BRCA1_HUMAN
ID BRCA1_HUMAN Reviewed; 1863 AA.
AC P38398; E9PFZ0; O15129; Q1RMC1; Q3LRJ0; Q3LRJ6; Q6IN79; Q7KYU9;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 2.
DT 03-AUG-2022, entry version 266.
DE RecName: Full=Breast cancer type 1 susceptibility protein;
DE EC=2.3.2.27 {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:12887909, ECO:0000269|PubMed:12890688, ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:18056443, ECO:0000269|PubMed:20351172};
DE AltName: Full=RING finger protein 53;
DE AltName: Full=RING-type E3 ubiquitin transferase BRCA1 {ECO:0000305};
GN Name=BRCA1; Synonyms=RNF53;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT BC ARG-1775.
RX PubMed=7545954; DOI=10.1126/science.7545954;
RA Miki Y., Swensen J., Shattuck-Eidens D., Futreal P.A., Harshman K.,
RA Tavtigian S., Liu Q., Cochran C., Bennett L.M., Ding W., Bell R.,
RA Rosenthal J., Hussey C., Tran T., McClure M., Frye C., Hattier T.,
RA Phelps R., Haugen-Strano A., Katcher H., Yakumo K., Gholami Z., Shaffer D.,
RA Stone S., Bayer S., Wray C., Bogden R., Dayananth P., Ward J., Tonin P.,
RA Narod S., Bristow P.K., Norris F.H., Helvering L., Morrison P., Rosteck P.,
RA Lai M., Barrett J.C., Lewis C., Neuhausen S., Cannon-Albright L.,
RA Godlgar D., Wiseman R., Kamb A., Skolnick M.H.;
RT "A strong candidate for the breast and ovarian cancer susceptibility gene
RT BRCA1.";
RL Science 266:66-71(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8938427; DOI=10.1101/gr.6.11.1029;
RA Smith T.M., Lee M.K., Szabo C.I., Jerome N., McEuen M., Taylor M., Hood L.,
RA King M.-C.;
RT "Complete genomic sequence and analysis of 117 kb of human DNA containing
RT the gene BRCA1.";
RL Genome Res. 6:1029-1049(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), SUBCELLULAR LOCATION (ISOFORM 2),
RP VARIANTS ARG-239 AND GLY-1613, AND TISSUE SPECIFICITY (ISOFORMS 1 AND 3).
RC TISSUE=Mammary gland;
RX PubMed=9010228; DOI=10.1038/sj.onc.1200924;
RA Wilson C.A., Payton M.N., Elliott G.S., Buaas F.W., Cajulis E.E.,
RA Grosshans D., Ramos L., Reese D.M., Slamon D.J., Calzone F.J.;
RT "Differential subcellular localization, expression and biological toxicity
RT of BRCA1 and the splice variant BRCA1-delta11b.";
RL Oncogene 14:1-16(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RA Holt J.T., Robinson-Benion C.;
RL Submitted (MAY-1997) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-356.
RA Raymond C.K., Paddock M., Subramanian S., Deodato C., Zhou Y., Haugen E.,
RA Kaul R., Olson M.V.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-275; ARG-356; ASN-693;
RP LEU-871; GLY-1038; ASN-1040; GLY-1140; ARG-1183; GLY-1613 AND ALA-1620.
RG NIEHS SNPs program;
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 6 AND 7), AND VARIANTS
RP LEU-871; GLY-1038; ARG-1183; GLY-1613 AND ILE-1652.
RC TISSUE=PNS;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 6-18 (ISOFORM 1), PROTEIN SEQUENCE OF 18-26 (ISOFORM
RP 4), AND ALTERNATIVE INITIATION (ISOFORM 4).
RX PubMed=10851077; DOI=10.1038/sj.onc.1203599;
RA Liu J., Prolla G., Rostagno A., Chiarle R., Feiner H., Inghirami G.;
RT "Initiation of translation from a downstream in-frame AUG codon on BRCA1
RT can generate the novel isoform protein DeltaBRCA1(17aa).";
RL Oncogene 19:2767-2773(2000).
RN [10]
RP ALTERNATIVE SPLICING (ISOFORM 5), AND SUBCELLULAR LOCATION (ISOFORM 5).
RX PubMed=8972225; DOI=10.1128/mcb.17.1.444;
RA Thakur S., Zhang H.B., Peng Y., Le H., Carroll B., Ward T., Yao J.,
RA Farid L.M., Couch F.J., Wilson R.B., Weber B.L.;
RT "Localization of BRCA1 and a splice variant identifies the nuclear
RT localization signal.";
RL Mol. Cell. Biol. 17:444-452(1997).
RN [11]
RP INTERACTION WITH DHX9.
RX PubMed=9662397; DOI=10.1038/930;
RA Anderson S.F., Schlegel B.P., Nakajima T., Wolpin E.S., Parvin J.D.;
RT "BRCA1 protein is linked to the RNA polymerase II holoenzyme complex via
RT RNA helicase A.";
RL Nat. Genet. 19:254-256(1998).
RN [12]
RP INTERACTION WITH BAP1, SUBCELLULAR LOCATION, VARIANTS GLY-61 AND GLY-64,
RP AND MUTAGENESIS OF ARG-71.
RX PubMed=9528852; DOI=10.1038/sj.onc.1201861;
RA Jensen D.E., Proctor M., Marquis S.T., Gardner H.P., Ha S.I., Chodosh L.A.,
RA Ishov A.M., Tommerup N., Vissing H., Sekido Y., Minna J., Borodovsky A.,
RA Schultz D.C., Wilkinson K.D., Maul G.G., Barlev N., Berger S.,
RA Prendergast G.C., Rauscher F.J. III;
RT "BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and
RT enhances BRCA1-mediated cell growth suppression.";
RL Oncogene 16:1097-1112(1998).
RN [13]
RP INTERACTION WITH RBBP8.
RX PubMed=9811458; DOI=10.1038/sj.onc.1202150;
RA Wong A.K., Ormonde P.A., Pero R., Chen Y., Lian L., Salada G., Berry S.,
RA Lawrence Q., Dayananth P., Ha P., Tavtigian S.V., Teng D.H., Bartel P.L.;
RT "Characterization of a carboxy-terminal BRCA1 interacting protein.";
RL Oncogene 17:2279-2285(1998).
RN [14]
RP FUNCTION AS AN E2-DEPENDENT UBIQUITIN-PROTEIN LIGASE, AND CATALYTIC
RP ACTIVITY.
RX PubMed=10500182; DOI=10.1073/pnas.96.20.11364;
RA Lorick K.L., Jensen J.P., Fang S., Ong A.M., Hatakeyama S., Weissman A.M.;
RT "RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent
RT ubiquitination.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:11364-11369(1999).
RN [15]
RP IDENTIFICATION IN THE BASC COMPLEX.
RX PubMed=10783165;
RA Wang Y., Cortez D., Yazdi P., Neff N., Elledge S.J., Qin J.;
RT "BASC, a super complex of BRCA1-associated proteins involved in the
RT recognition and repair of aberrant DNA structures.";
RL Genes Dev. 14:927-939(2000).
RN [16]
RP PHOSPHORYLATION AT SER-1143; SER-1280; SER-1387; THR-1394; SER-1423 AND
RP SER-1457, MUTAGENESIS OF SER-1143; SER-1239; SER-1280; SER-1298; SER-1330;
RP SER-1387; THR-1394; SER-1423; SER-1457; SER-1466; SER-1524 AND SER-1755,
RP AND CHARACTERIZATION OF VARIANT BC ALA-1720.
RX PubMed=11114888; DOI=10.1101/gad.851000;
RA Tibbetts R.S., Cortez D., Brumbaugh K.M., Scully R., Livingston D.,
RA Elledge S.J., Abraham R.T.;
RT "Functional interactions between BRCA1 and the checkpoint kinase ATR during
RT genotoxic stress.";
RL Genes Dev. 14:2989-3002(2000).
RN [17]
RP FUNCTION IN DNA DAMAGE RESPONSE, PHOSPHORYLATION AT SER-988 BY CHEK2, AND
RP INTERACTION WITH CHEK2.
RX PubMed=10724175; DOI=10.1038/35004614;
RA Lee J.S., Collins K.M., Brown A.L., Lee C.H., Chung J.H.;
RT "hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage
RT response.";
RL Nature 404:201-204(2000).
RN [18]
RP INTERACTION WITH BRIP1, CHARACTERIZATION OF VARIANT OVARIAN CANCER
RP ARG-1749, AND CHARACTERIZATION OF VARIANT BC ARG-1775.
RX PubMed=11301010; DOI=10.1016/s0092-8674(01)00304-x;
RA Cantor S.B., Bell D.W., Ganesan S., Kass E.M., Drapkin R., Grossman S.,
RA Wahrer D.C.R., Sgroi D.C., Lane W.S., Haber D.A., Livingston D.M.;
RT "BACH1, a novel helicase-like protein, interacts directly with BRCA1 and
RT contributes to its DNA repair function.";
RL Cell 105:149-160(2001).
RN [19]
RP INTERACTION WITH NELFB.
RX PubMed=11739404; DOI=10.1083/jcb.200108049;
RA Ye Q., Hu Y.-F., Zhong H., Nye A.C., Belmont A.S., Li R.;
RT "BRCA1-induced large-scale chromatin unfolding and allele-specific effects
RT of cancer-predisposing mutations.";
RL J. Cell Biol. 155:911-921(2001).
RN [20]
RP INTERACTION WITH FANCD2.
RX PubMed=11239454; DOI=10.1016/s1097-2765(01)00173-3;
RA Garcia-Higuera I., Taniguchi T., Ganesan S., Meyn M.S., Timmers C.,
RA Hejna J., Grompe M., D'Andrea A.D.;
RT "Interaction of the Fanconi anemia proteins and BRCA1 in a common
RT pathway.";
RL Mol. Cell 7:249-262(2001).
RN [21]
RP FUNCTION, PHOSPHORYLATION BY ATM, AND MUTAGENESIS OF SER-1387; SER-1423 AND
RP SER-1524.
RX PubMed=12183412;
RA Xu B., O'Donnell A.H., Kim S.-T., Kastan M.B.;
RT "Phosphorylation of serine 1387 in BRCA1 is specifically required for the
RT Atm-mediated S-phase checkpoint after ionizing irradiation.";
RL Cancer Res. 62:4588-4591(2002).
RN [22]
RP INTERACTION WITH H2AX.
RX PubMed=12419185; DOI=10.1016/s0960-9822(02)01259-9;
RA Kobayashi J., Tauchi H., Sakamoto S., Nakamura A., Morishima K.,
RA Matsuura S., Kobayashi T., Tamai K., Tanimoto K., Komatsu K.;
RT "NBS1 localizes to gamma-H2AX foci through interaction with the FHA/BRCT
RT domain.";
RL Curr. Biol. 12:1846-1851(2002).
RN [23]
RP INTERACTION WITH SMC1A.
RX PubMed=11877377; DOI=10.1101/gad.970702;
RA Yazdi P.T., Wang Y., Zhao S., Patel N., Lee E.Y.-H.P., Qin J.;
RT "SMC1 is a downstream effector in the ATM/NBS1 branch of the human S-phase
RT checkpoint.";
RL Genes Dev. 16:571-582(2002).
RN [24]
RP INTERACTION WITH LMO4.
RX PubMed=11751867; DOI=10.1074/jbc.m110603200;
RA Sum E.Y., Peng B., Yu X., Chen J., Byrne J., Lindeman G.J., Visvader J.E.;
RT "The LIM domain protein LMO4 interacts with the cofactor CtIP and the tumor
RT suppressor BRCA1 and inhibits BRCA1 activity.";
RL J. Biol. Chem. 277:7849-7856(2002).
RN [25]
RP FUNCTION, AND INTERACTION WITH CHEK1.
RX PubMed=11836499; DOI=10.1038/ng837;
RA Yarden R.I., Pardo-Reoyo S., Sgagias M., Cowan K.H., Brody L.C.;
RT "BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA
RT damage.";
RL Nat. Genet. 30:285-289(2002).
RN [26]
RP INTERACTION WITH ACACA.
RX PubMed=12360400; DOI=10.1038/sj.onc.1205915;
RA Magnard C., Bachelier R., Vincent A., Jaquinod M., Kieffer S., Lenoir G.M.,
RA Venezia N.D.;
RT "BRCA1 interacts with acetyl-CoA carboxylase through its tandem of BRCT
RT domains.";
RL Oncogene 21:6729-6739(2002).
RN [27]
RP FUNCTION, UBIQUITINATION, CATALYTIC ACTIVITY, AND INTERACTION WITH BARD1.
RX PubMed=12890688; DOI=10.1074/jbc.c300249200;
RA Wu-Baer F., Lagrazon K., Yuan W., Baer R.;
RT "The BRCA1/BARD1 heterodimer assembles polyubiquitin chains through an
RT unconventional linkage involving lysine residue K6 of ubiquitin.";
RL J. Biol. Chem. 278:34743-34746(2003).
RN [28]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=12887909; DOI=10.1016/s1097-2765(03)00281-8;
RA Vandenberg C.J., Gergely F., Ong C.Y., Pace P., Mallery D.L., Hiom K.,
RA Patel K.J.;
RT "BRCA1-independent ubiquitination of FANCD2.";
RL Mol. Cell 12:247-254(2003).
RN [29]
RP INTERACTION WITH BRCC3.
RX PubMed=14636569; DOI=10.1016/s1097-2765(03)00424-6;
RA Dong Y., Hakimi M.-A., Chen X., Kumaraswamy E., Cooch N.S., Godwin A.K.,
RA Shiekhattar R.;
RT "Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a
RT signalosome-like subunit and its role in DNA repair.";
RL Mol. Cell 12:1087-1099(2003).
RN [30]
RP FUNCTION, AND INTERACTION WITH BARD1.
RX PubMed=14976165; DOI=10.1093/hmg/ddh095;
RA Morris J.R., Solomon E.;
RT "BRCA1:BARD1 induces the formation of conjugated ubiquitin structures,
RT dependent on K6 of ubiquitin, in cells during DNA replication and repair.";
RL Hum. Mol. Genet. 13:807-817(2004).
RN [31]
RP RETRACTED PAPER.
RX PubMed=14990569; DOI=10.1074/jbc.m311780200;
RA Ouchi M., Fujiuchi N., Sasai K., Katayama H., Minamishima Y.A.,
RA Ongusaha P.P., Deng C., Sen S., Lee S.W., Ouchi T.;
RT "BRCA1 phosphorylation by Aurora-A in the regulation of G2 to M
RT transition.";
RL J. Biol. Chem. 279:19643-19648(2004).
RN [32]
RP RETRACTION NOTICE OF PUBMED:14990569.
RX PubMed=26341884; DOI=10.1074/jbc.a115.311780;
RA Ouchi M., Fujiuchi N., Sasai K., Katayama H., Minamishima Y.A.,
RA Ongusaha P.P., Deng C., Sen S., Lee S.W., Ouchi T.;
RL J. Biol. Chem. 290:22311-22311(2015).
RN [33]
RP INTERACTION WITH DCLRE1C.
RX PubMed=15456891; DOI=10.1128/mcb.24.20.9207-9220.2004;
RA Zhang X., Succi J., Feng Z., Prithivirajsingh S., Story M.D.,
RA Legerski R.J.;
RT "Artemis is a phosphorylation target of ATM and ATR and is involved in the
RT G2/M DNA damage checkpoint response.";
RL Mol. Cell. Biol. 24:9207-9220(2004).
RN [34]
RP INTERACTION WITH CLSPN.
RX PubMed=15096610; DOI=10.1073/pnas.0401847101;
RA Lin S.-Y., Li K., Stewart G.S., Elledge S.J.;
RT "Human claspin works with BRCA1 to both positively and negatively regulate
RT cell proliferation.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:6484-6489(2004).
RN [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1336, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [36]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH RBBP8, AND MUTAGENESIS OF
RP ILE-26.
RX PubMed=16818604; DOI=10.1101/gad.1431006;
RA Yu X., Fu S., Lai M., Baer R., Chen J.;
RT "BRCA1 ubiquitinates its phosphorylation-dependent binding partner CtIP.";
RL Genes Dev. 20:1721-1726(2006).
RN [37]
RP FUNCTION, AND INTERACTION WITH ACACA.
