BARD1_HUMAN
ID BARD1_HUMAN Reviewed; 777 AA.
AC Q99728; F6MDH7; F6MDH8; F6MDH9; O43574; Q53SS5;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 222.
DE RecName: Full=BRCA1-associated RING domain protein 1;
DE Short=BARD-1;
DE EC=2.3.2.27 {ECO:0000269|PubMed:12890688, ECO:0000269|PubMed:20351172};
DE AltName: Full=RING-type E3 ubiquitin transferase BARD1 {ECO:0000305};
GN Name=BARD1;
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 CHARACTERIZATION.
RC TISSUE=B-cell;
RX PubMed=8944023; DOI=10.1038/ng1296-430;
RA Wu L.C., Wang Z.W., Tsan J.T., Spillman M.A., Phung A., Xu X.L.,
RA Yang M.-C.W., Hwang L.-Y., Bowcock A.M., Baer R.;
RT "Identification of a RING protein that can interact in vivo with the BRCA1
RT gene product.";
RL Nat. Genet. 14:430-440(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-24; GLU-153; SER-378;
RP MET-507; SER-557; HIS-564; CYS-658; LEU-695 AND ASN-761.
RX PubMed=9425226; DOI=10.1093/hmg/7.2.195;
RA Thai T.H., Du F., Tsan J.T., Jin Y., Phung A., Spillman M.A., Massa H.F.,
RA Muller C.Y., Ashfaq R., Mathis J.M., Miller D.S., Trask B.J., Baer R.,
RA Bowcock A.M.;
RT "Mutations in the BRCA1-associated RING domain (BARD1) gene in primary
RT breast, ovarian and uterine cancers.";
RL Hum. Mol. Genet. 7:195-202(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA; BETA AND GAMMA), AND
RP ALTERNATIVE SPLICING.
RX PubMed=18089818; DOI=10.1158/0008-5472.can-07-2370;
RA Li L., Ryser S., Dizin E., Pils D., Krainer M., Jefford C.E., Bertoni F.,
RA Zeillinger R., Irminger-Finger I.;
RT "Oncogenic BARD1 isoforms expressed in gynecological cancers.";
RL Cancer Res. 67:11876-11885(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP DOMAINS.
RX PubMed=10026184; DOI=10.1074/jbc.274.9.5659;
RA Meza J.E., Brzovic P.S., King M.-C., Klevit R.E.;
RT "Mapping the functional domains of BRCA1. Interaction of the ring finger
RT domains of BRCA1 and BARD1.";
RL J. Biol. Chem. 274:5659-5665(1999).
RN [7]
RP POSSIBLE FUNCTION.
RX PubMed=10477523; DOI=10.1126/science.285.5433.1576;
RA Kleiman F.E., Manley J.L.;
RT "Functional interaction of BRCA1-associated BARD1 with polyadenylation
RT factor CstF-50.";
RL Science 285:1576-1579(1999).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH BRCA1.
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 [9]
RP FUNCTION, AND INTERACTION WITH BRCA1.
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 [10]
RP IDENTIFICATION IN THE BRCA1-A COMPLEX.
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-391 AND THR-394, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
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 [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH BRCA1.
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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186 AND THR-299, 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 [17]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-170, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [18]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-160; LYS-170; LYS-423 AND
RP LYS-548, AND 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 [19]
RP STRUCTURE BY NMR OF 26-140 IN COMPLEX WITH BRCA1 AND ZINC IONS, AND
RP 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 [20]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 568-777.
RX PubMed=17550235; DOI=10.1021/bi700323t;
RA Birrane G., Varma A.K., Soni A., Ladias J.A.;
RT "Crystal structure of the BARD1 BRCT domains.";
RL Biochemistry 46:7706-7712(2007).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 569-777, INTERACTION WITH CSTF1,
RP DOMAIN STRUCTURE, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=18842000; DOI=10.1021/bi801115g;
RA Edwards R.A., Lee M.S., Tsutakawa S.E., Williams R.S., Nazeer I.,
RA Kleiman F.E., Tainer J.A., Glover J.N.;
RT "The BARD1 C-terminal domain structure and interactions with
RT polyadenylation factor CstF-50.";
RL Biochemistry 47:11446-11456(2008).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 425-555, IDENTIFICATION BY MASS
RP SPECTROMETRY, DOMAINS ANK REPEATS, AND DOMAIN STRUCTURE.
