BRCA1_BOVIN
ID BRCA1_BOVIN Reviewed; 1849 AA.
AC Q864U1;
DT 23-NOV-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 25-MAY-2022, entry version 129.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH RNA POLYMERASE II.
RX PubMed=12955082; DOI=10.1038/sj.onc.1206515;
RA Krum S.A., Womack J.E., Lane T.F.;
RT "Bovine BRCA1 shows classic responses to genotoxic stress but low in vitro
RT transcriptional activation activity.";
RL Oncogene 22:6032-6044(2003).
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). {ECO:0000250|UniProtKB:P38398,
CC ECO:0000269|PubMed:12955082}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P38398}.
CC Chromosome {ECO:0000250|UniProtKB:P48754}. Cytoplasm
CC {ECO:0000250|UniProtKB:P38398}. 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. Translocated to the cytoplasm during
CC UV-induced apoptosis. {ECO:0000250|UniProtKB:P38398}.
CC -!- DOMAIN: The RING-type zinc finger domain interacts with BAP1.
CC {ECO:0000250|UniProtKB:P38398}.
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 -!- PTM: Phosphorylated in response to IR, UV, and various stimuli that
CC cause checkpoint activation, probably by ATM or ATR. Phosphorylation at
CC Ser-982 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; AY077732; AAL76094.1; -; mRNA.
DR RefSeq; NP_848668.1; NM_178573.1.
DR AlphaFoldDB; Q864U1; -.
DR SMR; Q864U1; -.
DR BioGRID; 160259; 2.
DR STRING; 9913.ENSBTAP00000011616; -.
DR PaxDb; Q864U1; -.
DR PRIDE; Q864U1; -.
DR GeneID; 353120; -.
DR KEGG; bta:353120; -.
DR CTD; 672; -.
DR eggNOG; KOG4362; Eukaryota.
DR InParanoid; Q864U1; -.
DR OrthoDB; 496760at2759; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0031436; C:BRCA1-BARD1 complex; ISS:UniProtKB.
DR GO; GO:0005694; C:chromosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0070063; F:RNA polymerase binding; ISS:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
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:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0045717; P:negative regulation of fatty acid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; ISS:UniProtKB.
DR GO; GO:0085020; P:protein K6-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR Gene3D; 3.40.50.10190; -; 2.
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; PTHR13763; 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; SSF52113; 2.
DR PROSITE; PS50172; BRCT; 2.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Cell cycle; Chromosome; Cytoplasm; DNA damage;
KW DNA recombination; DNA repair; DNA-binding; Fatty acid biosynthesis;
KW Fatty acid metabolism; Isopeptide bond; Lipid biosynthesis;
KW Lipid metabolism; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Transcription; Transcription regulation;
KW Transferase; Tumor suppressor; Ubl conjugation; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT CHAIN 1..1849
FT /note="Breast cancer type 1 susceptibility protein homolog"
FT /id="PRO_0000055827"
FT DOMAIN 1642..1729
FT /note="BRCT 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT DOMAIN 1749..1848
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 530..558
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 620..662
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 882..912
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1036..1070
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1172..1211
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1321..1389
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1392..1419
FT /note="Interaction with PALB2"
FT /evidence="ECO:0000250"
FT REGION 1412..1433
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1452..1493
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1562..1590
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1621..1640
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 628..642
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 888..907
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1036..1064
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1325..1339
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1340..1355