RX PubMed=16326698; DOI=10.1074/jbc.m504652200;
RA Moreau K., Dizin E., Ray H., Luquain C., Lefai E., Foufelle F., Billaud M.,
RA Lenoir G.M., Venezia N.D.;
RT "BRCA1 affects lipid synthesis through its interaction with acetyl-CoA
RT carboxylase.";
RL J. Biol. Chem. 281:3172-3181(2006).
RN [38]
RP INTERACTION WITH ACACA.
RX PubMed=16698035; DOI=10.1016/j.jmb.2006.04.010;
RA Ray H., Moreau K., Dizin E., Callebaut I., Venezia N.D.;
RT "ACCA phosphopeptide recognition by the BRCT repeats of BRCA1.";
RL J. Mol. Biol. 359:973-982(2006).
RN [39]
RP FUNCTION, CATALYTIC ACTIVITY, PHOSPHORYLATION BY AURKA, AND ACTIVITY
RP REGULATION.
RX PubMed=18056443; DOI=10.1158/0008-5472.can-07-2578;
RA Sankaran S., Crone D.E., Palazzo R.E., Parvin J.D.;
RT "Aurora-A kinase regulates breast cancer associated gene 1 inhibition of
RT centrosome-dependent microtubule nucleation.";
RL Cancer Res. 67:11186-11194(2007).
RN [40]
RP INTERACTION WITH ABRAXAS1.
RX PubMed=17643122; DOI=10.1038/nsmb1277;
RA Kim H., Huang J., Chen J.;
RT "CCDC98 is a BRCA1-BRCT domain-binding protein involved in the DNA damage
RT response.";
RL Nat. Struct. Mol. Biol. 14:710-715(2007).
RN [41]
RP INTERACTION WITH ABRAXAS1.
RX PubMed=17643121; DOI=10.1038/nsmb1279;
RA Liu Z., Wu J., Yu X.;
RT "CCDC98 targets BRCA1 to DNA damage sites.";
RL Nat. Struct. Mol. Biol. 14:716-720(2007).
RN [42]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [43]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH ABRAXAS1.
RX PubMed=17525340; DOI=10.1126/science.1139476;
RA Wang B., Matsuoka S., Ballif B.A., Zhang D., Smogorzewska A., Giyi S.,
RA Elledge S.J.;
RT "Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage
RT response.";
RL Science 316:1194-1198(2007).
RN [44]
RP INVOLVEMENT IN PNCA4.
RX PubMed=18762988; DOI=10.1007/s00439-008-0554-0;
RA Al-Sukhni W., Rothenmund H., Borgida A.E., Zogopoulos G., O'Shea A.M.,
RA Pollett A., Gallinger S.;
RT "Germline BRCA1 mutations predispose to pancreatic adenocarcinoma.";
RL Hum. Genet. 124:271-278(2008).
RN [45]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-395; SER-398; SER-753;
RP SER-1211; SER-1217 AND SER-1218, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [46]
RP FUNCTION, AND IDENTIFICATION IN THE BRCA1-A COMPLEX.
RX PubMed=19261748; DOI=10.1101/gad.1770609;
RA Feng L., Huang J., Chen J.;
RT "MERIT40 facilitates BRCA1 localization and DNA damage repair.";
RL Genes Dev. 23:719-728(2009).
RN [47]
RP IDENTIFICATION IN THE BRCA1-A COMPLEX.
RX PubMed=19261749; DOI=10.1101/gad.1770309;
RA Wang B., Hurov K., Hofmann K., Elledge S.J.;
RT "NBA1, a new player in the Brca1 A complex, is required for DNA damage
RT resistance and checkpoint control.";
RL Genes Dev. 23:729-739(2009).
RN [48]
RP IDENTIFICATION IN THE BRCA1-A COMPLEX.
RX PubMed=19261746; DOI=10.1101/gad.1739609;
RA Shao G., Patterson-Fortin J., Messick T.E., Feng D., Shanbhag N., Wang Y.,
RA Greenberg R.A.;
RT "MERIT40 controls BRCA1-Rap80 complex integrity and recruitment to DNA
RT double-strand breaks.";
RL Genes Dev. 23:740-754(2009).
RN [49]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH PALB2,
RP IDENTIFICATION IN A BRCA COMPLEX WITH BRCA1 AND PALB2, AND CHARACTERIZATION
RP OF VARIANT OVARIAN CANCER 1411-THR.
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 [50]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-395 AND SER-398, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [51]
RP FUNCTION, INTERACTION WITH CCAR2, AND SUBCELLULAR LOCATION.
RX PubMed=20160719; DOI=10.1038/sj.bjc.6605577;
RA Hiraike H., Wada-Hiraike O., Nakagawa S., Koyama S., Miyamoto Y., Sone K.,
RA Tanikawa M., Tsuruga T., Nagasaka K., Matsumoto Y., Oda K., Shoji K.,
RA Fukuhara H., Saji S., Nakagawa K., Kato S., Yano T., Taketani Y.;
RT "Identification of DBC1 as a transcriptional repressor for BRCA1.";
RL Br. J. Cancer 102:1061-1067(2010).
RN [52]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH BARD1 AND UBXN1,
RP UBIQUITINATION, AND MUTAGENESIS OF ILE-26.
RX PubMed=20351172; DOI=10.1128/mcb.01056-09;
RA Wu-Baer F., Ludwig T., Baer R.;
RT "The UBXN1 protein associates with autoubiquitinated forms of the BRCA1
RT tumor suppressor and inhibits its enzymatic function.";
RL Mol. Cell. Biol. 30:2787-2798(2010).
RN [53]
RP FUNCTION IN CHROMOSOMAL STABILITY, AND PHOSPHORYLATION AT SER-988 BY CHEK2.
RX PubMed=20364141; DOI=10.1038/ncb2051;
RA Stolz A., Ertych N., Kienitz A., Vogel C., Schneider V., Fritz B.,
RA Jacob R., Dittmar G., Weichert W., Petersen I., Bastians H.;
RT "The CHK2-BRCA1 tumour suppressor pathway ensures chromosomal stability in
RT human somatic cells.";
RL Nat. Cell Biol. 12:492-499(2010).
RN [54]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-114; SER-423; SER-694;
RP SER-1328; SER-1336 AND SER-1342, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [55]
RP PHOSPHORYLATION AT SER-1524, AND SUBCELLULAR LOCATION.
RX PubMed=21144835; DOI=10.1016/j.bbrc.2010.12.005;
RA Kang Y., Cheong H.M., Lee J.H., Song P.I., Lee K.H., Kim S.Y., Jun J.Y.,
RA You H.J.;
RT "Protein phosphatase 5 is necessary for ATR-mediated DNA repair.";
RL Biochem. Biophys. Res. Commun. 404:476-481(2011).
RN [56]
RP INTERACTION WITH PCLAF.
RX PubMed=21673012; DOI=10.1158/1541-7786.mcr-10-0503;
RA Kais Z., Barsky S.H., Mathsyaraja H., Zha A., Ransburgh D.J., He G.,
RA Pilarski R.T., Shapiro C.L., Huang K., Parvin J.D.;
RT "KIAA0101 interacts with BRCA1 and regulates centrosome number.";
RL Mol. Cancer Res. 9:1091-1099(2011).
RN [57]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-114; SER-1218; SER-1336 AND
RP SER-1342, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [58]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [59]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-114; SER-434; SER-551;
RP SER-694; SER-708; SER-1009; SER-1189; SER-1191 AND SER-1542, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [60]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-339; LYS-459; LYS-583; LYS-654;
RP LYS-734 AND LYS-739, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [61]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-339; LYS-443 AND LYS-583, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [62]
RP INTERACTION WITH EXD2.
RX PubMed=26807646; DOI=10.1038/ncb3303;
RA Broderick R., Nieminuszczy J., Baddock H.T., Deshpande R.A., Gileadi O.,
RA Paull T.T., McHugh P.J., Niedzwiedz W.;
RT "EXD2 promotes homologous recombination by facilitating DNA end
RT resection.";
RL Nat. Cell Biol. 18:271-280(2016).
RN [63]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-109; LYS-301; LYS-339; LYS-443;
RP LYS-459; LYS-519; LYS-583; LYS-918; LYS-987 AND LYS-1079, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [64]
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 [65]
RP STRUCTURE BY NMR OF 1-110 IN COMPLEX WITH ZINC IONS AND BARD1, AND SUBUNIT.
RX PubMed=11573085; DOI=10.1038/nsb1001-833;
RA Brzovic P.S., Rajagopal P., Hoyt D.W., King M.C., Klevit R.E.;
RT "Structure of a BRCA1-BARD1 heterodimeric RING-RING complex.";
RL Nat. Struct. Biol. 8:833-837(2001).
RN [66]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1646-1859, PARTIAL PROTEIN
RP SEQUENCE, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=11573086; DOI=10.1038/nsb1001-838;
RA Williams R.S., Green R., Glover J.N.;
RT "Crystal structure of the BRCT repeat region from the breast cancer-
RT associated protein BRCA1.";
RL Nat. Struct. Biol. 8:838-842(2001).
RN [67]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1646-1859 OF VARIANT BC ARG-1775,
RP CHARACTERIZATION OF VARIANT BC ARG-1775, AND CIRCULAR DICHROISM.
RX PubMed=12427738; DOI=10.1074/jbc.m210019200;
RA Williams R.S., Glover J.N.;
RT "Structural consequences of a cancer-causing BRCA1-BRCT missense
RT mutation.";
RL J. Biol. Chem. 278:2630-2635(2003).
RN [68]
RP STRUCTURE BY NMR OF 1755-1863.
RX PubMed=15609993; DOI=10.1021/bi049550q;
RA Gaiser O.J., Ball L.J., Schmieder P., Leitner D., Strauss H., Wahl M.,
RA Kuhne R., Oschkinat H., Heinemann U.;
RT "Solution structure, backbone dynamics, and association behavior of the C-
RT terminal BRCT domain from the breast cancer-associated protein BRCA1.";
RL Biochemistry 43:15983-15995(2004).
RN [69]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 1649-1859 IN COMPLEX WITH
RP PHOSPHORYLATED BRIP1 PEPTIDE, MUTAGENESIS OF SER-1655; LYS-1702 AND
RP GLY-1738, CHARACTERIZATION OF VARIANT OVARIAN CANCER ARG-1749,
RP CHARACTERIZATION OF VARIANT BC ARG-1775, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH PHOSPHORYLATED BRIP1.
RX PubMed=15133502; DOI=10.1038/nsmb775;
RA Clapperton J.A., Manke I.A., Lowery D.M., Ho T., Haire L.F., Yaffe M.B.,
RA Smerdon S.J.;
RT "Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated
RT BACH1 with implications for cancer.";
RL Nat. Struct. Mol. Biol. 11:512-518(2004).
RN [70]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1646-1859 IN COMPLEX WITH
RP PHOSPHORYLATED RBBP8 PEPTIDE, AND SUBUNIT.
RX PubMed=16101277; DOI=10.1021/bi0509651;
RA Varma A.K., Brown R.S., Birrane G., Ladias J.A.;
RT "Structural basis for cell cycle checkpoint control by the BRCA1-CtIP
RT complex.";
RL Biochemistry 44:10941-10946(2005).
RN [71]
RP X-RAY CRYSTALLOGRAPHY (3.21 ANGSTROMS) OF 1646-1859 IN COMPLEX WITH
RP PHOSPHORYLATED ACACA PEPTIDE, AND SUBUNIT.
RX PubMed=18452305; DOI=10.1021/bi800314m;
RA Shen Y., Tong L.;
RT "Structural evidence for direct interactions between the BRCT domains of
RT human BRCA1 and a phospho-peptide from human ACC1.";
RL Biochemistry 47:5767-5773(2008).
RN [72]
RP X-RAY CRYSTALLOGRAPHY (3.6 ANGSTROMS) OF 1649-1859 OF VARIANT BC LYS-1775,
RP VARIANT BC LYS-1775, AND CHARACTERIZATION OF VARIANT BC LYS-1775.
RX PubMed=18285836; DOI=10.1038/ejhg.2008.13;
RA Tischkowitz M., Hamel N., Carvalho M.A., Birrane G., Soni A.,
RA van Beers E.H., Joosse S.A., Wong N., Novak D., Quenneville L.A.,
RA Grist S.A., Nederlof P.M., Goldgar D.E., Tavtigian S.V., Monteiro A.N.,
RA Ladias J.A., Foulkes W.D.;
RT "Pathogenicity of the BRCA1 missense variant M1775K is determined by the
RT disruption of the BRCT phosphopeptide-binding pocket: a multi-modal
RT approach.";
RL Eur. J. Hum. Genet. 16:820-832(2008).
RN [73]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 1646-1859 IN COMPLEX WITH
RP PHOSPHORYLATED PEPTIDES, AND DOMAIN.
RX PubMed=20159462; DOI=10.1016/j.str.2009.12.008;
RA Campbell S.J., Edwards R.A., Glover J.N.;
RT "Comparison of the structures and peptide binding specificities of the BRCT
RT domains of MDC1 and BRCA1.";
RL Structure 18:167-176(2010).
RN [74]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 1646-1859 IN COMPLEX WITH
RP PHOSPHORYLATED BRIP1 PEPTIDE, INTERACTION WITH BRIP1, MUTAGENESIS OF
RP GLY-1656; THR-1700; ARG-1835 AND GLU-1836, AND CHARACTERIZATION OF VARIANTS
RP BC GLN-1699 AND TRP-1699.
RX PubMed=21473589; DOI=10.1021/bi2003795;
RA Coquelle N., Green R., Glover J.N.;
RT "Impact of BRCA1 BRCT domain missense substitutions on phosphopeptide
RT recognition.";
RL Biochemistry 50:4579-4589(2011).
RN [75]
RP X-RAY CRYSTALLOGRAPHY (3.50 ANGSTROMS) OF 1649-1859 IN COMPLEX WITH
RP ABRAXAS1, AND INTERACTION WITH ABRAXAS1.
RX PubMed=24316840; DOI=10.1107/s1744309113030649;
RA Badgujar D.C., Sawant U., Vikrant X., Yadav L., Hosur M.V., Varma A.K.;
RT "Preliminary crystallographic studies of BRCA1 BRCT-ABRAXAS complex.";
RL Acta Crystallogr. F 69:1401-1404(2013).
RN [76]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 1646-1859 IN COMPLEX WITH
RP ABRAXAS1, INTERACTION WITH ABRAXAS1, SUBUNIT, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF PHE-1662; MET-1663; TYR-1666; ARG-1670 AND LYS-1671.
RX PubMed=26778126; DOI=10.1016/j.molcel.2015.12.017;
RA Wu Q., Paul A., Su D., Mehmood S., Foo T.K., Ochi T., Bunting E.L., Xia B.,
RA Robinson C.V., Wang B., Blundell T.L.;
RT "Structure of BRCA1-BRCT/Abraxas complex reveals phosphorylation-dependent
RT BRCT dimerization at DNA damage sites.";
RL Mol. Cell 61:434-448(2016).
RN [77]
RP REVIEW ON VARIANTS.
RX PubMed=8807330; DOI=10.1002/humu.1380080102;
RA Couch F.J., Weber B.L.;
RT "Mutations and polymorphisms in the familial early-onset breast cancer
RT (BRCA1) gene.";
RL Hum. Mutat. 8:8-18(1996).
RN [78]
RP VARIANT BC ARG-1775, AND VARIANTS LEU-1637 AND GLU-1708.
RX PubMed=7939630; DOI=10.1126/science.7939630;
RA Futreal P.A., Liu Q., Shattuck-Eidens D., Cochran C., Harshman K.,
RA Tavtigian S., Bennett L.M., Haugen-Strano A., Swensen J., Miki Y.,
RA Eddington K., McClure M., Frye C., Weaver-Felhaus J., Ding W., Gholami Z.,
RA Soederkvist P., Terry L., Jhanwar S., Berchuk A., Iglehart J.D., Marks J.,
RA Ballinger D.G., Barrett J.C., Skolnick M.H., Kamb A., Wiseman R.;
RT "BRCA1 mutations in primary breast and ovarian carcinomas.";
RL Science 266:120-122(1994).
RN [79]
RP VARIANT BC GLY-64, AND VARIANTS ALA-772; ASN-1040 AND GLY-1443.
