BARD1_MOUSE
ID BARD1_MOUSE Reviewed; 765 AA.
AC O70445; A2VCQ1;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=BRCA1-associated RING domain protein 1;
DE Short=BARD-1;
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q99728};
DE AltName: Full=RING-type E3 ubiquitin transferase BARD1 {ECO:0000305};
GN Name=Bard1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9798686; DOI=10.1038/sj.onc.1202123;
RA Ayi T.-C., Tsan J.T., Hwang L.-Y., Bowcock A.M., Baer R.;
RT "Conservation of function and primary structure in the BRCA1-associated
RT RING domain (BARD1) protein.";
RL Oncogene 17:2143-2148(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP SUBCELLULAR LOCATION.
RX PubMed=15077185; DOI=10.1038/sj.onc.1207427;
RA Jefford C.E., Feki A., Harb J., Krause K.-H., Irminger-Finger I.;
RT "Nuclear-cytoplasmic translocation of BARD1 is linked to its apoptotic
RT activity.";
RL Oncogene 23:3509-3520(2004).
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:0000250|UniProtKB:Q99728}.
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:0000250|UniProtKB:Q99728};
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:0000250|UniProtKB:Q99728}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15077185}. Cytoplasm
CC {ECO:0000269|PubMed:15077185}. Note=Can translocate to the cytoplasm.
CC Localizes at sites of DNA damage at double-strand breaks (DSBs);
CC recruitment to DNA damage sites is mediated by the BRCA1-A complex.
CC {ECO:0000250|UniProtKB:Q99728}.
CC -!- PTM: Processed during apoptosis. The homodimer is more susceptible to
CC proteolytic cleavage than the BARD1/BRCA1 heterodimer.
CC {ECO:0000250|UniProtKB:Q99728}.
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DR EMBL; AF057157; AAC18095.1; -; mRNA.
DR EMBL; BC128370; AAI28371.1; -; mRNA.
DR EMBL; BC128371; AAI28372.1; -; mRNA.
DR CCDS; CCDS15029.1; -.
DR RefSeq; NP_031551.1; NM_007525.3.
DR AlphaFoldDB; O70445; -.
DR SMR; O70445; -.
DR BioGRID; 198301; 4.
DR ComplexPortal; CPX-4701; BRCA1-BARD1 complex.
DR ComplexPortal; CPX-972; BRCC ubiquitin ligase complex.
DR IntAct; O70445; 5.
DR STRING; 10090.ENSMUSP00000027393; -.
DR iPTMnet; O70445; -.
DR PhosphoSitePlus; O70445; -.
DR EPD; O70445; -.
DR MaxQB; O70445; -.
DR PaxDb; O70445; -.
DR PeptideAtlas; O70445; -.
DR PRIDE; O70445; -.
DR ProteomicsDB; 273437; -.
DR Antibodypedia; 20039; 299 antibodies from 35 providers.
DR DNASU; 12021; -.
DR Ensembl; ENSMUST00000027393; ENSMUSP00000027393; ENSMUSG00000026196.
DR GeneID; 12021; -.
DR KEGG; mmu:12021; -.
DR UCSC; uc007bjm.2; mouse.
DR CTD; 580; -.
DR MGI; MGI:1328361; Bard1.
DR VEuPathDB; HostDB:ENSMUSG00000026196; -.
DR eggNOG; KOG0504; Eukaryota.
DR eggNOG; KOG4362; Eukaryota.
DR GeneTree; ENSGT00940000156532; -.
DR HOGENOM; CLU_021642_0_0_1; -.
DR InParanoid; O70445; -.
DR OMA; GGCEHVF; -.
DR OrthoDB; 854133at2759; -.
DR PhylomeDB; O70445; -.
DR TreeFam; TF326440; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 12021; 27 hits in 113 CRISPR screens.
DR ChiTaRS; Bard1; mouse.
DR PRO; PR:O70445; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; O70445; protein.
DR Bgee; ENSMUSG00000026196; Expressed in ureteric bud trunk and 74 other tissues.
DR Genevisible; O70445; MM.
DR GO; GO:0070531; C:BRCA1-A complex; ISO:MGI.
