ID A0A2I3HB10_NOMLE Unreviewed; 721 AA.
AC A0A2I3HB10;
DT 28-FEB-2018, integrated into UniProtKB/TrEMBL.
DT 28-FEB-2018, sequence version 1.
DT 27-MAR-2024, entry version 24.
DE RecName: Full=Breast cancer type 1 susceptibility protein homolog {ECO:0000256|PIRNR:PIRNR001734};
DE EC=2.3.2.27 {ECO:0000256|PIRNR:PIRNR001734};
GN Name=BRCA1 {ECO:0000313|Ensembl:ENSNLEP00000040824.1};
OS Nomascus leucogenys (Northern white-cheeked gibbon) (Hylobates leucogenys).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hylobatidae;
OC Nomascus.
OX NCBI_TaxID=61853 {ECO:0000313|Ensembl:ENSNLEP00000040824.1, ECO:0000313|Proteomes:UP000001073};
RN [1] {ECO:0000313|Ensembl:ENSNLEP00000040824.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RG Gibbon Genome Sequencing Consortium;
RL Submitted (OCT-2012) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|Ensembl:ENSNLEP00000040824.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
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. It
CC is unclear whether it also mediates the formation of other types of
CC polyubiquitin chains. The BRCA1-BARD1 heterodimer coordinates a diverse
CC range of cellular pathways such as DNA damage repair, ubiquitination
CC and transcriptional regulation to maintain genomic stability. Regulates
CC centrosomal microtubule nucleation. Required for appropriate cell cycle
CC arrests after ionizing irradiation in both the S-phase and the G2 phase
CC of the cell cycle. Required for FANCD2 targeting to sites of DNA
CC damage. Inhibits lipid synthesis by binding to inactive phosphorylated
CC ACACA and preventing its dephosphorylation. Contributes to homologous
CC recombination repair (HRR) via its direct interaction with PALB2, fine-
CC tunes recombinational repair partly through its modulatory role in the
CC PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks.
CC Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation
CC and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-
CC mediated ubiquitination of RBBP8. Acts as a transcriptional activator.
CC {ECO:0000256|PIRNR:PIRNR001734}.
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:0000256|PIRNR:PIRNR001734};
CC -!- SUBUNIT: Heterodimer with BARD1. Part of the BRCA1-associated genome
CC surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1,
CC ATM, BLM, PMS2 and the MRE11-RAD50-NBN protein (MRN) complex. This
CC association could be a dynamic process changing throughout the cell
CC cycle and within subnuclear domains. Component of the BRCA1-A complex,
CC at least composed of BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36,
CC BABAM2 and BABAM1/NBA1. Interacts (via the BRCT domains) with ABRAXAS1
CC (phosphorylated form); this is important for recruitment to sites of
CC DNA damage. Can form a heterotetramer with two molecules of ABRAXAS1
CC (phosphorylated form). Component of the BRCA1-RBBP8 complex. Interacts
CC (via the BRCT domains) with RBBP8 ('Ser-327' phosphorylated form); the
CC interaction ubiquitinates RBBP8, regulates CHEK1 activation, and
CC involves RBBP8 in BRCA1-dependent G2/M checkpoint control on DNA
CC damage. Associates with RNA polymerase II holoenzyme. Interacts with
CC SMC1A, NELFB, DCLRE1C, CLSPN. CHEK1, CHEK2, BAP1, BRCC3, UBXN1 and
CC PCLAF. Interacts (via BRCT domains) with BRIP1 (phosphorylated form).
CC Interacts with FANCD2 (ubiquitinated form). Interacts with H2AX
CC (phosphorylated on 'Ser-140'). Interacts (via the BRCT domains) with
CC ACACA (phosphorylated form); the interaction prevents dephosphorylation
CC of ACACA. Part of a BRCA complex containing BRCA1, BRCA2 and PALB2.
CC Interacts directly with PALB2; the interaction is essential for its
CC function in HRR. Interacts directly with BRCA2; the interaction occurs
CC only in the presence of PALB2 which serves as the bridging protein.
CC Interacts (via the BRCT domains) with LMO4; the interaction represses
CC the transcriptional activity of BRCA1. Interacts (via the BRCT domains)
CC with CCAR2 (via N-terminus); the interaction represses the
CC transcriptional activator activity of BRCA1. Interacts with EXD2.
CC Interacts (via C-terminus) with DHX9; this interaction is direct and
CC links BRCA1 to the RNA polymerase II holoenzyme.
CC {ECO:0000256|PIRNR:PIRNR001734}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|ARBA:ARBA00004496}.
CC Nucleus {ECO:0000256|PIRNR:PIRNR001734}. Chromosome
CC {ECO:0000256|PIRNR:PIRNR001734}. Note=Localizes at sites of DNA damage
CC at double-strand breaks (DSBs); recruitment to DNA damage sites is
CC mediated by the BRCA1-A complex. {ECO:0000256|PIRNR:PIRNR001734}.
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DR AlphaFoldDB; A0A2I3HB10; -.
DR Ensembl; ENSNLET00000036592.1; ENSNLEP00000040824.1; ENSNLEG00000011944.3.
DR GeneTree; ENSGT00440000034289; -.
DR Proteomes; UP000001073; Unplaced.