RX PubMed=18480049; DOI=10.1074/jbc.m802333200;
RA Fox D. III, Le Trong I., Rajagopal P., Brzovic P.S., Stenkamp R.E.,
RA Klevit R.E.;
RT "Crystal structure of the BARD1 ankyrin repeat domain and its functional
RT consequences.";
RL J. Biol. Chem. 283:21179-21186(2008).
CC -!- FUNCTION: E3 ubiquitin-protein ligase. The BRCA1-BARD1 heterodimer
CC specifically mediates the formation of 'Lys-6'-linked polyubiquitin
CC chains and coordinates a diverse range of cellular pathways such as DNA
CC damage repair, ubiquitination and transcriptional regulation to
CC maintain genomic stability. Plays a central role in the control of the
CC cell cycle in response to DNA damage. Acts by mediating ubiquitin E3
CC ligase activity that is required for its tumor suppressor function.
CC Also forms a heterodimer with CSTF1/CSTF-50 to modulate mRNA processing
CC and RNAP II stability by inhibiting pre-mRNA 3' cleavage.
CC {ECO:0000269|PubMed:12890688, ECO:0000269|PubMed:14976165,
CC 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:12890688,
CC ECO:0000269|PubMed:20351172};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Homo- and heterodimer. Heterodimer (RING-type zinc finger)
CC with BRCA1. Heterodimer (via ANK repeats and BRCT domains) with
CC CSTF1/CSTF-50. Component of the BRCA1-A complex, at least composed of
CC the BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and
CC BABAM1/NBA1. Interacts with UBXN1. {ECO:0000269|PubMed:11573085,
CC ECO:0000269|PubMed:12890688, ECO:0000269|PubMed:14976165,
CC ECO:0000269|PubMed:17643122, ECO:0000269|PubMed:18842000,
CC ECO:0000269|PubMed:19261749, ECO:0000269|PubMed:20351172}.
CC -!- INTERACTION:
CC Q99728; Q9Y2T1: AXIN2; NbExp=3; IntAct=EBI-473181, EBI-4400025;
CC Q99728; P38398: BRCA1; NbExp=16; IntAct=EBI-473181, EBI-349905;
CC Q99728; P38398-1: BRCA1; NbExp=3; IntAct=EBI-473181, EBI-21498346;
CC Q99728; Q9P2H0: CEP126; NbExp=2; IntAct=EBI-473181, EBI-473176;
CC Q99728; Q8NHQ1: CEP70; NbExp=3; IntAct=EBI-473181, EBI-739624;
CC Q99728; Q12873: CHD3; NbExp=2; IntAct=EBI-473181, EBI-523590;
CC Q99728; Q05048: CSTF1; NbExp=4; IntAct=EBI-473181, EBI-1789619;
CC Q99728; P33240: CSTF2; NbExp=8; IntAct=EBI-473181, EBI-711360;
CC Q99728; O00471: EXOC5; NbExp=3; IntAct=EBI-473181, EBI-949824;
CC Q99728; Q8IZU0: FAM9B; NbExp=3; IntAct=EBI-473181, EBI-10175124;
CC Q99728; Q9Y2X7: GIT1; NbExp=2; IntAct=EBI-473181, EBI-466061;
CC Q99728; Q08379: GOLGA2; NbExp=6; IntAct=EBI-473181, EBI-618309;
CC Q99728; O75031: HSF2BP; NbExp=3; IntAct=EBI-473181, EBI-7116203;
CC Q99728; Q13422-7: IKZF1; NbExp=3; IntAct=EBI-473181, EBI-11522367;
CC Q99728; O95251: KAT7; NbExp=2; IntAct=EBI-473181, EBI-473199;
