D.K.; RT "BRCA2 germline mutations in familial pancreatic carcinoma."; RL J. Natl. Cancer Inst. 95:214-221(2003). RN [64] 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 [65] 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 RP ASP-991; 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 [66] RP VARIANTS BC ILE-64; GLY-462; ASN-1690; ASP-1771; MET-1887; MET-1915 RP AND GLU-2456, AND VARIANTS HIS-289; HIS-372; ASP-991; SER-1279; RP TYR-1420; 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 [67] 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 [68] 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 RT breast and breast-ovarian cancer families."; RL Hum. Mutat. 23:205-205(2004). RN [69] 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 RT defects in MLH1 and BRCA1."; RL Hum. Mutat. 24:272-272(2004). RN [70] RP VARIANTS BC THR-1445; VAL-1929 AND ALA-2031, AND VARIANTS HIS-289; RP HIS-372; 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., RA Lee H.S., Choe J.J., Choi C.W., Kim B.S., Shin S.W., Kim Y.H., RA Kim J.S., Son G.-S., Lee J.-B., Koo B.H.; RT "BRCA1 and BRCA2 germline mutations in Korean patients with sporadic RT breast cancer."; RL Hum. Mutat. 24:350-350(2004). RN [71] 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 RT unselected breast cancer cases."; RL J. Med. Genet. 42:E5-E5(2005). RN [72] 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., RA Couch F.J., 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- RT predisposition genes."; RL Am. J. Hum. Genet. 81:873-883(2007). RN [73] 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 RT in FANCD1/BRCA2."; RL J. Med. Genet. 44:1-9(2007). RN [74] 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., RA Lakhani S.R., Da Silva L.M., Tavtigian S.V., Goldgar D.E., Brown M.A., RA Spurdle A.B.; RT "Detection of splicing aberrations caused by BRCA1 and BRCA2 sequence RT variants encoding missense substitutions: implications for prediction RT of pathogenicity."; RL Hum. Mutat. 31:E1484-E1505(2010). RN [75] 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., RA North S.L., Burkett S., Brody L.C., Meyer S., Byrd R.A., Sharan S.K.; RT "A comprehensive functional characterization of BRCA2 variants RT associated with Fanconi anemia using mouse ES cell-based assay."; RL Blood 118:2430-2442(2011). RN [76] 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 CC repair by promoting assembly of RAD51 onto single-stranded DNA CC (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded CC DNA, enabling RAD51 to displace replication protein-A (RPA) from CC ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP CC hydrolysis. Part of a PALB2-scaffolded HR complex containing CC RAD51C and which is thought to play a role in DNA repair by HR. CC May participate in S phase checkpoint activation. Binds CC selectively to ssDNA, and to ssDNA in tailed duplexes and CC replication fork structures. May play a role in the extension step CC after strand invasion at replication-dependent DNA double-strand CC breaks; together with PALB2 is involved in both POLH localization CC at collapsed replication forks and DNA polymerization activity. In CC concert with NPM1, regulates centrosome duplication. Interacts CC with the TREX-2 complex (transcription and export complex 2) CC subunits PCID2 and SEM1, and is required to prevent R-loop- CC associated DNA damage and thus transcription-associated genomic CC instability. Silencing of BRCA2 promotes R-loop accumulation at CC actively transcribed genes in replicating and non-replicating CC cells, suggesting that BRCA2 mediates the control of R-loop CC associated genomic instability, independently of its known role in CC 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 CC RAD51; regulates RAD51 recruitment and function at sites of DNA CC repair (PubMed:12442171, PubMed:15800615, PubMed:18317453, CC PubMed:20729832, PubMed:20729859). Interacts with WDR16, USP11, CC DMC1, ROCK2 and NPM1 (PubMed:15314155, PubMed:15967112, CC PubMed:20729832, PubMed:21084279). Interacts with SEM1; the CC interaction masks a nuclear export signal in BRCA2 CC (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 CC and PALB2 (PubMed:19369211). Interacts directly with PALB2 which CC may serve as a scaffold for a HR complex containing PALB2, BRCA2, CC RAD51C, RAD51 and XRCC3 (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 CC subunits PCID2 and SEM1 (PubMed:24896180, PubMed:21719596). 