RX PubMed=7894491; DOI=10.1038/ng1294-387;
RA Castilla L.H., Couch F.J., Erdos M.R., Hoskins K.F., Calzone K.,
RA Garber J.E., Boyd J., Lubin M.B., Deshano M.L., Brody L.C., Collins F.S.,
RA Weber B.L.;
RT "Mutations in the BRCA1 gene in families with early-onset breast and
RT ovarian cancer.";
RL Nat. Genet. 8:387-391(1994).
RN [80]
RP VARIANT BC GLY-61, AND VARIANTS ARG-356; GLY-1038; ASN-1040; ARG-1183 AND
RP GLY-1613.
RX PubMed=7894493; DOI=10.1038/ng1294-399;
RA Friedman L.S., Ostermeyer E.A., Szabo C.I., Dowd P., Lynch E.D.,
RA Rowell S.E., King M.-C.;
RT "Confirmation of BRCA1 by analysis of germline mutations linked to breast
RT and ovarian cancer in ten families.";
RL Nat. Genet. 8:399-404(1994).
RN [81]
RP VARIANT BC GLY-61.
RX PubMed=8554067;
RA Serova O., Montagna M., Torchard D., Narod S.A., Tonin P., Sylla B.,
RA Lynch H.T., Feunteun J., Lenoir G.M.;
RT "A high incidence of BRCA1 mutations in 20 breast-ovarian cancer
RT families.";
RL Am. J. Hum. Genet. 58:42-51(1996).
RN [82]
RP VARIANT BROVCA1 TRP-841.
RX PubMed=8968716;
RX DOI=10.1002/(sici)1098-2272(1996)13:6<595::aid-gepi5>3.0.co;2-#;
RA Barker D.F., Almeida E.F.A., Casey G., Fain P.R., Liao S.-Y., Masunaka I.,
RA Noble B., Kurosaki T., Anton-Culver H.;
RT "BRCA1 R841W: a strong candidate for a common mutation with moderate
RT phenotype.";
RL Genet. Epidemiol. 13:595-604(1996).
RN [83]
RP VARIANTS BC AND BROVCA1.
RX PubMed=8776600; DOI=10.1093/hmg/5.6.835;
RA Durocher F., Shattuck-Eidens D., McClure M., Labrie F., Skolnick M.H.,
RA Goldgar D.E., Simard J.;
RT "Comparison of BRCA1 polymorphisms, rare sequence variants and/or missense
RT mutations in unaffected and breast/ovarian cancer populations.";
RL Hum. Mol. Genet. 5:835-842(1996).
RN [84]
RP VARIANTS BC MET-271 AND SER-1150.
RX PubMed=8723683;
RX DOI=10.1002/(sici)1098-1004(1996)7:4<334::aid-humu7>3.0.co;2-8;
RA Katagiri T., Emi M., Ito I., Kobayashi K., Yoshimoto M., Iwase T.,
RA Kasumi F., Miki Y., Skolnick M.H., Nakamura Y.;
RT "Mutations in the BRCA1 gene in Japanese breast cancer patients.";
RL Hum. Mutat. 7:334-339(1996).
RN [85]
RP VARIANT BC GLY-61, AND VARIANTS ARG-239; TRP-841 AND ILE-1512.
RX PubMed=9760198; DOI=10.1007/s004390050799;
RA Dong J., Chang-Claude J., Wu Y., Schumacher V., Debatin I., Tonin P.,
RA Royer-Pokora B.;
RT "A high proportion of mutations in the BRCA1 gene in German breast/ovarian
RT cancer families with clustering of mutations in the 3' third of the gene.";
RL Hum. Genet. 103:154-161(1998).
RN [86]
RP VARIANT BC GLY-64, AND VARIANTS ALA-772; GLU-820; ASN-1040; GLY-1443;
RP ILE-1512; LEU-1637 AND ILE-1652.
RX PubMed=9482581;
RX DOI=10.1002/(sici)1098-1004(1998)11:2<166::aid-humu10>3.0.co;2-x;
RA Andersen T.I., Eiken H.G., Couch F., Kaada G., Skrede M., Johnsen H.,
RA Aloysius T.A., Tveit K.M., Tranebjaerg L., Doerum A., Moeller P.,
RA Weber B.L., Boerresen-Dale A.-L.;
RT "Constant denaturant gel electrophoresis (CDGE) in BRCA1 mutation
RT screening.";
RL Hum. Mutat. 11:166-174(1998).
RN [87]
RP VARIANTS BC SER-22; LEU-461; ASP-465; VAL-552; SER-892; ASP-960; ILE-1025
RP AND ALA-1047.
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 [88]
RP VARIANT OVARIAN CANCER ARG-1749.
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 [89]
RP VARIANT BC SER-346, AND VARIANTS LEU-871; GLY-1038; ARG-1183 AND GLY-1613.
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 [90]
RP VARIANTS OVARIAN CANCER, AND VARIANTS.
RX PubMed=10196379; DOI=10.1093/hmg/8.5.889;
RA Janezic S.A., Ziogas A., Krumroy L.M., Krasner M., Plummer S.J., Cohen P.,
RA Gildea M., Barker D., Haile R., Casey G., Anton-Culver H.;
RT "Germline BRCA1 alterations in a population-based series of ovarian cancer
RT cases.";
RL Hum. Mol. Genet. 8:889-897(1999).
RN [91]
RP VARIANTS GLY-1347; ILE-1512 AND ILE-1652.
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 [92]
RP VARIANTS ILE-656; LEU-871 AND GLY-1613.
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 [93]
RP VARIANT BC TYR-749.
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 [94]
RP VARIANTS BC GLY-61; LYS-71; GLN-866; TYR-888; ILE-1139; GLY-1210 AND
RP PRO-1297, AND VARIANTS BROVCA1 TYR-835 AND PRO-1786.
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 [95]
RP VARIANTS ASN-693; ASN-1040; ALA-1060 AND MET-1665.
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 [96]
RP VARIANTS OVARIAN CANCER GLY-61; THR-1411; ARG-1697 AND TRP-1699.
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 [97]
RP VARIANTS BC/BROVCA1 LYS-10; LYS-23; ILE-1187; HIS-1200 AND TYR-1217,
RP VARIANTS BC ILE-1204 AND ASN-1207, VARIANTS BROVCA1 LEU-1226 AND GLY-1243,
RP AND VARIANT ARG-1183.
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 [98]
RP VARIANTS HIS-856; LEU-871; GLY-1038; ARG-1183; THR-1628; GLN-1690 AND
RP GLY-1713.
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 [99]
RP VARIANTS [LARGE SCALE ANALYSIS] PHE-30; PHE-758 AND CYS-778.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [100]
RP VARIANTS THR-18; MET-1495; GLY-1623; ILE-1685; ALA-1685; ARG-1689;
RP TRP-1699; GLU-1706; GLU-1708; ARG-1715; ARG-1738; PRO-1764; SER-1766 AND
RP VAL-1788.
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 [101]
RP CHARACTERIZATION OF VARIANTS GLY-1623 AND ILE-1685.
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 [102]
RP VARIANT FANCS ALA-1736, CHARACTERIZATION OF VARIANT FANCS ALA-1736,
RP SUBCELLULAR LOCATION, AND INTERACTION WITH UIMC1.
RX PubMed=23269703; DOI=10.1158/2159-8290.cd-12-0421;
RA Domchek S.M., Tang J., Stopfer J., Lilli D.R., Hamel N., Tischkowitz M.,
RA Monteiro A.N., Messick T.E., Powers J., Yonker A., Couch F.J.,
RA Goldgar D.E., Davidson H.R., Nathanson K.L., Foulkes W.D., Greenberg R.A.;
RT "Biallelic deleterious BRCA1 mutations in a woman with early-onset ovarian
RT cancer.";
RL Cancer Discov. 3:399-405(2013).
RN [103]
RP CHARACTERIZATION OF VARIANTS BC PHE-4; THR-18; GLN-45; GLY-61; GLY-64;
RP TYR-67; LYS-132; HIS-142; PHE-147; PRO-165; TRP-170; TYR-186; ILE-191;
RP MET-231; VAL-245; VAL-246; LEU-271; PHE-668; ASN-695; LEU-798; TYR-810;
RP LYS-826; GLN-841; HIS-856; ASN-1101; ASN-1140; GLY-1140; LYS-1214;
RP LYS-1236; SER-1267; VAL-1282; SER-1297 DEL; ARG-1301; LYS-1346; ILE-1378;
RP VAL-1400; PRO-1407; THR-1411; GLY-1443; GLY-1448; CYS-1486; MET-1534;
RP PRO-1589; THR-1628; PRO-1651; PHE-1651; PHE-1655; ARG-1686; GLN-1686;
RP VAL-1688 DEL; ILE-1691; TRP-1699; GLN-1699; GLU-1706; ALA-1706; GLU-1708;
RP CYS-1718; ALA-1720; LYS-1735; ALA-1736; GLY-1739; VAL-1739; GLN-1746;
RP THR-1753; PRO-1764; SER-1767; VAL-1770; CYS-1782; THR-1789; ASP-1794;
RP ASP-1804; ARG-1812; ARG-1837 AND LEU-1862, AND VARIANTS CYS-105; CYS-866;
RP ALA-1060; LYS-1250 AND ILE-1652.
RX PubMed=23867111; DOI=10.1158/2159-8290.cd-13-0094;
RA Bouwman P., van der Gulden H., van der Heijden I., Drost R., Klijn C.N.,
RA Prasetyanti P., Pieterse M., Wientjens E., Seibler J., Hogervorst F.B.,
RA Jonkers J.;
RT "A high-throughput functional complementation assay for classification of
RT BRCA1 missense variants.";
RL Cancer Discov. 3:1142-1155(2013).
RN [104]
RP VARIANT FANCS TRP-1699, AND SUBCELLULAR LOCATION.
RX PubMed=25472942; DOI=10.1158/2159-8290.cd-14-1156;
RG University of Washington Centre for Mendelian Genomics;
RG FORGE Canada Consortium;
RA Sawyer S.L., Tian L., Kaehkoenen M., Schwartzentruber J., Kircher M.,
RA Majewski J., Dyment D.A., Innes A.M., Boycott K.M., Moreau L.A.,
RA Moilanen J.S., Greenberg R.A.;
RT "Biallelic mutations in BRCA1 cause a new Fanconi anemia subtype.";
RL Cancer Discov. 5:135-142(2015).
RN [105]
RP VARIANT BC PRO-1780, VARIANT BROVCA1 PRO-1780, AND VARIANT OC PRO-1780.
RX PubMed=28364669; DOI=10.1016/j.breast.2017.03.006;
RA Ryu J.M., Kang G., Nam S.J., Kim S.W., Yu J., Lee S.K., Bae S.Y., Park S.,
RA Paik H.J., Kim J.W., Park S.S., Lee J.E., Kim S.W.;
RT "Suggestion of BRCA1 c.5339T>C (p.L1780P) variant confer from 'unknown
RT significance' to 'Likely pathogenic' based on clinical evidence in Korea.";
RL Breast 33:109-116(2017).
RN [106]
RP VARIANT FANCS 903-CYS--TYR-1863 DEL.
RX PubMed=29133208; DOI=10.1016/j.ejmg.2017.11.003;
RA Freire B.L., Homma T.K., Funari M.F.A., Lerario A.M., Leal A.M.,
RA Velloso E.D.R.P., Malaquias A.C., Jorge A.A.L.;
RT "Homozygous loss of function BRCA1 variant causing a Fanconi-anemia-like
RT phenotype, a clinical report and review of previous patients.";
RL Eur. J. Med. Genet. 61:130-133(2018).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that specifically mediates the
CC formation of 'Lys-6'-linked polyubiquitin chains and plays a central
CC role in DNA repair by facilitating cellular responses to DNA damage
CC (PubMed:12890688, PubMed:14976165, PubMed:16818604, PubMed:17525340,
CC PubMed:12887909, PubMed:10500182, PubMed:19261748). It is unclear
CC whether it also mediates the formation of other types of polyubiquitin
CC chains (PubMed:12890688). The BRCA1-BARD1 heterodimer coordinates a
CC diverse range of cellular pathways such as DNA damage repair,
CC ubiquitination and transcriptional regulation to maintain genomic
CC stability (PubMed:12890688, PubMed:14976165, PubMed:20351172).
CC Regulates centrosomal microtubule nucleation (PubMed:18056443).
CC Required for appropriate cell cycle arrests after ionizing irradiation
CC in both the S-phase and the G2 phase of the cell cycle
CC (PubMed:10724175, PubMed:12183412, PubMed:11836499, PubMed:19261748).
CC Required for FANCD2 targeting to sites of DNA damage (PubMed:12887909).
CC Inhibits lipid synthesis by binding to inactive phosphorylated ACACA
CC and preventing its dephosphorylation (PubMed:16326698). Contributes to
CC homologous recombination repair (HRR) via its direct interaction with
CC PALB2, fine-tunes recombinational repair partly through its modulatory
CC role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at
CC DNA breaks (PubMed:19369211). Component of the BRCA1-RBBP8 complex
CC which regulates CHEK1 activation and controls cell cycle G2/M
CC checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8
CC (PubMed:16818604). Acts as a transcriptional activator
CC (PubMed:20160719). {ECO:0000269|PubMed:10500182,
CC ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:11836499,
CC ECO:0000269|PubMed:12183412, ECO:0000269|PubMed:12887909,
CC ECO:0000269|PubMed:12890688, ECO:0000269|PubMed:14976165,
CC ECO:0000269|PubMed:16326698, ECO:0000269|PubMed:16818604,
CC ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:18056443,
CC ECO:0000269|PubMed:19261748, ECO:0000269|PubMed:19369211,
CC ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:20351172}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000269|PubMed:10500182,
CC ECO:0000269|PubMed:12887909, ECO:0000269|PubMed:12890688,
CC ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:18056443,
CC ECO:0000269|PubMed:20351172};
CC -!- ACTIVITY REGULATION: The E3 ubiquitin-protein ligase activity is
CC inhibited by phosphorylation by AURKA. Activity is increased by
CC phosphatase treatment. {ECO:0000269|PubMed:18056443}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Heterodimer with BARD1 (PubMed:11573085, PubMed:12890688,
CC PubMed:14976165). Part of the BRCA1-associated genome surveillance
CC complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2
CC and the MRE11-RAD50-NBN protein (MRN) complex (PubMed:10783165). This
CC association could be a dynamic process changing throughout the cell
CC cycle and within subnuclear domains (PubMed:10783165). Component of the
CC BRCA1-A complex, at least composed of BRCA1, BARD1, UIMC1/RAP80,
CC ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1 (PubMed:19261746,
CC PubMed:19261748, PubMed:19261749, PubMed:20351172). Interacts (via the
CC BRCT domains) with ABRAXAS1 (phosphorylated form); this is important
CC for recruitment to sites of DNA damage (PubMed:17525340,
CC PubMed:17643121, PubMed:17643122, PubMed:24316840, PubMed:26778126,
CC PubMed:23269703). Can form a heterotetramer with two molecules of
CC ABRAXAS1 (phosphorylated form) (PubMed:26778126). Component of the
CC BRCA1-RBBP8 complex (PubMed:16101277). Interacts (via the BRCT domains)
CC with RBBP8 ('Ser-327' phosphorylated form); the interaction
CC ubiquitinates RBBP8, regulates CHEK1 activation, and involves RBBP8 in
CC BRCA1-dependent G2/M checkpoint control on DNA damage (PubMed:16818604,
CC PubMed:9811458). Associates with RNA polymerase II holoenzyme
CC (PubMed:9662397). Interacts with SMC1A, NELFB, DCLRE1C, CLSPN
CC (PubMed:11877377, PubMed:15096610, PubMed:15456891, PubMed:11739404).