CC Q99728; Q9BVG8-5: KIFC3; NbExp=3; IntAct=EBI-473181, EBI-14069005;
CC Q99728; Q6A162: KRT40; NbExp=3; IntAct=EBI-473181, EBI-10171697;
CC Q99728; O95751: LDOC1; NbExp=7; IntAct=EBI-473181, EBI-740738;
CC Q99728; Q5JR59-3: MTUS2; NbExp=3; IntAct=EBI-473181, EBI-11522433;
CC Q99728; O95453: PARN; NbExp=4; IntAct=EBI-473181, EBI-372832;
CC Q99728; Q15276: RABEP1; NbExp=3; IntAct=EBI-473181, EBI-447043;
CC Q99728; O14776: TCERG1; NbExp=2; IntAct=EBI-473181, EBI-473271;
CC Q99728; Q13077: TRAF1; NbExp=3; IntAct=EBI-473181, EBI-359224;
CC Q99728; Q8N720: ZNF655; NbExp=3; IntAct=EBI-473181, EBI-625509;
CC Q99728-1; Q13526: PIN1; NbExp=4; IntAct=EBI-21498323, EBI-714158;
CC -!- SUBCELLULAR LOCATION: Nucleus. Note=During S phase of the cell cycle,
CC colocalizes with BRCA1 into discrete subnuclear foci. Can translocate
CC to the cytoplasm. Localizes at sites of DNA damage at double-strand
CC breaks (DSBs); recruitment to DNA damage sites is mediated by the
CC BRCA1-A complex.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=FL;
CC IsoId=Q99728-1; Sequence=Displayed;
CC Name=alpha;
CC IsoId=Q99728-2; Sequence=VSP_055876;
CC Name=beta;
CC IsoId=Q99728-3; Sequence=VSP_055874, VSP_055875;
CC Name=gamma;
CC IsoId=Q99728-4; Sequence=VSP_055877, VSP_055878;
CC -!- PTM: Processed during apoptosis. The homodimer is more susceptible to
CC proteolytic cleavage than the BARD1/BRCA1 heterodimer.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-26 is the initiator.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/BARD1ID756ch2q35.html";
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DR EMBL; U76638; AAB38316.1; -; mRNA.
DR EMBL; AF038042; AAB99978.1; -; Genomic_DNA.
DR EMBL; AF038034; AAB99978.1; JOINED; Genomic_DNA.
DR EMBL; AF038035; AAB99978.1; JOINED; Genomic_DNA.
DR EMBL; AF038036; AAB99978.1; JOINED; Genomic_DNA.
DR EMBL; AF038037; AAB99978.1; JOINED; Genomic_DNA.
DR EMBL; AF038038; AAB99978.1; JOINED; Genomic_DNA.
DR EMBL; AF038039; AAB99978.1; JOINED; Genomic_DNA.
DR EMBL; AF038040; AAB99978.1; JOINED; Genomic_DNA.
DR EMBL; AF038041; AAB99978.1; JOINED; Genomic_DNA.
DR EMBL; JF790280; AEF57471.1; -; mRNA.
DR EMBL; JF790281; AEF57472.1; -; mRNA.
DR EMBL; JF790282; AEF57473.1; -; mRNA.
DR EMBL; AC016708; AAX93130.1; -; Genomic_DNA.
DR EMBL; BC126426; AAI26427.1; -; mRNA.
DR CCDS; CCDS2397.1; -. [Q99728-1]
DR CCDS; CCDS74646.1; -. [Q99728-2]
DR RefSeq; NP_000456.2; NM_000465.3. [Q99728-1]
DR RefSeq; NP_001269472.1; NM_001282543.1. [Q99728-2]
DR PDB; 1JM7; NMR; -; B=26-140.
DR PDB; 2NTE; X-ray; 1.90 A; A/B=568-777.
DR PDB; 2R1Z; X-ray; 2.10 A; A/B=569-777.
DR PDB; 3C5R; X-ray; 2.00 A; A/B=425-555.
DR PDB; 3FA2; X-ray; 2.20 A; A/B=566-777.
