ID BRCA1_MOUSE Reviewed; 1812 AA. AC P48754; A2A4Q4; Q60957; Q60983; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 03-OCT-2012, sequence version 3. DT 27-MAR-2024, entry version 214. DE RecName: Full=Breast cancer type 1 susceptibility protein homolog; DE EC=2.3.2.27 {ECO:0000250|UniProtKB:P38398}; DE AltName: Full=RING-type E3 ubiquitin transferase BRCA1 {ECO:0000305}; GN Name=Brca1; 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]. RC STRAIN=C57BL/6J; TISSUE=Embryo; RX PubMed=8634697; DOI=10.1093/hmg/4.12.2265; RA Abel K.J., Xy J., Yin G.Y., Lyons R.H., Meisler M.H., Weber B.L.; RT "Mouse Brca1: localization sequence analysis and identification of RT evolutionarily conserved domains."; RL Hum. Mol. Genet. 4:2265-2273(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=C57BL/6J; RX PubMed=8634698; DOI=10.1093/hmg/4.12.2275; RA Sharan S.K., Wims M., Bradley A.; RT "Murine Brca1: sequence and significance for human missense mutations."; RL Hum. Mol. Genet. 4:2275-2278(1995). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=129/SvJ; RX PubMed=8575748; DOI=10.1006/geno.1995.9963; RA Bennett L.M., Haugen-Strano A., Cochran C., Brownlee H.A., RA Fiedorek F.T. Jr., Wiseman R.W.; RT "Isolation of the mouse homologue of BRCA1 and genetic mapping to mouse RT chromosome 11."; RL Genomics 29:576-581(1995). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=129/SvJ; TISSUE=Embryo; RX PubMed=7590247; DOI=10.1101/gad.9.21.2712; RA Lane T.F., Deng C., Elson A., Lyu M.S., Kozak C.A., Leder P.; RT "Expression of Brca1 is associated with terminal differentiation of RT ectodermally and mesodermally derived tissues in mice."; RL Genes Dev. 9:2712-2722(1995). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 727-1111. RC STRAIN=C57BL/6J; TISSUE=Embryo; RX PubMed=7550308; DOI=10.1038/ng0995-17; RA Marquis S.T., Rajan J.V., Wynshaw-Boris A., Xu J., Yin G.Y., Abel K.J., RA Weber B.L., Chodosh L.A.; RT "The developmental pattern of Brca1 expression implies a role in RT differentiation of the breast and other tissues."; RL Nat. Genet. 11:17-26(1995). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 789-1250. RC STRAIN=129/SvJ; RX PubMed=8566965; DOI=10.1007/bf02265277; RA Schroeck E., Badger P., Larson D., Erdos M., Wynshaw-Boris A., Ried T., RA Brody L.; RT "The murine homolog of the human breast and ovarian cancer susceptibility RT gene Brca1 maps to mouse chromosome 11D."; RL Hum. Genet. 97:256-259(1996). RN [8] RP INTERACTION WITH ACACA. RX PubMed=12360400; DOI=10.1038/sj.onc.1205915; RA Magnard C., Bachelier R., Vincent A., Jaquinod M., Kieffer S., Lenoir G.M., RA Venezia N.D.; RT "BRCA1 interacts with acetyl-CoA carboxylase through its tandem of BRCT RT domains."; RL Oncogene 21:6729-6739(2002). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-831, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-706 AND SER-717, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Lung, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [11] RP SUBCELLULAR LOCATION. RX PubMed=23039116; DOI=10.1111/gtc.12005; RA Kogo H., Tsutsumi M., Inagaki H., Ohye T., Kiyonari H., Kurahashi H.; RT "HORMAD2 is essential for synapsis surveillance during meiotic prophase via RT the recruitment of ATR activity."; RL Genes Cells 17:897-912(2012). RN [12] RP SUBCELLULAR LOCATION. RX PubMed=22549958; DOI=10.1101/gad.187559.112; RA Wojtasz L., Cloutier J.M., Baumann M., Daniel K., Varga J., Fu J., RA Anastassiadis K., Stewart A.F., Remenyi A., Turner J.M., Toth A.; RT "Meiotic DNA double-strand breaks and chromosome asynapsis in mice are RT monitored by distinct HORMAD2-independent and -dependent mechanisms."; RL Genes Dev. 26:958-973(2012). 