BARD1_CAEEL
ID BARD1_CAEEL Reviewed; 702 AA.
AC Q21209;
DT 08-FEB-2011, integrated into UniProtKB/Swiss-Prot.
DT 10-AUG-2010, sequence version 3.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=BRCA1-associated RING domain protein 1 {ECO:0000303|PubMed:16628214};
DE Short=BARD1 {ECO:0000303|PubMed:16628214};
DE Short=Ce-BRD-1 {ECO:0000303|PubMed:14711411};
DE Short=Cebrd-1 {ECO:0000303|PubMed:16628214};
DE EC=2.3.2.27 {ECO:0000269|PubMed:16628214};
DE AltName: Full=RING-type E3 ubiquitin transferase BARD1 {ECO:0000305};
GN Name=brd-1 {ECO:0000303|PubMed:14711411, ECO:0000312|WormBase:K04C2.4};
GN ORFNames=K04C2.4 {ECO:0000312|WormBase:K04C2.4};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2]
RP FUNCTION, INTERACTION WITH BRC-1; SMT-3; TAC-1 AND UBC-9, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=14711411; DOI=10.1016/j.cub.2003.11.029;
RA Boulton S.J., Martin J.S., Polanowska J., Hill D.E., Gartner A., Vidal M.;
RT "BRCA1/BARD1 orthologs required for DNA repair in Caenorhabditis elegans.";
RL Curr. Biol. 14:33-39(2004).
RN [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=16861894; DOI=10.4161/cc.5.14.2930;
RA Boulton S.J.;
RT "BRCA1-mediated ubiquitylation.";
RL Cell Cycle 5:1481-1486(2006).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, IDENTIFICATION IN CEBCD
RP COMPLEX WITH BRC-1; RAD-51 AND LET-70, SUBUNIT, SUBCELLULAR LOCATION,
RP AUTOUBIQUITINATION, PHOSPHORYLATION, AND DISRUPTION PHENOTYPE.
RX PubMed=16628214; DOI=10.1038/sj.emboj.7601102;
RA Polanowska J., Martin J.S., Garcia-Muse T., Petalcorin M.I.R.,
RA Boulton S.J.;
RT "A conserved pathway to activate BRCA1-dependent ubiquitylation at DNA
RT damage sites.";
RL EMBO J. 25:2178-2188(2006).
RN [5]
RP FUNCTION, INTERACTION WITH MSH-5 AND SYP-3, AND SUBCELLULAR LOCATION.
RX PubMed=30383754; DOI=10.1371/journal.pgen.1007653;
RA Janisiw E., Dello Stritto M.R., Jantsch V., Silva N.;
RT "BRCA1-BARD1 associate with the synaptonemal complex and pro-crossover
RT factors and influence RAD-51 dynamics during Caenorhabditis elegans
RT meiosis.";
RL PLoS Genet. 14:e1007653-e1007653(2018).
CC -!- FUNCTION: Constituent of the CeBCD complex that possesses E3 ubiquitin-
CC protein ligase activity (PubMed:16628214). When bound to chromatin, the
CC brc-1-brd-1 heterodimer within the CeBCD complex is inactive during
CC normal conditions, but in response to DNA damage, the brc-1-brd-1
CC heterodimer associates with other proteins such as the recombinase rad-
CC 51 or the E2-ubiquitin-conjugating enzyme let-70, which activate the
CC CeBCD complex as an E3-ubiquitin ligase (PubMed:16628214). Moreover,
CC association between the brc-1-brd-1 heterodimer and rad-51 and let-70,
CC probably requires DNA checkpoint proteins such as atl-1 and mre-11 in
CC order to induce ubiquitination at DNA damage sites (PubMed:16628214).
CC To this end, the brc-1-brd-1 heterodimer coordinates a diverse range of
CC cellular pathways such as DNA damage repair, ubiquitination and
CC transcriptional regulation to maintain genomic stability
CC (PubMed:14711411, PubMed:30383754). Plays a role in triggering cellular
CC responses at damage sites in response to DNA damage that may be induced
CC by ionizing radiation for example (PubMed:14711411, PubMed:30383754).
