BRCA2_HUMAN
ID BRCA2_HUMAN Reviewed; 3418 AA.
AC P51587; O00183; O15008; Q13879; Q5TBJ7;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 4.
DT 03-AUG-2022, entry version 233.
DE RecName: Full=Breast cancer type 2 susceptibility protein {ECO:0000305};
DE AltName: Full=Fanconi anemia group D1 protein;
GN Name=BRCA2 {ECO:0000312|HGNC:HGNC:1101}; Synonyms=FACD, FANCD1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-2466.
RX PubMed=8524414; DOI=10.1038/378789a0;
RA Wooster R., Bignell G., Lancaster J., Swift S., Seal S., Mangion J.,
RA Collins N., Gregory S., Gumbs C., Micklem G., Barfoot R., Hamoudi R.,
RA Patel S., Rice C., Biggs P., Hashim Y., Smith A., Connor F., Arason A.,
RA Gudmundsson J., Ficenec D., Kelsell D., Ford D., Tonin P., Bishop D.T.,
RA Spurr N.K., Ponder B.A.J., Eeles R., Peto J., Devilee P., Cornelisse C.,
RA Lynch H., Narod S., Lenoir G., Egilsson V., Barkadottir R.B., Easton D.F.,
RA Bentley D.R., Futreal P.A., Ashworth A., Stratton M.R.;
RT "Identification of the breast cancer susceptibility gene BRCA2.";
RL Nature 378:789-792(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANTS HIS-372 AND PHE-599, AND VARIANT
RP ALA-2466.
RX PubMed=8589730; DOI=10.1038/ng0396-333;
RA Tavtigian S.V., Simard J., Rommens J., Couch F., Shattuck-Eidens D.,
RA Neuhausen S., Merajver S., Thorlacius S., Offit K., Stoppa-Lyonnet D.,
RA Belanger C., Bell R., Berry S., Bogden R., Chen Q., Davis T., Dumont M.,
RA Frye C., Hattier T., Jammulapati S., Janecki T., Jiang P., Kehrer R.,
RA Leblanc J.-F., Mitchell J.T., McArthur-Morrison J., Nguyen K., Peng Y.,
RA Samson C., Schroeder M., Snyder S.C., Steele L., Stringfellow M.,
RA Stroup C., Swedlund B., Swensen J., Teng D., Thomas A., Tran T., Tran T.,
RA Tranchant M., Weaver-Feldhaus J., Wong A.K.C., Shizuya H., Eyfjord J.E.,
RA Cannon-Albright L., Labrie F., Skolnick M.H., Weber B., Kamb A.,
RA Goldar D.E.;
RT "The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds.";
RL Nat. Genet. 12:333-337(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-289; GLN-322; HIS-372;
RP VAL-784; SER-929; PHE-976; ILE-987; ASP-991; ASN-1561; LYS-1880; MET-1915;
RP PHE-2138; ARG-2162; ARG-2440; ALA-2466; THR-2490; PRO-2835; ALA-2856;
RP PHE-2944; THR-2951; ILE-3244 AND VAL-3412.
RG NIEHS SNPs program;
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ALA-2466.
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [5]
RP INVOLVEMENT IN PNCA2.
RX PubMed=9140390; DOI=10.1038/ng0597-17;
RA Ozcelik H., Schmocker B., Di Nicola N., Shi X.H., Langer B., Moore M.,
RA Taylor B.R., Narod S.A., Darlington G., Andrulis I.L., Gallinger S.,
RA Redston M.;
RT "Germline BRCA2 6174delT mutations in Ashkenazi Jewish pancreatic cancer
RT patients.";
RL Nat. Genet. 16:17-18(1997).
RN [6]
RP INTERACTION WITH SEM1.
RX PubMed=10373512; DOI=10.1128/mcb.19.7.4633;
RA Marston N.J., Richards W.J., Hughes D., Bertwistle D., Marshall C.J.,
RA Ashworth A.;
RT "Interaction between the product of the breast cancer susceptibility gene
RT BRCA2 and DSS1, a protein functionally conserved from yeast to mammals.";
RL Mol. Cell. Biol. 19:4633-4642(1999).
RN [7]
RP FUNCTION, AND INTERACTION WITH FANCD2.
RX PubMed=15115758; DOI=10.1093/hmg/ddh135;
RA Hussain S., Wilson J.B., Medhurst A.L., Hejna J., Witt E., Ananth S.,
RA Davies A., Masson J.-Y., Moses R., West S.C., de Winter J.P., Ashworth A.,
RA Jones N.J., Mathew C.G.;
RT "Direct interaction of FANCD2 with BRCA2 in DNA damage response pathways.";
RL Hum. Mol. Genet. 13:1241-1248(2004).
RN [8]
RP FUNCTION, PHOSPHORYLATION, AND INTERACTION WITH FANCD2.
RX PubMed=15199141; DOI=10.1128/mcb.24.13.5850-5862.2004;
RA Wang X.Z., Andreassen P.R., D'Andrea A.D.;
RT "Functional interaction of monoubiquitinated FANCD2 and BRCA2/FANCD1 in
RT chromatin.";
RL Mol. Cell. Biol. 24:5850-5862(2004).
RN [9]
RP UBIQUITINATION, DEUBIQUITINATION, AND INTERACTION WITH USP11.
RX PubMed=15314155; DOI=10.1128/mcb.24.17.7444-7455.2004;
RA Schoenfeld A.R., Apgar S., Dolios G., Wang R., Aaronson S.A.;
RT "BRCA2 is ubiquitinated in vivo and interacts with USP11, a
RT deubiquitinating enzyme that exhibits prosurvival function in the cellular
RT response to DNA damage.";
RL Mol. Cell. Biol. 24:7444-7455(2004).
RN [10]
RP INVOLVEMENT IN GLM3.
RX PubMed=15689453; DOI=10.1136/jmg.2004.022673;
RG The famillial Wilms tumor collaboration;
RA Reid S., Renwick A., Seal S., Baskcomb L., Barfoot R., Jayatilake H.,
RA Pritchard-Jones K., Stratton M.R., Ridolfi-Luethy A., Rahman N.;
RT "Biallelic BRCA2 mutations are associated with multiple malignancies in
RT childhood including familial Wilms tumour.";
RL J. Med. Genet. 42:147-151(2005).
RN [11]
RP FUNCTION.
RX PubMed=15671039; DOI=10.1074/jbc.m414669200;
RA Ohashi A., Zdzienicka M.Z., Chen J., Couch F.J.;
RT "FANCD2 functions independently of BRCA2 and RAD51 associated homologous
RT recombination in response to DNA damage.";
RL J. Biol. Chem. 280:14877-14883(2005).
RN [12]
RP PHOSPHORYLATION AT SER-3291 BY CDK2, INTERACTION WITH RAD51, AND
RP MUTAGENESIS OF SER-3291.
RX PubMed=15800615; DOI=10.1038/nature03404;
RA Esashi F., Christ N., Gannon J., Liu Y., Hunt T., Jasin M., West S.C.;
RT "CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for
RT recombinational repair.";
RL Nature 434:598-604(2005).
RN [13]
RP INTERACTION WITH WDR16.
RX PubMed=15967112; DOI=10.1593/neo.04544;
RA Silva F.P., Hamamoto R., Nakamura Y., Furukawa Y.;
RT "WDRPUH, a novel WD-repeat-containing protein, is highly expressed in human
RT hepatocellular carcinoma and involved in cell proliferation.";
RL Neoplasia 7:348-355(2005).
RN [14]
RP INTERACTION WITH PALB2, AND CHARACTERIZATION OF VARIANTS BC ARG-25; CYS-31
RP AND ARG-31.
RX PubMed=16793542; DOI=10.1016/j.molcel.2006.05.022;
RA Xia B., Sheng Q., Nakanishi K., Ohashi A., Wu J., Christ N., Liu X.,
RA Jasin M., Couch F.J., Livingston D.M.;
RT "Control of BRCA2 cellular and clinical functions by a nuclear partner,
RT PALB2.";
RL Mol. Cell 22:719-729(2006).
RN [15]
RP INTERACTION WITH SEM1.
RX PubMed=16205630; DOI=10.1038/sj.onc.1209153;
RA Li J., Zou C., Bai Y., Wazer D.E., Band V., Gao Q.;
RT "DSS1 is required for the stability of BRCA2.";
RL Oncogene 25:1186-1194(2006).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-755, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [17]
RP INTERACTION WITH FANCD2; FANCG AND XRCC3.
RX PubMed=18212739; DOI=10.1038/sj.onc.1211034;
RA Wilson J.B., Yamamoto K., Marriott A.S., Hussain S., Sung P., Hoatlin M.E.,
RA Mathew C.G., Takata M., Thompson L.H., Kupfer G.M., Jones N.J.;
RT "FANCG promotes formation of a newly identified protein complex containing
RT BRCA2, FANCD2 and XRCC3.";
RL Oncogene 27:3641-3652(2008).
RN [18]
RP FUNCTION IN RAD51-DEPENDENT DNA REPAIR, PHOSPHORYLATION AT THR-3387 BY
RP CHEK1 AND CHEK2, MUTAGENESIS OF THR-3387, AND INTERACTION WITH RAD51.
RX PubMed=18317453; DOI=10.1038/onc.2008.17;
RA Bahassi E.M., Ovesen J.L., Riesenberg A.L., Bernstein W.Z., Hasty P.E.,
RA Stambrook P.J.;
RT "The checkpoint kinases Chk1 and Chk2 regulate the functional associations
RT between hBRCA2 and Rad51 in response to DNA damage.";
RL Oncogene 27:3977-3985(2008).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN A BRCA COMPLEX
RP WITH BRCA1 AND PALB2.
RX PubMed=19369211; DOI=10.1073/pnas.0811159106;
RA Sy S.M., Huen M.S., Chen J.;
RT "PALB2 is an integral component of the BRCA complex required for homologous
RT recombination repair.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:7155-7160(2009).
RN [20]
RP FUNCTION, AND INTERACTION WITH RAD51.
RX PubMed=20729859; DOI=10.1038/nsmb.1904;
RA Liu J., Doty T., Gibson B., Heyer W.D.;
RT "Human BRCA2 protein promotes RAD51 filament formation on RPA-covered
RT single-stranded DNA.";
RL Nat. Struct. Mol. Biol. 17:1260-1262(2010).
RN [21]
RP FUNCTION, AND SUBUNIT.
RX PubMed=20729858; DOI=10.1038/nsmb.1905;
RA Thorslund T., McIlwraith M.J., Compton S.A., Lekomtsev S., Petronczki M.,
RA Griffith J.D., West S.C.;
RT "The breast cancer tumor suppressor BRCA2 promotes the specific targeting
RT of RAD51 to single-stranded DNA.";
RL Nat. Struct. Mol. Biol. 17:1263-1265(2010).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, AND INTERACTION WITH RAD51
RP AND DMC1.
RX PubMed=20729832; DOI=10.1038/nature09399;
RA Jensen R.B., Carreira A., Kowalczykowski S.C.;
RT "Purified human BRCA2 stimulates RAD51-mediated recombination.";
RL Nature 467:678-683(2010).
RN [23]
RP FUNCTION, AND INTERACTION WITH ROCK2 AND NPM1.
RX PubMed=21084279; DOI=10.1158/0008-5472.can-10-0030;
RA Wang H.F., Takenaka K., Nakanishi A., Miki Y.;
RT "BRCA2 and nucleophosmin coregulate centrosome amplification and form a
RT complex with the Rho effector kinase ROCK2.";
RL Cancer Res. 71:68-77(2011).
RN [24]
RP SUBCELLULAR LOCATION.
RX PubMed=21276791; DOI=10.1016/j.yexcr.2011.01.021;
RA Cappelli E., Townsend S., Griffin C., Thacker J.;
RT "Homologous recombination proteins are associated with centrosomes and are
RT required for mitotic stability.";
RL Exp. Cell Res. 317:1203-1213(2011).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70; SER-445; SER-492;
RP SER-1970; THR-2035; SER-2095 AND SER-3319, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [26]
RP INTERACTION WITH SEM1, CHARACTERIZATION OF VARIANT BC HIS-2723, MUTAGENESIS
RP OF TRP-2725, NUCLEAR EXPORT SIGNAL, AND SUBCELLULAR LOCATION.
RX PubMed=24013206; DOI=10.1038/nsmb.2666;
RA Jeyasekharan A.D., Liu Y., Hattori H., Pisupati V., Jonsdottir A.B.,
RA Rajendra E., Lee M., Sundaramoorthy E., Schlachter S., Kaminski C.F.,
RA Ofir-Rosenfeld Y., Sato K., Savill J., Ayoub N., Venkitaraman A.R.;
RT "A cancer-associated BRCA2 mutation reveals masked nuclear export signals
RT controlling localization.";
RL Nat. Struct. Mol. Biol. 20:1191-1198(2013).
RN [27]
RP INTERACTION WITH PALB2, AND IDENTIFICATION IN A PALB2-CONTAINING HR
RP COMPLEX.
RX PubMed=24141787; DOI=10.1038/onc.2013.421;
RA Park J.Y., Singh T.R., Nassar N., Zhang F., Freund M., Hanenberg H.,
RA Meetei A.R., Andreassen P.R.;
RT "Breast cancer-associated missense mutants of the PALB2 WD40 domain, which
RT directly binds RAD51C, RAD51 and BRCA2, disrupt DNA repair.";
RL Oncogene 33:4803-4812(2014).
RN [28]
RP FUNCTION, AND INTERACTION WITH POLH.
RX PubMed=24485656; DOI=10.1016/j.celrep.2014.01.009;
RA Buisson R., Niraj J., Pauty J., Maity R., Zhao W., Coulombe Y., Sung P.,
RA Masson J.Y.;
RT "Breast cancer proteins PALB2 and BRCA2 stimulate polymerase eta in
RT recombination-associated DNA synthesis at blocked replication forks.";
RL Cell Rep. 6:553-564(2014).