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:0000250|UniProtKB:P38398}. 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:P38398}; CC -!- PATHWAY: Protein modification; protein ubiquitination. 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 (By similarity). Interacts CC with EXD2 (By similarity). Interacts (via C-terminus) with DHX9; this CC interaction is direct and links BRCA1 to the RNA polymerase II CC holoenzyme (By similarity). Interacts with DNA helicase ZGRF1; the CC interaction is increased following DNA damage induction (By CC similarity). {ECO:0000250|UniProtKB:P38398, CC ECO:0000269|PubMed:12360400}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P38398}. CC Chromosome {ECO:0000269|PubMed:22549958, ECO:0000269|PubMed:23039116}. CC Cytoplasm {ECO:0000250|UniProtKB:P38398}. 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. Translocated to the cytoplasm CC during UV-induced apoptosis. {ECO:0000250|UniProtKB:P38398}. CC -!- TISSUE SPECIFICITY: In the embryo, expressed in otic vesicles at day CC 9.5. At day 10.5, this expression decreases and high levels are found CC in the neuroectoderm. At days 11-12.5, high levels in differentiating CC keratinocytes and whisker pad primordia. At days 14-17, expression also CC observed in kidney epithelial cells. In the adult, highest levels found CC in spleen, thymus, lymph nodes, epithelial organs, and alveolar and CC ductal epithelial cells of the mammary gland. Very low levels in brain, CC kidney, and skin. No expression in heart, liver or lung. CC -!- DEVELOPMENTAL STAGE: In the mammary gland, expression increases CC dramatically during pregnancy. Levels fall during lactation and CC increase again during post-lactational regression of the mammary gland. CC -!- DOMAIN: The BRCT domains recognize and bind phosphorylated pSXXF motif CC on proteins. The interaction with the phosphorylated pSXXF motif of CC ABRAXAS1, recruits BRCA1 at DNA damage sites. CC {ECO:0000250|UniProtKB:P38398}. CC -!- DOMAIN: The RING-type zinc finger domain interacts with BAP1. CC {ECO:0000250|UniProtKB:P38398}. CC -!- PTM: Phosphorylated in response to IR, UV, and various stimuli that CC cause checkpoint activation, probably by ATM or ATR. Phosphorylation at CC Ser-971 by CHEK2 regulates mitotic spindle assembly. Phosphorylation by CC AURKA regulates centrosomal microtubule nucleation. CC {ECO:0000250|UniProtKB:P38398}. CC -!- PTM: Autoubiquitinated, undergoes 'Lys-6'-linked polyubiquitination. CC 'Lys-6'-linked polyubiquitination does not promote degradation. CC {ECO:0000250|UniProtKB:P38398}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U31625; AAB17114.1; -; mRNA. DR EMBL; U35641; AAB17113.1; -; mRNA. DR EMBL; U32446; AAA96393.1; -; mRNA. DR EMBL; U36475; AAC52323.1; -; mRNA. DR EMBL; AL590996; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; U33835; AAA99742.1; -; Genomic_DNA. DR CCDS; CCDS25474.1; -. DR PIR; I49350; I49350. DR RefSeq; NP_033894.3; NM_009764.3. DR PDB; 