CC Interacts with CHEK1, CHEK2, BAP1, BRCC3, UBXN1 and PCLAF
CC (PubMed:10724175, PubMed:11836499, PubMed:14636569, PubMed:20351172,
CC PubMed:21673012). Interacts (via BRCT domains) with BRIP1
CC (phosphorylated form) (PubMed:11301010, PubMed:15133502,
CC PubMed:21473589). Interacts with FANCD2 (ubiquitinated form)
CC (PubMed:11239454). Interacts with H2AX (phosphorylated on 'Ser-140')
CC (PubMed:12419185). Interacts (via the BRCT domains) with ACACA
CC (phosphorylated form); the interaction prevents dephosphorylation of
CC ACACA (PubMed:12360400, PubMed:16326698, PubMed:16698035,
CC PubMed:18452305). Part of a BRCA complex containing BRCA1, BRCA2 and
CC PALB2 (PubMed:19369211). Interacts directly with PALB2; the interaction
CC is essential for its function in HRR (PubMed:19369211,
CC PubMed:28319063). Interacts directly with BRCA2; the interaction occurs
CC only in the presence of PALB2 which serves as the bridging protein
CC (PubMed:19369211). Interacts (via the BRCT domains) with LMO4; the
CC interaction represses the transcriptional activity of BRCA1
CC (PubMed:11751867). Interacts (via the BRCT domains) with CCAR2 (via N-
CC terminus); the interaction represses the transcriptional activator
CC activity of BRCA1 (PubMed:20160719). Interacts with EXD2
CC (PubMed:26807646). Interacts (via C-terminus) with DHX9; this
CC interaction is direct and links BRCA1 to the RNA polymerase II
CC holoenzyme (PubMed:9662397). {ECO:0000269|PubMed:10724175,
CC ECO:0000269|PubMed:10783165, ECO:0000269|PubMed:11239454,
CC ECO:0000269|PubMed:11301010, ECO:0000269|PubMed:11573085,
CC ECO:0000269|PubMed:11739404, ECO:0000269|PubMed:11751867,
CC ECO:0000269|PubMed:11836499, ECO:0000269|PubMed:11877377,
CC ECO:0000269|PubMed:12360400, ECO:0000269|PubMed:12419185,
CC ECO:0000269|PubMed:12890688, ECO:0000269|PubMed:14636569,
CC ECO:0000269|PubMed:14976165, ECO:0000269|PubMed:15096610,
CC ECO:0000269|PubMed:15133502, ECO:0000269|PubMed:15456891,
CC ECO:0000269|PubMed:16101277, ECO:0000269|PubMed:16326698,
CC ECO:0000269|PubMed:16698035, ECO:0000269|PubMed:16818604,
CC ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17643121,
CC ECO:0000269|PubMed:17643122, ECO:0000269|PubMed:18452305,
CC ECO:0000269|PubMed:19261746, ECO:0000269|PubMed:19261748,
CC ECO:0000269|PubMed:19261749, ECO:0000269|PubMed:19369211,
CC ECO:0000269|PubMed:20159462, ECO:0000269|PubMed:20160719,
CC ECO:0000269|PubMed:20351172, ECO:0000269|PubMed:21473589,
CC ECO:0000269|PubMed:21673012, ECO:0000269|PubMed:23269703,
CC ECO:0000269|PubMed:24316840, ECO:0000269|PubMed:26778126,
CC ECO:0000269|PubMed:26807646, ECO:0000269|PubMed:28319063,
CC ECO:0000269|PubMed:9528852, ECO:0000269|PubMed:9662397,
CC ECO:0000269|PubMed:9811458}.
CC -!- INTERACTION:
CC P38398; Q6UWZ7: ABRAXAS1; NbExp=15; IntAct=EBI-349905, EBI-1263451;
CC P38398; Q13085: ACACA; NbExp=2; IntAct=EBI-349905, EBI-717681;
CC P38398; Q92560: BAP1; NbExp=3; IntAct=EBI-349905, EBI-1791447;
CC P38398; Q99728: BARD1; NbExp=16; IntAct=EBI-349905, EBI-473181;
CC P38398; Q7Z569: BRAP; NbExp=3; IntAct=EBI-349905, EBI-349900;
CC P38398; Q6PJG6: BRAT1; NbExp=6; IntAct=EBI-349905, EBI-10826195;
CC P38398; Q9BX63: BRIP1; NbExp=24; IntAct=EBI-349905, EBI-3509650;
CC P38398; P24385: CCND1; NbExp=3; IntAct=EBI-349905, EBI-375001;
CC P38398; P24864: CCNE1; NbExp=2; IntAct=EBI-349905, EBI-519526;
CC P38398; O14757: CHEK1; NbExp=3; IntAct=EBI-349905, EBI-974488;
CC P38398; P03372: ESR1; NbExp=14; IntAct=EBI-349905, EBI-78473;
CC P38398; Q92731: ESR2; NbExp=4; IntAct=EBI-349905, EBI-78505;
CC P38398; Q14192: FHL2; NbExp=6; IntAct=EBI-349905, EBI-701903;
CC P38398; P78347: GTF2I; NbExp=5; IntAct=EBI-349905, EBI-359622;
CC P38398; P16104: H2AX; NbExp=4; IntAct=EBI-349905, EBI-494830;
CC P38398; O75330: HMMR; NbExp=4; IntAct=EBI-349905, EBI-2556203;
CC P38398; P10809: HSPD1; NbExp=2; IntAct=EBI-349905, EBI-352528;
CC P38398; Q16666: IFI16; NbExp=9; IntAct=EBI-349905, EBI-2867186;
CC P38398; P52292: KPNA2; NbExp=3; IntAct=EBI-349905, EBI-349938;
CC P38398; Q14676: MDC1; NbExp=4; IntAct=EBI-349905, EBI-495644;
CC P38398; Q8WX92: NELFB; NbExp=5; IntAct=EBI-349905, EBI-347721;
CC P38398; Q86YC2: PALB2; NbExp=27; IntAct=EBI-349905, EBI-1222653;
CC P38398; P62136: PPP1CA; NbExp=2; IntAct=EBI-349905, EBI-357253;
CC P38398; P62140: PPP1CB; NbExp=3; IntAct=EBI-349905, EBI-352350;
CC P38398; P36873: PPP1CC; NbExp=2; IntAct=EBI-349905, EBI-356283;
CC P38398; Q99708: RBBP8; NbExp=12; IntAct=EBI-349905, EBI-745715;
CC P38398; P63165: SUMO1; NbExp=3; IntAct=EBI-349905, EBI-80140;
CC P38398; P61956: SUMO2; NbExp=2; IntAct=EBI-349905, EBI-473220;
CC P38398; P11388: TOP2A; NbExp=3; IntAct=EBI-349905, EBI-539628;
CC P38398; Q12888: TP53BP1; NbExp=5; IntAct=EBI-349905, EBI-396540;
CC P38398; Q96RL1: UIMC1; NbExp=10; IntAct=EBI-349905, EBI-725300;
CC P38398; Q96RL1-1: UIMC1; NbExp=2; IntAct=EBI-349905, EBI-9640371;
CC P38398; Q6NZY4: ZCCHC8; NbExp=2; IntAct=EBI-349905, EBI-1263058;
CC P38398; Q9GZX5: ZNF350; NbExp=3; IntAct=EBI-349905, EBI-396421;
CC P38398; Q61188: Ezh2; Xeno; NbExp=5; IntAct=EBI-349905, EBI-904311;
CC P38398-1; Q99728: BARD1; NbExp=3; IntAct=EBI-21498346, EBI-473181;
CC P38398-1; Q13526: PIN1; NbExp=4; IntAct=EBI-21498346, EBI-714158;
CC P38398-5; Q92560: BAP1; NbExp=2; IntAct=EBI-2015072, EBI-1791447;
CC P38398-6; Q14457: BECN1; NbExp=3; IntAct=EBI-25833510, EBI-949378;
CC P38398-6; P42858: HTT; NbExp=3; IntAct=EBI-25833510, EBI-466029;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15133502,
CC ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:20160719,
CC ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:26778126,
CC ECO:0000269|PubMed:9528852}. Chromosome {ECO:0000269|PubMed:23269703,
CC ECO:0000269|PubMed:25472942, ECO:0000269|PubMed:26778126}. Cytoplasm
CC {ECO:0000269|PubMed:20160719}. Note=Localizes at sites of DNA damage at
CC double-strand breaks (DSBs); recruitment to DNA damage sites is
CC mediated by ABRAXAS1 and the BRCA1-A complex (PubMed:26778126).
CC Translocated to the cytoplasm during UV-induced apoptosis
CC (PubMed:20160719). {ECO:0000269|PubMed:20160719,
CC ECO:0000269|PubMed:26778126}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm.
CC -!- SUBCELLULAR LOCATION: [Isoform 5]: Cytoplasm
CC {ECO:0000269|PubMed:8972225}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=8;
CC Name=1;
CC IsoId=P38398-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P38398-2; Sequence=VSP_047891;
CC Name=3; Synonyms=Delta11b;
CC IsoId=P38398-3; Sequence=VSP_035399, VSP_043797;
CC Name=4; Synonyms=DeltaBRCA1(17aa);
CC IsoId=P38398-4; Sequence=VSP_035396;
CC Name=5; Synonyms=Delta11, Delta772-3095;
CC IsoId=P38398-5; Sequence=VSP_035398;
CC Name=6;
CC IsoId=P38398-6; Sequence=VSP_035399, VSP_043797, VSP_043798;
CC Name=7;
CC IsoId=P38398-7; Sequence=VSP_055404;
CC Name=8;
CC IsoId=P38398-8; Sequence=VSP_057569;
CC -!- TISSUE SPECIFICITY: Isoform 1 and isoform 3 are widely expressed.
CC Isoform 3 is reduced or absent in several breast and ovarian cancer
CC cell lines.
CC -!- DOMAIN: The BRCT domains recognize and bind phosphorylated pSXXF motif
CC on proteins. The interaction with the phosphorylated pSXXF motif of
CC ABRAXAS1, recruits BRCA1 at DNA damage sites.
CC {ECO:0000269|PubMed:20159462}.
CC -!- DOMAIN: The RING-type zinc finger domain interacts with BAP1.
CC {ECO:0000269|PubMed:20159462}.
CC -!- PTM: Phosphorylated in response to IR, UV, and various stimuli that
CC cause checkpoint activation, probably by ATM or ATR (PubMed:11114888,
CC PubMed:12183412, PubMed:21144835). Phosphorylation at Ser-988 by CHEK2
CC regulates mitotic spindle assembly (PubMed:10724175, PubMed:20364141).
CC Phosphorylation by AURKA regulates centrosomal microtubule nucleation
CC (PubMed:18056443). {ECO:0000269|PubMed:10724175,
CC ECO:0000269|PubMed:11114888, ECO:0000269|PubMed:12183412,
CC ECO:0000269|PubMed:18056443, ECO:0000269|PubMed:20364141,
CC ECO:0000269|PubMed:21144835}.
CC -!- PTM: Autoubiquitinated, undergoes 'Lys-6'-linked polyubiquitination.
CC 'Lys-6'-linked polyubiquitination does not promote degradation.
CC {ECO:0000269|PubMed:12890688, ECO:0000269|PubMed:20351172}.
CC -!- POLYMORPHISM: There is evidence that the presence of the rare form of
CC Gln-356-Arg and Leu-871-Pro polymorphisms may be associated with an
CC increased risk for developing ovarian cancer.
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:10323242,
CC ECO:0000269|PubMed:11114888, ECO:0000269|PubMed:11301010,
CC ECO:0000269|PubMed:12427738, ECO:0000269|PubMed:12442275,
CC ECO:0000269|PubMed:12938098, ECO:0000269|PubMed:14722926,
CC ECO:0000269|PubMed:15133502, ECO:0000269|PubMed:18285836,
CC ECO:0000269|PubMed:21473589, ECO:0000269|PubMed:23867111,
CC ECO:0000269|PubMed:28364669, ECO:0000269|PubMed:7545954,
CC ECO:0000269|PubMed:7894491, ECO:0000269|PubMed:7894493,
CC ECO:0000269|PubMed:7939630, ECO:0000269|PubMed:8554067,
CC ECO:0000269|PubMed:8723683, ECO:0000269|PubMed:8776600,
CC ECO:0000269|PubMed:9482581, ECO:0000269|PubMed:9609997,
CC ECO:0000269|PubMed:9760198}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry. Mutations
CC in BRCA1 are thought to be responsible for 45% of inherited breast
CC cancer. Moreover, BRCA1 carriers have a 4-fold increased risk of colon
CC cancer, whereas male carriers face a 3-fold increased risk of prostate
CC cancer. Cells lacking BRCA1 show defects in DNA repair by homologous
CC recombination.
CC -!- DISEASE: Breast-ovarian cancer, familial, 1 (BROVCA1) [MIM:604370]: A
CC condition associated with familial predisposition to cancer of the
CC breast and ovaries. Characteristic features in affected families are an
CC early age of onset of breast cancer (often before age 50), increased
CC chance of bilateral cancers (cancer that develop in both breasts, or
CC both ovaries, independently), frequent occurrence of breast cancer
CC among men, increased incidence of tumors of other specific organs, such
CC as the prostate. {ECO:0000269|PubMed:12938098,
CC ECO:0000269|PubMed:14722926, ECO:0000269|PubMed:28364669,
CC ECO:0000269|PubMed:8968716}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry. Mutations
CC in BRCA1 are thought to be responsible for more than 80% of inherited
CC breast-ovarian cancer.
CC -!- DISEASE: Ovarian cancer (OC) [MIM:167000]: The term ovarian cancer
CC defines malignancies originating from ovarian tissue. Although many
CC histologic types of ovarian tumors have been described, epithelial
CC ovarian carcinoma is the most common form. Ovarian cancers are often
CC asymptomatic and the recognized signs and symptoms, even of late-stage
CC disease, are vague. Consequently, most patients are diagnosed with
CC advanced disease. {ECO:0000269|PubMed:10196379,
CC ECO:0000269|PubMed:10486320, ECO:0000269|PubMed:14746861,
CC ECO:0000269|PubMed:28364669}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry.
CC -!- DISEASE: Pancreatic cancer 4 (PNCA4) [MIM:614320]: 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:18762988}.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry.
CC -!- DISEASE: Fanconi anemia, complementation group S (FANCS) [MIM:617883]:
CC A form of Fanconi anemia, a disorder affecting all bone marrow elements
CC and resulting in anemia, leukopenia and thrombopenia. It is associated
CC with cardiac, renal and limb malformations, dermal pigmentary changes,
CC and a predisposition to the development of malignancies. At the
CC cellular level it is associated with hypersensitivity to DNA-damaging
CC agents, chromosomal instability (increased chromosome breakage) and
CC defective DNA repair. {ECO:0000269|PubMed:23269703,
CC ECO:0000269|PubMed:25472942, ECO:0000269|PubMed:29133208}. Note=Disease
CC susceptibility is associated with variants affecting the gene
CC represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 4]: Produced by alternative initiation at Met-
CC 18 of isoform 1. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 8]: The N-terminus is confirmed by several
CC cDNAs. {ECO:0000305}.
CC -!- CAUTION: An article that concluded that AURKA-mediated phosphorylation
CC of BRCA1 Ser-308 plays a role in the normal cell cycle G2/M transition
CC was withdrawn due to data manipulation of flow cytometry data.
CC {ECO:0000305|PubMed:14990569, ECO:0000305|PubMed:26341884}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB61673.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305};
CC Sequence=AAI15038.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAI15038.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/BRCA1ID163ch17q21.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/brca1/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=BRCA1 entry;
CC URL="https://en.wikipedia.org/wiki/BRCA1";
CC ---------------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
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DR EMBL; U14680; AAA73985.1; -; mRNA.
DR EMBL; L78833; AAC37594.1; -; Genomic_DNA.
DR EMBL; U64805; AAC00049.1; -; mRNA.
DR EMBL; AF005068; AAB61673.1; ALT_SEQ; mRNA.
DR EMBL; DQ190450; ABA29208.1; -; Genomic_DNA.
DR EMBL; DQ190451; ABA29211.1; -; Genomic_DNA.
DR EMBL; DQ190452; ABA29214.1; -; Genomic_DNA.
DR EMBL; DQ190453; ABA29217.1; -; Genomic_DNA.
DR EMBL; DQ190454; ABA29220.1; -; Genomic_DNA.
DR EMBL; DQ190455; ABA29223.1; -; Genomic_DNA.
DR EMBL; DQ190456; ABA29226.1; -; Genomic_DNA.
DR EMBL; AY273801; AAP12647.1; -; Genomic_DNA.
DR EMBL; AC060780; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC135721; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC072418; AAH72418.1; -; mRNA.