RN [29]
RP FUNCTION IN R-LOOP PROCESSING, AND INTERACTION WITH SEM1 AND PCID2.
RX PubMed=24896180; DOI=10.1038/nature13374;
RA Bhatia V., Barroso S.I., Garcia-Rubio M.L., Tumini E., Herrera-Moyano E.,
RA Aguilera A.;
RT "BRCA2 prevents R-loop accumulation and associates with TREX-2 mRNA export
RT factor PCID2.";
RL Nature 511:362-365(2014).
RN [30]
RP IDENTIFICATION IN THE HR COMPLEX, INTERACTION WITH ERCC5 AND PALB2, AND
RP SUBCELLULAR LOCATION.
RX PubMed=26833090; DOI=10.1016/j.molcel.2015.12.026;
RA Trego K.S., Groesser T., Davalos A.R., Parplys A.C., Zhao W., Nelson M.R.,
RA Hlaing A., Shih B., Rydberg B., Pluth J.M., Tsai M.S., Hoeijmakers J.H.J.,
RA Sung P., Wiese C., Campisi J., Cooper P.K.;
RT "Non-catalytic Roles for XPG with BRCA1 and BRCA2 in Homologous
RT Recombination and Genome Stability.";
RL Mol. Cell 61:535-546(2016).
RN [31]
RP INTERACTION WITH PALB2.
RX PubMed=28319063; DOI=10.1038/onc.2017.46;
RA Foo T.K., Tischkowitz M., Simhadri S., Boshari T., Zayed N., Burke K.A.,
RA Berman S.H., Blecua P., Riaz N., Huo Y., Ding Y.C., Neuhausen S.L.,
RA Weigelt B., Reis-Filho J.S., Foulkes W.D., Xia B.;
RT "Compromised BRCA1-PALB2 interaction is associated with breast cancer
RT risk.";
RL Oncogene 36:4161-4170(2017).
RN [32]
RP INTERACTION WITH HSF2BP.
RX PubMed=31242413; DOI=10.1016/j.celrep.2019.05.096;
RA Brandsma I., Sato K., van Rossum-Fikkert S.E., van Vliet N., Sleddens E.,
RA Reuter M., Odijk H., van den Tempel N., Dekkers D.H.W., Bezstarosti K.,
RA Demmers J.A.A., Maas A., Lebbink J., Wyman C., Essers J., van Gent D.C.,
RA Baarends W.M., Knipscheer P., Kanaar R., Zelensky A.N.;
RT "HSF2BP Interacts with a Conserved Domain of BRCA2 and Is Required for
RT Mouse Spermatogenesis.";
RL Cell Rep. 27:3790.e7-3798.e7(2019).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1519-1551 IN COMPLEX WITH RAD51.
RX PubMed=12442171; DOI=10.1038/nature01230;
RA Pellegrini L., Yu D.S., Lo T., Anand S., Lee M., Blundell T.L.,
RA Venkitaraman A.R.;
RT "Insights into DNA recombination from the structure of a RAD51-BRCA2
RT complex.";
RL Nature 420:287-293(2002).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 21-39 IN COMPLEX WITH PALB2.
RX PubMed=19609323; DOI=10.1038/embor.2009.126;
RA Oliver A.W., Swift S., Lord C.J., Ashworth A., Pearl L.H.;
RT "Structural basis for recruitment of BRCA2 by PALB2.";
RL EMBO Rep. 10:990-996(2009).
RN [35]
RP VARIANT OVARIAN CANCER HIS-2787, AND VARIANTS HIS-372; MET-1915 AND
RP ALA-2466.
RX PubMed=8665505;
RA Takahashi H., Chiu H.-C., Bandera C.A., Behbakht K., Liu P.C., Couch F.J.,
RA Weber B.L., LiVolsi V.A., Furusato M., Rebane B.A., Cardonick A.,
RA Benjamin I., Morgan M.A., King S.A., Mikuta J.J., Rubin S.C., Boyd J.;
RT "Mutations of the BRCA2 gene in ovarian carcinomas.";
RL Cancer Res. 56:2738-2741(1996).
RN [36]
RP VARIANTS HIS-372; ASP-991; SER-1147; MET-1915 AND CYS-2034.
RX PubMed=8673091; DOI=10.1038/ng0596-123;
RA Couch F.J., Farid L.M., Deshano M.L., Tavtigian S.V., Calzone K.,
RA Campeau L., Peng Y., Bogden B., Chen Q., Neuhausen S., Shattuck-Eidens D.,
RA Godwin A.K., Daly M., Radford D.M., Sedlacek S., Rommens J., Simard J.,
RA Garber J., Merajver S., Weber B.L.;
RT "BRCA2 germline mutations in male breast cancer cases and breast cancer
RT families.";
RL Nat. Genet. 13:123-125(1996).
RN [37]
RP VARIANT GLU-3095.
RX PubMed=8640235; DOI=10.1038/ng0696-238;
RA Lancaster J.M., Wooster R., Mangion J., Phelan C.M., Cochran C., Gumbs C.,
RA Seal S., Barfoot R., Collins N., Bignell G., Patel S., Hamoudi R.,
RA Larsson C., Wiseman R.W., Berchuck A., Iglehart J.D., Marks J.R.,
RA Ashworth A., Stratton M.R., Futreal P.A.;
RT "BRCA2 mutations in primary breast and ovarian cancers.";
RL Nat. Genet. 13:238-240(1996).
RN [38]
RP VARIANTS.
RX PubMed=8640236; DOI=10.1038/ng0696-241;
RA Teng D.H.-F., Bogden R., Mitchell J., Baumgard M., Bell R., Berry S.,
RA Davis T., Ha P.C., Kehrer R., Jammulapati S., Chen Q., Offit K.,
RA Skolnick M.H., Tavtigian S.V., Jhanwar S., Swedlund B., Wong A.K.C.,
RA Kamb A.;
RT "Low incidence of BRCA2 mutations in breast carcinoma and other cancers.";
RL Nat. Genet. 13:241-244(1996).
RN [39]
RP VARIANT BC ASN-2415.
RX PubMed=8640237; DOI=10.1038/ng0696-245;
RA Miki Y., Katagiri T., Kasumi F., Yoshimoto T., Nakamura Y.;
RT "Mutation analysis in the BRCA2 gene in primary breast cancers.";
RL Nat. Genet. 13:245-247(1996).
RN [40]
RP VARIANT BC ASP-2089, AND VARIANT VAL-3412.
RX PubMed=9150152;
RA Vehmanen P., Friedman L.S., Eerola H., Sarantaus L., Pyrhoenen S.,
RA Ponder B.A.J., Muhonen T., Nevanlinna H.;
RT "A low proportion of BRCA2 mutations in Finnish breast cancer families.";
RL Am. J. Hum. Genet. 60:1050-1058(1997).
RN [41]
RP VARIANT BC/PANCREAS CANCER TRP-554.
RX PubMed=9654203; DOI=10.1007/s004390050738;
RA Ganguly T., Dhulipala R., Godmilow L., Ganguly A.;
RT "High throughput fluorescence-based conformation-sensitive gel
RT electrophoresis (F-CSGE) identifies six unique BRCA2 mutations and an
RT overall low incidence of BRCA2 mutations in high-risk BRCA1-negative breast
RT cancer families.";
RL Hum. Genet. 102:549-556(1998).
RN [42]
RP VARIANTS BC LEU-32; ARG-53; LEU-81; ARG-201; ALA-211; SER-222 AND THR-3118.
RX PubMed=9609997; DOI=10.1007/s100380050035;
RA Katagiri T., Kasumi F., Yoshimoto M., Nomizu T., Asaishi K., Abe R.,
RA Tsuchiya A., Sugano M., Takai S., Yoneda M., Fukutomi T., Nanba K.,
RA Makita M., Okazaki H., Hirata K., Okazaki M., Furutsuma Y., Morishita Y.,
RA Iino Y., Karino T., Ayabe H., Hara S., Kajiwara T., Houga S., Shimizu T.,
RA Toda M., Yamazaki Y., Uchida T., Kunitomo K., Sonoo H., Kurebayashi J.,
RA Shimotsuma K., Nakamura Y., Miki Y.;
RT "High proportion of missense mutations of the BRCA1 and BRCA2 genes in
RT Japanese breast cancer families.";
RL J. Hum. Genet. 43:42-48(1998).
RN [43]
RP VARIANTS OVARIAN CANCER PRO-75; HIS-2502 AND HIS-3098.
RX PubMed=10486320; DOI=10.1086/302583;
RA Gayther S.A., Russell P., Harrington P., Antoniou A.C., Easton D.F.,
RA Ponder B.A.J.;
RT "The contribution of germline BRCA1 and BRCA2 mutations to familial ovarian
RT cancer: no evidence for other ovarian cancer-susceptibility genes.";
RL Am. J. Hum. Genet. 65:1021-1029(1999).
RN [44]
RP VARIANTS HIS-289; HIS-372; ASP-991 AND VAL-3412.
RX PubMed=10323242; DOI=10.1007/s004390050936;
RA Li S.S.-L., Tseng H.-M., Yang T.-P., Liu C.-H., Teng S.-J., Huang H.-W.,
RA Chen L.-M., Kao H.-W., Chen J.H., Tseng J.-N., Chen A., Hou M.-F.,
RA Huang T.-J., Chang H.-T., Mok K.-T., Tsai J.-H.;
RT "Molecular characterization of germline mutations in the BRCA1 and BRCA2
RT genes from breast cancer families in Taiwan.";
RL Hum. Genet. 104:201-204(1999).
RN [45]
RP VARIANTS BC, AND VARIANTS.
RX PubMed=9971877; DOI=10.1093/hmg/8.3.413;
RA Wagner T.M.U., Hirtenlehner K., Shen P., Moeslinger R., Muhr D.,
RA Fleischmann E., Concin H., Doeller W., Haid A., Lang A.H., Mayer P.,
RA Petru E., Ropp E., Langbauer G., Kubista E., Scheiner O., Underhill P.,
RA Mountain J., Stierer M., Zielinski C., Oefner P.;
RT "Global sequence diversity of BRCA2: analysis of 71 breast cancer families
RT and 95 control individuals of worldwide populations.";
RL Hum. Mol. Genet. 8:413-423(1999).
RN [46]
RP VARIANT BC ARG-326, AND VARIANT ILE-2728.
RX PubMed=10399947;
RX DOI=10.1002/(sici)1097-0215(19990730)82:3<325::aid-ijc3>3.0.co;2-g;
RA Sinilnikova O.M., Egan K.M., Quinn J.L., Boutrand L., Lenoir G.M.,
RA Stoppa-Lyonnet D., Desjardins L., Levy C., Goldgar D., Gragoudas E.S.;
RT "Germline brca2 sequence variants in patients with ocular melanoma.";
RL Int. J. Cancer 82:325-328(1999).
RN [47]
RP VARIANT HIS-372.
RX PubMed=11062481; DOI=10.1038/81691;
RA Healey C.S., Dunning A.M., Teare M.D., Chase D., Parker L., Burn J.,
RA Chang-Claude J., Mannermaa A., Kataja V., Huntsman D.G., Pharoah P.D.P.,
RA Luben R.N., Easton D.F., Ponder B.A.J.;
RT "A common variant in BRCA2 is associated with both breast cancer risk and
RT prenatal viability.";
RL Nat. Genet. 26:362-364(2000).
RN [48]
RP VARIANTS BC MET-729; ILE-2515 AND ILE-2728, AND VARIANTS HIS-289; HIS-372;
RP ASP-991; MET-1915 AND VAL-3412.
RX PubMed=10978364; DOI=10.1136/jmg.37.9.e17;
RA Plaschke J., Commer T., Jacobi C., Schackert H.K., Chang-Claude J.;
RT "BRCA2 germline mutations among early onset breast cancer patients
RT unselected for family history of the disease.";
RL J. Med. Genet. 37:E17-E17(2000).
RN [49]
RP VARIANTS BC ASN-1179; ILE-3124 AND GLU-3196, AND VARIANT TYR-1420.
RX PubMed=11139248; DOI=10.1002/1098-1004(2001)17:1<73::aid-humu12>3.0.co;2-o;
RA Kwiatkowska E., Teresiak M., Lamperska K.M., Karczewska A., Breborowicz D.,
RA Stawicka M., Godlewski D., Krzyzosiak W.J., Mackiewicz A.;
RT "BRCA2 germline mutations in male breast cancer patients in the Polish
RT population.";
RL Hum. Mutat. 17:73-73(2001).
RN [50]
RP VARIANTS BC THR-505; TYR-1730; HIS-2135 AND CYS-2222, AND VARIANT LYS-1880.
RX PubMed=11241844; DOI=10.1002/humu.7;
RA Edwards S.M., Kote-Jarai Z., Hamoudi R., Eeles R.A.;
RT "An improved high throughput heteroduplex mutation detection system for
RT screening BRCA2 mutations-fluorescent mutation detection (F-MD).";
RL Hum. Mutat. 17:220-232(2001).
RN [51]
RP VARIANTS HIS-289 AND VAL-784, AND VARIANT BC GLU-3076.
RX PubMed=11149425;
RX DOI=10.1002/1097-0215(20010101)91:1<83::aid-ijc1013>3.0.co;2-5;
RA Ikeda N., Miyoshi Y., Yoneda K., Shiba E., Sekihara Y., Kinoshita M.,
RA Noguchi S.;
RT "Frequency of BRCA1 and BRCA2 germline mutations in Japanese breast cancer
RT families.";
RL Int. J. Cancer 91:83-88(2001).
RN [52]
RP VARIANT BC ARG-2722.
RX PubMed=12145750; DOI=10.1086/342192;
RA Fackenthal J.D., Cartegni L., Krainer A.R., Olopade O.I.;
RT "BRCA2 T2722R is a deleterious allele that causes exon skipping.";
RL Am. J. Hum. Genet. 71:625-631(2002).
RN [53]
RP ERRATUM OF PUBMED:12145750.