DR GO; GO:0070532; C:BRCA1-B complex; ISO:MGI.
DR GO; GO:0031436; C:BRCA1-BARD1 complex; ISS:UniProtKB.
DR GO; GO:0070533; C:BRCA1-C complex; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; ISO:MGI.
DR GO; GO:0016607; C:nuclear speck; ISO:MGI.
DR GO; GO:0000152; C:nuclear ubiquitin ligase complex; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0003723; F:RNA binding; ISO:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISO:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IC:ComplexPortal.
DR GO; GO:0071479; P:cellular response to ionizing radiation; ISO:MGI.
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; ISS:UniProtKB.
DR GO; GO:0046826; P:negative regulation of protein export from nucleus; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0045787; P:positive regulation of cell cycle; IC:ComplexPortal.
DR GO; GO:0051865; P:protein autoubiquitination; IC:ComplexPortal.
DR GO; GO:0085020; P:protein K6-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; ISO:MGI.
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; ISS: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 2: Evidence at transcript level;
KW ANK repeat; Cytoplasm; DNA damage; DNA repair; Isopeptide bond;
KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Transferase; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..765
FT /note="BRCA1-associated RING domain protein 1"
FT /id="PRO_0000055820"
FT REPEAT 415..447
FT /note="ANK 1"
FT REPEAT 448..480
FT /note="ANK 2"
FT REPEAT 481..513
FT /note="ANK 3"
FT REPEAT 514..534
FT /note="ANK 4; degenerate"
FT DOMAIN 549..641
FT /note="BRCT 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 655..765
FT /note="BRCT 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT ZN_FING 44..81
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 20..113
FT /note="Required for BRCA1 binding"
FT /evidence="ECO:0000250"
FT REGION 183..229
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 299..328
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 369..410
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 542..546
FT /note="Flexible linker"
FT /evidence="ECO:0000250"
FT COMPBIAS 204..229
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 310..328
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 369..406
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 378
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q99728"
FT MOD_RES 381
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q99728"
FT CROSSLNK 152
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99728"
FT CROSSLNK 411
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q99728"
SQ SEQUENCE 765 AA; 84254 MW; C43DD0625F2F1AE9 CRC64;
MPRRPPRVCS GNQPAPVPAM EPATDGLWAH SRAALARLEK LLRCSRCANI LKEPVCLGGC
EHIFCSGCIS DCVGSGCPVC YTPAWILDLK INRQLDSMIQ LSSKLQNLLH DNKDSKDNTS
RASLFGDAER KKNSIKMWFS PRSKKVRYVV TKVSVQTQPQ KAKDDKAQEA SMYEFVSATP
PVAVPKSAKT ASRTSAKKHP KKSVAKINRE ENLRPETKDS RFDSKEELKE EKVVSCSQIP
VMERPRVNGE IDLLASGSVV EPECSGSLTE VSLPLAEHIV SPDTVSKNEE TPEKKVCVKD
LRSGGSNGNR KGCHRPTTST SDSCGSNIPS TSRGIGEPAL LAENVVLVDC SSLPSGQLQV
DVTLRRKSNA SDDPLSLSPG TPPPLLNNST HRQMMSSPST VKLSSGMPAR KRNHRGETLL
HIASIKGDIP SVEYLLQNGN DPNVKDHAGW TPLHEACSHG HLKVVELLLQ HNALVNTPGY
QNDSPLHDAV KSGHIDIVKV LLSHGASRNA VNIFGVRPVD YTDNENIRSL LLLPEENESF
STSQCSIVNT GQRKNGPLVF IGSGLSSQQQ KMLSKLETVL KAKKCMEFDS TVTHVIVPDE
EAQSTLKCML GILSGCWILK FDWVKACLDS KVREQEEKYE VPGGPQRSRL NREQLLPKLF
DGCYFFLGGN FKHHPRDDLL KLIAAAGGKV LSRKPKPDSD VTQTINTVAY HAKPESDQRF
CTQYIVYEDL FNCHPERVRQ GKVWMAPSTW LISCIMAFEL LPLDS
