ID A0A2K5P309_CERAT Unreviewed; 1871 AA.
AC A0A2K5P309;
DT 28-MAR-2018, integrated into UniProtKB/TrEMBL.
DT 28-MAR-2018, sequence version 1.
DT 24-JAN-2024, entry version 28.
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:ENSCATP00000044041.1};
OS Cercocebus atys (Sooty mangabey) (Cercocebus torquatus atys).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Cercocebus.
OX NCBI_TaxID=9531 {ECO:0000313|Ensembl:ENSCATP00000044041.1, ECO:0000313|Proteomes:UP000233060};
RN [1] {ECO:0000313|Ensembl:ENSCATP00000044041.1}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (SEP-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|ARBA:ARBA00000900,
CC 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: Nucleus {ECO:0000256|PIRNR:PIRNR001734}.
CC Chromosome {ECO:0000256|PIRNR:PIRNR001734}. Note=Localizes at sites of
CC DNA damage at double-strand breaks (DSBs); recruitment to DNA damage
CC sites is mediated by the BRCA1-A complex.
CC {ECO:0000256|PIRNR:PIRNR001734}.
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DR STRING; 9531.ENSCATP00000044041; -.
DR Ensembl; ENSCATT00000068481.1; ENSCATP00000044041.1; ENSCATG00000044435.1.
DR GeneTree; ENSGT00440000034289; -.
DR Proteomes; UP000233060; Unplaced.
DR Bgee; ENSCATG00000044435; Expressed in bone marrow and 11 other cell types or tissues.
DR GO; GO:0070531; C:BRCA1-A complex; IEA:Ensembl.
DR GO; GO:0070532; C:BRCA1-B complex; IEA:Ensembl.
DR GO; GO:0031436; C:BRCA1-BARD1 complex; IEA:UniProtKB-UniRule.
DR GO; GO:0070533; C:BRCA1-C complex; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:1990391; C:DNA repair complex; IEA:Ensembl.
DR GO; GO:0000800; C:lateral element; IEA:Ensembl.
DR GO; GO:0001673; C:male germ cell nucleus; IEA:Ensembl.
DR GO; GO:0016604; C:nuclear body; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:1990904; C:ribonucleoprotein complex; IEA:Ensembl.
DR GO; GO:0001741; C:XY body; IEA:Ensembl.
DR GO; GO:0003684; F:damaged DNA binding; IEA:Ensembl.
DR GO; GO:0001216; F:DNA-binding transcription activator activity; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0002039; F:p53 binding; IEA:Ensembl.
DR GO; GO:0003723; F:RNA binding; IEA:Ensembl.
DR GO; GO:0070063; F:RNA polymerase binding; IEA:Ensembl.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IEA:Ensembl.
DR GO; GO:0003713; F:transcription coactivator activity; IEA:Ensembl.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0071681; P:cellular response to indole-3-methanol; IEA:Ensembl.
DR GO; GO:0071479; P:cellular response to ionizing radiation; IEA:Ensembl.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
DR GO; GO:0007098; P:centrosome cycle; IEA:Ensembl.
DR GO; GO:0043009; P:chordate embryonic development; IEA:Ensembl.
DR GO; GO:0007059; P:chromosome segregation; IEA:Ensembl.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IEA:Ensembl.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IEA:Ensembl.
DR GO; GO:0051179; P:localization; IEA:Ensembl.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; IEA:Ensembl.
DR GO; GO:0030308; P:negative regulation of cell growth; IEA:Ensembl.
DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IEA:Ensembl.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; IEA:Ensembl.
DR GO; GO:0045717; P:negative regulation of fatty acid biosynthetic process; IEA:Ensembl.
DR GO; GO:0044027; P:negative regulation of gene expression via CpG island methylation; IEA:Ensembl.
DR GO; GO:0033147; P:negative regulation of intracellular estrogen receptor signaling pathway; IEA:Ensembl.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IEA:Ensembl.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl.
DR GO; GO:0045739; P:positive regulation of DNA repair; IEA:Ensembl.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; IEA:Ensembl.
DR GO; GO:0006301; P:postreplication repair; IEA:Ensembl.
DR GO; GO:0051865; P:protein autoubiquitination; IEA:UniProtKB-UniRule.
DR GO; GO:0085020; P:protein K6-linked ubiquitination; IEA:UniProtKB-UniRule.
DR GO; GO:0060816; P:random inactivation of X chromosome; IEA:Ensembl.
DR GO; GO:0043627; P:response to estrogen; IEA:Ensembl.
DR CDD; cd17735; BRCT_BRCA1_rpt1; 1.
DR CDD; cd17721; BRCT_BRCA1_rpt2; 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; 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; IPR027370; Znf-RING_euk.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
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; PF12820; BRCT_assoc; 1.
DR Pfam; PF13445; zf-RING_UBOX; 1.
DR PIRSF; PIRSF001734; BRCA1; 1.
DR PRINTS; PR00493; BRSTCANCERI.
DR SMART; SM00292; BRCT; 2.
DR SUPFAM; SSF52113; BRCT domain; 2.
DR SUPFAM; SSF57850; RING/U-box; 1.
DR PROSITE; PS50172; BRCT; 2.
PE 4: Predicted;
KW Cell cycle {ECO:0000256|PIRNR:PIRNR001734};
KW Chromosome {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|PIRNR:PIRNR001734};
KW Membrane {ECO:0000256|SAM:Phobius};
KW Nucleus {ECO:0000256|ARBA:ARBA00023242, ECO:0000256|PIRNR:PIRNR001734};
KW Reference proteome {ECO:0000313|Proteomes:UP000233060};
KW Transmembrane {ECO:0000256|SAM:Phobius};
KW Transmembrane helix {ECO:0000256|SAM:Phobius};
KW Ubl conjugation pathway {ECO:0000256|ARBA:ARBA00022786,
KW ECO:0000256|PIRNR:PIRNR001734}.