RA Fackenthal J.D., Cartegni L., Krainer A.R., Olopade O.I.;
RL Am. J. Hum. Genet. 73:1477-1477(2002).
RN [54]
RP VARIANTS BC CYS-2072; CYS-2094 AND ASN-2128.
RX PubMed=12373604; DOI=10.1038/sj.bjc.6600562;
RA Jakubowska A., Nej K., Huzarski T., Scott R.J., Lubinski J.;
RT "BRCA2 gene mutations in families with aggregations of breast and stomach
RT cancers.";
RL Br. J. Cancer 87:888-891(2002).
RN [55]
RP VARIANT THR-192.
RX PubMed=12097290;
RA Murphy K.M., Brune K.A., Griffin C., Sollenberger J.E., Petersen G.M.,
RA Bansal R., Hruban R.H., Kern S.E.;
RT "Evaluation of candidate genes MAP2K4, MADH4, ACVR1B, and BRCA2 in familial
RT pancreatic cancer: deleterious BRCA2 mutations in 17%.";
RL Cancer Res. 62:3789-3793(2002).
RN [56]
RP VARIANTS HIS-118; SER-315; ILE-1988; CYS-2842 AND SER-3300.
RX PubMed=11948123;
RA Hu N., Li G., Li W.-J., Wang C., Goldstein A.M., Tang Z.-Z., Roth M.J.,
RA Dawsey S.M., Huang J., Wang Q.-H., Ding T., Giffen C., Taylor P.R.,
RA Emmert-Buck M.R.;
RT "Infrequent mutation in the BRCA2 gene in esophageal squamous cell
RT carcinoma.";
RL Clin. Cancer Res. 8:1121-1126(2002).
RN [57]
RP VARIANTS ALA-598; TYR-1420; CYS-2034; ILE-2728 AND THR-2951.
RX PubMed=12215251; DOI=10.1089/10906570260199375;
RA Deffenbaugh A.M., Frank T.S., Hoffman M., Cannon-Albright L.,
RA Neuhausen S.L.;
RT "Characterization of common BRCA1 and BRCA2 variants.";
RL Genet. Test. 6:119-121(2002).
RN [58]
RP VARIANTS ASP-1593 AND SER-2706.
RX PubMed=12442273; DOI=10.1002/humu.9082;
RA Saxena S., Szabo C.I., Chopin S., Barjhoux L., Sinilnikova O., Lenoir G.,
RA Goldgar D.E., Bhatanager D.;
RT "BRCA1 and BRCA2 in Indian breast cancer patients.";
RL Hum. Mutat. 20:473-474(2002).
RN [59]
RP VARIANT BC ASN-2729, AND VARIANT VAL-3412.
RX PubMed=12442274; DOI=10.1002/humu.9083;
RA Zhi X., Szabo C., Chopin S., Suter N., Wang Q.-S., Ostrander E.A.,
RA Sinilnikova O.M., Lenoir G.M., Goldgar D., Shi Y.-R.;
RT "BRCA1 and BRCA2 sequence variants in Chinese breast cancer families.";
RL Hum. Mutat. 20:474-474(2002).
RN [60]
RP VARIANTS BC CYS-42; ARG-613; LEU-2118; LEU-2293 AND ARG-2793, AND VARIANT
RP ILE-3374.
RX PubMed=12442275; DOI=10.1002/humu.9084;
RA Ruiz-Flores P., Sinilnikova O.M., Badzioch M., Calderon-Garciduenas A.L.,
RA Chopin S., Fabrice O., Gonzalez-Guerrero J.F., Szabo C., Lenoir G.,
RA Goldgar D.E., Barrera-Saldana H.A.;
RT "BRCA1 and BRCA2 mutation analysis of early-onset and familial breast
RT cancer cases in Mexico.";
RL Hum. Mutat. 20:474-475(2002).
RN [61]
RP VARIANTS BC TYR-1580 AND MET-1915.
RX PubMed=11948477; DOI=10.1002/ijc.10289;
RA Kwiatkowska E., Teresiak M., Breborowicz D., Mackiewicz A.;
RT "Somatic mutations in the BRCA2 gene and high frequency of allelic loss of
RT BRCA2 in sporadic male breast cancer.";
RL Int. J. Cancer 98:943-945(2002).
RN [62]
RP INVOLVEMENT IN FANCD1.
RX PubMed=12065746; DOI=10.1126/science.1073834;
RA Howlett N.G., Taniguchi T., Olson S., Cox B., Waisfisz Q.,
RA de Die-Smulders C., Persky N., Grompe M., Joenje H., Pals G., Ikeda H.,
RA Fox E.A., D'Andrea A.D.;
RT "Biallelic inactivation of BRCA2 in Fanconi anemia.";
RL Science 297:606-609(2002).
RN [63]
RP VARIANTS HIS-289; HIS-372; GLY-462; ASP-991; SER-1279; TYR-1420; ASP-1771
RP AND ALA-2466.
RX PubMed=12552570; DOI=10.1002/humu.9110;
RA Hadjisavvas A., Charalambous E., Adamou A., Christodoulou C.G.,
RA Kyriacou K.;
RT "BRCA2 germline mutations in Cypriot patients with familial breast/ovarian
RT cancer.";
RL Hum. Mutat. 21:171-171(2003).
RN [64]
RP VARIANTS BC ILE-431; LYS-1036; ARG-1106 AND VAL-1524.
RX PubMed=12938098; DOI=10.1002/humu.9174;
RA Meyer P., Voigtlaender T., Bartram C.R., Klaes R.;
RT "Twenty-three novel BRCA1 and BRCA2 sequence alterations in breast and/or
RT ovarian cancer families in Southern Germany.";
RL Hum. Mutat. 22:259-259(2003).
RN [65]
RP VARIANTS PRO-582; PHE-1522 AND VAL-2044.
RX PubMed=12624724; DOI=10.1007/s100380300020;
RA Sakayori M., Kawahara M., Shiraishi K., Nomizu T., Shimada A., Kudo T.,
RA Abe R., Ohuchi N., Takenoshita S., Kanamaru R., Ishioka C.;
RT "Evaluation of the diagnostic accuracy of the stop codon (SC) assay for
RT identifying protein-truncating mutations in the BRCA1and BRCA2genes in
RT familial breast cancer.";
RL J. Hum. Genet. 48:130-137(2003).
RN [66]
RP VARIANT CYS-2034, AND VARIANT BC GLU-3076.
RX PubMed=12569143; DOI=10.1093/jnci/95.3.214;
RA Hahn S.A., Greenhalf B., Ellis I., Sina-Frey M., Rieder H., Korte B.,
RA Gerdes B., Kress R., Ziegler A., Raeburn J.A., Campra D., Gruetzmann R.,
RA Rehder H., Rothmund M., Schmiegel W., Neoptolemos J.P., Bartsch D.K.;
RT "BRCA2 germline mutations in familial pancreatic carcinoma.";
RL J. Natl. Cancer Inst. 95:214-221(2003).
RN [67]
RP VARIANT FANCD1 PRO-2510.
RX PubMed=14670928; DOI=10.1182/blood-2003-06-1970;
RA Hirsch B., Shimamura A., Moreau L., Baldinger S., Hag-alshiekh M.,
RA Bostrom B., Sencer S., D'Andrea A.D.;
RT "Association of biallelic BRCA2/FANCD1 mutations with spontaneous
RT chromosomal instability and solid tumors of childhood.";
RL Blood 103:2554-2559(2004).
RN [68]
RP VARIANTS BC SER-60; ARG-405; HIS-448; GLY-462; GLY-2275; ARG-2353;
RP LYS-2488; HIS-2723; ASN-2950; ILE-3013 AND HIS-3098, AND VARIANTS ASP-991;
RP ALA-2856 AND VAL-3412.
RX PubMed=15026808; DOI=10.1038/sj.bjc.6601656;
RA Claes K., Poppe B., Coene I., De Paepe A., Messiaen L.;
RT "BRCA1 and BRCA2 germline mutation spectrum and frequencies in Belgian
RT breast/ovarian cancer families.";
RL Br. J. Cancer 90:1244-1251(2004).
RN [69]
RP VARIANTS BC ILE-64; GLY-462; ASN-1690; ASP-1771; MET-1887; MET-1915 AND
RP GLU-2456, AND VARIANTS HIS-289; HIS-372; ASP-991; SER-1279; TYR-1420;
RP CYS-2108 AND ALA-2466.
RX PubMed=15172753; DOI=10.1016/j.cancergencyto.2003.09.020;
RA Hadjisavvas A., Charalambous E., Adamou A., Neuhausen S.L.,
RA Christodoulou C.G., Kyriacou K.;
RT "Hereditary breast and ovarian cancer in Cyprus: identification of a
RT founder BRCA2 mutation.";
RL Cancer Genet. Cytogenet. 151:152-156(2004).
RN [70]
RP VARIANT OVARIAN CANCER CYS-42, AND VARIANTS SER-3063 AND VAL-3412.
RX PubMed=14746861; DOI=10.1016/j.ejca.2003.09.016;
RA Malander S., Ridderheim M., Masbaeck A., Loman N., Kristoffersson U.,
RA Olsson H., Nilbert M., Borg A.;
RT "One in 10 ovarian cancer patients carry germ line BRCA1 or BRCA2
RT mutations: results of a prospective study in Southern Sweden.";
RL Eur. J. Cancer 40:422-428(2004).
RN [71]
RP VARIANTS BC ILE-1679; ALA-1804; LYS-1901 AND LEU-2096.
RX PubMed=14722926; DOI=10.1002/humu.9213;
RA Valarmathi M.T., Sawhney M., Deo S.S.V., Shukla N.K., Das S.N.;
RT "Novel germline mutations in the BRCA1 and BRCA2 genes in Indian breast and
RT breast-ovarian cancer families.";
RL Hum. Mutat. 23:205-205(2004).
RN [72]
RP VARIANT ALA-225, AND CHARACTERIZATION OF VARIANT ALA-225.
RX PubMed=15300854; DOI=10.1002/humu.9267;
RA Sharp A., Pichert G., Lucassen A., Eccles D.;
RT "RNA analysis reveals splicing mutations and loss of expression defects in
RT MLH1 and BRCA1.";
RL Hum. Mutat. 24:272-272(2004).
RN [73]
RP VARIANTS BC THR-1445; VAL-1929 AND ALA-2031, AND VARIANTS HIS-289; HIS-372;
RP VAL-784; ASP-991 AND VAL-3412.
RX PubMed=15365993; DOI=10.1002/humu.9275;
RA Seo J.H., Cho D.-Y., Ahn S.-H., Yoon K.-S., Kang C.-S., Cho H.M., Lee H.S.,
RA Choe J.J., Choi C.W., Kim B.S., Shin S.W., Kim Y.H., Kim J.S., Son G.-S.,
RA Lee J.-B., Koo B.H.;
RT "BRCA1 and BRCA2 germline mutations in Korean patients with sporadic breast
RT cancer.";
RL Hum. Mutat. 24:350-350(2004).
RN [74]
RP VARIANTS LEU-1172; TYR-1420; PHE-2944; ASN-2950 AND ILE-3013.
RX PubMed=15635067; DOI=10.1136/jmg.2004.025056;
RA Kim S.-W., Lee C.S., Fey J.V., Borgen P.I., Boyd J.;
RT "Prevalence of BRCA2 mutations in a hospital based series of unselected
RT breast cancer cases.";
RL J. Med. Genet. 42:E5-E5(2005).
RN [75]
RP VARIANTS HIS-2336; CYS-2502; CYS-2626; PHE-2627; PRO-2653; LYS-2659;
RP VAL-2663; ARG-2722; GLY-2723; ASP-2748 AND GLU-3095.
RX PubMed=17924331; DOI=10.1086/521032;
RA Easton D.F., Deffenbaugh A.M., Pruss D., Frye C., Wenstrup R.J.,
RA Allen-Brady K., Tavtigian S.V., Monteiro A.N.A., Iversen E.S., Couch F.J.,
RA Goldgar D.E.;
RT "A systematic genetic assessment of 1,433 sequence variants of unknown
RT clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition
RT genes.";
RL Am. J. Hum. Genet. 81:873-883(2007).
RN [76]
RP VARIANTS FANCD1 HIS-2336 AND CYS-2626.
RX PubMed=16825431; DOI=10.1136/jmg.2006.043257;
RA Alter B.P., Rosenberg P.S., Brody L.C.;
RT "Clinical and molecular features associated with biallelic mutations in
RT FANCD1/BRCA2.";
RL J. Med. Genet. 44:1-9(2007).
RN [77]
RP CHARACTERIZATION OF VARIANTS VAL-2663; GLY-2723 AND TRP-3052.
RX PubMed=20513136; DOI=10.1002/humu.21267;
RA Walker L.C., Whiley P.J., Couch F.J., Farrugia D.J., Healey S.,
RA Eccles D.M., Lin F., Butler S.A., Goff S.A., Thompson B.A., Lakhani S.R.,
RA Da Silva L.M., Tavtigian S.V., Goldgar D.E., Brown M.A., Spurdle A.B.;
RT "Detection of splicing aberrations caused by BRCA1 and BRCA2 sequence
RT variants encoding missense substitutions: implications for prediction of
RT pathogenicity.";
RL Hum. Mutat. 31:E1484-E1505(2010).
RN [78]
RP CHARACTERIZATION OF VARIANTS FANCD1 HIS-2336; PRO-2510 AND CYS-2626,
RP CHARACTERIZATION OF VARIANTS THR-2490 AND ASN-2729, FUNCTION, AND
RP INTERACTION WITH SEM1.
RX PubMed=21719596; DOI=10.1182/blood-2010-12-324541;
RA Biswas K., Das R., Alter B.P., Kuznetsov S.G., Stauffer S., North S.L.,
RA Burkett S., Brody L.C., Meyer S., Byrd R.A., Sharan S.K.;
RT "A comprehensive functional characterization of BRCA2 variants associated
RT with Fanconi anemia using mouse ES cell-based assay.";
RL Blood 118:2430-2442(2011).