DR PDB; 6M14; X-ray; 1.88 A; A/B=568-777.
DR PDB; 7E8I; EM; 3.10 A; K=425-777.
DR PDB; 7JZV; EM; 3.90 A; B=26-140.
DR PDB; 7LYB; EM; 3.28 A; N=26-122.
DR PDB; 7LYC; EM; 2.94 A; N=415-777.
DR PDBsum; 1JM7; -.
DR PDBsum; 2NTE; -.
DR PDBsum; 2R1Z; -.
DR PDBsum; 3C5R; -.
DR PDBsum; 3FA2; -.
DR PDBsum; 6M14; -.
DR PDBsum; 7E8I; -.
DR PDBsum; 7JZV; -.
DR PDBsum; 7LYB; -.
DR PDBsum; 7LYC; -.
DR AlphaFoldDB; Q99728; -.
DR SMR; Q99728; -.
DR BioGRID; 107056; 306.
DR ComplexPortal; CPX-715; BRCA1-BARD1 complex.
DR ComplexPortal; CPX-955; BRCC ubiquitin ligase complex.
DR CORUM; Q99728; -.
DR DIP; DIP-5972N; -.
DR IntAct; Q99728; 51.
DR MINT; Q99728; -.
DR STRING; 9606.ENSP00000260947; -.
DR BindingDB; Q99728; -.
DR iPTMnet; Q99728; -.
DR PhosphoSitePlus; Q99728; -.
DR BioMuta; BARD1; -.
DR DMDM; 116241265; -.
DR EPD; Q99728; -.
DR jPOST; Q99728; -.
DR MassIVE; Q99728; -.
DR MaxQB; Q99728; -.
DR PaxDb; Q99728; -.
DR PeptideAtlas; Q99728; -.
DR PRIDE; Q99728; -.
DR ProteomicsDB; 78442; -. [Q99728-1]
DR Antibodypedia; 20039; 299 antibodies from 35 providers.
DR DNASU; 580; -.
DR Ensembl; ENST00000260947.9; ENSP00000260947.4; ENSG00000138376.11. [Q99728-1]
DR Ensembl; ENST00000617164.5; ENSP00000480470.1; ENSG00000138376.11. [Q99728-2]
DR Ensembl; ENST00000620057.4; ENSP00000481988.1; ENSG00000138376.11. [Q99728-4]
DR GeneID; 580; -.
DR KEGG; hsa:580; -.
DR MANE-Select; ENST00000260947.9; ENSP00000260947.4; NM_000465.4; NP_000456.2.
DR UCSC; uc002veu.4; human. [Q99728-1]
DR CTD; 580; -.
DR DisGeNET; 580; -.
DR GeneCards; BARD1; -.
DR HGNC; HGNC:952; BARD1.
DR HPA; ENSG00000138376; Low tissue specificity.
DR MalaCards; BARD1; -.
DR MIM; 601593; gene.
DR neXtProt; NX_Q99728; -.
DR OpenTargets; ENSG00000138376; -.
DR Orphanet; 145; Hereditary breast and ovarian cancer syndrome.
DR PharmGKB; PA25256; -.
DR VEuPathDB; HostDB:ENSG00000138376; -.
DR eggNOG; KOG0504; Eukaryota.
DR eggNOG; KOG4362; Eukaryota.
DR GeneTree; ENSGT00940000156532; -.
DR HOGENOM; CLU_021642_0_0_1; -.
DR InParanoid; Q99728; -.
DR OMA; GGCEHVF; -.
DR OrthoDB; 854133at2759; -.
DR PhylomeDB; Q99728; -.
DR TreeFam; TF326440; -.
DR BRENDA; 2.3.2.27; 2681.
DR PathwayCommons; Q99728; -.
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-5689603; UCH proteinases.
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-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-HSA-69473; G2/M DNA damage checkpoint.
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; Q99728; -.
DR SIGNOR; Q99728; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 580; 496 hits in 1130 CRISPR screens.
DR ChiTaRS; BARD1; human.
DR EvolutionaryTrace; Q99728; -.