CC In particular, protects against chromosome non-disjunction and nuclear
CC fragmentation during meiotic double-strand break repair to ensure
CC sister chromatid recombination and aid chromosome stability
CC (PubMed:14711411). {ECO:0000269|PubMed:14711411,
CC ECO:0000269|PubMed:16628214, ECO:0000269|PubMed:30383754}.
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:16628214};
CC -!- ACTIVITY REGULATION: E3 ubiquitin-protein ligase activity of CeBCD
CC complexes occurs at DNA damage sites. Following DNA damage, E3
CC ubiquitin-protein ligase activity is reduced by caffeine treatment
CC (inhibitor of ATM and ATK kinase activity).
CC {ECO:0000269|PubMed:16628214}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:14711411}.
CC -!- SUBUNIT: Heterodimer (via RING-type zinc finger) with brc-1 to form the
CC core CeBCD complex (PubMed:16628214). Brc-1-brd-1 heterodimer-
CC containing CeBCD complexes bound to chromatin are activated as an E3-
CC ubiquitin ligase in response to DNA damage (PubMed:16628214). The
CC heterodimer interacts with the recombinase rad-51 following ionizing
CC irradiation; the interaction is direct (PubMed:16628214). The
CC heterodimer interacts the E2-ubiquitin-conjugating enzyme let-70
CC following ionizing irradiation (PubMed:16628214). The heterodimer
CC interacts with the pro-crossover proteins msh-5 and syp-3
CC (PubMed:30383754). Interacts with smt-3, tac-1 and ubc-9
CC (PubMed:14711411). {ECO:0000269|PubMed:14711411,
CC ECO:0000269|PubMed:16628214, ECO:0000269|PubMed:30383754}.
CC -!- INTERACTION:
CC Q21209; B6VQ60: brc-1; NbExp=4; IntAct=EBI-3895480, EBI-3895496;
CC Q21209; P55853: smo-1; NbExp=3; IntAct=EBI-3895480, EBI-313647;
CC Q21209; Q95017: ubc-9; NbExp=4; IntAct=EBI-3895480, EBI-328938;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16628214}. Nucleus
CC {ECO:0000269|PubMed:16628214, ECO:0000269|PubMed:30383754}. Chromosome
CC {ECO:0000269|PubMed:16628214, ECO:0000269|PubMed:30383754}. Note=Co-
CC localizes with brc-1 in germline nuclei at meiotic prophase I
CC (PubMed:30383754). At the transition between mid- and late- pachytene,
CC localization together with brc-1 is less diffuse and becomes a linear
CC pattern along the chromosomes (PubMed:30383754). In late pachytene
CC nuclei, co-localizes with brc-1 at crossover sites and the short arm of
CC homologous chromosomes (PubMed:30383754).
CC {ECO:0000269|PubMed:30383754}.
CC -!- PTM: Autoubiquitinated. {ECO:0000269|PubMed:16628214}.
CC -!- PTM: Phosphorylation of CeBCD complexes is required for E3 ubiquitin-
CC protein ligase activity. {ECO:0000269|PubMed:16628214}.
CC -!- DISRUPTION PHENOTYPE: DNA damage repair defects following ionizing
CC radiation with reduced ubiquitination at DNA damage sites
CC (PubMed:16628214). RNAi-mediated knockdown results in elevated levels
CC of chromosome non-disjunction that manifest as a high incidence of
CC males, impaired progeny survival and chromosome fragmentation after
CC irradiation and elevated levels of p53-dependent germ cell death before
CC and after irradiation (PubMed:14711411). Absence of S-phase checkpoint
CC function. {ECO:0000269|PubMed:14711411, ECO:0000269|PubMed:16628214,
CC ECO:0000269|PubMed:16861894}.
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DR EMBL; FO081584; CCD72622.1; -; Genomic_DNA.
DR RefSeq; NP_498498.3; NM_066097.6.
DR AlphaFoldDB; Q21209; -.
DR SMR; Q21209; -.
DR BioGRID; 41174; 9.
DR ComplexPortal; CPX-375; brc-1/brd-1 complex.
DR IntAct; Q21209; 5.