RN [79]
RP CHARACTERIZATION OF VARIANTS BC PHE-2627; PRO-2653; ARG-2722; GLY-2723;
RP HIS-2723; ASN-2729; HIS-2787; PRO-2792; ARG-2793; ALA-2856; THR-2951;
RP ILE-3013; TRP-3052; GLU-3076; GLU-3095; HIS-3098 AND ILE-3124,
RP CHARACTERIZATION OF VARIANTS ARG-2440; ALA-2466; CYS-2842 AND SER-3063, AND
RP CHARACTERIZATION OF VARIANT FANCD1 PRO-2510 AND CYS-2626.
RX PubMed=23108138; DOI=10.1158/0008-5472.can-12-2081;
RA Guidugli L., Pankratz V.S., Singh N., Thompson J., Erding C.A., Engel C.,
RA Schmutzler R., Domchek S., Nathanson K., Radice P., Singer C., Tonin P.N.,
RA Lindor N.M., Goldgar D.E., Couch F.J.;
RT "A classification model for BRCA2 DNA binding domain missense variants
RT based on homology-directed repair activity.";
RL Cancer Res. 73:265-275(2013).
RN [80]
RP VARIANTS LEU-606 AND TYR-1420.
RX PubMed=26566883; DOI=10.1136/jmedgenet-2015-103179;
RA Rafiullah R., Aslamkhan M., Paramasivam N., Thiel C., Mustafa G.,
RA Wiemann S., Schlesner M., Wade R.C., Rappold G.A., Berkel S.;
RT "Homozygous missense mutation in the LMAN2L gene segregates with
RT intellectual disability in a large consanguineous Pakistani family.";
RL J. Med. Genet. 53:138-144(2016).
CC -!- FUNCTION: Involved in double-strand break repair and/or homologous
CC recombination. Binds RAD51 and potentiates recombinational DNA repair
CC by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts
CC by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to
CC displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-
CC ssDNA filaments by blocking ATP hydrolysis. Part of a PALB2-scaffolded
CC HR complex containing RAD51C and which is thought to play a role in DNA
CC repair by HR. May participate in S phase checkpoint activation. Binds
CC selectively to ssDNA, and to ssDNA in tailed duplexes and replication
CC fork structures. May play a role in the extension step after strand
CC invasion at replication-dependent DNA double-strand breaks; together
CC with PALB2 is involved in both POLH localization at collapsed
CC replication forks and DNA polymerization activity. In concert with
CC NPM1, regulates centrosome duplication. Interacts with the TREX-2
CC complex (transcription and export complex 2) subunits PCID2 and SEM1,
CC and is required to prevent R-loop-associated DNA damage and thus
CC transcription-associated genomic instability. Silencing of BRCA2
CC promotes R-loop accumulation at actively transcribed genes in
CC replicating and non-replicating cells, suggesting that BRCA2 mediates
CC the control of R-loop associated genomic instability, independently of
CC its known role in homologous recombination (PubMed:24896180).
CC {ECO:0000269|PubMed:15115758, ECO:0000269|PubMed:15199141,
CC ECO:0000269|PubMed:15671039, ECO:0000269|PubMed:18317453,
CC ECO:0000269|PubMed:20729832, ECO:0000269|PubMed:20729858,
CC ECO:0000269|PubMed:20729859, ECO:0000269|PubMed:21084279,
CC ECO:0000269|PubMed:21719596, ECO:0000269|PubMed:24485656,
CC ECO:0000269|PubMed:24896180}.
CC -!- SUBUNIT: Monomer and dimer (PubMed:20729858). Interacts with RAD51;
CC regulates RAD51 recruitment and function at sites of DNA repair
CC (PubMed:12442171, PubMed:15800615, PubMed:18317453, PubMed:20729832,
CC PubMed:20729859). Interacts with WDR16, USP11, DMC1, ROCK2 and NPM1
CC (PubMed:15314155, PubMed:15967112, PubMed:20729832, PubMed:21084279).
CC Interacts with SEM1; the interaction masks a nuclear export signal in
CC BRCA2 (PubMed:10373512, PubMed:16205630, PubMed:21719596,
CC PubMed:24013206). Interacts with both nonubiquitinated and
CC monoubiquitinated FANCD2; this complex also includes XRCC3 and
CC phosphorylated FANCG (PubMed:15115758, PubMed:15199141,
CC PubMed:18212739). Part of a BRCA complex containing BRCA1, BRCA2 and
CC PALB2 (PubMed:19369211). Component of the homologous recombination
CC repair (HR) complex composed of ERCC5/XPG, BRCA2, PALB2, DSS1 and RAD51
CC (PubMed:26833090). Within the complex, interacts with ERCC5/XPG and
CC PALB2 (PubMed:26833090). Interacts directly with PALB2 which may serve
CC as a scaffold for a HR complex containing PALB2, BRCA2, RAD51C, RAD51
CC and XRCC3 (PubMed:26833090, PubMed:19369211, PubMed:24141787,
CC PubMed:28319063, PubMed:16793542, PubMed:19609323). Interacts with
CC BRCA1 only in the presence of PALB2 which serves as the bridging
CC protein (PubMed:19369211). Interacts with POLH; the interaction is
CC direct (PubMed:24485656). Interacts with the TREX-2 complex subunits
CC PCID2 and SEM1 (PubMed:24896180, PubMed:21719596). Interacts with
CC HSF2BP and BRME1; the interaction with HSF2BP is direct and allows the
CC formation of a ternary complex (PubMed:31242413). The complex
CC BRME1:HSF2BP:BRCA2 interacts with SPATA22, MEIOB and RAD51 (By
CC similarity). {ECO:0000250|UniProtKB:P97929,
CC ECO:0000269|PubMed:10373512, ECO:0000269|PubMed:12442171,
CC ECO:0000269|PubMed:15115758, ECO:0000269|PubMed:15199141,
CC ECO:0000269|PubMed:15314155, ECO:0000269|PubMed:15800615,
CC ECO:0000269|PubMed:15967112, ECO:0000269|PubMed:16205630,
CC ECO:0000269|PubMed:16793542, ECO:0000269|PubMed:18212739,
CC ECO:0000269|PubMed:18317453, ECO:0000269|PubMed:19369211,
CC ECO:0000269|PubMed:19609323, ECO:0000269|PubMed:20729832,
CC ECO:0000269|PubMed:20729858, ECO:0000269|PubMed:20729859,
CC ECO:0000269|PubMed:21084279, ECO:0000269|PubMed:21719596,
CC ECO:0000269|PubMed:24013206, ECO:0000269|PubMed:24141787,
CC ECO:0000269|PubMed:24485656, ECO:0000269|PubMed:24896180,
CC ECO:0000269|PubMed:26833090, ECO:0000269|PubMed:28319063,
CC ECO:0000269|PubMed:31242413}.
CC -!- INTERACTION:
CC P51587; P51587: BRCA2; NbExp=3; IntAct=EBI-79792, EBI-79792;
CC P51587; Q14565: DMC1; NbExp=12; IntAct=EBI-79792, EBI-930865;
CC P51587; Q9BXW9: FANCD2; NbExp=16; IntAct=EBI-79792, EBI-359343;
CC P51587; Q9BXW9-2: FANCD2; NbExp=3; IntAct=EBI-79792, EBI-596878;
CC P51587; Q9P0W2: HMG20B; NbExp=8; IntAct=EBI-79792, EBI-713401;
CC P51587; Q86YC2: PALB2; NbExp=25; IntAct=EBI-79792, EBI-1222653;
CC P51587; Q9NTI5: PDS5B; NbExp=26; IntAct=EBI-79792, EBI-1175604;
CC P51587; Q9Y253: POLH; NbExp=6; IntAct=EBI-79792, EBI-2827270;
CC P51587; Q06609: RAD51; NbExp=46; IntAct=EBI-79792, EBI-297202;
CC P51587; Q06609-1: RAD51; NbExp=12; IntAct=EBI-79792, EBI-15557721;
CC P51587; P60896: SEM1; NbExp=10; IntAct=EBI-79792, EBI-79819;
CC P51587; P04637: TP53; NbExp=7; IntAct=EBI-79792, EBI-366083;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:24013206,
CC ECO:0000269|PubMed:26833090, ECO:0000305|PubMed:21276791}. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000269|PubMed:21276791}. Note=Colocalizes with ERCC5/XPG to
CC nuclear foci following DNA replication stress.
CC {ECO:0000269|PubMed:26833090}.
CC -!- TISSUE SPECIFICITY: Highest levels of expression in breast and thymus,
CC with slightly lower levels in lung, ovary and spleen.
CC -!- PTM: Phosphorylated by ATM upon irradiation-induced DNA damage.
CC Phosphorylation by CHEK1 and CHEK2 regulates interaction with RAD51.
CC Phosphorylation at Ser-3291 by CDK1 and CDK2 is low in S phase when
CC recombination is active, but increases as cells progress towards
CC mitosis; this phosphorylation prevents homologous recombination-
CC dependent repair during S phase and G2 by inhibiting RAD51 binding.
CC {ECO:0000269|PubMed:15199141, ECO:0000269|PubMed:15800615,
CC ECO:0000269|PubMed:18317453}.
CC -!- PTM: Ubiquitinated in the absence of DNA damage; this does not lead to
CC proteasomal degradation. In contrast, ubiquitination in response to DNA
CC damage leads to proteasomal degradation. {ECO:0000269|PubMed:15314155}.
CC -!- DISEASE: Breast cancer (BC) [MIM:114480]: A common malignancy
CC originating from breast epithelial tissue. Breast neoplasms can be
CC distinguished by their histologic pattern. Invasive ductal carcinoma is
CC by far the most common type. Breast cancer is etiologically and
CC genetically heterogeneous. Important genetic factors have been
CC indicated by familial occurrence and bilateral involvement. Mutations
CC at more than one locus can be involved in different families or even in
CC the same case. {ECO:0000269|PubMed:10399947,
CC ECO:0000269|PubMed:10978364, ECO:0000269|PubMed:11139248,
CC ECO:0000269|PubMed:11149425, ECO:0000269|PubMed:11241844,
CC ECO:0000269|PubMed:11948477, ECO:0000269|PubMed:12145750,
CC ECO:0000269|PubMed:12373604, ECO:0000269|PubMed:12442274,
CC ECO:0000269|PubMed:12442275, ECO:0000269|PubMed:12569143,
CC ECO:0000269|PubMed:12938098, ECO:0000269|PubMed:14722926,
CC ECO:0000269|PubMed:15026808, ECO:0000269|PubMed:15172753,
CC ECO:0000269|PubMed:15365993, ECO:0000269|PubMed:16793542,
CC ECO:0000269|PubMed:23108138, ECO:0000269|PubMed:24013206,
CC ECO:0000269|PubMed:8640237, ECO:0000269|PubMed:9150152,
CC ECO:0000269|PubMed:9609997, ECO:0000269|PubMed:9654203,
CC ECO:0000269|PubMed:9971877}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry.
CC -!- DISEASE: Pancreatic cancer 2 (PNCA2) [MIM:613347]: A malignant neoplasm
CC of the pancreas. Tumors can arise from both the exocrine and endocrine
CC portions of the pancreas, but 95% of them develop from the exocrine
CC portion, including the ductal epithelium, acinar cells, connective
CC tissue, and lymphatic tissue. {ECO:0000269|PubMed:9140390}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Breast-ovarian cancer, familial, 2 (BROVCA2) [MIM:612555]: A
CC condition associated with familial predisposition to cancer of the
CC breast and ovaries. Characteristic features in affected families are an
CC early age of onset of breast cancer (often before age 50), increased
CC chance of bilateral cancers (cancer that develop in both breasts, or
CC both ovaries, independently), frequent occurrence of breast cancer
CC among men, increased incidence of tumors of other specific organs, such
CC as the prostate. Note=Disease susceptibility is associated with
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Fanconi anemia complementation group D1 (FANCD1) [MIM:605724]:
CC A disorder affecting all bone marrow elements and resulting in anemia,
CC leukopenia and thrombopenia. It is associated with cardiac, renal and
CC limb malformations, dermal pigmentary changes, and a predisposition to
CC the development of malignancies. At the cellular level it is associated
CC with hypersensitivity to DNA-damaging agents, chromosomal instability
CC (increased chromosome breakage) and defective DNA repair.
CC {ECO:0000269|PubMed:12065746, ECO:0000269|PubMed:14670928,
CC ECO:0000269|PubMed:16825431, ECO:0000269|PubMed:21719596,
CC ECO:0000269|PubMed:23108138}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Glioma 3 (GLM3) [MIM:613029]: Gliomas are benign or malignant
CC central nervous system neoplasms derived from glial cells. They
CC comprise astrocytomas and glioblastoma multiforme that are derived from
CC astrocytes, oligodendrogliomas derived from oligodendrocytes and
CC ependymomas derived from ependymocytes. {ECO:0000269|PubMed:15689453}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- WEB RESOURCE: Name=Fanconi Anemia Mutation Database;
CC URL="https://www2.rockefeller.edu/fanconi/genes/jumpd1";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/brca2/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=BRCA2 entry;
CC URL="https://en.wikipedia.org/wiki/BRCA2";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/BRCA2ID164ch13q13.html";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X95152; CAA64484.1; -; Genomic_DNA.
DR EMBL; X95153; CAA64484.1; JOINED; Genomic_DNA.
DR EMBL; X95154; CAA64484.1; JOINED; Genomic_DNA.
DR EMBL; X95155; CAA64484.1; JOINED; Genomic_DNA.
DR EMBL; X95156; CAA64484.1; JOINED; Genomic_DNA.
DR EMBL; X95157; CAA64484.1; JOINED; Genomic_DNA.
DR EMBL; X95158; CAA64484.1; JOINED; Genomic_DNA.
DR EMBL; X95159; CAA64484.1; JOINED; Genomic_DNA.
DR EMBL; X95160; CAA64484.1; JOINED; Genomic_DNA.
DR EMBL; X95161; CAA64484.1; JOINED; Genomic_DNA.