7K3S; NMR; -; A=1337-1388. DR PDBsum; 7K3S; -. DR AlphaFoldDB; P48754; -. DR SMR; P48754; -. DR BioGRID; 198383; 46. DR ComplexPortal; CPX-4701; BRCA1-BARD1 complex. DR ComplexPortal; CPX-972; BRCC ubiquitin ligase complex. DR DIP; DIP-41981N; -. DR IntAct; P48754; 21. DR MINT; P48754; -. DR STRING; 10090.ENSMUSP00000017290; -. DR iPTMnet; P48754; -. DR PhosphoSitePlus; P48754; -. DR EPD; P48754; -. DR jPOST; P48754; -. DR MaxQB; P48754; -. DR PaxDb; 10090-ENSMUSP00000017290; -. DR PeptideAtlas; P48754; -. DR ProteomicsDB; 273840; -. DR Pumba; P48754; -. DR Antibodypedia; 4527; 2576 antibodies from 45 providers. DR DNASU; 12189; -. DR Ensembl; ENSMUST00000017290.11; ENSMUSP00000017290.5; ENSMUSG00000017146.13. DR GeneID; 12189; -. DR KEGG; mmu:12189; -. DR UCSC; uc007lpd.2; mouse. DR AGR; MGI:104537; -. DR CTD; 672; -. DR MGI; MGI:104537; Brca1. DR VEuPathDB; HostDB:ENSMUSG00000017146; -. DR eggNOG; KOG4362; Eukaryota. DR GeneTree; ENSGT00440000034289; -. DR HOGENOM; CLU_002290_0_0_1; -. DR InParanoid; P48754; -. DR OMA; VTECQSS; -. DR OrthoDB; 5405431at2759; -. DR PhylomeDB; P48754; -. DR TreeFam; TF105060; -. DR Reactome; R-MMU-3108214; SUMOylation of DNA damage response and repair proteins. DR Reactome; R-MMU-5685938; HDR through Single Strand Annealing (SSA). DR Reactome; R-MMU-5685942; HDR through Homologous Recombination (HRR). DR Reactome; R-MMU-5689901; Metalloprotease DUBs. DR Reactome; R-MMU-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks. DR Reactome; R-MMU-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates. DR Reactome; R-MMU-5693571; Nonhomologous End-Joining (NHEJ). DR Reactome; R-MMU-5693579; Homologous DNA Pairing and Strand Exchange. DR Reactome; R-MMU-5693607; Processing of DNA double-strand break ends. DR Reactome; R-MMU-5693616; Presynaptic phase of homologous DNA pairing and strand exchange. DR Reactome; R-MMU-6804756; Regulation of TP53 Activity through Phosphorylation. DR Reactome; R-MMU-69473; G2/M DNA damage checkpoint. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 12189; 27 hits in 122 CRISPR screens. DR ChiTaRS; Brca1; mouse. DR PRO; PR:P48754; -. DR Proteomes; UP000000589; Chromosome 11. DR RNAct; P48754; Protein. DR Bgee; ENSMUSG00000017146; Expressed in secondary oocyte and 233 other cell types or tissues. DR ExpressionAtlas; P48754; baseline and differential. 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:0005813; C:centrosome; TAS:UniProtKB. DR GO; GO:0005694; C:chromosome; IDA:UniProtKB. DR GO; GO:0000793; C:condensed chromosome; IDA:MGI. DR GO; GO:0000794; C:condensed nuclear chromosome; IDA:MGI. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:1990391; C:DNA repair complex; ISO:MGI. DR GO; GO:0043232; C:intracellular non-membrane-bounded organelle; ISO:MGI. DR GO; GO:0000800; C:lateral element; ISO:MGI. DR GO; GO:0001673; C:male germ cell nucleus; IDA:MGI. DR GO; GO:0005759; C:mitochondrial matrix; ISO:MGI. DR GO; GO:0016604; C:nuclear body; 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; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; ISO:MGI. DR GO; GO:0032991; C:protein-containing complex; ISO:MGI. DR GO; GO:1990904; C:ribonucleoprotein complex; ISO:MGI. DR GO; GO:0001741; C:XY body; IDA:MGI. DR GO; GO:0003682; F:chromatin binding; ISO:MGI. DR GO; GO:0003684; F:damaged DNA binding; IDA:MGI. DR GO; GO:0001216; F:DNA-binding transcription activator activity; IDA:BHF-UCL. DR GO; GO:0019899; F:enzyme binding; ISO:MGI. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0002039; F:p53 binding; ISO:MGI. DR GO; GO:0003723; F:RNA binding; ISO:MGI. DR GO; GO:0070063; F:RNA polymerase binding; ISS:UniProtKB. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:BHF-UCL. DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0071681; P:cellular response to indole-3-methanol; ISO:MGI. DR GO; GO:0071479; P:cellular response to ionizing radiation; ISO:MGI. DR GO; GO:0071356; P:cellular response to tumor necrosis factor; ISO:MGI. DR GO; GO:0007098; P:centrosome cycle; IGI:MGI. DR GO; GO:0051298; P:centrosome duplication; TAS:UniProtKB. DR GO; GO:0043009; P:chordate embryonic development; IMP:MGI. DR GO; GO:0007059; P:chromosome segregation; ISO:MGI. DR GO; GO:0006974; P:DNA damage response; IMP:MGI. DR GO; GO:0006281; P:DNA repair; NAS:ComplexPortal. DR GO; GO:0110025; P:DNA strand resection involved in replication fork processing; NAS:ComplexPortal. DR GO; GO:0009048; P:dosage compensation by inactivation of X chromosome; IBA:GO_Central. DR GO; GO:0006302; P:double-strand break repair; IMP:CACAO. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; ISO:MGI. DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW. DR GO; GO:0035825; P:homologous recombination; NAS:ComplexPortal. DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; ISO:MGI. DR GO; GO:0051179; P:localization; ISO:MGI. DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; ISO:MGI. DR GO; GO:0044818; P:mitotic G2/M transition checkpoint; IMP:MGI. DR GO; GO:0030308; P:negative regulation of cell growth; ISO:MGI. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISO:MGI. DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; ISO:MGI. DR GO; GO:0045717; P:negative regulation of fatty acid biosynthetic process; ISS:UniProtKB. DR GO; GO:0044027; P:negative regulation of gene expression via CpG island methylation; IDA:BHF-UCL. DR GO; GO:0035067; P:negative regulation of histone acetylation; IBA:GO_Central. DR GO; GO:0033147; P:negative regulation of intracellular estrogen receptor signaling pathway; ISO:MGI. DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; ISO:MGI. DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:MGI. DR GO; GO:0045787; P:positive regulation of cell cycle; NAS:ComplexPortal. DR GO; GO:0045739; P:positive regulation of DNA repair; ISO:MGI. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISS:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI. DR GO; GO:0035066; P:positive regulation of histone acetylation; IBA:GO_Central. DR GO; GO:0042307; P:positive regulation of protein import into nucleus; ISO:MGI. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL. DR GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; ISO:MGI. DR GO; GO:0006301; P:postreplication repair; ISO:MGI. DR GO; GO:0051865; P:protein autoubiquitination; ISS:UniProtKB. DR GO; GO:0085020; P:protein K6-linked ubiquitination; ISS:UniProtKB. DR GO; GO:0000209; P:protein polyubiquitination; ISO:MGI. DR GO; GO:0016567; P:protein ubiquitination; ISO:MGI. DR GO; GO:0060816; P:random inactivation of X chromosome; IGI:MGI. DR GO; GO:0051726; P:regulation of cell cycle; ISO:MGI. DR GO; GO:2000001; P:regulation of DNA damage checkpoint; NAS:ComplexPortal. DR GO; GO:0006282; P:regulation of DNA repair; NAS:ComplexPortal. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:UniProtKB. DR GO; GO:0010212; P:response to ionizing radiation; ISO:MGI. 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; 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; 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; PF12820; BRCT_assoc; 1. DR Pfam; PF00097; zf-C3HC4; 1. DR PIRSF; PIRSF001734; BRCA1; 1. DR PRINTS; PR00493; BRSTCANCERI. 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. DR Genevisible; P48754; MM. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Cell cycle; Chromosome; Cytoplasm; KW DNA damage; DNA recombination; DNA repair; DNA-binding; KW Fatty acid biosynthesis; Fatty acid metabolism; Isopeptide bond; KW Lipid biosynthesis; Lipid metabolism; Metal-binding; Nucleus; KW Phosphoprotein; Reference proteome; Repeat; Transcription; KW Transcription regulation; Transferase; Tumor suppressor; Ubl conjugation; KW Ubl conjugation pathway; Zinc; Zinc-finger. FT CHAIN 1..1812 FT /note="Breast cancer type 1 susceptibility protein homolog" FT /id="PRO_0000055832" FT DOMAIN 1585..1679 FT /note="BRCT 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033" FT DOMAIN 1698..1797 FT /note="BRCT 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033" FT ZN_FING 24..65 FT /note="RING-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175" FT REGION 165..198 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 321..362 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 492..581 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 640..767 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 864..899 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 947..995 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1030..1056 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1147..1185 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1205..1230 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1244..1289 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1313..1343 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1353..1380 FT /note="Interaction with PALB2" FT /evidence="ECO:0000250" FT REGION 1437..1547 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 173..195 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 321..339 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 494..508 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 520..561 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 640..655 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 659..691 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 699..729 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 885..899 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 947..975 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 976..990 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1147..1163 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1247..1289 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1329..1343 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1472..1507 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0000250|UniProtKB:P38398" FT MOD_RES 114 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P38398" FT MOD_RES 392 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P38398" FT