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:28319063}. CC -!- INTERACTION: CC Self; NbExp=3; IntAct=EBI-79792, EBI-79792; CC Q14565:DMC1; NbExp=12; IntAct=EBI-79792, EBI-930865; CC Q9BXW9:FANCD2; NbExp=16; IntAct=EBI-79792, EBI-359343; CC Q9BXW9-2:FANCD2; NbExp=3; IntAct=EBI-79792, EBI-596878; CC Q9P0W2:HMG20B; NbExp=8; IntAct=EBI-79792, EBI-713401; CC Q86YC2:PALB2; NbExp=22; IntAct=EBI-79792, EBI-1222653; CC Q9NTI5:PDS5B; NbExp=26; IntAct=EBI-79792, EBI-1175604; CC Q9Y253:POLH; NbExp=6; IntAct=EBI-79792, EBI-2827270; CC Q06609:RAD51; NbExp=45; IntAct=EBI-79792, EBI-297202; CC Q06609-1:RAD51; NbExp=12; IntAct=EBI-79792, EBI-15557721; CC P60896:SEM1; NbExp=10; IntAct=EBI-79792, EBI-79819; CC 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 CC thymus, 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 CC RAD51. Phosphorylation at Ser-3291 by CDK1 and CDK2 is low in S CC phase when recombination is active, but increases as cells CC progress towards mitosis; this phosphorylation prevents homologous CC recombination-dependent repair during S phase and G2 by inhibiting CC RAD51 binding. {ECO:0000269|PubMed:15199141, CC ECO:0000269|PubMed:15800615, ECO:0000269|PubMed:18317453}. CC -!- PTM: Ubiquitinated in the absence of DNA damage; this does not CC lead to proteasomal degradation. In contrast, ubiquitination in CC response to DNA damage leads to proteasomal degradation. CC {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 CC carcinoma is by far the most common type. Breast cancer is CC etiologically and genetically heterogeneous. Important genetic CC factors have been indicated by familial occurrence and bilateral CC involvement. Mutations at more than one locus can be involved in CC different families or even in the same case. CC {ECO:0000269|PubMed:10399947, ECO:0000269|PubMed:10978364, CC ECO:0000269|PubMed:11139248, 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:12938098, CC ECO:0000269|PubMed:14722926, ECO:0000269|PubMed:15026808, CC ECO:0000269|PubMed:15172753, ECO:0000269|PubMed:15365993, CC ECO:0000269|PubMed:16793542, 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 CC associated with variations affecting the gene represented in this CC entry. CC -!- DISEASE: Pancreatic cancer 2 (PNCA2) [MIM:613347]: A malignant CC neoplasm of the pancreas. Tumors can arise from both the exocrine CC and endocrine portions of the pancreas, but 95% of them develop CC from the exocrine portion, including the ductal epithelium, acinar CC cells, connective tissue, and lymphatic tissue. CC {ECO:0000269|PubMed:9140390}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- DISEASE: Breast-ovarian cancer, familial, 2 (BROVCA2) CC [MIM:612555]: A condition associated with familial predisposition CC to cancer of the breast and ovaries. Characteristic features in CC affected families are an early age of onset of breast cancer CC (often before age 50), increased chance of bilateral cancers CC (cancer that develop in both breasts, or both ovaries, CC independently), frequent occurrence of breast cancer among men, CC increased incidence of tumors of other specific organs, such as CC 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) CC [MIM:605724]: A disorder affecting all bone marrow elements and CC resulting in anemia, leukopenia and thrombopenia. It is associated CC with cardiac, renal and limb malformations, dermal pigmentary CC changes, and a predisposition to the development of malignancies. CC At the cellular level it is associated with hypersensitivity to CC DNA-damaging agents, chromosomal instability (increased chromosome CC breakage) and defective DNA repair. {ECO:0000269|PubMed:12065746, CC ECO:0000269|PubMed:14670928, ECO:0000269|PubMed:16825431, CC