DR EMBL; X95162; CAA64484.1; JOINED; Genomic_DNA.
DR EMBL; X95163; CAA64484.1; JOINED; Genomic_DNA.
DR EMBL; X95164; CAA64484.1; JOINED; Genomic_DNA.
DR EMBL; X95165; CAA64484.1; JOINED; Genomic_DNA.
DR EMBL; X95166; CAA64484.1; JOINED; Genomic_DNA.
DR EMBL; X95167; CAA64484.1; JOINED; Genomic_DNA.
DR EMBL; X95168; CAA64484.1; JOINED; Genomic_DNA.
DR EMBL; X95169; CAA64484.1; JOINED; Genomic_DNA.
DR EMBL; X95170; CAA64484.1; JOINED; Genomic_DNA.
DR EMBL; X95171; CAA64484.1; JOINED; Genomic_DNA.
DR EMBL; X95172; CAA64484.1; JOINED; Genomic_DNA.
DR EMBL; X95173; CAA64484.1; JOINED; Genomic_DNA.
DR EMBL; X95174; CAA64484.1; JOINED; Genomic_DNA.
DR EMBL; X95175; CAA64484.1; JOINED; Genomic_DNA.
DR EMBL; X95176; CAA64484.1; JOINED; Genomic_DNA.
DR EMBL; X95177; CAA64484.1; JOINED; Genomic_DNA.
DR EMBL; U43746; AAB07223.1; -; mRNA.
DR EMBL; AY436640; AAQ97181.1; -; Genomic_DNA.
DR EMBL; AL137247; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL445212; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z74739; CAA98995.2; -; Genomic_DNA.
DR EMBL; Z73359; CAA97728.1; -; Genomic_DNA.
DR CCDS; CCDS9344.1; -.
DR PIR; G02334; G02334.
DR RefSeq; NP_000050.2; NM_000059.3.
DR PDB; 1N0W; X-ray; 1.70 A; B=1517-1551.
DR PDB; 3EU7; X-ray; 2.20 A; X=21-39.
DR PDB; 6GY2; X-ray; 3.11 A; C/D=194-210.
DR PDB; 6HQU; X-ray; 1.97 A; I/J/K/L/M/N=1226-1253, O=2054-2064.
DR PDB; 7BDX; X-ray; 2.60 A; E/F=2291-2343.
DR PDB; 7LDG; X-ray; 2.56 A; B/D=2271-2335.
DR PDBsum; 1N0W; -.
DR PDBsum; 3EU7; -.
DR PDBsum; 6GY2; -.
DR PDBsum; 6HQU; -.
DR PDBsum; 7BDX; -.
DR PDBsum; 7LDG; -.
DR SMR; P51587; -.
DR BioGRID; 107142; 236.
DR ComplexPortal; CPX-845; BRCA1-PALB2-BRCA2 homologous recombination DNA repair complex.
DR ComplexPortal; CPX-955; BRCC ubiquitin ligase complex.
DR CORUM; P51587; -.
DR DIP; DIP-24214N; -.
DR ELM; P51587; -.
DR IntAct; P51587; 56.
DR MINT; P51587; -.
DR STRING; 9606.ENSP00000369497; -.
DR BindingDB; P51587; -.
DR iPTMnet; P51587; -.
DR PhosphoSitePlus; P51587; -.
DR BioMuta; BRCA2; -.
DR DMDM; 14424438; -.
DR CPTAC; CPTAC-3279; -.
DR CPTAC; CPTAC-3280; -.
DR EPD; P51587; -.
DR jPOST; P51587; -.
DR MassIVE; P51587; -.
DR PaxDb; P51587; -.
DR PeptideAtlas; P51587; -.
DR PRIDE; P51587; -.
DR ProteomicsDB; 56340; -.
DR Antibodypedia; 7788; 332 antibodies from 41 providers.
DR DNASU; 675; -.
DR Ensembl; ENST00000380152.8; ENSP00000369497.3; ENSG00000139618.17.
DR Ensembl; ENST00000544455.6; ENSP00000439902.1; ENSG00000139618.17.
DR Ensembl; ENST00000680887.1; ENSP00000505508.1; ENSG00000139618.17.
DR GeneID; 675; -.
DR KEGG; hsa:675; -.
DR MANE-Select; ENST00000380152.8; ENSP00000369497.3; NM_000059.4; NP_000050.3.
DR UCSC; uc001uub.2; human.
DR CTD; 675; -.
DR DisGeNET; 675; -.
DR GeneCards; BRCA2; -.
DR GeneReviews; BRCA2; -.
DR HGNC; HGNC:1101; BRCA2.
DR HPA; ENSG00000139618; Tissue enhanced (bone marrow, lymphoid tissue, testis).
DR MalaCards; BRCA2; -.
DR MIM; 114480; phenotype.
DR MIM; 600185; gene.
DR MIM; 605724; phenotype.
DR MIM; 612555; phenotype.
DR MIM; 613029; phenotype.
DR MIM; 613347; phenotype.
DR neXtProt; NX_P51587; -.
DR OpenTargets; ENSG00000139618; -.
DR Orphanet; 70567; Cholangiocarcinoma.
DR Orphanet; 1333; Familial pancreatic carcinoma.
DR Orphanet; 1331; Familial prostate cancer.
DR Orphanet; 84; Fanconi anemia.
DR Orphanet; 145; Hereditary breast and ovarian cancer syndrome.
DR Orphanet; 227535; Hereditary breast cancer.
DR Orphanet; 213524; Hereditary site-specific ovarian cancer syndrome.
DR Orphanet; 319462; Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations.
DR Orphanet; 654; Nephroblastoma.
DR Orphanet; 618572; Selection of therapeutic option in ovarian cancer.
DR PharmGKB; PA25412; -.
DR VEuPathDB; HostDB:ENSG00000139618; -.
DR eggNOG; KOG4751; Eukaryota.
DR GeneTree; ENSGT00390000003602; -.
DR HOGENOM; CLU_000344_0_0_1; -.
DR InParanoid; P51587; -.
DR OrthoDB; 257485at2759; -.
DR PhylomeDB; P51587; -.
DR TreeFam; TF105041; -.
DR PathwayCommons; P51587; -.
DR Reactome; R-HSA-5685939; HDR through MMEJ (alt-NHEJ).
DR Reactome; R-HSA-5685942; HDR through Homologous Recombination (HRR).
DR Reactome; R-HSA-5693554; Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA).
DR Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR Reactome; R-HSA-5693579; Homologous DNA Pairing and Strand Exchange.
DR Reactome; R-HSA-5693616; Presynaptic phase of homologous DNA pairing and strand exchange.
DR Reactome; R-HSA-912446; Meiotic recombination.
DR Reactome; R-HSA-9701192; Defective HDR through Homologous Recombination (HRR) due to BRCA1 loss-of-function.
DR Reactome; R-HSA-9704331; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function.
DR Reactome; R-HSA-9704646; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function.
DR Reactome; R-HSA-9709275; Impaired BRCA2 translocation to the nucleus.
DR Reactome; R-HSA-9709570; Impaired BRCA2 binding to RAD51.
DR Reactome; R-HSA-9709603; Impaired BRCA2 binding to PALB2.
DR Reactome; R-HSA-9763198; Impaired BRCA2 binding to SEM1 (DSS1).
DR SignaLink; P51587; -.
DR SIGNOR; P51587; -.
DR BioGRID-ORCS; 675; 323 hits in 1089 CRISPR screens.
DR ChiTaRS; BRCA2; human.
DR EvolutionaryTrace; P51587; -.
DR GeneWiki; BRCA2; -.
DR GenomeRNAi; 675; -.
DR Pharos; P51587; Tbio.
DR PRO; PR:P51587; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; P51587; protein.
DR Bgee; ENSG00000139618; Expressed in secondary oocyte and 114 other tissues.
DR ExpressionAtlas; P51587; baseline and differential.
DR Genevisible; P51587; HS.
DR GO; GO:0033593; C:BRCA2-MAGE-D1 complex; IDA:UniProtKB.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0000781; C:chromosome, telomeric region; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:1990391; C:DNA repair complex; IPI:ComplexPortal.
DR GO; GO:0000800; C:lateral element; IDA:MGI.
DR GO; GO:0000152; C:nuclear ubiquitin ligase complex; IDA:ComplexPortal.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0030141; C:secretory granule; IDA:UniProtKB.
DR GO; GO:0043015; F:gamma-tubulin binding; IPI:UniProtKB.
DR GO; GO:0010484; F:H3 histone acetyltransferase activity; IDA:UniProtKB.
DR GO; GO:0010485; F:H4 histone acetyltransferase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0002020; F:protease binding; IPI:UniProtKB.
DR GO; GO:0008022; F:protein C-terminus binding; IDA:MGI.
DR GO; GO:0003697; F:single-stranded DNA binding; IDA:UniProtKB.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0071479; P:cellular response to ionizing radiation; IMP:ComplexPortal.
DR GO; GO:0090398; P:cellular senescence; IEA:Ensembl.
DR GO; GO:0051298; P:centrosome duplication; IMP:UniProtKB.
DR GO; GO:0006978; P:DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; IEA:Ensembl.
DR GO; GO:0006302; P:double-strand break repair; IMP:UniProtKB.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IDA:UniProtKB.
DR GO; GO:0070200; P:establishment of protein localization to telomere; IDA:BHF-UCL.
DR GO; GO:0008585; P:female gonad development; IEA:Ensembl.
DR GO; GO:0071425; P:hematopoietic stem cell proliferation; IEA:Ensembl.
DR GO; GO:0035518; P:histone H2A monoubiquitination; IC:ComplexPortal.
DR GO; GO:0043966; P:histone H3 acetylation; IDA:UniProtKB.
DR GO; GO:0043967; P:histone H4 acetylation; IDA:UniProtKB.
DR GO; GO:0001833; P:inner cell mass cell proliferation; IEA:Ensembl.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IEA:Ensembl.
DR GO; GO:0007141; P:male meiosis I; IEA:Ensembl.
DR GO; GO:1990426; P:mitotic recombination-dependent replication fork processing; IMP:BHF-UCL.
DR GO; GO:0033600; P:negative regulation of mammary gland epithelial cell proliferation; IDA:UniProtKB.
DR GO; GO:0006289; P:nucleotide-excision repair; IMP:UniProtKB.
DR GO; GO:0001556; P:oocyte maturation; IEA:Ensembl.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; IC:ComplexPortal.
DR GO; GO:0032465; P:regulation of cytokinesis; IEA:Ensembl.
DR GO; GO:2000001; P:regulation of DNA damage checkpoint; IC:ComplexPortal.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR GO; GO:0048478; P:replication fork protection; IEA:Ensembl.
DR GO; GO:0010332; P:response to gamma radiation; IEA:Ensembl.
DR GO; GO:0010225; P:response to UV-C; IEA:Ensembl.
DR GO; GO:0010165; P:response to X-ray; IEA:Ensembl.
DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR GO; GO:0000722; P:telomere maintenance via recombination; IEA:Ensembl.
DR CDD; cd04493; BRCA2DBD_OB1; 1.
DR CDD; cd04495; BRCA2DBD_OB3; 1.
DR DisProt; DP01869; -.
DR Gene3D; 2.40.50.140; -; 3.
DR IDEAL; IID00237; -.
DR InterPro; IPR015525; BRCA2.
DR InterPro; IPR015252; BRCA2_hlx.
DR InterPro; IPR036315; BRCA2_hlx_sf.
DR InterPro; IPR015187; BRCA2_OB_1.
DR InterPro; IPR015188; BRCA2_OB_3.
DR InterPro; IPR002093; BRCA2_repeat.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR InterPro; IPR015205; Tower_dom.
DR PANTHER; PTHR11289; PTHR11289; 1.
DR Pfam; PF09169; BRCA-2_helical; 1.
DR Pfam; PF09103; BRCA-2_OB1; 1.
DR Pfam; PF09104; BRCA-2_OB3; 1.
DR Pfam; PF00634; BRCA2; 7.
DR Pfam; PF09121; Tower; 1.
DR PIRSF; PIRSF002397; BRCA2; 1.
DR SMART; SM01341; Tower; 1.
DR SUPFAM; SSF50249; SSF50249; 3.
DR SUPFAM; SSF81872; SSF81872; 1.
DR PROSITE; PS50138; BRCA2_REPEAT; 8.
PE 1: Evidence at protein level;
KW 3D-structure; Cell cycle; Cytoplasm; Cytoskeleton; Disease variant;
KW DNA damage; DNA recombination; DNA repair; DNA-binding; Fanconi anemia;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Tumor suppressor;
KW Ubl conjugation.