DR EMBL; BC115037; AAI15038.1; ALT_SEQ; mRNA.
DR CCDS; CCDS11453.1; -. [P38398-1]
DR CCDS; CCDS11454.2; -. [P38398-3]
DR CCDS; CCDS11455.2; -. [P38398-6]
DR CCDS; CCDS11456.2; -. [P38398-7]
DR CCDS; CCDS11459.2; -. [P38398-8]
DR PIR; A58881; A58881.
DR RefSeq; NP_009225.1; NM_007294.3. [P38398-1]
DR RefSeq; NP_009228.2; NM_007297.3. [P38398-8]
DR RefSeq; NP_009229.2; NM_007298.3. [P38398-3]
DR RefSeq; NP_009230.2; NM_007299.3. [P38398-6]
DR RefSeq; NP_009231.2; NM_007300.3. [P38398-7]
DR PDB; 1JM7; NMR; -; A=1-110.
DR PDB; 1JNX; X-ray; 2.50 A; X=1646-1859.
DR PDB; 1N5O; X-ray; 2.80 A; X=1646-1859.
DR PDB; 1OQA; NMR; -; A=1755-1863.
DR PDB; 1T15; X-ray; 1.85 A; A=1646-1859.
DR PDB; 1T29; X-ray; 2.30 A; A=1646-1859.
DR PDB; 1T2U; X-ray; 2.80 A; A=1646-1859.
DR PDB; 1T2V; X-ray; 3.30 A; A/B/C/D/E=1646-1859.
DR PDB; 1Y98; X-ray; 2.50 A; A=1646-1859.
DR PDB; 2ING; X-ray; 3.60 A; X=1649-1859.
DR PDB; 3COJ; X-ray; 3.21 A; A/B/C/D/E/F/G/X=1646-1859.
DR PDB; 3K0H; X-ray; 2.70 A; A=1646-1859.
DR PDB; 3K0K; X-ray; 2.70 A; A=1646-1859.
DR PDB; 3K15; X-ray; 2.80 A; A=1646-1859.
DR PDB; 3K16; X-ray; 3.00 A; A=1646-1859.
DR PDB; 3PXA; X-ray; 2.55 A; A=1646-1859.
DR PDB; 3PXB; X-ray; 2.50 A; A=1646-1859.
DR PDB; 3PXC; X-ray; 2.80 A; X=1646-1859.
DR PDB; 3PXD; X-ray; 2.80 A; A=1646-1859.
DR PDB; 3PXE; X-ray; 2.85 A; A/B/C/D=1646-1859.
DR PDB; 4IFI; X-ray; 2.20 A; A=1646-1859.
DR PDB; 4IGK; X-ray; 1.75 A; A/B=1646-1859.
DR PDB; 4JLU; X-ray; 3.50 A; A=1649-1859.
DR PDB; 4OFB; X-ray; 3.05 A; A=1646-1859.
DR PDB; 4U4A; X-ray; 3.51 A; A/B/C=1646-1859.
DR PDB; 4Y18; X-ray; 3.50 A; A/B/C/D/E/F/G/H=1646-1859.
DR PDB; 4Y2G; X-ray; 2.50 A; A=1646-1859.
DR PDB; 6G2I; EM; 5.90 A; H/K/M/O/S/U/W/Y=1646-1859.
DR PDB; 7JZV; EM; 3.90 A; A=2-104.
DR PDB; 7LYB; EM; 3.28 A; M=1-100.
DR PDBsum; 1JM7; -.
DR PDBsum; 1JNX; -.
DR PDBsum; 1N5O; -.
DR PDBsum; 1OQA; -.
DR PDBsum; 1T15; -.
DR PDBsum; 1T29; -.
DR PDBsum; 1T2U; -.
DR PDBsum; 1T2V; -.
DR PDBsum; 1Y98; -.
DR PDBsum; 2ING; -.
DR PDBsum; 3COJ; -.
DR PDBsum; 3K0H; -.
DR PDBsum; 3K0K; -.
DR PDBsum; 3K15; -.
DR PDBsum; 3K16; -.
DR PDBsum; 3PXA; -.
DR PDBsum; 3PXB; -.
DR PDBsum; 3PXC; -.
DR PDBsum; 3PXD; -.
DR PDBsum; 3PXE; -.
DR PDBsum; 4IFI; -.
DR PDBsum; 4IGK; -.
DR PDBsum; 4JLU; -.
DR PDBsum; 4OFB; -.
DR PDBsum; 4U4A; -.
DR PDBsum; 4Y18; -.
DR PDBsum; 4Y2G; -.
DR PDBsum; 6G2I; -.
DR PDBsum; 7JZV; -.
DR PDBsum; 7LYB; -.
DR AlphaFoldDB; P38398; -.
DR BMRB; P38398; -.
DR SMR; P38398; -.
DR BioGRID; 107140; 1166.
DR ComplexPortal; CPX-715; BRCA1-BARD1 complex.
DR ComplexPortal; CPX-845; BRCA1-PALB2-BRCA2 homologous recombination DNA repair complex.
DR ComplexPortal; CPX-955; BRCC ubiquitin ligase complex.
DR CORUM; P38398; -.
DR DIP; DIP-5971N; -.
DR IntAct; P38398; 230.
DR MINT; P38398; -.
DR STRING; 9606.ENSP00000418960; -.
DR BindingDB; P38398; -.
DR ChEMBL; CHEMBL5990; -.
DR GlyConnect; 2024; 1 N-Linked glycan (1 site).
DR GlyGen; P38398; 1 site, 2 N-linked glycans (1 site).
DR iPTMnet; P38398; -.
DR PhosphoSitePlus; P38398; -.
DR BioMuta; BRCA1; -.
DR DMDM; 728984; -.
DR CPTAC; CPTAC-2610; -.
DR CPTAC; CPTAC-2611; -.
DR CPTAC; CPTAC-3218; -.
DR CPTAC; CPTAC-3219; -.
DR CPTAC; CPTAC-916; -.
DR EPD; P38398; -.
DR jPOST; P38398; -.
DR MassIVE; P38398; -.
DR MaxQB; P38398; -.
DR PaxDb; P38398; -.
DR PeptideAtlas; P38398; -.
DR PRIDE; P38398; -.
DR ProteomicsDB; 20208; -.
DR ProteomicsDB; 55287; -. [P38398-1]
DR ProteomicsDB; 55288; -. [P38398-2]
DR ProteomicsDB; 55289; -. [P38398-3]
DR ProteomicsDB; 55290; -. [P38398-4]
DR ProteomicsDB; 55291; -. [P38398-5]
DR ProteomicsDB; 55292; -. [P38398-6]
DR Antibodypedia; 4527; 2285 antibodies from 45 providers.
DR CPTC; P38398; 4 antibodies.
DR DNASU; 672; -.
DR Ensembl; ENST00000352993.7; ENSP00000312236.5; ENSG00000012048.23. [P38398-5]
DR Ensembl; ENST00000357654.9; ENSP00000350283.3; ENSG00000012048.23. [P38398-1]
DR Ensembl; ENST00000461221.5; ENSP00000418548.1; ENSG00000012048.23. [P38398-2]
DR Ensembl; ENST00000461798.5; ENSP00000417988.1; ENSG00000012048.23. [P38398-2]
DR Ensembl; ENST00000468300.5; ENSP00000417148.1; ENSG00000012048.23. [P38398-6]
DR Ensembl; ENST00000471181.7; ENSP00000418960.2; ENSG00000012048.23. [P38398-7]
DR Ensembl; ENST00000491747.6; ENSP00000420705.2; ENSG00000012048.23. [P38398-3]
DR Ensembl; ENST00000493795.5; ENSP00000418775.1; ENSG00000012048.23. [P38398-8]
DR GeneID; 672; -.
DR KEGG; hsa:672; -.
DR MANE-Select; ENST00000357654.9; ENSP00000350283.3; NM_007294.4; NP_009225.1.
DR UCSC; uc002icq.4; human. [P38398-1]
DR UCSC; uc010cyx.4; human.
DR CTD; 672; -.
DR DisGeNET; 672; -.
DR GeneCards; BRCA1; -.
DR GeneReviews; BRCA1; -.
DR HGNC; HGNC:1100; BRCA1.
DR HPA; ENSG00000012048; Low tissue specificity.
DR MalaCards; BRCA1; -.
DR MIM; 113705; gene.
DR MIM; 114480; phenotype.
DR MIM; 167000; phenotype.
DR MIM; 604370; phenotype.
DR MIM; 614320; phenotype.
DR MIM; 617883; phenotype.
DR neXtProt; NX_P38398; -.
DR OpenTargets; ENSG00000012048; -.
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; 168829; Primary peritoneal carcinoma.
DR Orphanet; 618572; Selection of therapeutic option in ovarian cancer.
DR PharmGKB; PA25411; -.
DR VEuPathDB; HostDB:ENSG00000012048; -.
DR eggNOG; KOG4362; Eukaryota.
DR GeneTree; ENSGT00440000034289; -.
DR HOGENOM; CLU_002290_0_0_1; -.
DR InParanoid; P38398; -.
DR OMA; DMTTEHL; -.
DR OrthoDB; 496760at2759; -.
DR PhylomeDB; P38398; -.
DR BRENDA; 2.3.2.27; 2681.
DR PathwayCommons; P38398; -.
DR Reactome; R-HSA-1221632; Meiotic synapsis.
DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins.
DR Reactome; R-HSA-5685938; HDR through Single Strand Annealing (SSA).
DR Reactome; R-HSA-5685942; HDR through Homologous Recombination (HRR).
DR Reactome; R-HSA-5689901; Metalloprotease DUBs.
DR Reactome; R-HSA-5693554; Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA).
DR Reactome; R-HSA-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR Reactome; R-HSA-5693571; Nonhomologous End-Joining (NHEJ).
DR Reactome; R-HSA-5693579; Homologous DNA Pairing and Strand Exchange.
DR Reactome; R-HSA-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-HSA-5693616; Presynaptic phase of homologous DNA pairing and strand exchange.
DR Reactome; R-HSA-6796648; TP53 Regulates Transcription of DNA Repair Genes.
DR Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-HSA-69473; G2/M DNA damage checkpoint.
DR Reactome; R-HSA-8953750; Transcriptional Regulation by E2F6.
DR Reactome; R-HSA-912446; Meiotic recombination.
DR Reactome; R-HSA-9663199; Defective DNA double strand break response due to BRCA1 loss of function.
DR Reactome; R-HSA-9699150; Defective DNA double strand break response due to BARD1 loss of function.
DR Reactome; R-HSA-9701192; Defective HDR through Homologous Recombination (HRR) due to BRCA1 loss-of-function.
DR Reactome; R-HSA-9704331; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function.
DR Reactome; R-HSA-9704646; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function.
DR Reactome; R-HSA-9709570; Impaired BRCA2 binding to RAD51.
DR Reactome; R-HSA-9709603; Impaired BRCA2 binding to PALB2.
DR SignaLink; P38398; -.
DR SIGNOR; P38398; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 672; 384 hits in 1137 CRISPR screens.
DR ChiTaRS; BRCA1; human.
DR EvolutionaryTrace; P38398; -.
DR GeneWiki; BRCA1; -.
DR GenomeRNAi; 672; -.
DR Pharos; P38398; Tchem.
DR PRO; PR:P38398; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P38398; protein.
DR Bgee; ENSG00000012048; Expressed in ventricular zone and 134 other tissues.
DR ExpressionAtlas; P38398; baseline and differential.
DR Genevisible; P38398; HS.
DR GO; GO:0070531; C:BRCA1-A complex; IDA:UniProtKB.
DR GO; GO:0070532; C:BRCA1-B complex; IPI:ComplexPortal.
DR GO; GO:0031436; C:BRCA1-BARD1 complex; IDA:UniProtKB.
DR GO; GO:0070533; C:BRCA1-C complex; IPI:ComplexPortal.
DR GO; GO:0005694; C:chromosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:1990391; C:DNA repair complex; IPI:ComplexPortal.
DR GO; GO:0000931; C:gamma-tubulin large complex; NAS:UniProtKB.
DR GO; GO:0000800; C:lateral element; IDA:MGI.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
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:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:MGI.
DR GO; GO:0000151; C:ubiquitin ligase complex; NAS:UniProtKB.
DR GO; GO:0003684; F:damaged DNA binding; IEA:Ensembl.
DR GO; GO:0003677; F:DNA binding; TAS:ProtInc.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IDA:MGI.
DR GO; GO:0070063; F:RNA polymerase binding; IDA:UniProtKB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:BHF-UCL.
DR GO; GO:0003713; F:transcription coactivator activity; IMP:UniProtKB.
DR GO; GO:0015631; F:tubulin binding; NAS:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; TAS:ProtInc.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; TAS:ProtInc.
DR GO; GO:0071681; P:cellular response to indole-3-methanol; IDA:UniProtKB.
DR GO; GO:0071479; P:cellular response to ionizing radiation; IMP:ComplexPortal.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IMP:BHF-UCL.
DR GO; GO:0007098; P:centrosome cycle; IEA:Ensembl.
DR GO; GO:0043009; P:chordate embryonic development; IBA:GO_Central.
DR GO; GO:0007059; P:chromosome segregation; IMP:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IC:ComplexPortal.
DR GO; GO:0110025; P:DNA strand resection involved in replication fork processing; IC:ComplexPortal.
DR GO; GO:0009048; P:dosage compensation by inactivation of X chromosome; IBA:GO_Central.
DR GO; GO:0006302; P:double-strand break repair; IDA:CACAO.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IDA:HGNC-UCL.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0070537; P:histone H2A K63-linked deubiquitination; IC:ComplexPortal.
DR GO; GO:0035518; P:histone H2A monoubiquitination; IC:ComplexPortal.
DR GO; GO:0035825; P:homologous recombination; IC:ComplexPortal.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IDA:MGI.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0044818; P:mitotic G2/M transition checkpoint; IC:ComplexPortal.
DR GO; GO:0045786; P:negative regulation of cell cycle; IC:ComplexPortal.
DR GO; GO:0046600; P:negative regulation of centriole replication; NAS:UniProtKB.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; IMP:BHF-UCL.
DR GO; GO:0045717; P:negative regulation of fatty acid biosynthetic process; IMP:UniProtKB.
DR GO; GO:0035067; P:negative regulation of histone acetylation; IBA:GO_Central.
DR GO; GO:0051572; P:negative regulation of histone H3-K4 methylation; IEA:Ensembl.
DR GO; GO:0051573; P:negative regulation of histone H3-K9 methylation; IDA:BHF-UCL.
DR GO; GO:0033147; P:negative regulation of intracellular estrogen receptor signaling pathway; IMP:CACAO.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IMP:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:BHF-UCL.
DR GO; GO:0045739; P:positive regulation of DNA repair; IMP:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:0035066; P:positive regulation of histone acetylation; IDA:BHF-UCL.
DR GO; GO:0051571; P:positive regulation of histone H3-K4 methylation; IDA:BHF-UCL.
DR GO; GO:2000617; P:positive regulation of histone H3-K9 acetylation; IDA:BHF-UCL.
DR GO; GO:0051574; P:positive regulation of histone H3-K9 methylation; IEA:Ensembl.
DR GO; GO:2000620; P:positive regulation of histone H4-K16 acetylation; IDA:BHF-UCL.
DR GO; GO:0070512; P:positive regulation of histone H4-K20 methylation; IDA:BHF-UCL.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; IMP:BHF-UCL.
DR GO; GO:0006301; P:postreplication repair; IDA:HGNC-UCL.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
DR GO; GO:0085020; P:protein K6-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:ComplexPortal.
DR GO; GO:0016567; P:protein ubiquitination; IDA:HGNC-UCL.
DR GO; GO:0051726; P:regulation of cell cycle; IDA:BHF-UCL.
DR GO; GO:2000001; P:regulation of DNA damage checkpoint; IC:ComplexPortal.
DR GO; GO:0044030; P:regulation of DNA methylation; IEA:Ensembl.
DR GO; GO:0006282; P:regulation of DNA repair; IC:ComplexPortal.
DR GO; GO:0006349; P:regulation of gene expression by genomic imprinting; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0043627; P:response to estrogen; IDA:UniProtKB.