DR GeneWiki; BARD1; -.
DR GenomeRNAi; 580; -.
DR Pharos; Q99728; Tbio.
DR PRO; PR:Q99728; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q99728; protein.
DR Bgee; ENSG00000138376; Expressed in secondary oocyte and 202 other tissues.
DR ExpressionAtlas; Q99728; baseline and differential.
DR Genevisible; Q99728; 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:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:HPA.
DR GO; GO:0016607; C:nuclear speck; 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:0000151; C:ubiquitin ligase complex; NAS:UniProtKB.
DR GO; GO:0019900; F:kinase binding; NAS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IDA:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; NAS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; NAS:UniProtKB.
DR GO; GO:0071479; P:cellular response to ionizing radiation; IMP:ComplexPortal.
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: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:0044818; P:mitotic G2/M transition checkpoint; IC:ComplexPortal.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0045786; P:negative regulation of cell cycle; IC:ComplexPortal.
DR GO; GO:0031441; P:negative regulation of mRNA 3'-end processing; NAS:UniProtKB.
DR GO; GO:0046826; P:negative regulation of protein export from nucleus; IDA:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; NAS:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; IC:ComplexPortal.
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; NAS:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; NAS:UniProtKB.
DR GO; GO:2000001; P:regulation of DNA damage checkpoint; IC:ComplexPortal.
DR GO; GO:0006282; P:regulation of DNA repair; IC:ComplexPortal.
DR GO; GO:0042325; P:regulation of phosphorylation; IMP:UniProtKB.
DR GO; GO:0001894; P:tissue homeostasis; TAS:UniProtKB.
DR CDD; cd16496; RING-HC_BARD1; 1.
DR Gene3D; 1.25.40.20; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR Gene3D; 3.40.50.10190; -; 2.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR039503; BARD1_Znf-RING.
DR InterPro; IPR001357; BRCT_dom.
DR InterPro; IPR036420; BRCT_dom_sf.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF14835; zf-RING_6; 1.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 3.
DR SMART; SM00292; BRCT; 2.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF52113; SSF52113; 2.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 3.
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; Alternative splicing; ANK repeat; DNA damage; DNA repair;
KW Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..777
FT /note="BRCA1-associated RING domain protein 1"
FT /id="PRO_0000055819"
FT REPEAT 427..459
FT /note="ANK 1"
FT REPEAT 460..492
FT /note="ANK 2"
FT REPEAT 493..525
FT /note="ANK 3"
FT REPEAT 526..546
FT /note="ANK 4; degenerate"
FT DOMAIN 560..653
FT /note="BRCT 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 667..777
FT /note="BRCT 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT ZN_FING 50..87
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 1..32
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 26..119