FT CHAIN 1..3418
FT /note="Breast cancer type 2 susceptibility protein"
FT /id="PRO_0000064984"
FT REPEAT 1002..1036
FT /note="BRCA2 1"
FT REPEAT 1212..1246
FT /note="BRCA2 2"
FT REPEAT 1421..1455
FT /note="BRCA2 3"
FT REPEAT 1517..1551
FT /note="BRCA2 4"
FT REPEAT 1664..1698
FT /note="BRCA2 5"
FT REPEAT 1837..1871
FT /note="BRCA2 6"
FT REPEAT 1971..2005
FT /note="BRCA2 7"
FT REPEAT 2051..2085
FT /note="BRCA2 8"
FT REGION 1..40
FT /note="Interaction with PALB2"
FT REGION 37..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 358..381
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 639..1000
FT /note="Interaction with NPM1"
FT /evidence="ECO:0000269|PubMed:21084279"
FT REGION 1003..2082
FT /note="Interaction with RAD51"
FT /evidence="ECO:0000250|UniProtKB:P97929"
FT REGION 1338..1781
FT /note="Interaction with POLH"
FT /evidence="ECO:0000269|PubMed:24485656"
FT REGION 1410..1595
FT /note="Required for stimulation of POLH DNA polymerization
FT activity"
FT REGION 2270..2337
FT /note="Interaction with HSF2BP"
FT /evidence="ECO:0000269|PubMed:31242413"
FT REGION 2350..2545
FT /note="Interaction with FANCD2"
FT REGION 2430..2450
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2481..2832
FT /note="Interaction with SEM1"
FT /evidence="ECO:0000269|PubMed:10373512,
FT ECO:0000269|PubMed:16205630"
FT REGION 3393..3418
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 2682..2698
FT /note="Nuclear export signal; masked by interaction with
FT SEM1"
FT /evidence="ECO:0000269|PubMed:24013206"
FT COMPBIAS 362..378
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3398..3418
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 70
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 445
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 492
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 755
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332"
FT MOD_RES 1970
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2035
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2095
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 3291
FT /note="Phosphoserine; by CDK1 and CDK2"
FT /evidence="ECO:0000269|PubMed:15800615"
FT MOD_RES 3319
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 3387
FT /note="Phosphothreonine; by CHEK1 and CHEK2"
FT /evidence="ECO:0000269|PubMed:18317453"
FT VARIANT 25
FT /note="G -> R (in BC; abolishes interaction with PALB2;
FT dbSNP:rs80358961)"
FT /evidence="ECO:0000269|PubMed:16793542"
FT /id="VAR_028167"
FT VARIANT 31
FT /note="W -> C (in BC; abolishes interaction with PALB2;
FT dbSNP:rs80359214)"
FT /evidence="ECO:0000269|PubMed:16793542"
FT /id="VAR_028168"
FT VARIANT 31
FT /note="W -> R (in BC; abolishes interaction with PALB2;
FT dbSNP:rs80359182)"
FT /evidence="ECO:0000269|PubMed:16793542"
FT /id="VAR_028169"
FT VARIANT 32
FT /note="F -> L (in BC; dbSNP:rs397508057 and
FT dbSNP:rs1555280339)"
FT /evidence="ECO:0000269|PubMed:9609997"
FT /id="VAR_005085"
FT VARIANT 42
FT /note="Y -> C (in BC and ovarian cancer; unknown
FT pathological significance; dbSNP:rs4987046)"
FT /evidence="ECO:0000269|PubMed:12442275,
FT ECO:0000269|PubMed:14746861"
FT /id="VAR_020705"
FT VARIANT 53
FT /note="K -> R (in BC; dbSNP:rs397507595)"
FT /evidence="ECO:0000269|PubMed:9609997"
FT /id="VAR_005086"
FT VARIANT 60
FT /note="N -> S (in BC; unknown pathological significance;
FT dbSNP:rs80358463)"
FT /evidence="ECO:0000269|PubMed:15026808"
FT /id="VAR_020706"
FT VARIANT 64
FT /note="T -> I (in BC; dbSNP:rs397507615)"
FT /evidence="ECO:0000269|PubMed:15172753"
FT /id="VAR_032712"
FT VARIANT 75
FT /note="A -> P (in ovarian cancer and renal cancer; unknown
FT pathological significance; dbSNP:rs28897701)"
FT /evidence="ECO:0000269|PubMed:10486320"
FT /id="VAR_005087"
FT VARIANT 81
FT /note="F -> L (in BC; dbSNP:rs80358507)"
FT /evidence="ECO:0000269|PubMed:9609997"
FT /id="VAR_005088"
FT VARIANT 108
FT /note="N -> H (in dbSNP:rs80358567)"
FT /id="VAR_008766"
FT VARIANT 118
FT /note="R -> H (in one patient with esophageal carcinoma;
FT dbSNP:rs80358603)"
FT /evidence="ECO:0000269|PubMed:11948123"
FT /id="VAR_032713"
FT VARIANT 192
FT /note="M -> T (in one patient with pancreatic cancer;
FT dbSNP:rs80358805)"
FT /evidence="ECO:0000269|PubMed:12097290"
FT /id="VAR_032714"
FT VARIANT 201
FT /note="P -> R (in BC; dbSNP:rs397507822)"
FT /evidence="ECO:0000269|PubMed:9609997"
FT /id="VAR_005089"
FT VARIANT 211
FT /note="V -> A (in BC)"
FT /evidence="ECO:0000269|PubMed:9609997"
FT /id="VAR_005090"
FT VARIANT 222
FT /note="P -> S (in BC; dbSNP:rs397507873)"
FT /evidence="ECO:0000269|PubMed:9609997"
FT /id="VAR_005091"
FT VARIANT 225
FT /note="T -> A (in one patient with BC; normal RNA
FT expression and splicing; dbSNP:rs80358897)"
FT /evidence="ECO:0000269|PubMed:15300854"
FT /id="VAR_032715"
FT VARIANT 289
FT /note="N -> H (in dbSNP:rs766173)"
FT /evidence="ECO:0000269|PubMed:10323242,
FT ECO:0000269|PubMed:10978364, ECO:0000269|PubMed:11149425,
FT ECO:0000269|PubMed:12552570, ECO:0000269|PubMed:15172753,
FT ECO:0000269|PubMed:15365993, ECO:0000269|Ref.3"
FT /id="VAR_005092"
FT VARIANT 315
FT /note="C -> S (in one patient with esophageal carcinoma;
FT dbSNP:rs79483201)"
FT /evidence="ECO:0000269|PubMed:11948123"
FT /id="VAR_032716"
FT VARIANT 322
FT /note="K -> Q (in dbSNP:rs11571640)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_018908"
FT VARIANT 326
FT /note="S -> R (in BC; dbSNP:rs28897706)"
FT /evidence="ECO:0000269|PubMed:10399947"
FT /id="VAR_032717"
FT VARIANT 327
FT /note="K -> E (in BC; unknown pathological significance;
FT dbSNP:rs80359242)"
FT /id="VAR_008767"
FT VARIANT 355
FT /note="V -> L (in lung cancer)"
FT /id="VAR_005093"
FT VARIANT 372
FT /note="N -> H (in dbSNP:rs144848)"
FT /evidence="ECO:0000269|PubMed:10323242,
FT ECO:0000269|PubMed:10978364, ECO:0000269|PubMed:11062481,
FT ECO:0000269|PubMed:12552570, ECO:0000269|PubMed:15057823,
FT ECO:0000269|PubMed:15172753, ECO:0000269|PubMed:15365993,
FT ECO:0000269|PubMed:8665505, ECO:0000269|PubMed:8673091,
FT ECO:0000269|Ref.3"
FT /id="VAR_005094"
FT VARIANT 405
FT /note="G -> R (in BC; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:15026808"
FT /id="VAR_020707"
FT VARIANT 431
FT /note="T -> I (in BC; unknown pathological significance;
FT dbSNP:rs876660828)"
FT /evidence="ECO:0000269|PubMed:12938098"
FT /id="VAR_020708"
FT VARIANT 448
FT /note="R -> H (in BC; unknown pathological significance;
FT dbSNP:rs80358423)"
FT /evidence="ECO:0000269|PubMed:15026808"
FT /id="VAR_020709"
FT VARIANT 462
FT /note="E -> G (in BC; unknown pathological significance;
FT dbSNP:rs56403624)"
FT /evidence="ECO:0000269|PubMed:12552570,
FT ECO:0000269|PubMed:15026808, ECO:0000269|PubMed:15172753"
FT /id="VAR_020710"
FT VARIANT 505
FT /note="I -> T (in BC; dbSNP:rs28897708)"
FT /evidence="ECO:0000269|PubMed:11241844"
FT /id="VAR_032718"
FT VARIANT 513
FT /note="K -> R (in dbSNP:rs28897709)"
FT /id="VAR_056751"
FT VARIANT 554
FT /note="C -> W (in BC and pancreas cancer;
FT dbSNP:rs80358451)"
FT /evidence="ECO:0000269|PubMed:9654203"
FT /id="VAR_005095"
FT VARIANT 582
FT /note="T -> P (in dbSNP:rs80358457)"
FT /evidence="ECO:0000269|PubMed:12624724"
FT /id="VAR_008768"
FT VARIANT 598
FT /note="T -> A (in dbSNP:rs28897710)"
FT /evidence="ECO:0000269|PubMed:12215251"
FT /id="VAR_020711"
FT VARIANT 599
FT /note="S -> F (in dbSNP:rs1046984)"
FT /evidence="ECO:0000269|PubMed:8589730"
FT /id="VAR_035436"
FT VARIANT 606
FT /note="P -> L (in dbSNP:rs80358469)"
FT /evidence="ECO:0000269|PubMed:26566883"
FT /id="VAR_076440"
FT VARIANT 613
FT /note="L -> R (in BC; unknown pathological significance;
FT dbSNP:rs587780646)"
FT /evidence="ECO:0000269|PubMed:12442275"
FT /id="VAR_020712"
FT VARIANT 630
FT /note="T -> I (in ovarian cancer; dbSNP:rs80358479)"
FT /id="VAR_005096"
FT VARIANT 707
FT /note="D -> Y (in dbSNP:rs80358487)"
FT /id="VAR_008769"
FT VARIANT 728
FT /note="D -> A (in BC; dbSNP:rs757577670)"
FT /id="VAR_005097"
FT VARIANT 729
FT /note="I -> M (in BC; dbSNP:rs397507620)"
FT /evidence="ECO:0000269|PubMed:10978364"
FT /id="VAR_032719"
FT VARIANT 784
FT /note="M -> V (in dbSNP:rs11571653)"
FT /evidence="ECO:0000269|PubMed:11149425,
FT ECO:0000269|PubMed:15365993, ECO:0000269|Ref.3"
FT /id="VAR_008770"
FT VARIANT 886
FT /note="N -> I (in dbSNP:rs80358526)"
FT /id="VAR_008771"
FT VARIANT 929
FT /note="L -> S (in dbSNP:rs2227943)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_018909"
FT VARIANT 935
FT /note="D -> N (in BC; unknown pathological significance;
FT dbSNP:rs28897716)"
FT /id="VAR_008772"
FT VARIANT 976
FT /note="S -> F (in dbSNP:rs11571656)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_018910"
FT VARIANT 982
FT /note="I -> L (in dbSNP:rs28897717)"
FT /id="VAR_056752"
FT VARIANT 987
FT /note="N -> I (in dbSNP:rs2227944)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_018911"
FT VARIANT 991
FT /note="N -> D (in dbSNP:rs1799944)"
FT /evidence="ECO:0000269|PubMed:10323242,
FT ECO:0000269|PubMed:10978364, ECO:0000269|PubMed:12552570,
FT ECO:0000269|PubMed:15026808, ECO:0000269|PubMed:15172753,
FT ECO:0000269|PubMed:15365993, ECO:0000269|PubMed:8673091,
FT ECO:0000269|Ref.3"
FT /id="VAR_005098"
FT VARIANT 1036
FT /note="E -> K (in BC; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:12938098"
FT /id="VAR_020713"
FT VARIANT 1106
FT /note="S -> R (in BC; unknown pathological significance;
FT dbSNP:rs1298550035)"
FT /evidence="ECO:0000269|PubMed:12938098"
FT /id="VAR_020714"
FT VARIANT 1147
FT /note="N -> S (in dbSNP:rs1799951)"
FT /evidence="ECO:0000269|PubMed:8673091"
FT /id="VAR_005099"
FT VARIANT 1172
FT /note="S -> L (in BC; unknown pathological significance;
FT dbSNP:rs80358600)"
FT /evidence="ECO:0000269|PubMed:15635067"
FT /id="VAR_032720"
FT VARIANT 1179
FT /note="S -> N (in BC; dbSNP:rs397507674)"
FT /evidence="ECO:0000269|PubMed:11139248"
FT /id="VAR_020715"
FT VARIANT 1279
FT /note="N -> S (in dbSNP:rs1060502384)"
FT /evidence="ECO:0000269|PubMed:12552570,
FT ECO:0000269|PubMed:15172753"
FT /id="VAR_020716"
FT VARIANT 1286
FT /note="Missing"
FT /id="VAR_008773"
FT VARIANT 1290
FT /note="C -> Y (in dbSNP:rs41293485)"
FT /id="VAR_008774"
FT VARIANT 1302
FT /note="Missing (in BC)"
FT /id="VAR_005100"
FT VARIANT 1414
FT /note="T -> M (in dbSNP:rs70953664)"
FT /id="VAR_008775"
FT VARIANT 1420
FT /note="D -> Y (in dbSNP:rs28897727)"
FT /evidence="ECO:0000269|PubMed:11139248,
FT ECO:0000269|PubMed:12215251, ECO:0000269|PubMed:12552570,
FT ECO:0000269|PubMed:15172753, ECO:0000269|PubMed:15635067,
FT ECO:0000269|PubMed:26566883"
FT /id="VAR_008776"
FT VARIANT 1445
FT /note="K -> T (in BC; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:15365993"
FT /id="VAR_020717"
FT VARIANT 1513
FT /note="D -> N (in dbSNP:rs80358687)"
FT /id="VAR_008777"
FT VARIANT 1522
FT /note="L -> F (in one patient with BC; dbSNP:rs397507729)"
FT /evidence="ECO:0000269|PubMed:12624724"
FT /id="VAR_032721"
FT VARIANT 1524
FT /note="F -> V (in BC; unknown pathological significance;
FT dbSNP:rs56386506)"
FT /evidence="ECO:0000269|PubMed:12938098"
FT /id="VAR_020718"
FT VARIANT 1529
FT /note="G -> R (in bladder cancer; dbSNP:rs28897728)"
FT /id="VAR_005101"
FT VARIANT 1542
FT /note="V -> M (in dbSNP:rs28897729)"
FT /id="VAR_056753"
FT VARIANT 1561
FT /note="H -> N (in dbSNP:rs2219594)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_018912"
FT VARIANT 1580
FT /note="C -> Y (in BC; somatic mutation; dbSNP:rs398122784)"
FT /evidence="ECO:0000269|PubMed:11948477"
FT /id="VAR_020719"
FT VARIANT 1593
FT /note="E -> D (in dbSNP:rs80358703)"
FT /evidence="ECO:0000269|PubMed:12442273"
FT /id="VAR_008778"
FT VARIANT 1643
FT /note="V -> A (in dbSNP:rs28897731)"
FT /id="VAR_056754"
FT VARIANT 1679
FT /note="T -> I (in BC)"
FT /evidence="ECO:0000269|PubMed:14722926"
FT /id="VAR_020720"
FT VARIANT 1690
FT /note="K -> N (in BC; dbSNP:rs56087561)"
FT /evidence="ECO:0000269|PubMed:15172753"
FT /id="VAR_032722"
FT VARIANT 1730
FT /note="N -> Y (in BC; dbSNP:rs397507770)"
FT /evidence="ECO:0000269|PubMed:11241844"
FT /id="VAR_032723"
FT VARIANT 1771
FT /note="G -> D (in BC; unknown pathological significance;
FT dbSNP:rs80358755)"
FT /evidence="ECO:0000269|PubMed:12552570,
FT ECO:0000269|PubMed:15172753"
FT /id="VAR_008779"
FT VARIANT 1804
FT /note="V -> A (in BC; dbSNP:rs370252983)"
FT /evidence="ECO:0000269|PubMed:14722926"
FT /id="VAR_020721"
FT VARIANT 1805
FT /note="N -> S (in dbSNP:rs80358765)"