DR GO; GO:0010212; P:response to ionizing radiation; IMP:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR Gene3D; 3.40.50.10190; -; 2.
DR IDEAL; IID00042; -.
DR InterPro; IPR011364; BRCA1.
DR InterPro; IPR031099; BRCA1-associated.
DR InterPro; IPR025994; BRCA1_serine_dom.
DR InterPro; IPR001357; BRCT_dom.
DR InterPro; IPR036420; BRCT_dom_sf.
DR InterPro; IPR018957; Znf_C3HC4_RING-type.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR PANTHER; PTHR13763; PTHR13763; 1.
DR Pfam; PF00533; BRCT; 2.
DR Pfam; PF12820; BRCT_assoc; 1.
DR Pfam; PF00097; zf-C3HC4; 1.
DR PIRSF; PIRSF001734; BRCA1; 1.
DR PRINTS; PR00493; BRSTCANCERI.
DR SMART; SM00292; BRCT; 2.
DR SMART; SM00184; RING; 1.
DR SUPFAM; SSF52113; SSF52113; 2.
DR PROSITE; PS50172; BRCT; 2.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Alternative initiation;
KW Alternative splicing; Cell cycle; Chromosome; Cytoplasm;
KW Direct protein sequencing; Disease variant; DNA damage; DNA recombination;
KW DNA repair; DNA-binding; Fanconi anemia; Fatty acid biosynthesis;
KW Fatty acid metabolism; Isopeptide bond; Lipid biosynthesis;
KW Lipid metabolism; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Transcription; Transcription regulation;
KW Transferase; Tumor suppressor; Ubl conjugation; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT CHAIN 1..1863
FT /note="Breast cancer type 1 susceptibility protein"
FT /id="PRO_0000055830"
FT DOMAIN 1642..1736
FT /note="BRCT 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 1756..1855
FT /note="BRCT 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT ZN_FING 24..65
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 230..270
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 306..338
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 534..570
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 654..709
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1181..1216
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1322..1387
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1397..1424
FT /note="Interaction with PALB2"
FT /evidence="ECO:0000269|PubMed:19369211"
FT REGION 1440..1505
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1565..1596
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 230..248
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 324..338
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 534..569
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 676..698
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1181..1196
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1338..1353
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1354..1387
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1440..1468
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1478..1492
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 114
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 395
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 398
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 423
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 434
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 551
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 694
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 708
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 725
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48754"
FT MOD_RES 753
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 840
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48754"
FT MOD_RES 988
FT /note="Phosphoserine; by CHEK2"
FT /evidence="ECO:0000269|PubMed:10724175,
FT ECO:0000269|PubMed:20364141"
FT MOD_RES 1009
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1143
FT /note="Phosphoserine; by ATR; in vitro"
FT /evidence="ECO:0000269|PubMed:11114888"
FT MOD_RES 1189
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1191
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1211
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1217
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1218
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 1280
FT /note="Phosphoserine; by ATR; in vitro"
FT /evidence="ECO:0000269|PubMed:11114888"
FT MOD_RES 1328
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 1336
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT MOD_RES 1342
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 1387
FT /note="Phosphoserine; by ATM and ATR"
FT /evidence="ECO:0000269|PubMed:11114888"
FT MOD_RES 1394
FT /note="Phosphothreonine; by ATR; in vitro"
FT /evidence="ECO:0000269|PubMed:11114888"
FT MOD_RES 1423
FT /note="Phosphoserine; by ATM and ATR"
FT /evidence="ECO:0000269|PubMed:11114888"
FT MOD_RES 1457
FT /note="Phosphoserine; by ATR; in vitro"
FT /evidence="ECO:0000269|PubMed:11114888"
FT MOD_RES 1524
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000269|PubMed:21144835"
FT MOD_RES 1542
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 109
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 301
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 339
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:28112733"
FT CROSSLNK 443
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 459
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 519
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 583
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:28112733"
FT CROSSLNK 654
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447"
FT CROSSLNK 734
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447"
FT CROSSLNK 739
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447"
FT CROSSLNK 918
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 987
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1079
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..47
FT /note="Missing (in isoform 8)"
FT /id="VSP_057569"
FT VAR_SEQ 1..17
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_035396"
FT VAR_SEQ 64..1863
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_047891"
FT VAR_SEQ 224..1365
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_035398"
FT VAR_SEQ 264..1366
FT /note="Missing (in isoform 3 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9010228"
FT /id="VSP_035399"
FT VAR_SEQ 1453
FT /note="Missing (in isoform 3 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9010228"
FT /id="VSP_043797"
FT VAR_SEQ 1453
FT /note="A -> DSHIHGQRNNSMFSKRPREHIS (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_055404"
FT VAR_SEQ 1778..1863
FT /note="DQLEWMVQLCGASVVKELSSFTLGTGVHPIVVVQPDAWTEDNGFHAIGQMCE
FT APVVTREWVLDSVALYQCQELDTYLIPQIPHSHY -> GCPPNCGCAARCLDRGQWLPC
FT NWADV (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_043798"
FT VARIANT 4
FT /note="S -> F (in BC; unknown pathological significance;
FT dbSNP:rs786203152)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070458"
FT VARIANT 10
FT /note="E -> K (in BC and BROVCA1)"
FT /evidence="ECO:0000269|PubMed:14722926"
FT /id="VAR_020679"
FT VARIANT 11
FT /note="V -> A (found in breast-ovarian cancer patients;
FT unknown pathological significance; dbSNP:rs80357017)"
FT /id="VAR_007754"
FT VARIANT 18
FT /note="M -> T (in BC; unknown pathological significance;
FT dbSNP:rs80356929)"
FT /evidence="ECO:0000269|PubMed:17924331,
FT ECO:0000269|PubMed:23867111"
FT /id="VAR_063899"
FT VARIANT 21
FT /note="I -> V (found in breast-ovarian cancer patients;
FT unknown pathological significance; dbSNP:rs80357406)"
FT /id="VAR_007755"
FT VARIANT 22
FT /note="L -> S (in BC; dbSNP:rs80357438)"
FT /evidence="ECO:0000269|PubMed:9609997"
FT /id="VAR_007756"
FT VARIANT 23
FT /note="E -> K (in BC and BROVCA1)"
FT /evidence="ECO:0000269|PubMed:14722926"
FT /id="VAR_020680"
FT VARIANT 30
FT /note="L -> F (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035947"
FT VARIANT 45
FT /note="K -> Q (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs769650474)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070459"
FT VARIANT 61
FT /note="C -> G (in BC and ovarian cancer; no interaction
FT with BAP1; dbSNP:rs28897672)"
FT /evidence="ECO:0000269|PubMed:12938098,
FT ECO:0000269|PubMed:14746861, ECO:0000269|PubMed:23867111,
FT ECO:0000269|PubMed:7894493, ECO:0000269|PubMed:8554067,
FT ECO:0000269|PubMed:9528852, ECO:0000269|PubMed:9760198"
FT /id="VAR_007757"
FT VARIANT 64
FT /note="C -> G (in BC; no interaction with BAP1;
FT dbSNP:rs80357064)"
FT /evidence="ECO:0000269|PubMed:23867111,
FT ECO:0000269|PubMed:7894491, ECO:0000269|PubMed:9482581,
FT ECO:0000269|PubMed:9528852"
FT /id="VAR_007758"
FT VARIANT 64
FT /note="C -> Y (in dbSNP:rs55851803)"
FT /id="VAR_007759"
FT VARIANT 67
FT /note="D -> Y (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs80357102)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070460"
FT VARIANT 71
FT /note="R -> K (in BC; unknown pathological significance;
FT dbSNP:rs80356913)"
FT /evidence="ECO:0000269|PubMed:12938098"
FT /id="VAR_020681"
FT VARIANT 105
FT /note="Y -> C (in dbSNP:rs28897673)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070461"
FT VARIANT 132
FT /note="N -> K (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs80357413)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070462"
FT VARIANT 142
FT /note="P -> H (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs55971303)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070463"
FT VARIANT 147
FT /note="L -> F (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs748876625)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070464"
FT VARIANT 153
FT /note="S -> R (in dbSNP:rs28897674)"
FT /id="VAR_052077"
FT VARIANT 165
FT /note="L -> P (in BC; unknown pathological significance;
FT functionally neutral in vitro)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070465"
FT VARIANT 170
FT /note="R -> W (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs80357325)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070466"
FT VARIANT 186
FT /note="S -> Y (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs55688530)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070467"
FT VARIANT 191
FT /note="V -> I (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs80357090)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070468"
FT VARIANT 227
FT /note="E -> K (in ovarian cancer; unknown pathological
FT significance)"
FT /id="VAR_008759"
FT VARIANT 231
FT /note="T -> M (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs80357001)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070469"
FT VARIANT 239
FT /note="H -> R (in dbSNP:rs80357396)"
FT /evidence="ECO:0000269|PubMed:9010228,
FT ECO:0000269|PubMed:9760198"
FT /id="VAR_007760"
FT VARIANT 245
FT /note="D -> V (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs80356865)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070470"
FT VARIANT 246
FT /note="L -> V (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs28897675)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070471"
FT VARIANT 271
FT /note="V -> L (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs80357244)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070472"
FT VARIANT 271
FT /note="V -> M (in BC; dbSNP:rs80357244)"
FT /evidence="ECO:0000269|PubMed:8723683"
FT /id="VAR_007761"
FT VARIANT 275
FT /note="G -> S (in dbSNP:rs8176153)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_019944"
FT VARIANT 346
FT /note="P -> S (in BC; unknown pathological significance;
FT dbSNP:rs80357015)"
FT /evidence="ECO:0000269|PubMed:10323242"
FT /id="VAR_008760"
FT VARIANT 356
FT /note="Q -> R (in dbSNP:rs1799950)"
FT /evidence="ECO:0000269|PubMed:7894493, ECO:0000269|Ref.5,
FT ECO:0000269|Ref.6"
FT /id="VAR_007762"
FT VARIANT 369
FT /note="Missing (in BC; dbSNP:rs80358325)"
FT /id="VAR_007763"
FT VARIANT 379
FT /note="I -> M (in dbSNP:rs56128296)"
FT /id="VAR_007764"
FT VARIANT 461
FT /note="F -> L (in BC; dbSNP:rs56046357)"
FT /evidence="ECO:0000269|PubMed:9609997"
FT /id="VAR_007765"
FT VARIANT 465
FT /note="Y -> D (in BC; dbSNP:rs397508869)"
FT /evidence="ECO:0000269|PubMed:9609997"
FT /id="VAR_007766"
FT VARIANT 507
FT /note="R -> I (found in breast-ovarian cancer patients;
FT unknown pathological significance; dbSNP:rs80357224)"
FT /id="VAR_007767"
FT VARIANT 552
FT /note="G -> V (in BC; dbSNP:rs397508893)"
FT /evidence="ECO:0000269|PubMed:9609997"
FT /id="VAR_007768"
FT VARIANT 656
FT /note="N -> I"
FT /evidence="ECO:0000269|PubMed:12442274"
FT /id="VAR_020682"
FT VARIANT 668
FT /note="L -> F (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs80357250)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070473"
FT VARIANT 693
FT /note="D -> N (in dbSNP:rs4986850)"
FT /evidence="ECO:0000269|PubMed:15026808, ECO:0000269|Ref.6"
FT /id="VAR_007769"
FT VARIANT 695
FT /note="D -> N (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs28897681)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070474"
FT VARIANT 723
FT /note="N -> D (in dbSNP:rs4986845)"
FT /id="VAR_020110"
FT VARIANT 749
FT /note="D -> Y (in BC; dbSNP:rs80357114)"
FT /evidence="ECO:0000269|PubMed:12442275"
FT /id="VAR_020683"
FT VARIANT 758
FT /note="L -> F (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035948"
FT VARIANT 772
FT /note="V -> A (in dbSNP:rs80357467)"
FT /evidence="ECO:0000269|PubMed:7894491,
FT ECO:0000269|PubMed:9482581"
FT /id="VAR_007770"
FT VARIANT 778
FT /note="G -> C (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035949"
FT VARIANT 798
FT /note="P -> L (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs876660005)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070475"
FT VARIANT 810
FT /note="N -> Y (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs28897682)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070476"
FT VARIANT 820
FT /note="K -> E (in dbSNP:rs56082113)"
FT /evidence="ECO:0000269|PubMed:9482581"
FT /id="VAR_007771"
FT VARIANT 826
FT /note="T -> K (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs28897683)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_007772"
FT VARIANT 835
FT /note="H -> Y (in BROVCA1; unknown pathological
FT significance; dbSNP:rs751656678)"
FT /evidence="ECO:0000269|PubMed:12938098"
FT /id="VAR_020684"
FT VARIANT 841
FT /note="R -> Q (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs80357337)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070477"
FT VARIANT 841
FT /note="R -> W (in BROVCA1; unknown pathological
FT significance; dbSNP:rs1800709)"
FT /evidence="ECO:0000269|PubMed:8968716,
FT ECO:0000269|PubMed:9760198"
FT /id="VAR_007773"
FT VARIANT 856
FT /note="Y -> H (in a patient with sporadic breast cancer;
FT unknown pathological significance; dbSNP:rs80356892)"
FT /evidence="ECO:0000269|PubMed:15365993,
FT ECO:0000269|PubMed:23867111"
FT /id="VAR_020685"
FT VARIANT 866
FT /note="R -> C (in dbSNP:rs41286300)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070478"
FT VARIANT 866
FT /note="R -> Q (in BC; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:12938098"
FT /id="VAR_020686"
FT VARIANT 871
FT /note="P -> L (in dbSNP:rs799917)"
FT /evidence="ECO:0000269|PubMed:10323242,
FT ECO:0000269|PubMed:12442274, ECO:0000269|PubMed:15365993,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.6"
FT /id="VAR_007774"
FT VARIANT 888
FT /note="H -> Y (in BC; unknown pathological significance;
FT dbSNP:rs80357480)"
FT /evidence="ECO:0000269|PubMed:12938098"
FT /id="VAR_020687"
FT VARIANT 892
FT /note="L -> S (in BC; dbSNP:rs397508994)"
FT /evidence="ECO:0000269|PubMed:9609997"
FT /id="VAR_007775"
FT VARIANT 903..1863
FT /note="Missing (in FANCS)"
FT /evidence="ECO:0000269|PubMed:29133208"
FT /id="VAR_080693"
FT VARIANT 925
FT /note="I -> L (in dbSNP:rs4986847)"
FT /id="VAR_021913"
FT VARIANT 960
FT /note="G -> D (in BC; dbSNP:rs397509022)"
FT /evidence="ECO:0000269|PubMed:9609997"
FT /id="VAR_007776"
FT VARIANT 989
FT /note="F -> S (in dbSNP:rs4986848)"
FT /id="VAR_020111"
FT VARIANT 1008
FT /note="M -> I (in dbSNP:rs1800704)"
FT /id="VAR_007777"
FT VARIANT 1025
FT /note="T -> I (in BC; dbSNP:rs397509034)"
FT /evidence="ECO:0000269|PubMed:9609997"
FT /id="VAR_007778"
FT VARIANT 1038
FT /note="E -> G (in dbSNP:rs16941)"
FT /evidence="ECO:0000269|PubMed:10323242,
FT ECO:0000269|PubMed:15365993, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:7894493, ECO:0000269|Ref.6"
FT /id="VAR_007779"
FT VARIANT 1040
FT /note="S -> N (in dbSNP:rs4986852)"
FT /evidence="ECO:0000269|PubMed:15026808,
FT ECO:0000269|PubMed:7894491, ECO:0000269|PubMed:7894493,
FT ECO:0000269|PubMed:9482581, ECO:0000269|Ref.6"
FT /id="VAR_007780"
FT VARIANT 1047
FT /note="V -> A (in BC; dbSNP:rs397509037)"
FT /evidence="ECO:0000269|PubMed:9609997"
FT /id="VAR_007781"
FT VARIANT 1060
FT /note="E -> A (in dbSNP:rs80357184)"
FT /evidence="ECO:0000269|PubMed:15026808,
FT ECO:0000269|PubMed:23867111"
FT /id="VAR_020688"
FT VARIANT 1101
FT /note="S -> N (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs41293447)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070479"
