Protein: Breast cancer type 1 susceptibility protein (EC 2.3.2.27) (RING finger protein 53) (RING-type E3 ubiquitin transferase BRCA1) (P38398)
Organism: Homo sapiens (Human)
Function: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Required for FANCD2 targeting to sites of DNA damage. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8. Acts as a transcriptional activator.
Subcellular location: Nucleus {ECO:0000269|PubMed:15133502, ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:26778126, ECO:0000269|PubMed:9528852}. Chromosome {ECO:0000269|PubMed:23269703, ECO:0000269|PubMed:25472942, ECO:0000269|PubMed:26778126}. Cytoplasm {ECO:0000269|PubMed:20160719}. Note=Localizes at sites of DNA damage at double-strand breaks (DSBs); recruitment to DNA damage sites is mediated by ABRAXAS1 and the BRCA1-A complex (PubMed:26778126). Translocated to the cytoplasm during UV-induced apoptosis (PubMed:20160719). {ECO:0000269|PubMed:20160719, ECO:0000269|PubMed:26778126}.; SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm.; SUBCELLULAR LOCATION: [Isoform 5]: Cytoplasm {ECO:0000269|PubMed:8972225}.
Sequence: MDLSALRVEEVQNVINAMQKILECPICLELIKEPVSTKCDHIFCKFCMLKLLNQKKGPSQCPLCKNDITKRSLQESTRFSQLVEELLKIICAFQLDTGLEYANSYNFAKKENNSPEHLKDEVSIIQSMGYRNRAKRLLQSEPENPSLQETSLSVQLSNLGTVRTLRTKQRIQPQKTSVYIELGSDSSEDTVNKATYCSVGDQELLQITPQGTRDEISLDSAKKAACEFSETDVTNTEHHQPSNNDLNTTEKRAAERHPEKYQGSSVSNLHVEPCGTNTHASSLQHENSSLLLTKDRMNVEKAEFCNKSKQPGLARSQHNRWAGSKETCNDRRTPSTEKKVDLNADPLCERKEWNKQKLPCSENPRDTEDVPWITLNSSIQKVNEWFSRSDELLGSDDSHDGESESNAKVADVLDVLNEVDEYSGSSEKIDLLASDPHEALICKSERVHSKSVESNIEDKIFGKTYRKKASLPNLSHVTENLIIGAFVTEPQIIQERPLTNKLKRKRRPTSGLHPEDFIKKADLAVQKTPEMINQGTNQTEQNGQVMNITNSGHENKTKGDSIQNEKNPNPIESLEKESAFKTKAEPISSSISNMELELNIHNSKAPKKNRLRRKSSTRHIHALELVVSRNLSPPNCTELQIDSCSSSEEIKKKKYNQMPVRHSRNLQLMEGKEPATGAKKSNKPNEQTSKRHDSDTFPELKLTNAPGSFTKCSNTSELKEFVNPSLPREEKEEKLETVKVSNNAEDPKDLMLSGERVLQTERSVESSSISLVPGTDYGTQESISLLEVSTLGKAKTEPNKCVSQCAAFENPKGLIHGCSKDNRNDTEGFKYPLGHEVNHSRETSIEMEESELDAQYLQNTFKVSKRQSFAPFSNPGNAEEECATFSAHSGSLKKQSPKVTFECEQKEENQGKNESNIKPVQTVNITAGFPVVGQKDKPVDNAKCSIKGGSRFCLSSQFRGNETGLITPNKHGLLQNPYRIPPLFPIKSFVKTKCKKNLLEENFEEHSMSPEREMGNENIPSTVSTISRNNIRENVFKEASSSNINEVGSSTNEVGSSINEIGSSDENIQAELGRNRGPKLNAMLRLGVLQPEVYKQSLPGSNCKHPEIKKQEYEEVVQTVNTDFSPYLISDNLEQPMGSSHASQVCSETPDDLLDDGEIKEDTSFAENDIKESSAVFSKSVQKGELSRSPSPFTHTHLAQGYRRGAKKLESSEENLSSEDEELPCFQHLLFGKVNNIPSQSTRHSTVATECLSKNTEENLLSLKNSLNDCSNQVILAKASQEHHLSEETKCSASLFSSQCSELEDLTANTNTQDPFLIGSSKQMRHQSESQGVGLSDKELVSDDEERGTGLEENNQEEQSMDSNLGEAASGCESETSVSEDCSGLSSQSDILTTQQRDTMQHNLIKLQQEMAELEAVLEQHGSQPSNSYPSIISDSSALEDLRNPEQSTSEKAVLTSQKSSEYPISQNPEGLSADKFEVSADSSTSKNKEPGVERSSPSKCPSLDDRWYMHSCSGSLQNRNYPSQEELIKVVDVEEQQLEESGPHDLTETSYLPRQDLEGTPYLESGISLFSDDPESDPSEDRAPESARVGNIPSSTSALKVPQLKVAESAQSPAAAHTTDTAGYNAMEESVSREKPELTASTERVNKRMSMVVSGLTPEEFMLVYKFARKHHITLTNLITEETTHVVMKTDAEFVCERTLKYFLGIAGGKWVVSYFWVTQSIKERKMLNEHDFEVRGDVVNGRNHQGPKRARESQDRKIFRGLEICCYGPFTNMPTDQLEWMVQLCGASVVKELSSFTLGTGVHPIVVVQPDAWTEDNGFHAIGQMCEAPVVTREWVLDSVALYQCQELDTYLIPQIPHSHY
InterPro domains: - IPR017907: Zinc finger, RING-type, conserved site (conserved_site) [39-48]
- IPR018957: Zinc finger, C3HC4 RING-type (domain) [24-64]
- IPR013083: Zinc finger, RING/FYVE/PHD-type (homologous_superfamily) [1-112]
- IPR031099: BRCA1-associated (family) [1-1858]
- IPR025994: BRCA1, serine-rich domain (domain) [345-508]