FT /id="VAR_008780"
FT VARIANT 1880
FT /note="N -> K (in dbSNP:rs11571657)"
FT /evidence="ECO:0000269|PubMed:11241844, ECO:0000269|Ref.3"
FT /id="VAR_005102"
FT VARIANT 1887
FT /note="T -> M (in BC; dbSNP:rs397507795)"
FT /evidence="ECO:0000269|PubMed:15172753"
FT /id="VAR_032724"
FT VARIANT 1901
FT /note="E -> K (in BC)"
FT /evidence="ECO:0000269|PubMed:14722926"
FT /id="VAR_020722"
FT VARIANT 1902
FT /note="D -> N (in dbSNP:rs4987048)"
FT /id="VAR_008781"
FT VARIANT 1915
FT /note="T -> M (in dbSNP:rs4987117)"
FT /evidence="ECO:0000269|PubMed:10978364,
FT ECO:0000269|PubMed:11948477, ECO:0000269|PubMed:15172753,
FT ECO:0000269|PubMed:8665505, ECO:0000269|PubMed:8673091,
FT ECO:0000269|Ref.3"
FT /id="VAR_005103"
FT VARIANT 1929
FT /note="I -> V (in BC; unknown pathological significance;
FT dbSNP:rs79538375)"
FT /evidence="ECO:0000269|PubMed:15365993"
FT /id="VAR_020723"
FT VARIANT 1979
FT /note="S -> R (in dbSNP:rs28897737)"
FT /id="VAR_056755"
FT VARIANT 1988
FT /note="V -> I (in one patient with esophageal carcinoma;
FT somatic mutation; dbSNP:rs28897739)"
FT /evidence="ECO:0000269|PubMed:11948123"
FT /id="VAR_032725"
FT VARIANT 2031
FT /note="T -> A (in BC; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:15365993"
FT /id="VAR_020724"
FT VARIANT 2034
FT /note="R -> C (in dbSNP:rs1799954)"
FT /evidence="ECO:0000269|PubMed:12215251,
FT ECO:0000269|PubMed:12569143, ECO:0000269|PubMed:8673091"
FT /id="VAR_005104"
FT VARIANT 2044
FT /note="G -> V (in one patient with BC; dbSNP:rs56191579)"
FT /evidence="ECO:0000269|PubMed:12624724"
FT /id="VAR_032726"
FT VARIANT 2072
FT /note="S -> C (in BC; dbSNP:rs80358862)"
FT /evidence="ECO:0000269|PubMed:12373604"
FT /id="VAR_020725"
FT VARIANT 2074
FT /note="H -> N (in dbSNP:rs34309943)"
FT /id="VAR_008782"
FT VARIANT 2089
FT /note="E -> D (in BC)"
FT /evidence="ECO:0000269|PubMed:9150152"
FT /id="VAR_008783"
FT VARIANT 2094
FT /note="Y -> C (in BC; dbSNP:rs397507838)"
FT /evidence="ECO:0000269|PubMed:12373604"
FT /id="VAR_020726"
FT VARIANT 2096
FT /note="P -> L (in BC)"
FT /evidence="ECO:0000269|PubMed:14722926"
FT /id="VAR_020727"
FT VARIANT 2108
FT /note="R -> C (in dbSNP:rs55794205)"
FT /evidence="ECO:0000269|PubMed:15172753"
FT /id="VAR_032727"
FT VARIANT 2116
FT /note="H -> R (in dbSNP:rs55953736)"
FT /id="VAR_061563"
FT VARIANT 2118
FT /note="V -> L (in BC; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:12442275"
FT /id="VAR_020728"
FT VARIANT 2128
FT /note="K -> N (in BC; dbSNP:rs397507847)"
FT /evidence="ECO:0000269|PubMed:12373604"
FT /id="VAR_020729"
FT VARIANT 2135
FT /note="N -> H (in BC; dbSNP:rs80358876)"
FT /evidence="ECO:0000269|PubMed:11241844"
FT /id="VAR_032728"
FT VARIANT 2138
FT /note="V -> F (in dbSNP:rs11571659)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_008784"
FT VARIANT 2162
FT /note="K -> R (in dbSNP:rs11571660)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_018913"
FT VARIANT 2222
FT /note="Y -> C (in BC; dbSNP:rs397507875)"
FT /evidence="ECO:0000269|PubMed:11241844"
FT /id="VAR_032729"
FT VARIANT 2238
FT /note="D -> E (in dbSNP:rs28897742)"
FT /id="VAR_056756"
FT VARIANT 2274
FT /note="G -> V (in BC; dbSNP:rs55712212)"
FT /id="VAR_005105"
FT VARIANT 2275
FT /note="E -> G (in BC; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:15026808"
FT /id="VAR_020730"
FT VARIANT 2293
FT /note="F -> L (in BC; unknown pathological significance;
FT dbSNP:rs80358912 and dbSNP:rs1381512588)"
FT /evidence="ECO:0000269|PubMed:12442275"
FT /id="VAR_020731"
FT VARIANT 2336
FT /note="R -> H (in FANCD1; affects protein splicing and
FT expression; decreases homologous recombination-mediated DNA
FT repair; dbSNP:rs28897743)"
FT /evidence="ECO:0000269|PubMed:16825431,
FT ECO:0000269|PubMed:17924331, ECO:0000269|PubMed:21719596"
FT /id="VAR_032730"
FT VARIANT 2336
FT /note="R -> Q (in dbSNP:rs28897743)"
FT /id="VAR_056757"
FT VARIANT 2353
FT /note="G -> R (in BC; unknown pathological significance;
FT dbSNP:rs80358935)"
FT /evidence="ECO:0000269|PubMed:15026808"
FT /id="VAR_020732"
FT VARIANT 2415
FT /note="H -> N (in BC)"
FT /evidence="ECO:0000269|PubMed:8640237"
FT /id="VAR_005106"
FT VARIANT 2421
FT /note="Q -> H (in BC)"
FT /id="VAR_005107"
FT VARIANT 2440
FT /note="H -> R (benign variant; no effect on homology-
FT directed repair activity; dbSNP:rs4986860)"
FT /evidence="ECO:0000269|PubMed:23108138, ECO:0000269|Ref.3"
FT /id="VAR_018914"
FT VARIANT 2447
FT /note="N -> D (in dbSNP:rs4986859)"
FT /id="VAR_056758"
FT VARIANT 2456
FT /note="Q -> E (in BC; dbSNP:rs397507912)"
FT /evidence="ECO:0000269|PubMed:15172753"
FT /id="VAR_032731"
FT VARIANT 2466
FT /note="V -> A (in BC; benign variant; no effect on
FT homology-directed repair activity; dbSNP:rs169547)"
FT /evidence="ECO:0000269|PubMed:12552570,
FT ECO:0000269|PubMed:15057823, ECO:0000269|PubMed:15172753,
FT ECO:0000269|PubMed:23108138, ECO:0000269|PubMed:8524414,
FT ECO:0000269|PubMed:8589730, ECO:0000269|PubMed:8665505,
FT ECO:0000269|Ref.3"
FT /id="VAR_008785"
FT VARIANT 2480
FT /note="L -> V (in dbSNP:rs80358965)"
FT /id="VAR_008786"
FT VARIANT 2488
FT /note="R -> K (in BC; unknown pathological significance;
FT dbSNP:rs80358968)"
FT /evidence="ECO:0000269|PubMed:15026808"
FT /id="VAR_020733"
FT VARIANT 2490
FT /note="I -> T (benign variant; no effect on homologous
FT recombination-mediated DNA repair; no effect on interaction
FT with SEM1; dbSNP:rs11571707)"
FT /evidence="ECO:0000269|PubMed:21719596, ECO:0000269|Ref.3"
FT /id="VAR_008787"
FT VARIANT 2502
FT /note="R -> C (in BC; unknown pathological significance;
FT dbSNP:rs55716624)"
FT /evidence="ECO:0000269|PubMed:17924331"
FT /id="VAR_063911"
FT VARIANT 2502
FT /note="R -> H (in ovarian cancer; unknown pathological
FT significance; dbSNP:rs56070345)"
FT /evidence="ECO:0000269|PubMed:10486320"
FT /id="VAR_008788"
FT VARIANT 2510
FT /note="L -> P (in FANCD1; hypersensitive to DNA damage;
FT disrupts interaction with SEM1; decreased homology-directed
FT repair activity; dbSNP:rs80358979)"
FT /evidence="ECO:0000269|PubMed:14670928,
FT ECO:0000269|PubMed:21719596, ECO:0000269|PubMed:23108138"
FT /id="VAR_032732"
FT VARIANT 2515
FT /note="T -> I (in BC; unknown pathological significance;
FT dbSNP:rs28897744)"
FT /evidence="ECO:0000269|PubMed:10978364"
FT /id="VAR_008789"
FT VARIANT 2626
FT /note="W -> C (in FANCD1; hypersensitive to DNA damage;
FT reduced homology-directed repair activity; no effect on
FT interaction with SEM1; dbSNP:rs80359013)"
FT /evidence="ECO:0000269|PubMed:16825431,
FT ECO:0000269|PubMed:17924331, ECO:0000269|PubMed:21719596,
FT ECO:0000269|PubMed:23108138"
FT /id="VAR_032733"
FT VARIANT 2627
FT /note="I -> F (in BC; unknown pathological significance;
FT reduced homology-directed repair activity;
FT dbSNP:rs80359014)"
FT /evidence="ECO:0000269|PubMed:17924331,
FT ECO:0000269|PubMed:23108138"
FT /id="VAR_063912"
FT VARIANT 2653
FT /note="L -> P (in BC; unknown pathological significance;
FT reduced homology-directed repair activity;
FT dbSNP:rs80359022)"
FT /evidence="ECO:0000269|PubMed:17924331,
FT ECO:0000269|PubMed:23108138"
FT /id="VAR_063913"
FT VARIANT 2659
FT /note="R -> K (in BC; unknown pathological significance;
FT dbSNP:rs80359027)"
FT /evidence="ECO:0000269|PubMed:17924331"
FT /id="VAR_063914"
FT VARIANT 2663
FT /note="E -> V (probable disease-associated variant; may be
FT associated with cancer susceptibility; major splicing
FT aberration identified with this mutant; multifactorial
FT likelihood analysis provides evidence for pathogenicity;
FT dbSNP:rs80359031)"
FT /evidence="ECO:0000269|PubMed:17924331,
FT ECO:0000269|PubMed:20513136"
FT /id="VAR_063915"
FT VARIANT 2686
FT /note="L -> P (in dbSNP:rs28897746)"
FT /id="VAR_056759"
FT VARIANT 2706
FT /note="N -> S (in dbSNP:rs80359055)"
FT /evidence="ECO:0000269|PubMed:12442273"
FT /id="VAR_020734"
FT VARIANT 2722
FT /note="T -> R (in BC; reduced homology-directed repair
FT activity; dbSNP:rs80359062)"
FT /evidence="ECO:0000269|PubMed:12145750,
FT ECO:0000269|PubMed:17924331, ECO:0000269|PubMed:23108138"
FT /id="VAR_018661"
FT VARIANT 2723
FT /note="D -> G (in BC; has defective function consistent
FT with pathogenicity; major splicing aberration identified
FT with this mutant; reduced homology-directed repair
FT activity; dbSNP:rs41293513)"
FT /evidence="ECO:0000269|PubMed:17924331,
FT ECO:0000269|PubMed:20513136, ECO:0000269|PubMed:23108138"
FT /id="VAR_063916"
FT VARIANT 2723
FT /note="D -> H (in BC; unknown pathological significance;
FT disrupts interaction with SEM1 promoting interaction with
FT XPO1 and BRCA2 cytoplasmic localization; in heterozygous
FT state promotes RAD51 cytoplasmic localization; reduced
FT homology-directed repair activity; dbSNP:rs41293511)"
FT /evidence="ECO:0000269|PubMed:15026808,
FT ECO:0000269|PubMed:23108138, ECO:0000269|PubMed:24013206"
FT /id="VAR_020735"
FT VARIANT 2728
FT /note="V -> I (in BC; dbSNP:rs28897749)"
FT /evidence="ECO:0000269|PubMed:10399947,
FT ECO:0000269|PubMed:10978364, ECO:0000269|PubMed:12215251"
FT /id="VAR_020736"
FT VARIANT 2729
FT /note="K -> N (in BC; unknown pathological significance; no
FT effect on homologous recombination-mediated DNA repair; no
FT effect on interaction with SEM1; dbSNP:rs80359065)"
FT /evidence="ECO:0000269|PubMed:12442274,
FT ECO:0000269|PubMed:21719596, ECO:0000269|PubMed:23108138"
FT /id="VAR_020737"
FT VARIANT 2748
FT /note="G -> D (in BC; unknown pathological significance;
FT dbSNP:rs80359071)"
FT /evidence="ECO:0000269|PubMed:17924331"
FT /id="VAR_063917"
FT VARIANT 2787
FT /note="R -> H (in ovarian cancer and BC; somatic mutation;
FT unknown pathological significance; small decrease of
FT homology-directed repair activity; dbSNP:rs80359078)"
FT /evidence="ECO:0000269|PubMed:23108138,
FT ECO:0000269|PubMed:8665505"
FT /id="VAR_008790"
FT VARIANT 2792
FT /note="L -> P (in BC; unknown pathological significance;
FT decreased homology-directed repair activity;
FT dbSNP:rs28897751)"
FT /evidence="ECO:0000269|PubMed:23108138"
FT /id="VAR_056760"
FT VARIANT 2793
FT /note="G -> R (in BC; unknown pathological significance;
FT decreased homology-directed repair activity;
FT dbSNP:rs80359082)"
FT /evidence="ECO:0000269|PubMed:12442275,
FT ECO:0000269|PubMed:23108138"
FT /id="VAR_020738"
FT VARIANT 2835
FT /note="S -> P (in dbSNP:rs11571746)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_018915"
FT VARIANT 2842
FT /note="R -> C (in one patient with esophageal carcinoma;
FT somatic mutation; decreased homology-directed repair
FT activity; dbSNP:rs80359104)"
FT /evidence="ECO:0000269|PubMed:11948123,
FT ECO:0000269|PubMed:23108138"
FT /id="VAR_032734"
FT VARIANT 2856
FT /note="E -> A (in BC; unknown pathological significance; no
FT effect on homology-directed repair activity;
FT dbSNP:rs11571747)"
FT /evidence="ECO:0000269|PubMed:15026808,
FT ECO:0000269|PubMed:23108138, ECO:0000269|Ref.3"
FT /id="VAR_018916"
FT VARIANT 2944
FT /note="I -> F (in dbSNP:rs4987047)"
FT /evidence="ECO:0000269|PubMed:15635067, ECO:0000269|Ref.3"
FT /id="VAR_008791"
FT VARIANT 2950
FT /note="K -> N (in BC; unknown pathological significance;
FT dbSNP:rs28897754)"
FT /evidence="ECO:0000269|PubMed:15026808,
FT ECO:0000269|PubMed:15635067"
FT /id="VAR_020739"
FT VARIANT 2951
FT /note="A -> T (in BC; unknown pathological significance; no
FT effect on homology-directed repair activity;
FT dbSNP:rs11571769)"
FT /evidence="ECO:0000269|PubMed:12215251,
FT ECO:0000269|PubMed:23108138, ECO:0000269|Ref.3"
FT /id="VAR_008792"
FT VARIANT 2969
FT /note="V -> M (in dbSNP:rs59004709)"
FT /id="VAR_008793"
FT VARIANT 3013
FT /note="T -> I (in BC; unknown pathological significance; no
FT effect on homology-directed repair activity;
FT dbSNP:rs28897755)"
FT /evidence="ECO:0000269|PubMed:15026808,
FT ECO:0000269|PubMed:15635067, ECO:0000269|PubMed:23108138"
FT /id="VAR_020740"
FT VARIANT 3052
FT /note="R -> W (in BC; has defective function consistent
FT with pathogenicity; multifactorial likelihood analysis
FT provides evidence for pathogenicity; reduced 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 (in dbSNP:rs1801426)"
FT /evidence="ECO:0000269|PubMed:10323242,
FT ECO:0000269|PubMed:10978364, ECO:0000269|PubMed:12442274,
FT ECO:0000269|PubMed:14746861, ECO:0000269|PubMed:15026808,
FT ECO:0000269|PubMed:15365993, ECO:0000269|PubMed:9150152,
FT ECO:0000269|Ref.3"
FT /id="VAR_005112"
FT MUTAGEN 2725
FT /note="W->A: Disrupts interaction with SEM1."