FT /note="Interaction with BRCA1"
FT REGION 167..211
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 356..404
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 554..558
FT /note="Flexible linker"
FT COMPBIAS 1..15
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 167..183
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 374..404
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 186
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 299
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 391
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 394
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT CROSSLNK 160
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 170
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 423
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 548
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..24
FT /note="MPDNRQPRNRQPRIRSGNEPRSAP -> MVAVPGPTVAPRSTAWRSCCAARV
FT (in isoform beta)"
FT /evidence="ECO:0000303|PubMed:18089818"
FT /id="VSP_055874"
FT VAR_SEQ 25..121
FT /note="Missing (in isoform beta)"
FT /evidence="ECO:0000303|PubMed:18089818"
FT /id="VSP_055875"
FT VAR_SEQ 54..72
FT /note="Missing (in isoform alpha)"
FT /evidence="ECO:0000303|PubMed:18089818"
FT /id="VSP_055876"
FT VAR_SEQ 122..127
FT /note="DLKEDK -> GRHTFC (in isoform gamma)"
FT /evidence="ECO:0000303|PubMed:18089818"
FT /id="VSP_055877"
FT VAR_SEQ 128..777
FT /note="Missing (in isoform gamma)"
FT /evidence="ECO:0000303|PubMed:18089818"
FT /id="VSP_055878"
FT VARIANT 24
FT /note="P -> S (in dbSNP:rs1048108)"
FT /evidence="ECO:0000269|PubMed:9425226"
FT /id="VAR_010354"
FT VARIANT 153
FT /note="K -> E (in dbSNP:rs753377280)"
FT /evidence="ECO:0000269|PubMed:9425226"
FT /id="VAR_010355"
FT VARIANT 186
FT /note="S -> G (in dbSNP:rs16852741)"
FT /id="VAR_038371"
FT VARIANT 241
FT /note="S -> C (in dbSNP:rs3738885)"
FT /id="VAR_020109"
FT VARIANT 378
FT /note="R -> S (in dbSNP:rs2229571)"
FT /evidence="ECO:0000269|PubMed:9425226"
FT /id="VAR_024611"
FT VARIANT 507
FT /note="V -> M (in dbSNP:rs2070094)"
FT /evidence="ECO:0000269|PubMed:9425226"
FT /id="VAR_010356"
FT VARIANT 557
FT /note="C -> S (in dbSNP:rs28997576)"
FT /evidence="ECO:0000269|PubMed:9425226"
FT /id="VAR_010357"
FT VARIANT 564
FT /note="Q -> H (in an ovarian clear cell adenocarcinoma)"
FT /evidence="ECO:0000269|PubMed:9425226"
FT /id="VAR_010358"
FT VARIANT 645
FT /note="C -> R (in dbSNP:rs2228456)"
FT /id="VAR_038372"
FT VARIANT 658
FT /note="R -> C (in dbSNP:rs3738888)"
FT /evidence="ECO:0000269|PubMed:9425226"
FT /id="VAR_010359"
FT VARIANT 695
FT /note="V -> L (in a breast cancer sample; somatic mutation;
FT dbSNP:rs111367604)"
FT /evidence="ECO:0000269|PubMed:9425226"
FT /id="VAR_010360"
FT VARIANT 728
FT /note="S -> F (in dbSNP:rs13389423)"
FT /id="VAR_028309"
FT VARIANT 761
FT /note="S -> N (in an uterine cancer sample; somatic
FT mutation; dbSNP:rs142155101)"
FT /evidence="ECO:0000269|PubMed:9425226"
FT /id="VAR_010361"
FT CONFLICT 85
FT /note="V -> A (in Ref. 3; AEF57473)"
FT /evidence="ECO:0000305"
FT CONFLICT 406
FT /note="R -> Q (in Ref. 1; AAB38316 and 3; AEF57471/