MOD_RES 686 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P38398" FT MOD_RES 706 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 717 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 831 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17525332" FT MOD_RES 971 FT /note="Phosphoserine; by CHEK2" FT /evidence="ECO:0000250|UniProtKB:P38398" FT MOD_RES 992 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P38398" FT MOD_RES 1152 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P38398" FT MOD_RES 1154 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P38398" FT MOD_RES 1174 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P38398" FT MOD_RES 1180 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P38398" FT MOD_RES 1241 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P38398" FT MOD_RES 1297 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P38398" FT MOD_RES 1303 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P38398" FT MOD_RES 1343 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P38398" FT MOD_RES 1350 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P38398" FT MOD_RES 1413 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P38398" FT MOD_RES 1481 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P38398" FT MOD_RES 1495 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P38398" FT CROSSLNK 109 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:P38398" FT CROSSLNK 298 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:P38398" FT CROSSLNK 336 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:P38398" FT CROSSLNK 440 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:P38398" FT CROSSLNK 456 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:P38398" FT CROSSLNK 512 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:P38398" FT CROSSLNK 1048 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:P38398" FT CONFLICT 93 FT /note="F -> L (in Ref. 3; AAA96393)" FT /evidence="ECO:0000305" FT CONFLICT 305 FT /note="S -> T (in Ref. 2; AAB17113)" FT /evidence="ECO:0000305" FT CONFLICT 319 FT /note="A -> P (in Ref. 2; AAB17113)" FT /evidence="ECO:0000305" FT CONFLICT 377 FT /note="Q -> E (in Ref. 3; AAA96393)" FT /evidence="ECO:0000305" FT CONFLICT 550 FT /note="K -> Q (in Ref. 3; AAA96393)" FT /evidence="ECO:0000305" FT CONFLICT 652 FT /note="P -> A (in Ref. 2; AAB17113)" FT /evidence="ECO:0000305" FT CONFLICT 765 FT /note="S -> P (in Ref. 3; AAA96393 and 4; AAC52323)" FT /evidence="ECO:0000305" FT CONFLICT 917 FT /note="P -> L (in Ref. 3; AAA96393)" FT /evidence="ECO:0000305" FT CONFLICT 933 FT /note="C -> S (in Ref. 3; AAA96393 and 7; AAA99742)" FT /evidence="ECO:0000305" FT CONFLICT 1091 FT /note="C -> R (in Ref. 1; AAB17114)" FT /evidence="ECO:0000305" FT CONFLICT 1122 FT /note="I -> K (in Ref. 2; AAB17113)" FT /evidence="ECO:0000305" FT CONFLICT 1206 FT /note="S -> R (in Ref. 3; AAA96393)" FT /evidence="ECO:0000305" FT CONFLICT 1212..1213 FT /note="RM -> GI (in Ref. 3; AAA96393)" FT /evidence="ECO:0000305" FT CONFLICT 1255 FT /note="S -> R (in Ref. 3; AAA96393)" FT /evidence="ECO:0000305" FT CONFLICT 1261 FT /note="H -> N (in Ref. 3; AAA96393)" FT /evidence="ECO:0000305" FT CONFLICT 1264 FT /note="A -> V (in Ref. 2; AAB17113)" FT /evidence="ECO:0000305" FT CONFLICT 1269 FT /note="A -> P (in Ref. 2; AAB17113)" FT /evidence="ECO:0000305" FT CONFLICT 1283 FT /note="K -> T (in Ref. 2; AAB17113)" FT /evidence="ECO:0000305" FT CONFLICT 1337 FT /note="N -> T (in Ref. 2; AAB17113)" FT /evidence="ECO:0000305" FT CONFLICT 1349 FT /note="T -> P (in Ref. 2; AAB17113)" FT /evidence="ECO:0000305" FT CONFLICT 1352..1353 FT /note="QR -> EG (in Ref. 2; AAB17113)" FT /evidence="ECO:0000305" FT CONFLICT 1381 FT /note="P -> S (in Ref. 2; AAB17113)" FT /evidence="ECO:0000305" FT CONFLICT 1390 FT /note="A -> G (in Ref. 2; AAB17113)" FT /evidence="ECO:0000305" FT CONFLICT 1400 FT /note="D -> V (in Ref. 2; AAB17113)" FT /evidence="ECO:0000305" FT CONFLICT 1503 FT /note="Q -> E (in Ref. 2; AAB17113)" FT /evidence="ECO:0000305" FT CONFLICT 1549 FT /note="A -> V (in Ref. 2; AAB17113)" FT /evidence="ECO:0000305" FT CONFLICT 1680 FT /note="K -> T (in Ref. 2; AAB17113)" FT /evidence="ECO:0000305" FT CONFLICT 1712 FT /note="E -> D (in Ref. 2; AAB17113)" FT /evidence="ECO:0000305" FT CONFLICT 1721 FT /note="E -> D (in Ref. 2; AAB17113)" FT /evidence="ECO:0000305" FT CONFLICT 1791 FT /note="D -> G (in Ref. 1; AAB17114)" FT /evidence="ECO:0000305" FT STRAND 1346..1348 FT /evidence="ECO:0007829|PDB:7K3S" FT HELIX 1350..1377 FT /evidence="ECO:0007829|PDB:7K3S" FT TURN 1378..1382 FT /evidence="ECO:0007829|PDB:7K3S" SQ SEQUENCE 1812 AA; 198795 MW; 2B47FB55B149FD71 CRC64; MDLSAVQIQE VQNVLHAMQK ILECPICLEL IKEPVSTKCD HIFCKFCMLK LLNQKKGPSQ CPLCKNEITK RSLQGSTRFS QLAEELLRIM AAFELDTGMQ LTNGFSFSKK RNNSCERLNE EASIIQSVGY RNRVRRLPQV EPGNATLKDS LGVQLSNLGI VRSVKKNRQT QPRKKSVYIE LDSDSSEETV TKPGDCSVRD QELLQTAPQE AGDEGKLHSA EEAACEFSEG IRNIEHHQCS DDLNPTENHA TERHPEKCQS ISISNVCVEP CGTDAHASSL QPETSSLLLI EDRMNAEKAE FCNKSKQPGI AVSQQSRWAA SKGTCNDRQV PSTGEKVGPN ADSLSDREKW THPQSLCPEN SGATTDVPWI TLNSSVQKVN EWFSRTGEML TSDSASARRH ESNAEAAVVL EVSNEVDGGF SSSRKTDLVT PDPHHTLMCK SGRDFSKPVE DNISDKIFGK SYQRKGSRPH LNHVTEIIGT FITEPQITQE QPFTNKLKRK RSTSLQPEDF IKKADSAGVQ RTPDNINQGT DLMEPNEQAV STTSNCQENK IAGSNLQKEK SAHPTESLRK EPASTAGAKS ISNSVSDLEV ELNVHSSKAP KKNRLRRKSS IRCALPLEPI SRNPSPPTCA ELQIDSCGSS EETKKNHSNQ QPAGHLREPQ LIEDTEPAAD AKKNEPNEHI RKRRASDAFP EEKLMNKAGL LTSCSSPRKS QGPVNPSPQR TGTEQLETRQ MSDSAKELGD RVLGGEPSGK TTDRSEESTS VSLVSDTDYD TQNSVSVLDA HTVRYARTGS AQCMTQFVAS ENPKELVHGS NNAGSGTEGL KPPLRHALNL SQEKVEMEDS ELDTQYLQNT FQVSKRQSFA LFSKPRSPQK DCAHSVPSKE LSPKVTAKGK QKERQGQEEF EISHVQAVAA TVGLPVPCQE GKLAADTMCD RGCRLCPSSH YRSGENGLSA TGKSGISQNS HFKQSVSPIR SSIKTDNRKP LTEGRFERHT SSTEMAVGNE NILQSTVHTV SLNNRGNACQ EAGSGSIHEV CSTGDSFPGQ LGRNRGPKVN TVPPLDSMQP GVCQQSVPVS DKYLEIKKQE GEAVCADFSP CLFSDHLEQS MSGKVFQVCS ETPDDLLDDV EIQGHTSFGE GDIMERSAVF NGSILRRESS RSPSPVTHAS KSQSLHRASR KLESSEESDS TEDEDLPCFQ HLLSRISNTP ELTRCSSAVT QRMPEKAEGT QAPWKGSSSD CNNEVIMIEA SQEHQFSEDP RCSGSMFSSQ HSAAQGSTAN ANSQDSNFIP PSKQRSHQCG NEEAFLSDKE LISDNEEMAT CLEEDNDQEE DSIIPDSEAS GYESETNLSE DCSQSDILTT QQRATMKYNL IKLQQEMAHL EAVLEQRGNQ PSGHSPSLLA DPCALEDLPD LEPNMSGAAI LTSKNINENP VSQNLKSACD DKFQLQHLEG PTSGDDESGM GRPSPFKSPL AGSRGSAHGC SRHLQKRNSP SQEELLQPAG SEASSEPHNS TGQSCLPRRE LEGTPYLGSG ISLFSSRDPE SESPKEPAHI GTTPASTSAL KIPQGQVAFR SAAAAGADKA VVGIVSKIKP ELTSSEERAD RDISMVVSGL TPKEVMTVQK FAEKYRLTLT DAITEETTHV IIKTDAEFVC ERTLKYFLGI AGGKWIVSYS WVVRSIQERR LLNVHEFEVK GDVVTGRNHQ GPRRSRESRE KLFKGLQVYC CEPFTNMPKD ELERMLQLCG ASVVKELPSL THDTGAHLVV IVQPSAWTED SNCPDIGQLC KARLVMWDWV LDSLSSYRCR DLDAYLVQNI TCDSSEPQDS ND //