DR MINT; Q21209; -.
DR STRING; 6239.K04C2.4.1; -.
DR EPD; Q21209; -.
DR PaxDb; Q21209; -.
DR PeptideAtlas; Q21209; -.
DR EnsemblMetazoa; K04C2.4.1; K04C2.4.1; WBGene00000265.
DR GeneID; 175959; -.
DR KEGG; cel:CELE_K04C2.4; -.
DR UCSC; K04C2.4.1; c. elegans.
DR CTD; 175959; -.
DR WormBase; K04C2.4; CE44987; WBGene00000265; brd-1.
DR eggNOG; KOG4362; Eukaryota.
DR HOGENOM; CLU_401278_0_0_1; -.
DR InParanoid; Q21209; -.
DR OMA; WLIEAIL; -.
DR OrthoDB; 507939at2759; -.
DR PhylomeDB; Q21209; -.
DR Reactome; R-CEL-8951664; Neddylation.
DR Reactome; R-CEL-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; Q21209; -.
DR UniPathway; UPA00143; -.
DR PRO; PR:Q21209; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00000265; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0031436; C:BRCA1-BARD1 complex; IPI:WormBase.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:WormBase.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:WormBase.
DR GO; GO:0006281; P:DNA repair; IMP:WormBase.
DR GO; GO:1905168; P:positive regulation of double-strand break repair via homologous recombination; EXP:ComplexPortal.
DR GO; GO:2001022; P:positive regulation of response to DNA damage stimulus; EXP:ComplexPortal.
DR GO; GO:0016567; P:protein ubiquitination; IDA:WormBase.
DR Gene3D; 1.25.40.20; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR Gene3D; 3.40.50.10190; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
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 PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 2.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF52113; SSF52113; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 2.
DR PROSITE; PS50172; BRCT; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW ANK repeat; Chromosome; Cytoplasm; DNA damage; DNA repair; Metal-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Transferase;
KW Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..702
FT /note="BRCA1-associated RING domain protein 1"
FT /id="PRO_0000403993"
FT REPEAT 347..376
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 379..408
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT REPEAT 413..442
FT /note="ANK 3"
FT /evidence="ECO:0000255"
FT DOMAIN 601..702
FT /note="BRCT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT ZN_FING 18..67
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 153..205
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 281..346
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 153..176
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 185..200
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 290..323
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 702 AA; 78804 MW; 2BEE4F198D1180FE CRC64;
MFENTKKALE TFRTAIECVK CKKPRGDLQY LGSSCKHAYC WECIATFQQK PSGKRSSVAR
HMCPSCAFPL DTSKITEAHM LKTCFDTLSE LNDLLQKVGT TSLTQAEFAC TQNIFNKEKT
PADAVEKFLE TQAHMPDEMG QLGEEDDDLM CKDENRENSN SPELDIFHDY SKEASPTRNS
TKRPSTVSVH ERKPKRSSIL KTSVKNEPAA PVVDLFASQV PQRTHQNDLL TPFIERRSTA
PAATGVATYA QAFGSSSNPV KAEIIEEDIF SKAIPLTKRQ ASMSASAKKQ PKLEPEEPEE
VPSTSRSRKN SIKSDKIERR SQSPMSFGEK SMSVKSEQRR SSYGTRRGEA VLVNSIRNNR
IPQLRSAVEA GTCVNEKEDG KTPLYVAVEN SSLEAVKILV EAGAVINASC GSTLETTLHE
AVRRQNTQIV EYLLSKGASI KIRNIAGKTV EEMAKSDPKI RKIIEKFKTE QRVLQPVVAP
PKSRLHFVQL IDEKMLTESE KRKLPGKINI VPADMDSPTH VVVTVDLKTR VLNINKEHIG
EILKAIIKSG MIVSRDWLRA CIIDPSKVDD DRSYMVQKVR WMEGEVFENT IEQWKKTITK
MQPKLFAGCK FFIPKPKYNF LDRPALFEII RSAGGQAAAR EPIIDEKDPP PYHNANLKPN
FVLYSLTHDI GDKFRDCTKY NLVSEQWLIE AILGCSITTP PH