FT /evidence="ECO:0000269|PubMed:24013206"
FT MUTAGEN 3291
FT /note="S->E: Impaired interaction with RAD51."
FT /evidence="ECO:0000269|PubMed:15800615"
FT MUTAGEN 3387
FT /note="T->A: Loss of phosphorylation by CHEK1 and CHEK2 (in
FT vitro)."
FT /evidence="ECO:0000269|PubMed:18317453"
FT CONFLICT 758
FT /note="S -> N (in Ref. 1; CAA64484)"
FT /evidence="ECO:0000305"
FT CONFLICT 1761..1762
FT /note="GY -> RI (in Ref. 1; CAA64484)"
FT /evidence="ECO:0000305"
FT CONFLICT 1767
FT /note="K -> N (in Ref. 1; CAA64484)"
FT /evidence="ECO:0000305"
FT CONFLICT 2536
FT /note="S -> P (in Ref. 4; CAA98995)"
FT /evidence="ECO:0000305"
FT CONFLICT 3216
FT /note="L -> LVS (in Ref. 4; CAA97728)"
FT /evidence="ECO:0000305"
FT HELIX 31..35
FT /evidence="ECO:0007829|PDB:3EU7"
FT STRAND 203..206
FT /evidence="ECO:0007829|PDB:6GY2"
FT STRAND 1228..1230
FT /evidence="ECO:0007829|PDB:6HQU"
FT HELIX 1231..1241
FT /evidence="ECO:0007829|PDB:6HQU"
FT HELIX 1520..1522
FT /evidence="ECO:0007829|PDB:1N0W"
FT HELIX 1536..1541
FT /evidence="ECO:0007829|PDB:1N0W"
FT TURN 1542..1546
FT /evidence="ECO:0007829|PDB:1N0W"
FT STRAND 2300..2302
FT /evidence="ECO:0007829|PDB:7LDG"
FT HELIX 2311..2314
FT /evidence="ECO:0007829|PDB:7LDG"
FT STRAND 2315..2317
FT /evidence="ECO:0007829|PDB:7LDG"
SQ SEQUENCE 3418 AA; 384230 MW; 98A48F16848D2644 CRC64;
MPIGSKERPT FFEIFKTRCN KADLGPISLN WFEELSSEAP PYNSEPAEES EHKNNNYEPN
LFKTPQRKPS YNQLASTPII FKEQGLTLPL YQSPVKELDK FKLDLGRNVP NSRHKSLRTV
KTKMDQADDV SCPLLNSCLS ESPVVLQCTH VTPQRDKSVV CGSLFHTPKF VKGRQTPKHI
SESLGAEVDP DMSWSSSLAT PPTLSSTVLI VRNEEASETV FPHDTTANVK SYFSNHDESL
KKNDRFIASV TDSENTNQRE AASHGFGKTS GNSFKVNSCK DHIGKSMPNV LEDEVYETVV
DTSEEDSFSL CFSKCRTKNL QKVRTSKTRK KIFHEANADE CEKSKNQVKE KYSFVSEVEP
NDTDPLDSNV ANQKPFESGS DKISKEVVPS LACEWSQLTL SGLNGAQMEK IPLLHISSCD
QNISEKDLLD TENKRKKDFL TSENSLPRIS SLPKSEKPLN EETVVNKRDE EQHLESHTDC
ILAVKQAISG TSPVASSFQG IKKSIFRIRE SPKETFNASF SGHMTDPNFK KETEASESGL
EIHTVCSQKE DSLCPNLIDN GSWPATTTQN SVALKNAGLI STLKKKTNKF IYAIHDETSY
KGKKIPKDQK SELINCSAQF EANAFEAPLT FANADSGLLH SSVKRSCSQN DSEEPTLSLT
SSFGTILRKC SRNETCSNNT VISQDLDYKE AKCNKEKLQL FITPEADSLS CLQEGQCEND
PKSKKVSDIK EEVLAAACHP VQHSKVEYSD TDFQSQKSLL YDHENASTLI LTPTSKDVLS
NLVMISRGKE SYKMSDKLKG NNYESDVELT KNIPMEKNQD VCALNENYKN VELLPPEKYM
RVASPSRKVQ FNQNTNLRVI QKNQEETTSI SKITVNPDSE ELFSDNENNF VFQVANERNN
LALGNTKELH ETDLTCVNEP IFKNSTMVLY GDTGDKQATQ VSIKKDLVYV LAEENKNSVK
QHIKMTLGQD LKSDISLNID KIPEKNNDYM NKWAGLLGPI SNHSFGGSFR TASNKEIKLS
EHNIKKSKMF FKDIEEQYPT SLACVEIVNT LALDNQKKLS KPQSINTVSA HLQSSVVVSD
CKNSHITPQM LFSKQDFNSN HNLTPSQKAE ITELSTILEE SGSQFEFTQF RKPSYILQKS
TFEVPENQMT ILKTTSEECR DADLHVIMNA PSIGQVDSSK QFEGTVEIKR KFAGLLKNDC
NKSASGYLTD ENEVGFRGFY SAHGTKLNVS TEALQKAVKL FSDIENISEE TSAEVHPISL
SSSKCHDSVV SMFKIENHND KTVSEKNNKC QLILQNNIEM TTGTFVEEIT ENYKRNTENE
DNKYTAASRN SHNLEFDGSD SSKNDTVCIH KDETDLLFTD QHNICLKLSG QFMKEGNTQI
KEDLSDLTFL EVAKAQEACH GNTSNKEQLT ATKTEQNIKD FETSDTFFQT ASGKNISVAK
ESFNKIVNFF DQKPEELHNF SLNSELHSDI RKNKMDILSY EETDIVKHKI LKESVPVGTG
NQLVTFQGQP ERDEKIKEPT LLGFHTASGK KVKIAKESLD KVKNLFDEKE QGTSEITSFS
HQWAKTLKYR EACKDLELAC ETIEITAAPK CKEMQNSLNN DKNLVSIETV VPPKLLSDNL
CRQTENLKTS KSIFLKVKVH ENVEKETAKS PATCYTNQSP YSVIENSALA FYTSCSRKTS
VSQTSLLEAK KWLREGIFDG QPERINTADY VGNYLYENNS NSTIAENDKN HLSEKQDTYL
SNSSMSNSYS YHSDEVYNDS GYLSKNKLDS GIEPVLKNVE DQKNTSFSKV ISNVKDANAY
PQTVNEDICV EELVTSSSPC KNKNAAIKLS ISNSNNFEVG PPAFRIASGK IVCVSHETIK
KVKDIFTDSF SKVIKENNEN KSKICQTKIM AGCYEALDDS EDILHNSLDN DECSTHSHKV
FADIQSEEIL QHNQNMSGLE KVSKISPCDV SLETSDICKC SIGKLHKSVS SANTCGIFST
ASGKSVQVSD ASLQNARQVF SEIEDSTKQV FSKVLFKSNE HSDQLTREEN TAIRTPEHLI
SQKGFSYNVV NSSAFSGFST ASGKQVSILE SSLHKVKGVL EEFDLIRTEH SLHYSPTSRQ
NVSKILPRVD KRNPEHCVNS EMEKTCSKEF KLSNNLNVEG GSSENNHSIK VSPYLSQFQQ
DKQQLVLGTK VSLVENIHVL GKEQASPKNV KMEIGKTETF SDVPVKTNIE VCSTYSKDSE
NYFETEAVEI AKAFMEDDEL TDSKLPSHAT HSLFTCPENE EMVLSNSRIG KRRGEPLILV
GEPSIKRNLL NEFDRIIENQ EKSLKASKST PDGTIKDRRL FMHHVSLEPI TCVPFRTTKE
RQEIQNPNFT APGQEFLSKS HLYEHLTLEK SSSNLAVSGH PFYQVSATRN EKMRHLITTG
RPTKVFVPPF KTKSHFHRVE QCVRNINLEE NRQKQNIDGH GSDDSKNKIN DNEIHQFNKN
NSNQAVAVTF TKCEEEPLDL ITSLQNARDI QDMRIKKKQR QRVFPQPGSL YLAKTSTLPR
ISLKAAVGGQ VPSACSHKQL YTYGVSKHCI KINSKNAESF QFHTEDYFGK ESLWTGKGIQ
LADGGWLIPS NDGKAGKEEF YRALCDTPGV DPKLISRIWV YNHYRWIIWK LAAMECAFPK
EFANRCLSPE RVLLQLKYRY DTEIDRSRRS AIKKIMERDD TAAKTLVLCV SDIISLSANI
SETSSNKTSS ADTQKVAIIE LTDGWYAVKA QLDPPLLAVL KNGRLTVGQK IILHGAELVG
SPDACTPLEA PESLMLKISA NSTRPARWYT KLGFFPDPRP FPLPLSSLFS DGGNVGCVDV
IIQRAYPIQW MEKTSSGLYI FRNEREEEKE AAKYVEAQQK RLEALFTKIQ EEFEEHEENT
TKPYLPSRAL TRQQVRALQD GAELYEAVKN AADPAYLEGY FSEEQLRALN NHRQMLNDKK
QAQIQLEIRK AMESAEQKEQ GLSRDVTTVW KLRIVSYSKK EKDSVILSIW RPSSDLYSLL
TEGKRYRIYH LATSKSKSKS ERANIQLAAT KKTQYQQLPV SDEILFQIYQ PREPLHFSKF
LDPDFQPSCS EVDLIGFVVS VVKKTGLAPF VYLSDECYNL LAIKFWIDLN EDIIKPHMLI
AASNLQWRPE SKSGLLTLFA GDFSVFSASP KEGHFQETFN KMKNTVENID ILCNEAENKL
MHILHANDPK WSTPTKDCTS GPYTAQIIPG TGNKLLMSSP NCEIYYQSPL SLCMAKRKSV
STPVSAQMTS KSCKGEKEID DQKNCKKRRA LDFLSRLPLP PPVSPICTFV SPAAQKAFQP
PRSCGTKYET PIKKKELNSP QMTPFKKFNE ISLLESNSIA DEELALINTQ ALLSGSTGEK
QFISVSESTR TAPTSSEDYL RLKRRCTTSL IKEQESSQAS TEECEKNKQD TITTKKYI