ECO:0000269|PubMed:21719596}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- DISEASE: Glioma 3 (GLM3) [MIM:613029]: Gliomas are benign or CC malignant central nervous system neoplasms derived from glial CC cells. They comprise astrocytomas and glioblastoma multiforme that CC are derived from astrocytes, oligodendrogliomas derived from CC oligodendrocytes and ependymomas derived from ependymocytes. CC {ECO:0000269|PubMed:15689453}. Note=The disease is caused by CC mutations affecting the gene represented 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 CC and 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 UniGene; Hs.34012; -. DR PDB; 1N0W; X-ray; 1.70 A; B=1517-1551. DR PDB; 3EU7; X-ray; 2.20 A; X=21-39. DR PDBsum; 1N0W; -. DR PDBsum; 3EU7; -. DR ProteinModelPortal; P51587; -. DR SMR; P51587; -. DR BioGrid; 107142; 110. DR ComplexPortal; CPX-955; BRCC ubiquitin ligase complex. DR CORUM; P51587; -. DR DIP; DIP-24214N; -. DR ELM; P51587; -. DR IntAct; P51587; 36. DR MINT; P51587; -. DR STRING; 9606.ENSP00000369497; -. DR iPTMnet; P51587; -. DR PhosphoSitePlus; P51587; -. DR BioMuta; BRCA2; -. DR DMDM; 14424438; -. DR EPD; P51587; -. DR PaxDb; P51587; -. DR PeptideAtlas; P51587; -. DR PRIDE; P51587; -. DR ProteomicsDB; 56340; -. 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 EuPathDB; HostDB:ENSG00000139618.14; -. DR GeneCards; BRCA2; -. DR GeneReviews; BRCA2; -. DR HGNC; HGNC:1101; BRCA2. DR HPA; HPA026815; -. 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 PharmGKB; PA25412; -. DR eggNOG; KOG4751; Eukaryota. DR eggNOG; ENOG410Y06W; LUCA. DR HOGENOM; HOG000139693; -. DR HOVERGEN; HBG050731; -. DR InParanoid; P51587; -. DR KO; K08775; -. DR OrthoDB; EOG091G0C79; -. 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 PRO; PR:P51587; -. DR Proteomes; UP000005640; Chromosome 13. DR Bgee; ENSG00000139618; Expressed in 127 organ(s), highest expression level in secondary oocyte. DR CleanEx; HS_BRCA2; -. 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:0000281; P:mitotic cytokinesis; IDA:UniProtKB. 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: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 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; 2. 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; 4. DR SUPFAM; SSF81872; SSF81872; 1. DR PROSITE; PS50138; BRCA2_REPEAT; 8. PE 1: Evidence at protein level; KW 3D-structure; Cell cycle; Complete proteome; Cytoplasm; Cytoskeleton; KW Disease mutation; DNA damage; DNA recombination; DNA repair; KW DNA-binding; Fanconi anemia; Nucleus; Phosphoprotein; Polymorphism; KW Reference proteome; Repeat; Tumor suppressor; Ubl conjugation. FT CHAIN 1 3418 Breast cancer type 2 susceptibility FT protein. FT /FTId=PRO_0000064984. FT REPEAT 1002 1036 BRCA2 1. FT REPEAT 1212 1246 BRCA2 2. FT REPEAT 1421 1455 BRCA2 3. FT REPEAT 1517 1551 BRCA2 4. FT REPEAT 1664 1698 BRCA2 5. FT REPEAT 1837 1871 BRCA2 6. FT REPEAT 1971 2005 BRCA2 7. FT REPEAT 2051 2085 BRCA2 8. FT REGION 1 40 Interaction with PALB2. FT REGION 639 1000 Interaction with NPM1. FT {ECO:0000269|PubMed:21084279}. FT REGION 1338 1781 Interaction with POLH. FT {ECO:0000269|PubMed:24485656}. FT REGION 1410 1595 Required for stimulation of POLH DNA FT polymerization activity. FT REGION 2350 2545 Interaction with FANCD2. FT REGION 2481 2832 Interaction with SEM1. FT {ECO:0000269|PubMed:10373512, FT ECO:0000269|PubMed:16205630}. FT MOTIF 2682 2698 Nuclear export signal; masked by FT interaction with SEM1. FT {ECO:0000269|PubMed:24013206}. FT MOD_RES 70 70 Phosphoserine. FT {ECO:0000244|PubMed:23186163}. FT MOD_RES 445 445 Phosphoserine. FT {ECO:0000244|PubMed:23186163}. FT MOD_RES 492 492 Phosphoserine. FT {ECO:0000244|PubMed:23186163}. FT MOD_RES 755 755 Phosphoserine. FT {ECO:0000244|PubMed:17525332}. FT MOD_RES 1970 1970 Phosphoserine. FT {ECO:0000244|PubMed:23186163}. FT MOD_RES 2035 2035 Phosphothreonine. FT {ECO:0000244|PubMed:23186163}. FT MOD_RES 2095 2095 Phosphoserine. FT {ECO:0000244|PubMed:23186163}. FT MOD_RES 3291 3291 Phosphoserine; by CDK1 and CDK2. FT {ECO:0000269|PubMed:15800615}. FT MOD_RES 3319 3319 Phosphoserine. FT {ECO:0000244|PubMed:23186163}. FT