FT AEF57472)"
FT /evidence="ECO:0000305"
FT HELIX 35..45
FT /evidence="ECO:0007829|PDB:7LYB"
FT TURN 51..53
FT /evidence="ECO:0007829|PDB:7LYB"
FT STRAND 58..61
FT /evidence="ECO:0007829|PDB:7LYB"
FT STRAND 64..67
FT /evidence="ECO:0007829|PDB:7LYB"
FT HELIX 72..75
FT /evidence="ECO:0007829|PDB:7LYB"
FT TURN 78..81
FT /evidence="ECO:0007829|PDB:7LYB"
FT TURN 84..86
FT /evidence="ECO:0007829|PDB:7LYB"
FT HELIX 99..115
FT /evidence="ECO:0007829|PDB:7LYB"
FT HELIX 431..438
FT /evidence="ECO:0007829|PDB:3C5R"
FT HELIX 441..449
FT /evidence="ECO:0007829|PDB:3C5R"
FT STRAND 459..461
FT /evidence="ECO:0007829|PDB:7LYC"
FT HELIX 464..470
FT /evidence="ECO:0007829|PDB:3C5R"
FT HELIX 474..482
FT /evidence="ECO:0007829|PDB:3C5R"
FT HELIX 492..494
FT /evidence="ECO:0007829|PDB:3C5R"
FT HELIX 497..503
FT /evidence="ECO:0007829|PDB:3C5R"
FT HELIX 507..515
FT /evidence="ECO:0007829|PDB:3C5R"
FT HELIX 530..533
FT /evidence="ECO:0007829|PDB:3C5R"
FT HELIX 537..543
FT /evidence="ECO:0007829|PDB:3C5R"
FT STRAND 571..576
FT /evidence="ECO:0007829|PDB:6M14"
FT HELIX 579..591
FT /evidence="ECO:0007829|PDB:6M14"
FT STRAND 595..599
FT /evidence="ECO:0007829|PDB:2NTE"
FT STRAND 606..613
FT /evidence="ECO:0007829|PDB:6M14"
FT HELIX 618..625
FT /evidence="ECO:0007829|PDB:6M14"
FT STRAND 629..632
FT /evidence="ECO:0007829|PDB:6M14"
FT HELIX 634..642
FT /evidence="ECO:0007829|PDB:6M14"
FT HELIX 648..651
FT /evidence="ECO:0007829|PDB:6M14"
FT HELIX 656..665
FT /evidence="ECO:0007829|PDB:6M14"
FT TURN 671..674
FT /evidence="ECO:0007829|PDB:6M14"
FT STRAND 676..679
FT /evidence="ECO:0007829|PDB:6M14"
FT STRAND 684..686
FT /evidence="ECO:0007829|PDB:6M14"
FT HELIX 688..697
FT /evidence="ECO:0007829|PDB:6M14"
FT STRAND 701..705
FT /evidence="ECO:0007829|PDB:2NTE"
FT HELIX 709..711
FT /evidence="ECO:0007829|PDB:2NTE"
FT HELIX 712..716
FT /evidence="ECO:0007829|PDB:6M14"
FT HELIX 729..731
FT /evidence="ECO:0007829|PDB:6M14"
FT STRAND 735..739
FT /evidence="ECO:0007829|PDB:6M14"
FT STRAND 741..744
FT /evidence="ECO:0007829|PDB:6M14"
FT STRAND 748..752
FT /evidence="ECO:0007829|PDB:6M14"
FT STRAND 755..759
FT /evidence="ECO:0007829|PDB:6M14"
FT HELIX 760..769
FT /evidence="ECO:0007829|PDB:6M14"
SQ SEQUENCE 777 AA; 86648 MW; 95E2D904046B5646 CRC64;
MPDNRQPRNR QPRIRSGNEP RSAPAMEPDG RGAWAHSRAA LDRLEKLLRC SRCTNILREP
VCLGGCEHIF CSNCVSDCIG TGCPVCYTPA WIQDLKINRQ LDSMIQLCSK LRNLLHDNEL
SDLKEDKPRK SLFNDAGNKK NSIKMWFSPR SKKVRYVVSK ASVQTQPAIK KDASAQQDSY
EFVSPSPPAD VSERAKKASA RSGKKQKKKT LAEINQKWNL EAEKEDGEFD SKEESKQKLV
SFCSQPSVIS SPQINGEIDL LASGSLTESE CFGSLTEVSL PLAEQIESPD TKSRNEVVTP
EKVCKNYLTS KKSLPLENNG KRGHHNRLSS PISKRCRTSI LSTSGDFVKQ TVPSENIPLP
ECSSPPSCKR KVGGTSGRKN SNMSDEFISL SPGTPPSTLS SSSYRRVMSS PSAMKLLPNM
AVKRNHRGET LLHIASIKGD IPSVEYLLQN GSDPNVKDHA GWTPLHEACN HGHLKVVELL
LQHKALVNTT GYQNDSPLHD AAKNGHVDIV KLLLSYGASR NAVNIFGLRP VDYTDDESMK
SLLLLPEKNE SSSASHCSVM NTGQRRDGPL VLIGSGLSSE QQKMLSELAV ILKAKKYTEF
DSTVTHVVVP GDAVQSTLKC MLGILNGCWI LKFEWVKACL RRKVCEQEEK YEIPEGPRRS
RLNREQLLPK LFDGCYFYLW GTFKHHPKDN LIKLVTAGGG QILSRKPKPD SDVTQTINTV
AYHARPDSDQ RFCTQYIIYE DLCNYHPERV RQGKVWKAPS SWFIDCVMSF ELLPLDS