- IPR011364: Breast cancer type 1 susceptibility protein (BRCA1) (family) [55-1794]
- IPR036420: BRCT domain superfamily (homologous_superfamily) [1608-1859]
- IPR001357: BRCT domain (domain) [1642-1855]
- IPR001841: Zinc finger, RING-type (domain) [24-65]
Interaction partners: - Mediator of DNA damage checkpoint protein 1
- Partner and localizer of BRCA2
- Breast cancer type 2 susceptibility protein
- DNA repair protein RAD50
- BRCA1-associated RING domain protein 1
- Cellular tumor antigen p53
- Double-strand break repair protein MRE11
- BRCA1-A complex subunit Abraxas 1
- Fanconi anemia group D2 protein
- Histone H2AX
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003682 (chromatin binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0065007 (biological regulation), GO:0048518 (positive regulation of biological process), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0009987 (cellular process), GO:0044237 (cellular metabolic process), GO:0048522 (positive regulation of cellular process), GO:0019222 (regulation of metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0050794 (regulation of cellular process), GO:0009893 (positive regulation of metabolic process), GO:0051716 (cellular response to stimulus), GO:0006950 (response to stress), GO:0071704 (organic substance metabolic process), GO:0044238 (primary metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:0006139 (nucleobase-containing compound metabolic process), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0046483 (heterocycle metabolic process), GO:0031325 (positive regulation of cellular metabolic process), GO:0033554 (cellular response to stress), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0060255 (regulation of macromolecule metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0080090 (regulation of primary metabolic process), GO:0044260 (cellular macromolecule metabolic process), GO:0043170 (macromolecule metabolic process), GO:0009891 (positive regulation of biosynthetic process), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0010557 (positive regulation of macromolecule biosynthetic process), GO:0045935 (positive regulation of nucleobase-containing compound metabolic process), GO:0051254 (positive regulation of RNA metabolic process), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0090304 (nucleic acid metabolic process), GO:0006974 (cellular response to DNA damage stimulus), GO:0031326 (regulation of cellular biosynthetic process), GO:0006259 (DNA metabolic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0051252 (regulation of RNA metabolic process), GO:0031328 (positive regulation of cellular biosynthetic process), GO:0010468 (regulation of gene expression), GO:1902680 (positive regulation of RNA biosynthetic process), GO:2001141 (regulation of RNA biosynthetic process), GO:0006355 (regulation of DNA-templated transcription), GO:0006281 (DNA repair), GO:0045893 (positive regulation of DNA-templated transcription), GO:1903508 (positive regulation of nucleic acid-templated transcription), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0006302 (double-strand break repair)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0031974 (membrane-enclosed lumen), GO:0016604 (nuclear body), GO:0005654 (nucleoplasm), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)