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Database: UniProt
Entry: A0A2K5P309_CERAT
LinkDB: A0A2K5P309_CERAT
Original site: A0A2K5P309_CERAT 
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
//
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