FT TRANSMEM 52..74
FT /note="Helical"
FT /evidence="ECO:0000256|SAM:Phobius"
FT DOMAIN 1650..1744
FT /note="BRCT"
FT /evidence="ECO:0000259|PROSITE:PS50172"
FT DOMAIN 1764..1863
FT /note="BRCT"
FT /evidence="ECO:0000259|PROSITE:PS50172"
FT REGION 239..294
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 313..343
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 561..590
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 661..707
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 894..923
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1189..1222
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1331..1405
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1450..1509
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1573..1605
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1405..1432
FT /evidence="ECO:0000256|SAM:Coils"
FT COMPBIAS 268..294
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 317..337
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 561..576
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 672..705
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 902..921
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1189..1204
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1354..1368
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1369..1405
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1450..1476
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1486..1509
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 1871 AA; 209040 MW; 3898C15E20EDD370 CRC64;
MDLSAVRVEE VQNVINAMQK ILECPICLEL IKEPVSTKCD HIFCSDVLII EVFYCCCILF
LFVYMSFLIL VVFLKQFNFR SLQESTRFSQ LVEELLKIIH AFQLDTGLQF ANSYNFAKKE
NHSPEHLKDE VSIIQSMGYR NRAKRLLQSE PENPSLQETS LSVPLSNFGI VRTLRTKQRI
QPQKKSVYIE LGSDSSEDTV NKATYCSVGD QELLQITPQG TRDETSLDSA KAACEFSEKD
ITNTEHHQSS NNDLNTTEKH ATERHPEKYQ GSSVSNLHVE PCGTNTHASS LQHENSLLLT
KDRMNVEKAE FCNKSKQPGL ARSQHNRWTG SKETCNDRQT PSTEKKVDLN ANALYERKEW
NKQKLPCSEN PRDTEDVPWI TLNSSIQKVN EWFSRSDELL NSDDSHDGGS ESNAKVADVL
DVLNEVDEYS GSSEKIDLLA SDPHEPLICK SERVHSSSVE INIKDKIFGK TYRRKANLPN
LSHVTENLII GALVTESQIM QERPLTNKLK RKRRTTSGLH PEDFIKKADL AVQKTPEIIN
QGTNQMEQNG QVMNITNSAH ENKTKGDSIQ NEKNPNPIES LEEESAFKTK AEPISSSINN
MELELNIHNS KAPKKNRLRR KSSTRHIHAL ELVVSRNLSP PNCTELQIDS CSSSEEIKKK
NYNQMPVRHS RNLQLMEDKE SATGAKKSNK PNEQTSKRHA SDTFPELKLT KVPGSFTNCS
NTSELKEFVN PSLSREEKEE KLETVKVSNN AKDPKDLMLS GERVLQTERS VESSSISLVP
GTDYGTQESI SLLEVSTLGK AKTERNKCMS QCAAFENPKE LIHGCSEDTR NDTEGFKYPL
GREVNHSQET SIEIEESELD TQYLQNTFKV SKRQSFALFS NPGNPEEECA TFSAHSRSLK
KQSPKVTSEC EQKKENQGKK ESNIKPVQTV NITASFSVVC QKDKPVDNAK CSIKGGSRFC
LSSQFRGNET GLITPNKHGL LQNPYHIPPL FPVKSFVKTK CNKNLLEENS EEHSVSPERA
VGNENIIPST VSIISHNNIR ENAFKEASSS SINEVGSSTN EVGSSINEVG SSDENIQAEL
GRNRGPKLNA VLRLGLLQPE VCKQSLPISN CKHPEIKKQE HEELVQTVNT DFSPCLISDN
LEQPMGSSHA SEVCSETPDD LLDDGEIKED TSFAENDIKE SSAVFSKSVQ RGELSRSPSP
FTHTHLAQGY RKGAKKLESS EENFSSEDEE LPCFQHLLFG KVSNIPSQTT RHSTVATECL
SKNTEENLLS LKSSLTDCSN QVILSKASQE HHLSEETKCS GSLFSSQCSE LEDLTANTNT
QDPFLIGSSK RMRHQSESQG VGLSDKELVS DDEERGTGLE EDNQEEQSVD SNLGEAASGY
GSETSVSEDC SRLSSQSEIL TTQQRDTMQD NLIKLQQEMA ELEAVLEQHG SQPSNSYPSI
ITDSSALEDL RNPEQSTSEK AVLTSQKSSE YPINQNPEGL SADKFEVSAD SSTSKNKEPG
VERSSPSKCQ SLEDRWYVHS SSGSLQNGNY PSQEELIKVV DVETQQLEKS GSHDLMEPSY
LPRQDLEGTP YLESGISLFS DDPESDPSED RAPESAHVGS IPSSTSALKV PQWQVAESAQ
SPAAAHNTNT AGYNAMEESV SREKPKLTAS TERVNKRMSL VVSGLTPEEF MLVYKFARRY
HIALTNLISE ETTHVVMKTD AEFVCERTLK YFLGIAGGKW VVSYFWVTQS IKERKMLNEH
DFEVRGDVVN GRNHQGPKRA RESPDRKIFR GLEICCYGPF TNMPTDQLEW MVQLCGASVV
KELSSFTLGT GFHPIVVVQP DAWTEDNGFH AIGQMCEAPV VTREWVLDSV ALYQCQELDT
YLIPQIPHSH Y
//