FT VARIANT 1139
FT /note="S -> I (in BC; unknown pathological significance;
FT dbSNP:rs80357228)"
FT /evidence="ECO:0000269|PubMed:12938098"
FT /id="VAR_020689"
FT VARIANT 1140
FT /note="S -> G (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs2227945)"
FT /evidence="ECO:0000269|PubMed:23867111, ECO:0000269|Ref.6"
FT /id="VAR_019945"
FT VARIANT 1140
FT /note="S -> N (in BC; unknown pathological significance;
FT functionally neutral in vitro)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070480"
FT VARIANT 1150
FT /note="P -> S (in BC; dbSNP:rs80357272)"
FT /evidence="ECO:0000269|PubMed:8723683"
FT /id="VAR_007782"
FT VARIANT 1183
FT /note="K -> R (in dbSNP:rs16942)"
FT /evidence="ECO:0000269|PubMed:10323242,
FT ECO:0000269|PubMed:14722926, ECO:0000269|PubMed:15365993,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:7894493,
FT ECO:0000269|Ref.6"
FT /id="VAR_007783"
FT VARIANT 1187
FT /note="S -> I (in BC and BROVCA1)"
FT /evidence="ECO:0000269|PubMed:14722926"
FT /id="VAR_020690"
FT VARIANT 1200
FT /note="Q -> H (in BC and BROVCA1; dbSNP:rs56214134)"
FT /evidence="ECO:0000269|PubMed:14722926"
FT /id="VAR_020691"
FT VARIANT 1204
FT /note="R -> I (in BC)"
FT /evidence="ECO:0000269|PubMed:14722926"
FT /id="VAR_020692"
FT VARIANT 1207
FT /note="K -> N (in BC)"
FT /evidence="ECO:0000269|PubMed:14722926"
FT /id="VAR_020693"
FT VARIANT 1210
FT /note="E -> G (in BC; unknown pathological significance;
FT dbSNP:rs1060502347)"
FT /evidence="ECO:0000269|PubMed:12938098"
FT /id="VAR_020694"
FT VARIANT 1214
FT /note="E -> K (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs80356923)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070481"
FT VARIANT 1217
FT /note="S -> Y (in BC and BROVCA1)"
FT /evidence="ECO:0000269|PubMed:14722926"
FT /id="VAR_020695"
FT VARIANT 1219
FT /note="E -> D (found in breast-ovarian cancer patients;
FT unknown pathological significance; dbSNP:rs80356876)"
FT /id="VAR_007784"
FT VARIANT 1226
FT /note="F -> L (in BROVCA1)"
FT /evidence="ECO:0000269|PubMed:14722926"
FT /id="VAR_020696"
FT VARIANT 1236
FT /note="N -> K (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs28897687)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_052078"
FT VARIANT 1243
FT /note="R -> G (in BROVCA1)"
FT /evidence="ECO:0000269|PubMed:14722926"
FT /id="VAR_020697"
FT VARIANT 1250
FT /note="E -> K (in dbSNP:rs28897686)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_052079"
FT VARIANT 1267
FT /note="L -> S (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs587782190)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070482"
FT VARIANT 1282
FT /note="E -> V (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs80357217)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070483"
FT VARIANT 1297
FT /note="S -> P (in BC; unknown pathological significance;
FT dbSNP:rs1450793674)"
FT /evidence="ECO:0000269|PubMed:12938098"
FT /id="VAR_020698"
FT VARIANT 1297
FT /note="Missing (in BC; unknown pathological significance;
FT functionally neutral in vitro)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070484"
FT VARIANT 1301
FT /note="S -> R (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs273900719)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070485"
FT VARIANT 1346
FT /note="E -> K (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs80357407)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070486"
FT VARIANT 1347
FT /note="R -> G (in dbSNP:rs28897689)"
FT /evidence="ECO:0000269|PubMed:12215251"
FT /id="VAR_007785"
FT VARIANT 1378
FT /note="V -> I (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs28897690)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070487"
FT VARIANT 1400
FT /note="M -> V (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs80357306)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070488"
FT VARIANT 1406
FT /note="K -> N (in dbSNP:rs1800707)"
FT /id="VAR_008761"
FT VARIANT 1407
FT /note="L -> P (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs80357492)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070489"
FT VARIANT 1411
FT /note="M -> T (in BC and ovarian cancer; unknown
FT pathological significance; decreased interaction with
FT PALB2; dbSNP:rs273900729)"
FT /evidence="ECO:0000269|PubMed:14746861,
FT ECO:0000269|PubMed:19369211, ECO:0000269|PubMed:23867111"
FT /id="VAR_020699"
FT VARIANT 1431
FT /note="S -> P"
FT /id="VAR_007786"
FT VARIANT 1443
FT /note="R -> G (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs41293455)"
FT /evidence="ECO:0000269|PubMed:23867111,
FT ECO:0000269|PubMed:7894491, ECO:0000269|PubMed:9482581"
FT /id="VAR_007787"
FT VARIANT 1443
FT /note="R -> Q (in dbSNP:rs4986849)"
FT /id="VAR_020112"
FT VARIANT 1448
FT /note="S -> G (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs80357486)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070490"
FT VARIANT 1486
FT /note="S -> C (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs397507232)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070491"
FT VARIANT 1495
FT /note="R -> M (in BC; unknown pathological significance;
FT dbSNP:rs80357389)"
FT /evidence="ECO:0000269|PubMed:17924331"
FT /id="VAR_063900"
FT VARIANT 1512
FT /note="S -> I (in dbSNP:rs1800744)"
FT /evidence="ECO:0000269|PubMed:12215251,
FT ECO:0000269|PubMed:9482581, ECO:0000269|PubMed:9760198"
FT /id="VAR_007788"
FT VARIANT 1534
FT /note="V -> M (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs55815649)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070492"
FT VARIANT 1561
FT /note="T -> I (found in breast cancer; unknown pathological
FT significance; dbSNP:rs56158747)"
FT /id="VAR_007789"
FT VARIANT 1589
FT /note="R -> P (in BC; unknown pathological significance;
FT functionally neutral in vitro)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070493"
FT VARIANT 1606
FT /note="K -> E (found in breast cancer; unknown pathological
FT significance; dbSNP:rs80356943)"
FT /id="VAR_007790"
FT VARIANT 1613
FT /note="S -> G (in dbSNP:rs1799966)"
FT /evidence="ECO:0000269|PubMed:10323242,
FT ECO:0000269|PubMed:12442274, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:7894493, ECO:0000269|PubMed:9010228,
FT ECO:0000269|Ref.6"
FT /id="VAR_007791"
FT VARIANT 1620
FT /note="T -> A (in dbSNP:rs8176219)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_019946"
FT VARIANT 1623
FT /note="A -> G (could be associated with cancer
FT susceptibility; major splicing aberration identified with
FT this mutant; dbSNP:rs80356862)"
FT /evidence="ECO:0000269|PubMed:17924331,
FT ECO:0000269|PubMed:20513136"
FT /id="VAR_063901"
FT VARIANT 1628
FT /note="M -> T (in some patients with sporadic breast
FT cancer; unknown pathological significance;
FT dbSNP:rs4986854)"
FT /evidence="ECO:0000269|PubMed:15365993,
FT ECO:0000269|PubMed:23867111"
FT /id="VAR_007793"
FT VARIANT 1628
FT /note="M -> V (found in breast and ovarian cancer patients;
FT unknown pathological significance; dbSNP:rs80357465)"
FT /id="VAR_007792"
FT VARIANT 1637
FT /note="P -> L (in dbSNP:rs80357048)"
FT /evidence="ECO:0000269|PubMed:7939630,
FT ECO:0000269|PubMed:9482581"
FT /id="VAR_007794"
FT VARIANT 1641
FT /note="A -> P (in ovarian cancer; unknown pathological
FT significance; dbSNP:rs1800726)"
FT /id="VAR_008762"
FT VARIANT 1651
FT /note="S -> F (in BC; unknown pathological significance;
FT dbSNP:rs80356938)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070494"
FT VARIANT 1651
FT /note="S -> P (in BC; unknown pathological significance;
FT dbSNP:rs879254042)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070495"
FT VARIANT 1652
FT /note="M -> I (in dbSNP:rs1799967)"
FT /evidence="ECO:0000269|PubMed:12215251,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:23867111,
FT ECO:0000269|PubMed:9482581"
FT /id="VAR_007795"
FT VARIANT 1655
FT /note="S -> F (in BC; unknown pathological significance;
FT functionally impaired in vitro; dbSNP:rs80357390)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070496"
FT VARIANT 1662
FT /note="F -> C (in dbSNP:rs28897695)"
FT /id="VAR_052080"
FT VARIANT 1665
FT /note="V -> M (in dbSNP:rs80357169)"
FT /evidence="ECO:0000269|PubMed:15026808"
FT /id="VAR_020700"
FT VARIANT 1685
FT /note="T -> A (in BC; unknown pathological significance;
FT dbSNP:rs80356890)"
FT /evidence="ECO:0000269|PubMed:17924331"
FT /id="VAR_063902"
FT VARIANT 1685
FT /note="T -> I (could be associated with cancer
FT susceptibility; multifactorial likelihood analysis provides
FT evidence for pathogenicity; dbSNP:rs80357043)"
FT /evidence="ECO:0000269|PubMed:17924331,
FT ECO:0000269|PubMed:20513136"
FT /id="VAR_063903"
FT VARIANT 1686
FT /note="H -> Q (in BC; unknown pathological significance;
FT functionally impaired in vitro; dbSNP:rs397509218)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070497"
FT VARIANT 1686
FT /note="H -> R (in BC; unknown pathological significance;
FT functionally impaired in vitro; dbSNP:rs730882166)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070498"
FT VARIANT 1688
FT /note="Missing (in BC; unknown pathological significance;
FT functionally impaired in vitro; dbSNP:rs80358344)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070499"
FT VARIANT 1689
FT /note="M -> R (in BC; unknown pathological significance;
FT dbSNP:rs80357061)"
FT /evidence="ECO:0000269|PubMed:17924331"
FT /id="VAR_063904"
FT VARIANT 1690
FT /note="K -> Q (in some patients with sporadic breast
FT cancer; unknown pathological significance;
FT dbSNP:rs397507239)"
FT /evidence="ECO:0000269|PubMed:15365993"
FT /id="VAR_020701"
FT VARIANT 1691
FT /note="T -> I (in BC; unknown pathological significance;
FT functionally impaired in vitro; dbSNP:rs80357034)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070500"
FT VARIANT 1692
FT /note="D -> N (in ovarian cancer; unknown pathological
FT significance; dbSNP:rs80187739)"
FT /id="VAR_008763"
FT VARIANT 1697
FT /note="C -> R (in ovarian cancer; dbSNP:rs80356993)"
FT /evidence="ECO:0000269|PubMed:14746861"
FT /id="VAR_020702"
FT VARIANT 1699
FT /note="R -> Q (in BC; unknown pathological significance;
FT strongly reduces affinity for a BRIP1 phosphopeptide;
FT functionally impaired in vitro; dbSNP:rs41293459)"
FT /evidence="ECO:0000269|PubMed:21473589,
FT ECO:0000269|PubMed:23867111"
FT /id="VAR_070501"
FT VARIANT 1699
FT /note="R -> W (in BC, ovarian cancer and FANCS; impairs
FT protein stability; functionally impaired in vitro;
FT dbSNP:rs55770810)"
FT /evidence="ECO:0000269|PubMed:14746861,
FT ECO:0000269|PubMed:17924331, ECO:0000269|PubMed:21473589,
FT ECO:0000269|PubMed:23867111, ECO:0000269|PubMed:25472942"
FT /id="VAR_075666"
FT VARIANT 1706
FT /note="G -> A (in BC; unknown pathological significance;
FT dbSNP:rs80356860)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070502"
FT VARIANT 1706
FT /note="G -> E (in BC; unknown pathological significance;
FT dbSNP:rs80356860)"
FT /evidence="ECO:0000269|PubMed:17924331,
FT ECO:0000269|PubMed:23867111"
FT /id="VAR_063905"
FT VARIANT 1708
FT /note="A -> E (in BC; abolishes ACACA binding;
FT dbSNP:rs28897696)"
FT /evidence="ECO:0000269|PubMed:17924331,
FT ECO:0000269|PubMed:23867111, ECO:0000269|PubMed:7939630"
FT /id="VAR_007796"
FT VARIANT 1713
FT /note="V -> G"
FT /evidence="ECO:0000269|PubMed:15365993"
FT /id="VAR_007797"
FT VARIANT 1715
FT /note="S -> R (in BC; unknown pathological significance;
FT dbSNP:rs80357094)"
FT /evidence="ECO:0000269|PubMed:17924331"
FT /id="VAR_063906"
FT VARIANT 1718
FT /note="W -> C (in BC; unknown pathological significance;
FT functionally impaired in vitro; dbSNP:rs80357239)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070503"
FT VARIANT 1720
FT /note="T -> A (in BC; unknown pathological significance;
FT functionally neutral in vitro; no effect on in vitro
FT phosphorylation by ATR; dbSNP:rs56195342)"
FT /evidence="ECO:0000269|PubMed:11114888,
FT ECO:0000269|PubMed:23867111"
FT /id="VAR_070504"
FT VARIANT 1735
FT /note="E -> K (in BC; unknown pathological significance;
FT dbSNP:rs397509238)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070505"
FT VARIANT 1736
FT /note="V -> A (in BC and FANCS; unknown pathological
FT significance; Decreased localization to DNA damage sites
FT and reduced interaction with UIMC1/RAP80;
FT dbSNP:rs45553935)"
FT /evidence="ECO:0000269|PubMed:23269703,
FT ECO:0000269|PubMed:23867111"
FT /id="VAR_070506"
FT VARIANT 1738
FT /note="G -> R (in BC; unknown pathological significance;
FT dbSNP:rs80356937)"
FT /evidence="ECO:0000269|PubMed:17924331"
FT /id="VAR_063907"
FT VARIANT 1739
FT /note="D -> G (in BC; unknown pathological significance;
FT functionally impaired in vitro; dbSNP:rs80357227)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070507"
FT VARIANT 1739
FT /note="D -> V (in BC; unknown pathological significance;
FT functionally impaired in vitro; dbSNP:rs80357227)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070508"
FT VARIANT 1746
FT /note="H -> Q (in BC; unknown pathological significance;
FT dbSNP:rs786202389)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070509"
FT VARIANT 1749
FT /note="P -> R (in ovarian cancer; unknown pathological
FT significance; abolishes ACACA binding and strongly reduces
FT BRIP1 binding; dbSNP:rs80357462)"
FT /evidence="ECO:0000269|PubMed:10486320,
FT ECO:0000269|PubMed:11301010, ECO:0000269|PubMed:15133502"
FT /id="VAR_007798"
FT VARIANT 1753
FT /note="R -> T (in BC; unknown pathological significance;
FT dbSNP:rs397509246)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070510"
FT VARIANT 1764
FT /note="L -> P (in BC; unknown pathological significance;
FT functionally impaired in vitro; dbSNP:rs80357281)"
FT /evidence="ECO:0000269|PubMed:17924331,
FT ECO:0000269|PubMed:23867111"
FT /id="VAR_063908"
FT VARIANT 1766
FT /note="I -> S (in BC; unknown pathological significance;
FT dbSNP:rs80357463)"
FT /evidence="ECO:0000269|PubMed:17924331"
FT /id="VAR_063909"
FT VARIANT 1767
FT /note="C -> S (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs1597804426)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070511"
FT VARIANT 1770
FT /note="G -> V (in BC; unknown pathological significance;
FT functionally impaired in vitro; dbSNP:rs863224765)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070512"
FT VARIANT 1775
FT /note="M -> K (in BC; strongly reduced transcription
FT transactivation; abolishes interaction with BRIP1 and
FT RBBP8; dbSNP:rs41293463)"
FT /evidence="ECO:0000269|PubMed:18285836"
FT /id="VAR_063212"
FT VARIANT 1775
FT /note="M -> R (in BC; alters protein stability and
FT abolishes ACACA and BRIP1 binding; dbSNP:rs41293463)"
FT /evidence="ECO:0000269|PubMed:11301010,
FT ECO:0000269|PubMed:12427738, ECO:0000269|PubMed:15133502,
FT ECO:0000269|PubMed:7545954, ECO:0000269|PubMed:7939630"
FT /id="VAR_007799"
FT VARIANT 1776
FT /note="P -> S (in ovarian cancer; unknown pathological
FT significance; dbSNP:rs1800757)"
FT /id="VAR_008764"
FT VARIANT 1780
FT /note="L -> P (in BC, BROVCA1 and OC; unknown pathological
FT significance; dbSNP:rs80357474)"
FT /evidence="ECO:0000269|PubMed:28364669"
FT /id="VAR_079607"
FT VARIANT 1782
FT /note="W -> C (in BC; unknown pathological significance;
FT functionally neutral in vitro)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070513"
FT VARIANT 1786
FT /note="L -> P (in BROVCA1; unknown pathological
FT significance; dbSNP:rs398122697)"
FT /evidence="ECO:0000269|PubMed:12938098"
FT /id="VAR_020704"
FT VARIANT 1788
FT /note="G -> V (in BC; unknown pathological significance;
FT dbSNP:rs80357069)"
FT /evidence="ECO:0000269|PubMed:17924331"
FT /id="VAR_063910"
FT VARIANT 1789
FT /note="A -> T (in BC; unknown pathological significance;
FT functionally impaired in vitro; dbSNP:rs80357078)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070514"
FT VARIANT 1794
FT /note="E -> D (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs397509275)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070515"
FT VARIANT 1804
FT /note="V -> D (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs80356920)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070516"
FT VARIANT 1812
FT /note="P -> R (in BC; unknown pathological significance;
FT functionally neutral in vitro)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070517"
FT VARIANT 1812
FT /note="P -> S (in ovarian cancer; unknown pathological
FT significance; dbSNP:rs1800751)"
FT /id="VAR_008765"
FT VARIANT 1837
FT /note="W -> R (in BC; unknown pathological significance;
FT functionally impaired in vitro; dbSNP:rs80356959)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070518"
FT VARIANT 1862
FT /note="H -> L (in BC; unknown pathological significance;
FT functionally neutral in vitro; dbSNP:rs80357183)"
FT /evidence="ECO:0000269|PubMed:23867111"
FT /id="VAR_070519"
FT MUTAGEN 26
FT /note="I->A: Disrupts the interaction with E2 enzymes,
FT thereby abolishing the E3 ubiquitin-protein ligase
FT activity."