MOD_RES 3387 3387 Phosphothreonine; by CHEK1 and CHEK2. FT {ECO:0000269|PubMed:18317453}. FT VARIANT 25 25 G -> R (in BC; abolishes interaction with FT PALB2). {ECO:0000269|PubMed:16793542}. FT /FTId=VAR_028167. FT VARIANT 31 31 W -> C (in BC; abolishes interaction with FT PALB2). {ECO:0000269|PubMed:16793542}. FT /FTId=VAR_028168. FT VARIANT 31 31 W -> R (in BC; abolishes interaction with FT PALB2). {ECO:0000269|PubMed:16793542}. FT /FTId=VAR_028169. FT VARIANT 32 32 F -> L (in BC). FT {ECO:0000269|PubMed:9609997}. FT /FTId=VAR_005085. FT VARIANT 42 42 Y -> C (in BC and ovarian cancer; unknown FT pathological significance; FT dbSNP:rs4987046). FT {ECO:0000269|PubMed:12442275, FT ECO:0000269|PubMed:14746861}. FT /FTId=VAR_020705. FT VARIANT 53 53 K -> R (in BC). FT {ECO:0000269|PubMed:9609997}. FT /FTId=VAR_005086. FT VARIANT 60 60 N -> S (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:15026808}. FT /FTId=VAR_020706. FT VARIANT 64 64 T -> I (in BC). FT {ECO:0000269|PubMed:15172753}. FT /FTId=VAR_032712. FT VARIANT 75 75 A -> P (in ovarian cancer and renal FT cancer; unknown pathological FT significance; dbSNP:rs28897701). FT {ECO:0000269|PubMed:10486320}. FT /FTId=VAR_005087. FT VARIANT 81 81 F -> L (in BC). FT {ECO:0000269|PubMed:9609997}. FT /FTId=VAR_005088. FT VARIANT 108 108 N -> H. FT /FTId=VAR_008766. FT VARIANT 118 118 R -> H (in one patient with esophageal FT carcinoma). FT {ECO:0000269|PubMed:11948123}. FT /FTId=VAR_032713. FT VARIANT 192 192 M -> T (in one patient with pancreatic FT cancer). {ECO:0000269|PubMed:12097290}. FT /FTId=VAR_032714. FT VARIANT 201 201 P -> R (in BC). FT {ECO:0000269|PubMed:9609997}. FT /FTId=VAR_005089. FT VARIANT 211 211 V -> A (in BC). FT {ECO:0000269|PubMed:9609997}. FT /FTId=VAR_005090. FT VARIANT 222 222 P -> S (in BC). FT {ECO:0000269|PubMed:9609997}. FT /FTId=VAR_005091. FT VARIANT 225 225 T -> A (in one patient with BC; normal FT RNA expression and splicing). FT {ECO:0000269|PubMed:15300854}. FT /FTId=VAR_032715. FT VARIANT 289 289 N -> H (common polymorphism; was FT originally thought to be linked to FT ovarian cancer; dbSNP:rs766173). FT {ECO:0000269|PubMed:10323242, FT ECO:0000269|PubMed:10978364, FT ECO:0000269|PubMed:12552570, FT ECO:0000269|PubMed:15172753, FT ECO:0000269|PubMed:15365993, FT ECO:0000269|Ref.3}. FT /FTId=VAR_005092. FT VARIANT 315 315 C -> S (in one patient with esophageal FT carcinoma; dbSNP:rs79483201). FT {ECO:0000269|PubMed:11948123}. FT /FTId=VAR_032716. FT VARIANT 322 322 K -> Q (in dbSNP:rs11571640). FT {ECO:0000269|Ref.3}. FT /FTId=VAR_018908. FT VARIANT 326 326 S -> R (in BC; dbSNP:rs28897706). FT {ECO:0000269|PubMed:10399947}. FT /FTId=VAR_032717. FT VARIANT 327 327 K -> E (in BC; unknown pathological FT significance). FT /FTId=VAR_008767. FT VARIANT 355 355 V -> L (in lung cancer). FT /FTId=VAR_005093. FT VARIANT 372 372 N -> H (common polymorphism; may be FT associated with an increased risk of FT breast cancer; dbSNP:rs144848). FT {ECO:0000269|PubMed:10323242, FT ECO:0000269|PubMed:10978364, FT ECO:0000269|PubMed:11062481, FT ECO:0000269|PubMed:12552570, FT ECO:0000269|PubMed:15057823, FT ECO:0000269|PubMed:15172753, FT ECO:0000269|PubMed:15365993, FT ECO:0000269|PubMed:8665505, FT ECO:0000269|PubMed:8673091, FT ECO:0000269|Ref.3}. FT /FTId=VAR_005094. FT VARIANT 405 405 G -> R (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:15026808}. FT /FTId=VAR_020707. FT VARIANT 431 431 T -> I (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:12938098}. FT /FTId=VAR_020708. FT VARIANT 448 448 R -> H (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:15026808}. FT /FTId=VAR_020709. FT VARIANT 462 462 E -> G (in BC; unknown pathological FT significance; dbSNP:rs56403624). FT {ECO:0000269|PubMed:12552570, FT ECO:0000269|PubMed:15026808, FT ECO:0000269|PubMed:15172753}. FT /FTId=VAR_020710. FT VARIANT 505 505 I -> T (in BC; dbSNP:rs28897708). FT {ECO:0000269|PubMed:11241844}. FT /FTId=VAR_032718. FT VARIANT 513 513 K -> R (in dbSNP:rs28897709). FT /FTId=VAR_056751. FT VARIANT 554 554 C -> W (in BC and pancreas cancer). FT {ECO:0000269|PubMed:9654203}. FT /FTId=VAR_005095. FT VARIANT 582 582 T -> P (in dbSNP:rs80358457). FT {ECO:0000269|PubMed:12624724}. FT /FTId=VAR_008768. FT VARIANT 598 598 T -> A (in dbSNP:rs28897710). FT {ECO:0000269|PubMed:12215251}. FT /FTId=VAR_020711. FT VARIANT 599 599 S -> F (in dbSNP:rs1046984). FT {ECO:0000269|PubMed:8589730}. FT /FTId=VAR_035436. FT VARIANT 606 606 P -> L. {ECO:0000269|PubMed:26566883}. FT /FTId=VAR_076440. FT VARIANT 613 613 L -> R (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:12442275}. FT /FTId=VAR_020712. FT VARIANT 630 630 T -> I (in ovarian cancer). FT /FTId=VAR_005096. FT VARIANT 707 707 D -> Y (in dbSNP:rs80358487). FT /FTId=VAR_008769. FT VARIANT 728 728 D -> A (in BC). FT /FTId=VAR_005097. FT VARIANT 729 729 I -> M (in BC). FT {ECO:0000269|PubMed:10978364}. FT /FTId=VAR_032719. FT VARIANT 784 784 M -> V (in dbSNP:rs11571653). FT {ECO:0000269|PubMed:15365993, FT ECO:0000269|Ref.3}. FT /FTId=VAR_008770. FT VARIANT 886 886 N -> I. FT /FTId=VAR_008771. FT VARIANT 929 929 L -> S (in dbSNP:rs2227943). FT {ECO:0000269|Ref.3}. FT /FTId=VAR_018909. FT VARIANT 935 935 D -> N (in BC; unknown pathological FT significance; dbSNP:rs28897716). FT /FTId=VAR_008772. FT VARIANT 976 976 S -> F (in dbSNP:rs11571656). FT {ECO:0000269|Ref.3}. FT /FTId=VAR_018910. FT VARIANT 982 982 I -> L (in dbSNP:rs28897717). FT /FTId=VAR_056752. FT VARIANT 987 987 N -> I (in dbSNP:rs2227944). FT {ECO:0000269|Ref.3}. FT /FTId=VAR_018911. FT VARIANT 991 991 N -> D (common polymorphism; FT dbSNP:rs1799944). FT {ECO:0000269|PubMed:10323242, FT ECO:0000269|PubMed:10978364, FT ECO:0000269|PubMed:12552570, FT ECO:0000269|PubMed:15026808, FT ECO:0000269|PubMed:15172753, FT ECO:0000269|PubMed:15365993, FT ECO:0000269|PubMed:8673091, FT ECO:0000269|Ref.3}. FT /FTId=VAR_005098. FT VARIANT 1036 1036 E -> K (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:12938098}. FT /FTId=VAR_020713. FT VARIANT 1106 1106 S -> R (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:12938098}. FT /FTId=VAR_020714. FT VARIANT 1147 1147 N -> S (in dbSNP:rs1799951). FT {ECO:0000269|PubMed:8673091}. FT /FTId=VAR_005099. FT VARIANT 1172 1172 S -> L (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:15635067}. FT /FTId=VAR_032720. FT VARIANT 1179 1179 S -> N (in BC). FT {ECO:0000269|PubMed:11139248}. FT /FTId=VAR_020715. FT VARIANT 1279 1279 N -> S. {ECO:0000269|PubMed:12552570, FT ECO:0000269|PubMed:15172753}. FT /FTId=VAR_020716. FT VARIANT 1286 1286 Missing. FT /FTId=VAR_008773. FT VARIANT 1290 1290 C -> Y (in dbSNP:rs41293485). FT /FTId=VAR_008774. FT VARIANT 1302 1302 Missing (in BC). FT /FTId=VAR_005100. FT VARIANT 1414 1414 T -> M (in dbSNP:rs70953664). FT /FTId=VAR_008775. FT VARIANT 1420 1420 D -> Y (in dbSNP:rs28897727). FT {ECO:0000269|PubMed:11139248, FT ECO:0000269|PubMed:12215251, FT ECO:0000269|PubMed:12552570, FT ECO:0000269|PubMed:15172753, FT ECO:0000269|PubMed:15635067, FT ECO:0000269|PubMed:26566883}. FT /FTId=VAR_008776. FT VARIANT 1445 1445 K -> T (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:15365993}. FT /FTId=VAR_020717. FT VARIANT 1513 1513 D -> N. FT /FTId=VAR_008777. FT VARIANT 1522 1522 L -> F (in one patient with BC). FT {ECO:0000269|PubMed:12624724}. FT /FTId=VAR_032721. FT VARIANT 1524 1524 F -> V (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:12938098}. FT /FTId=VAR_020718. FT VARIANT 1529 1529 G -> R (in bladder cancer; FT dbSNP:rs28897728). FT /FTId=VAR_005101. FT VARIANT 1542 1542 V -> M (in dbSNP:rs28897729). FT /FTId=VAR_056753. FT VARIANT 1561 1561 H -> N (in dbSNP:rs2219594). FT {ECO:0000269|Ref.3}. FT /FTId=VAR_018912. FT VARIANT 1580 1580 C -> Y (in BC; somatic mutation). FT {ECO:0000269|PubMed:11948477}. FT /FTId=VAR_020719. FT VARIANT 1593 1593 E -> D. {ECO:0000269|PubMed:12442273}. FT /FTId=VAR_008778. FT VARIANT 1643 1643 V -> A (in dbSNP:rs28897731). FT /FTId=VAR_056754. FT VARIANT 1679 1679 T -> I (in BC). FT {ECO:0000269|PubMed:14722926}. FT /FTId=VAR_020720. FT VARIANT 1690 1690 K -> N (in BC). FT {ECO:0000269|PubMed:15172753}. FT /FTId=VAR_032722. FT VARIANT 1730 1730 N -> Y (in BC). FT {ECO:0000269|PubMed:11241844}. FT /FTId=VAR_032723. FT VARIANT 1771 1771 G -> D (in BC; unknown pathological FT significance; dbSNP:rs80358755). FT {ECO:0000269|PubMed:12552570, FT ECO:0000269|PubMed:15172753}. FT /FTId=VAR_008779. FT VARIANT 1804 1804 V -> A (in BC). FT {ECO:0000269|PubMed:14722926}. FT /FTId=VAR_020721. FT VARIANT 1805 1805 N -> S (in dbSNP:rs80358765). FT /FTId=VAR_008780. FT VARIANT 1880 1880 N -> K (polymorphism; was originally FT thought to be linked to breast cancer; FT dbSNP:rs11571657). FT {ECO:0000269|PubMed:11241844, FT ECO:0000269|Ref.3}. FT /FTId=VAR_005102. FT VARIANT 1887 1887 T -> M (in BC). FT {ECO:0000269|PubMed:15172753}. FT /FTId=VAR_032724. FT VARIANT 1901 1901 E -> K (in BC). FT {ECO:0000269|PubMed:14722926}. FT /FTId=VAR_020722. FT VARIANT 1902 1902 D -> N (in dbSNP:rs4987048). FT /FTId=VAR_008781. FT VARIANT 1915 1915 T -> M (may be a rare polymorphism; FT somatic mutation; dbSNP:rs4987117). FT {ECO:0000269|PubMed:10978364, FT ECO:0000269|PubMed:11948477, FT ECO:0000269|PubMed:15172753, FT ECO:0000269|PubMed:8665505, FT ECO:0000269|PubMed:8673091, FT ECO:0000269|Ref.3}. FT /FTId=VAR_005103. FT VARIANT 1929 1929 I -> V (in BC; unknown pathological FT significance; dbSNP:rs79538375). FT {ECO:0000269|PubMed:15365993}. FT /FTId=VAR_020723. FT VARIANT 1979 1979 S -> R (in dbSNP:rs28897737). FT /FTId=VAR_056755. FT VARIANT 1988 1988 V -> I (in one patient with esophageal FT carcinoma; somatic mutation). FT {ECO:0000269|PubMed:11948123}. FT /FTId=VAR_032725. FT VARIANT 2031 2031 T -> A (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:15365993}. FT /FTId=VAR_020724. FT VARIANT 2034 2034 R -> C (in dbSNP:rs1799954). FT {ECO:0000269|PubMed:12215251, FT ECO:0000269|PubMed:12569143, FT ECO:0000269|PubMed:8673091}. FT /FTId=VAR_005104. FT VARIANT 2044 2044 G -> V (in one patient with BC; FT dbSNP:rs56191579). FT {ECO:0000269|PubMed:12624724}. FT /FTId=VAR_032726. FT VARIANT 2072 2072 S -> C (in BC). FT {ECO:0000269|PubMed:12373604}. FT /FTId=VAR_020725. FT VARIANT 2074 2074 H -> N (in dbSNP:rs34309943). FT /FTId=VAR_008782. FT VARIANT 2089 2089 E -> D (in BC). FT {ECO:0000269|PubMed:9150152}. FT /FTId=VAR_008783. FT VARIANT 2094 2094 Y -> C (in BC). FT {ECO:0000269|PubMed:12373604}. FT /FTId=VAR_020726. FT VARIANT 2096 2096 P -> L (in BC). FT {ECO:0000269|PubMed:14722926}. FT /FTId=VAR_020727. FT VARIANT 2108 2108 R -> C (in dbSNP:rs55794205). FT {ECO:0000269|PubMed:15172753}. FT /FTId=VAR_032727. FT VARIANT 2116 2116 H -> R (in dbSNP:rs55953736). FT /FTId=VAR_061563. FT VARIANT 2118 2118 V -> L (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:12442275}. FT /FTId=VAR_020728. FT VARIANT 2128 2128 K -> N (in BC). FT {ECO:0000269|PubMed:12373604}. FT /FTId=VAR_020729. FT VARIANT 2135 2135 N -> H (in BC). FT {ECO:0000269|PubMed:11241844}. FT /FTId=VAR_032728. FT VARIANT 2138 2138 V -> F (in dbSNP:rs11571659). FT {ECO:0000269|Ref.3}. FT /FTId=VAR_008784. FT VARIANT 2162 2162 K -> R (in dbSNP:rs11571660). FT {ECO:0000269|Ref.3}. FT /FTId=VAR_018913. FT VARIANT 2222 2222 Y -> C (in BC). FT {ECO:0000269|PubMed:11241844}. FT /FTId=VAR_032729. FT VARIANT 2238 2238 D -> E (in dbSNP:rs28897742). FT /FTId=VAR_056756. FT VARIANT 2274 2274 G -> V (in BC). FT /FTId=VAR_005105. FT VARIANT 2275 2275 E -> G (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:15026808}. FT /FTId=VAR_020730. FT VARIANT 2293 2293 F -> L (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:12442275}. FT /FTId=VAR_020731. FT VARIANT 2336 2336 R -> H (in FANCD1; affects protein FT splicing and expression; decreases FT homologous recombination-mediated DNA FT repair; dbSNP:rs28897743). FT {ECO:0000269|PubMed:16825431, FT ECO:0000269|PubMed:17924331, FT ECO:0000269|PubMed:21719596}. FT /FTId=VAR_032730. FT VARIANT 2336 2336 R -> Q (in dbSNP:rs28897743). FT /FTId=VAR_056757. FT VARIANT 2353 2353 G -> R (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:15026808}. FT /FTId=VAR_020732. FT VARIANT 2415 2415 H -> N (in BC). FT {ECO:0000269|PubMed:8640237}. FT /FTId=VAR_005106. FT VARIANT 2421 2421 Q -> H (in BC). FT /FTId=VAR_005107. FT VARIANT 2440 2440 H -> R (in dbSNP:rs4986860). FT {ECO:0000269|Ref.3}. FT /FTId=VAR_018914. FT VARIANT 2447 2447 N -> D (in dbSNP:rs4986859). FT /FTId=VAR_056758. FT VARIANT 2456 2456 Q -> E (in BC). FT {ECO:0000269|PubMed:15172753}. FT /FTId=VAR_032731. FT VARIANT 2466 2466 A -> V (polymorphism; was originally FT thought to be linked to ovarian cancer). FT {ECO:0000269|PubMed:12552570, FT ECO:0000269|PubMed:15057823, FT ECO:0000269|PubMed:15172753, FT ECO:0000269|PubMed:8665505, FT ECO:0000269|Ref.3}. FT /FTId=VAR_008785. FT VARIANT 2480 2480 L -> V (in dbSNP:rs80358965). FT /FTId=VAR_008786. FT VARIANT 2488 2488 R -> K (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:15026808}. FT /FTId=VAR_020733. FT VARIANT 2490 2490 I -> T (polymorphism; no effect on FT homologous recombination-mediated DNA FT repair; no effect on interaction with FT SEM1; dbSNP:rs11571707). FT {ECO:0000269|PubMed:21719596, FT ECO:0000269|Ref.3}. FT /FTId=VAR_008787. FT VARIANT 2502 2502 R -> C (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:17924331}. FT /FTId=VAR_063911. FT VARIANT 2502 2502 R -> H (in ovarian cancer; unknown FT pathological significance). FT {ECO:0000269|PubMed:10486320}. FT /FTId=VAR_008788. FT VARIANT 2510 2510 L -> P (in FANCD1; hypersensitive to DNA FT damage; disrupts interaction with SEM1). FT {ECO:0000269|PubMed:14670928, FT ECO:0000269|PubMed:21719596}. FT /FTId=VAR_032732. FT VARIANT 2515 2515 T -> I (in BC; unknown pathological FT significance; dbSNP:rs28897744). FT {ECO:0000269|PubMed:10978364}. FT /FTId=VAR_008789. FT VARIANT 2626 2626 W -> C (in FANCD1; hypersensitive to DNA FT damage; no effect on interaction with FT SEM1). {ECO:0000269|PubMed:16825431, FT ECO:0000269|PubMed:17924331, FT ECO:0000269|PubMed:21719596}. FT /FTId=VAR_032733. FT VARIANT 2627 2627 I -> F (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:17924331}. FT /FTId=VAR_063912. FT VARIANT 2653 2653 L -> P (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:17924331}. FT /FTId=VAR_063913. FT VARIANT 2659 2659 R -> K (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:17924331}. FT /FTId=VAR_063914. FT VARIANT 2663 2663 E -> V (could be associated with cancer FT susceptibility; major splicing aberration FT identified with this mutant; FT multifactorial likelihood analysis FT provides evidence for pathogenicity). FT {ECO:0000269|PubMed:17924331, FT ECO:0000269|PubMed:20513136}. FT /FTId=VAR_063915. FT VARIANT 2686 2686 L -> P (in dbSNP:rs28897746). FT /FTId=VAR_056759. FT VARIANT 2706 2706 N -> S. {ECO:0000269|PubMed:12442273}. FT /FTId=VAR_020734. FT VARIANT 2722 2722 T -> R (in BC). FT {ECO:0000269|PubMed:12145750, FT ECO:0000269|PubMed:17924331}. FT /FTId=VAR_018661. FT VARIANT 2723 2723 D -> G (could be associated with cancer FT susceptibility; has abrogated function FT consistent with pathogenicity; major FT splicing aberration identified with this FT mutant). {ECO:0000269|PubMed:17924331, FT ECO:0000269|PubMed:20513136}. FT /FTId=VAR_063916. FT VARIANT 2723 2723 D -> H (in BC; unknown pathological FT significance; disrupts interaction with FT SEM1 promoting interaction with XPO1 and FT BRCA2 cytoplasmic localization; in FT heterozygous state promotes RAD51 FT cytoplasmic localization). FT {ECO:0000269|PubMed:15026808, FT ECO:0000269|PubMed:24013206}. FT /FTId=VAR_020735. FT VARIANT 2728 2728 V -> I (in BC; dbSNP:rs28897749). FT {ECO:0000269|PubMed:10399947, FT ECO:0000269|PubMed:10978364, FT ECO:0000269|PubMed:12215251}. FT /FTId=VAR_020736. FT VARIANT 2729 2729 K -> N (in BC; unknown pathological FT significance; no effect on homologous FT recombination-mediated DNA repair; no FT effect on interaction with SEM1; FT dbSNP:rs80359065). FT {ECO:0000269|PubMed:12442274, FT ECO:0000269|PubMed:21719596}. FT /FTId=VAR_020737. FT VARIANT 2748 2748 G -> D (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:17924331}. FT /FTId=VAR_063917. FT VARIANT 2787 2787 R -> H (in ovarian cancer; somatic FT mutation). {ECO:0000269|PubMed:8665505}. FT /FTId=VAR_008790. FT VARIANT 2792 2792 L -> P (in dbSNP:rs28897751). FT /FTId=VAR_056760. FT VARIANT 2793 2793 G -> R (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:12442275}. FT /FTId=VAR_020738. FT VARIANT 2835 2835 S -> P (in dbSNP:rs11571746). FT {ECO:0000269|Ref.3}. FT /FTId=VAR_018915. FT VARIANT 2842 2842 R -> C (in one patient with esophageal FT carcinoma; somatic mutation). FT {ECO:0000269|PubMed:11948123}. FT /FTId=VAR_032734. FT VARIANT 2856 2856 E -> A (in dbSNP:rs11571747). FT {ECO:0000269|PubMed:15026808, FT ECO:0000269|Ref.3}. FT /FTId=VAR_018916. FT VARIANT 2944 2944 I -> F (in dbSNP:rs4987047). FT {ECO:0000269|PubMed:15635067, FT ECO:0000269|Ref.3}. FT /FTId=VAR_008791. FT VARIANT 2950 2950 K -> N (in BC; unknown pathological FT significance; dbSNP:rs28897754). FT {ECO:0000269|PubMed:15026808, FT ECO:0000269|PubMed:15635067}. FT /FTId=VAR_020739. FT VARIANT 2951 2951 A -> T (in dbSNP:rs11571769). FT {ECO:0000269|PubMed:12215251, FT ECO:0000269|Ref.3}. FT /FTId=VAR_008792. FT VARIANT 2969 2969 V -> M (in dbSNP:rs59004709). FT /FTId=VAR_008793. FT VARIANT 3013 3013 T -> I (in BC; unknown pathological FT significance; dbSNP:rs28897755). FT {ECO:0000269|PubMed:15026808, FT ECO:0000269|PubMed:15635067}. FT /FTId=VAR_020740. FT VARIANT 3052 3052 R -> W (could be associated with cancer FT susceptibility; has abrogated function FT consistent with pathogenicity; FT multifactorial likelihood analysis FT provides evidence for pathogenicity). FT {ECO:0000269|PubMed:20513136}. FT /FTId=VAR_063918. FT VARIANT 3063 3063 P -> S (in a patient with ovarian cancer; FT unknown pathological significance). FT {ECO:0000269|PubMed:14746861}. FT /FTId=VAR_020741. FT VARIANT 3076 3076 G -> E. {ECO:0000269|PubMed:12569143}. FT /FTId=VAR_020742. FT VARIANT 3095 3095 D -> E (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:17924331, FT ECO:0000269|PubMed:8640235}. FT /FTId=VAR_005108. FT VARIANT 3098 3098 Y -> H (in BC and ovarian cancer; unknown FT pathological significance; FT dbSNP:rs41293521). FT {ECO:0000269|PubMed:10486320, FT ECO:0000269|PubMed:15026808}. FT /FTId=VAR_008794. FT VARIANT 3101 3101 L -> R (in dbSNP:rs28897758). FT /FTId=VAR_056761. FT VARIANT 3103 3103 I -> M (in melanoma). FT /FTId=VAR_005109. FT VARIANT 3118 3118 M -> T (in BC). FT {ECO:0000269|PubMed:9609997}. FT /FTId=VAR_005110. FT VARIANT 3124 3124 N -> I (in BC). FT {ECO:0000269|PubMed:11139248}. FT /FTId=VAR_020743. FT VARIANT 3196 3196 K -> E (in BC; dbSNP:rs80359228). FT {ECO:0000269|PubMed:11139248}. FT /FTId=VAR_020744. FT VARIANT 3244 3244 V -> I (in dbSNP:rs11571831). FT {ECO:0000269|Ref.3}. FT /FTId=VAR_018917. FT VARIANT 3257 3257 K -> R. FT /FTId=VAR_008795. FT VARIANT 3276 3276 R -> S. FT /FTId=VAR_008796. FT VARIANT 3300 3300 P -> S (in one patient with esophageal FT carcinoma). FT {ECO:0000269|PubMed:11948123}. FT /FTId=VAR_032735. FT VARIANT 3357 3357 T -> R (in BC). FT /FTId=VAR_005111. FT VARIANT 3374 3374 T -> I (in dbSNP:rs56309455). FT {ECO:0000269|PubMed:12442275}. FT /FTId=VAR_020745. FT VARIANT 3412 3412 I -> V (polymorphism; was originally FT thought to be associated with breast FT cancer; dbSNP:rs1801426). FT {ECO:0000269|PubMed:10323242, FT ECO:0000269|PubMed:10978364, FT ECO:0000269|PubMed:12442274, FT ECO:0000269|PubMed:14746861, FT ECO:0000269|PubMed:15026808, FT ECO:0000269|PubMed:15365993, FT ECO:0000269|PubMed:9150152, FT ECO:0000269|Ref.3}. FT /FTId=VAR_005112. FT MUTAGEN 2725 2725 W->A: Disrupts interaction with SEM1. FT {ECO:0000269|PubMed:24013206}. FT MUTAGEN 3291 3291 S->E: Impaired interaction with RAD51. FT {ECO:0000269|PubMed:15800615}. FT MUTAGEN 3387 3387 T->A: Loss of phosphorylation by CHEK1 FT and CHEK2 (in vitro). FT {ECO:0000269|PubMed:18317453}. FT CONFLICT 758 758 S -> N (in Ref. 1; CAA64484). FT {ECO:0000305}. FT CONFLICT 1761 1762 GY -> RI (in Ref. 1; CAA64484). FT {ECO:0000305}. FT CONFLICT 1767 1767 K -> N (in Ref. 1; CAA64484). FT {ECO:0000305}. FT CONFLICT 2536 2536 S -> P (in Ref. 4; CAA98995). FT {ECO:0000305}. FT CONFLICT 3216 3216 L -> LVS (in Ref. 4; CAA97728). FT {ECO:0000305}. FT HELIX 31 35 {ECO:0000244|PDB:3EU7}. FT HELIX 1520 1522 {ECO:0000244|PDB:1N0W}. FT HELIX 1536 1541 {ECO:0000244|PDB:1N0W}. FT TURN 1542 1546 {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 //