DR GO; GO:0031436; C:BRCA1-BARD1 complex; IEA:UniProtKB-UniRule.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006310; P:DNA recombination; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0051865; P:protein autoubiquitination; IEA:UniProtKB-UniRule.
DR GO; GO:0085020; P:protein K6-linked ubiquitination; IEA:UniProtKB-UniRule.
DR CDD; cd17735; BRCT_BRCA1_rpt1; 1.
DR CDD; cd17721; BRCT_BRCA1_rpt2; 1.
DR CDD; cd16498; RING-HC_BRCA1; 1.
DR Gene3D; 3.40.50.10190; BRCT domain; 2.
DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1.
DR InterPro; IPR031099; BRCA1-associated.
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:SF0; BREAST CANCER TYPE 1 SUSCEPTIBILITY PROTEIN; 1.
DR PANTHER; PTHR13763; BREAST CANCER TYPE 1 SUSCEPTIBILITY PROTEIN BRCA1; 1.
DR Pfam; PF00533; BRCT; 2.
DR Pfam; PF00097; zf-C3HC4; 1.
DR PIRSF; PIRSF001734; BRCA1; 2.
DR SMART; SM00292; BRCT; 2.
DR SMART; SM00184; RING; 1.
DR SUPFAM; SSF52113; BRCT domain; 2.
DR SUPFAM; SSF57850; RING/U-box; 1.
DR PROSITE; PS50172; BRCT; 2.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 4: Predicted;
KW Acetylation {ECO:0000256|ARBA:ARBA00022990};
KW Cell cycle {ECO:0000256|PIRNR:PIRNR001734};
KW Chromosome {ECO:0000256|ARBA:ARBA00022454, ECO:0000256|PIRNR:PIRNR001734};
KW Coiled coil {ECO:0000256|SAM:Coils};
KW DNA damage {ECO:0000256|PIRNR:PIRNR001734};
KW DNA recombination {ECO:0000256|PIRNR:PIRNR001734};
KW DNA repair {ECO:0000256|PIRNR:PIRNR001734};
KW DNA-binding {ECO:0000256|ARBA:ARBA00023125, ECO:0000256|PIRNR:PIRNR001734};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723};
KW Nucleus {ECO:0000256|ARBA:ARBA00023242, ECO:0000256|PIRNR:PIRNR001734};
KW Reference proteome {ECO:0000313|Proteomes:UP000001073};
KW Transcription {ECO:0000256|ARBA:ARBA00023163};
KW Transcription regulation {ECO:0000256|ARBA:ARBA00023015};
KW Ubl conjugation pathway {ECO:0000256|PIRNR:PIRNR001734};
KW Zinc {ECO:0000256|ARBA:ARBA00022833};
KW Zinc-finger {ECO:0000256|ARBA:ARBA00022771, ECO:0000256|PROSITE-
KW ProRule:PRU00175}.
FT DOMAIN 24..65
FT /note="RING-type"
FT /evidence="ECO:0000259|PROSITE:PS50089"
FT DOMAIN 500..594
FT /note="BRCT"
FT /evidence="ECO:0000259|PROSITE:PS50172"
FT DOMAIN 614..713
FT /note="BRCT"
FT /evidence="ECO:0000259|PROSITE:PS50172"
FT REGION 228..252
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 298..326
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 340..359
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 396..454
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 463..482
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 255..282
FT /evidence="ECO:0000256|SAM:Coils"
FT COMPBIAS 230..252
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 298..325
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 721 AA; 80411 MW; 267C4793F4E14888 CRC64;
MDLSAVRVEE VQNVINAMQK ILECPICLEL IKEPVSTKCD HIFCKFCMLK LLNQKKGPSQ
CPLCKNDITK RSLQESTRFS QLVEELLKII CAFQLDTGLQ YANSYNFAKK ENNSPEHLKD
EVSIIQSMGY RNRAKRLLQS EPENPSLQET SFSVQLSNLG TVRTLRTKQQ IQPQKKSVYI
ELGSDSSEDT VNKATYCSVG DQELLQITPQ GTRDEISLDS AKKGEAASGY ASETSVSEDC
SGLSSQSDIL TTQQRDTMQD NLIKLQQEMA ELEAVLEQHG SQPSHSYPSI ISDSSALEDL
QNPEQSTSEK AVLTSQKSSA YPISQNPEGL FADKFEVSAD SSTSKNKEPG VERSSPSKCQ
SLDDRWYMHS CSGSLQNGNY PSQEELIKVV DVEEQQLEES GPHDLTEPSY LPRQDLEGTP
YLESGISLFS DDSESDPSAD RAPESAHVGN IPSSTSALKV PQLKVAESAQ SPAAAHTTNT
AGYNAMEESV SREKPELTAS TERVNKRMSM VVSGLTPEEF MLVYNFARKH HITLTNLITE
ETTHVVMKTD AEFVCERTLK YFLGIAGGKW VVSYFWVTQS IKERKMLNEH DFEVRGDVVN
GRNHQGPKRA RESQDRKIFR GLEICCYGPF TNMPTDQLEW MVQLCGASVV KELSSFTLGT
GVHPIVVVQP DAWTEDNGFH AIGQMCEAPV VTREWVLDSV ALYQCQELDT YLIPQIPHSH
Y
//