FT /evidence="ECO:0000269|PubMed:16818604,
FT ECO:0000269|PubMed:20351172"
FT MUTAGEN 26
FT /note="I->E: No ubiquitination of RBBP8. No restoration
FT RBBP8-mediated focus formation or G2/M checkpoint control
FT upon DNA damage."
FT /evidence="ECO:0000269|PubMed:16818604,
FT ECO:0000269|PubMed:20351172"
FT MUTAGEN 71
FT /note="R->G: No effect on interaction with BAP1."
FT /evidence="ECO:0000269|PubMed:9528852"
FT MUTAGEN 1143
FT /note="S->A: Reduces in vitro phosphorylation by ATR."
FT /evidence="ECO:0000269|PubMed:11114888"
FT MUTAGEN 1239
FT /note="S->A: No effect on in vitro phosphorylation by ATR."
FT /evidence="ECO:0000269|PubMed:11114888"
FT MUTAGEN 1280
FT /note="S->A: Reduces in vitro phosphorylation by ATR."
FT /evidence="ECO:0000269|PubMed:11114888"
FT MUTAGEN 1298
FT /note="S->A: No effect on in vitro phosphorylation by ATR."
FT /evidence="ECO:0000269|PubMed:11114888"
FT MUTAGEN 1330
FT /note="S->A: No effect on in vitro phosphorylation by ATR."
FT /evidence="ECO:0000269|PubMed:11114888"
FT MUTAGEN 1387
FT /note="S->A: Loss of IR-induced S-phase checkpoint. Reduces
FT in vitro phosphorylation by ATR."
FT /evidence="ECO:0000269|PubMed:11114888,
FT ECO:0000269|PubMed:12183412"
FT MUTAGEN 1394
FT /note="T->A: Reduces in vitro phosphorylation by ATR."
FT /evidence="ECO:0000269|PubMed:11114888"
FT MUTAGEN 1423
FT /note="S->A: Inhibition of the infrared-induced G2 arrest.
FT Reduces phosphorylation by ATR."
FT /evidence="ECO:0000269|PubMed:11114888,
FT ECO:0000269|PubMed:12183412"
FT MUTAGEN 1457
FT /note="S->A: Reduces in vitro phosphorylation by ATR."
FT /evidence="ECO:0000269|PubMed:11114888"
FT MUTAGEN 1466
FT /note="S->A: No effect on in vitro phosphorylation by ATR."
FT /evidence="ECO:0000269|PubMed:11114888"
FT MUTAGEN 1524
FT /note="S->A: No change in infrared S-phase delay; when
FT associated with A-1387. No effect on in vitro
FT phosphorylation by ATR."
FT /evidence="ECO:0000269|PubMed:11114888,
FT ECO:0000269|PubMed:12183412"
FT MUTAGEN 1655
FT /note="S->A: Abolishes interaction with BRIP1."
FT /evidence="ECO:0000269|PubMed:15133502"
FT MUTAGEN 1656
FT /note="G->D: No effect on affinity for a BRIP1
FT phosphopeptide."
FT /evidence="ECO:0000269|PubMed:21473589"
FT MUTAGEN 1662
FT /note="F->S: Does not abolish ABRAXAS1 binding, but
FT abolishes formation of a heterotetramer with ABRAXAS1."
FT /evidence="ECO:0000269|PubMed:26778126"
FT MUTAGEN 1663
FT /note="M->K: Does not abolish ABRAXAS1 binding, but
FT abolishes formation of a heterotetramer with ABRAXAS1."
FT /evidence="ECO:0000269|PubMed:26778126"
FT MUTAGEN 1666
FT /note="Y->A: Does not abolish ABRAXAS1 binding, but impairs
FT formation of a heterotetramer with ABRAXAS1."
FT /evidence="ECO:0000269|PubMed:26778126"
FT MUTAGEN 1670
FT /note="R->E: Impairs formation of a heterotetramer with
FT ABRAXAS1."
FT /evidence="ECO:0000269|PubMed:26778126"
FT MUTAGEN 1671
FT /note="K->E: Impairs formation of a heterotetramer with
FT ABRAXAS1."
FT /evidence="ECO:0000269|PubMed:26778126"
FT MUTAGEN 1700
FT /note="T->A: Strongly reduces affinity for a BRIP1
FT phosphopeptide."
FT /evidence="ECO:0000269|PubMed:21473589"
FT MUTAGEN 1702
FT /note="K->M: Abolishes interaction with BRIP1."
FT /evidence="ECO:0000269|PubMed:15133502"
FT MUTAGEN 1738
FT /note="G->E: Abolishes interaction with BRIP1."
FT /evidence="ECO:0000269|PubMed:15133502"
FT MUTAGEN 1755
FT /note="S->A: No effect on in vitro phosphorylation by ATR."
FT /evidence="ECO:0000269|PubMed:11114888"
FT MUTAGEN 1835
FT /note="R->P: Mildly reduces affinity for a BRIP1
FT phosphopeptide."
FT /evidence="ECO:0000269|PubMed:21473589"
FT MUTAGEN 1836
FT /note="E->K: Slightly reduces affinity for a BRIP1
FT phosphopeptide."
FT /evidence="ECO:0000269|PubMed:21473589"
FT CONFLICT 89
FT /note="I -> T (in Ref. 4; AAB61673)"
FT /evidence="ECO:0000305"
FT CONFLICT 148
FT /note="Missing (in Ref. 4; AAB61673)"
FT /evidence="ECO:0000305"
FT CONFLICT 253
FT /note="A -> V (in Ref. 3; AAC00049)"
FT /evidence="ECO:0000305"
FT CONFLICT 713
FT /note="S -> P (in Ref. 8; AAI15038)"
FT /evidence="ECO:0000305"
FT CONFLICT 1077
FT /note="G -> R (in Ref. 4; AAB61673)"
FT /evidence="ECO:0000305"
FT CONFLICT 1426
FT /note="S -> P (in Ref. 3; AAC00049)"
FT /evidence="ECO:0000305"
FT CONFLICT 1527
FT /note="E -> G (in Ref. 8; AAI15038)"
FT /evidence="ECO:0000305"
FT TURN 5..7
FT /evidence="ECO:0007829|PDB:7LYB"
FT HELIX 8..21
FT /evidence="ECO:0007829|PDB:7LYB"
FT STRAND 25..27
FT /evidence="ECO:0007829|PDB:7LYB"
FT HELIX 49..52
FT /evidence="ECO:0007829|PDB:7LYB"
FT STRAND 54..58
FT /evidence="ECO:0007829|PDB:1JM7"
FT STRAND 62..64
FT /evidence="ECO:0007829|PDB:7LYB"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:7LYB"
FT TURN 70..72
FT /evidence="ECO:0007829|PDB:7LYB"
FT HELIX 80..96
FT /evidence="ECO:0007829|PDB:7LYB"
FT STRAND 1651..1656
FT /evidence="ECO:0007829|PDB:4IGK"
FT HELIX 1659..1671
FT /evidence="ECO:0007829|PDB:4IGK"
FT STRAND 1675..1679
FT /evidence="ECO:0007829|PDB:1T29"
FT STRAND 1686..1689
FT /evidence="ECO:0007829|PDB:4IGK"
FT STRAND 1695..1697
FT /evidence="ECO:0007829|PDB:4IGK"
FT HELIX 1701..1708
FT /evidence="ECO:0007829|PDB:4IGK"
FT STRAND 1712..1715
FT /evidence="ECO:0007829|PDB:4IGK"
FT HELIX 1717..1725
FT /evidence="ECO:0007829|PDB:4IGK"
FT HELIX 1731..1734
FT /evidence="ECO:0007829|PDB:4IGK"
FT TURN 1740..1742
FT /evidence="ECO:0007829|PDB:4IGK"
FT STRAND 1743..1745
FT /evidence="ECO:0007829|PDB:1T29"
FT HELIX 1748..1754
FT /evidence="ECO:0007829|PDB:4IGK"
FT TURN 1755..1757
FT /evidence="ECO:0007829|PDB:1T29"
FT TURN 1760..1763
FT /evidence="ECO:0007829|PDB:4IGK"
FT STRAND 1765..1768
FT /evidence="ECO:0007829|PDB:4IGK"
FT STRAND 1770..1772
FT /evidence="ECO:0007829|PDB:1T2V"
FT STRAND 1773..1775
FT /evidence="ECO:0007829|PDB:4IGK"
FT HELIX 1777..1786
FT /evidence="ECO:0007829|PDB:4IGK"
FT STRAND 1790..1794
FT /evidence="ECO:0007829|PDB:4IGK"
FT HELIX 1795..1797
FT /evidence="ECO:0007829|PDB:4IGK"
FT STRAND 1801..1803
FT /evidence="ECO:0007829|PDB:4IGK"
FT STRAND 1806..1810
FT /evidence="ECO:0007829|PDB:4IGK"
FT HELIX 1812..1814
FT /evidence="ECO:0007829|PDB:4IGK"
FT STRAND 1817..1819
FT /evidence="ECO:0007829|PDB:1OQA"
FT HELIX 1820..1822
FT /evidence="ECO:0007829|PDB:4IGK"
FT HELIX 1824..1827
FT /evidence="ECO:0007829|PDB:4IGK"
FT STRAND 1828..1830
FT /evidence="ECO:0007829|PDB:3PXE"
FT STRAND 1832..1834
FT /evidence="ECO:0007829|PDB:4IGK"
FT HELIX 1835..1844
FT /evidence="ECO:0007829|PDB:4IGK"
FT HELIX 1851..1853
FT /evidence="ECO:0007829|PDB:4IGK"
FT CONFLICT P38398-7:1461
FT /note="N -> D (in Ref. 8; AAI15038)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1863 AA; 207721 MW; 89C6D83FF56312AF CRC64;
MDLSALRVEE VQNVINAMQK ILECPICLEL IKEPVSTKCD HIFCKFCMLK LLNQKKGPSQ
CPLCKNDITK RSLQESTRFS QLVEELLKII CAFQLDTGLE YANSYNFAKK ENNSPEHLKD
EVSIIQSMGY RNRAKRLLQS EPENPSLQET SLSVQLSNLG TVRTLRTKQR IQPQKTSVYI
ELGSDSSEDT VNKATYCSVG DQELLQITPQ GTRDEISLDS AKKAACEFSE TDVTNTEHHQ
PSNNDLNTTE KRAAERHPEK YQGSSVSNLH VEPCGTNTHA SSLQHENSSL LLTKDRMNVE
KAEFCNKSKQ PGLARSQHNR WAGSKETCND RRTPSTEKKV DLNADPLCER KEWNKQKLPC
SENPRDTEDV PWITLNSSIQ KVNEWFSRSD ELLGSDDSHD GESESNAKVA DVLDVLNEVD
EYSGSSEKID LLASDPHEAL ICKSERVHSK SVESNIEDKI FGKTYRKKAS LPNLSHVTEN
LIIGAFVTEP QIIQERPLTN KLKRKRRPTS GLHPEDFIKK ADLAVQKTPE MINQGTNQTE
QNGQVMNITN SGHENKTKGD SIQNEKNPNP IESLEKESAF KTKAEPISSS ISNMELELNI
HNSKAPKKNR LRRKSSTRHI HALELVVSRN LSPPNCTELQ IDSCSSSEEI KKKKYNQMPV
RHSRNLQLME GKEPATGAKK SNKPNEQTSK RHDSDTFPEL KLTNAPGSFT KCSNTSELKE
FVNPSLPREE KEEKLETVKV SNNAEDPKDL MLSGERVLQT ERSVESSSIS LVPGTDYGTQ
ESISLLEVST LGKAKTEPNK CVSQCAAFEN PKGLIHGCSK DNRNDTEGFK YPLGHEVNHS
RETSIEMEES ELDAQYLQNT FKVSKRQSFA PFSNPGNAEE ECATFSAHSG SLKKQSPKVT
FECEQKEENQ GKNESNIKPV QTVNITAGFP VVGQKDKPVD NAKCSIKGGS RFCLSSQFRG
NETGLITPNK HGLLQNPYRI PPLFPIKSFV KTKCKKNLLE ENFEEHSMSP EREMGNENIP
STVSTISRNN IRENVFKEAS SSNINEVGSS TNEVGSSINE IGSSDENIQA ELGRNRGPKL
NAMLRLGVLQ PEVYKQSLPG SNCKHPEIKK QEYEEVVQTV NTDFSPYLIS DNLEQPMGSS
HASQVCSETP DDLLDDGEIK EDTSFAENDI KESSAVFSKS VQKGELSRSP SPFTHTHLAQ
GYRRGAKKLE SSEENLSSED EELPCFQHLL FGKVNNIPSQ STRHSTVATE CLSKNTEENL
LSLKNSLNDC SNQVILAKAS QEHHLSEETK CSASLFSSQC SELEDLTANT NTQDPFLIGS
SKQMRHQSES QGVGLSDKEL VSDDEERGTG LEENNQEEQS MDSNLGEAAS GCESETSVSE
DCSGLSSQSD ILTTQQRDTM QHNLIKLQQE MAELEAVLEQ HGSQPSNSYP SIISDSSALE
DLRNPEQSTS EKAVLTSQKS SEYPISQNPE GLSADKFEVS ADSSTSKNKE PGVERSSPSK
CPSLDDRWYM HSCSGSLQNR NYPSQEELIK VVDVEEQQLE ESGPHDLTET SYLPRQDLEG
TPYLESGISL FSDDPESDPS EDRAPESARV GNIPSSTSAL KVPQLKVAES AQSPAAAHTT
DTAGYNAMEE SVSREKPELT ASTERVNKRM SMVVSGLTPE EFMLVYKFAR KHHITLTNLI
TEETTHVVMK TDAEFVCERT LKYFLGIAGG KWVVSYFWVT QSIKERKMLN EHDFEVRGDV
VNGRNHQGPK RARESQDRKI FRGLEICCYG PFTNMPTDQL EWMVQLCGAS VVKELSSFTL
GTGVHPIVVV QPDAWTEDNG FHAIGQMCEA PVVTREWVLD SVALYQCQEL DTYLIPQIPH
SHY