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1365..1389
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1461..1493
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1621..1638
FT /note="Basic and acidic 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 395
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 398
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 423
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 434
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 691
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 711
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48754"
FT MOD_RES 720
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P48754"
FT MOD_RES 982
FT /note="Phosphoserine; by CHEK2"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1002
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1138
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1184
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1211
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1212
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1274
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1323
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1330
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1336
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1382
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1389
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1418
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1452
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT MOD_RES 1518
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT CROSSLNK 301
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT CROSSLNK 339
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT CROSSLNK 457
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT CROSSLNK 517
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT CROSSLNK 981
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P38398"
FT CROSSLNK 1073
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P38398"
SQ SEQUENCE 1849 AA; 206279 MW; 66354C5D0BAFE8A8 CRC64;
MDLSADHVEE VQNVLNAMQK ILECPICLEL IKEPVSTKCD HIFCKFCMLK LLNQKKGPSQ
CPLCKNDITK RSLQESTRFS QLVEELLKII HAFELDTGLQ FANSYNFSRK EDNSPEHLKE
EVSIIQSMGY RNRAKRLWQS EPENPTLQET SLTVELSNLG IVRSLRTKQQ TQSQNKSVYI
ELGSDSSEDT VNKASYFSVG DHELLEITPQ GAKAKTNLNP AEKAACEFSE KDITNTEHHQ
LSIKDLITTQ KHATETHPEK YQGISVSDFH VEPCGTDTHA SSLQHENSSL LLTENRLNVE
KAEFCNKSKQ PVLVKSQQSR WAESKGTCKD RQIPSTEKKI VLNTDPLYRR KELRKQKPAC
PDSPGDSQDV PWVTLNNSIQ KVNDWFSRSD EILTSDDSCD GGSESNNEVA GAVEIPNKVD
GYSGSSEKIN LMASDPHGTL IHERVHSKPV ESNIEDKIFG KTYRRKSSLP NFSHIAEDLI
LGAFTVEPQI TQEQPLTNKL KCKRRGTSGL QPEDFIKKVD LTIVPKTPEK MTEGTDQTEQ
KCHGMNITSD GHENKTKRDY VQKEQNANPA ESLEKESVFR TEAEPISISI SNMELELNIH
RSKAPKNRLK RKSSTRKIPE LELVVSRNPS LPNHTELPID SSSSNEEMKK KHSSQMPVRQ
SQKLQLIGDK ELTAGAKNNK TYEQINKRLA SDAFPELKLT NTPGYFTNCS SKPEEFVHPS
LQREENLGTI QVSNSTKDPK DLILREGKAL QIERSVESTN ISLVPDTDYS TQDSISLLEA
KTPEKAKTAP NPCVSLCTAT KNLKELIHRD FKDTKNNTEG FQDLLGHDIN YVIQETSREM
EDSELDTQYL QNTFKASKRQ TFALFSNPGN PQKECATVFA HSGSLRDQSP RDPLKCRQKE
DSQGKSESKS QHVQAICTTV HFPVADQQDR TPGDDAKCSA KEVTRVCQSS QLRGHKTELV
FANKQGVSEK PNLIPSLSPI KSSVKTICKK SPSEKFEEPV TSPEKTLGSE SIIQSAVSTI
SQNNIQESTF KEVSSNSVNE VGSSTNEVGS SVNEVGSSGE NIQAEPGRNR EPKLRALLGL
GLTQPEVYKQ SLPVSNCHHP EIKRQGENED MPQAVKADFS PCLISDNLEQ PTGSRHASQV
CSETPDNLLN DDEIKENSHF AESDIKERSA VFSESVQKGE FRGSPGPFTH THLAQGHQRG
AGKLESEETV SSEDEELPCF QQLLFGKVTS TLSPSTGCNT VATEGLSKET EGNLESLKSG
LNDCSGQVTS AKVSQEHHLN EEARCSGSLF SSQCSAMEDL TTNTNTQDPF LMFERPSKQV
YQSESEEVLS DKELVSDDEE RETGLEEDSC QEEQSVDSDL GEAVSDHVSE TSLSEDGVGL
SSQSDILTTQ QRDTMQDNLL KLQQEMAELE AVLERHGSQP SHSSASLTAD SRGPEHLLNL
EQDTSERAIL TSEKSRDYSR SQNPESLSAD KFPVSLDSST NKNKEPGMER SSASKFQLSY
NRWYMHSSRS LQDRNCPSQK EPINVADMEE QQLAKREAQD LMGSFLPRQD QEGTPYLKSG
ISLFSHEPES DPSEDRAAEP AHVHSMPPSA SALKLSQFRV EESTKNPAAA HIANTTRCNL
REESMSKEKP EVISSTERSK KRLSMVASGL TPKELMLVQK FARKHHVTLT NLITEETTHV
IMKTDPEFVC ERTLKYFLGI AGGKWVVSYF WVTQSIKEGK MLDEHDFEVR GDVVNGRNHQ
GPKRARESRD KKIFKGLEIC CYGPFTNMPT DQLEWMVQLC GASVVKEPSS FTPDQGTHPV
VVVQPDAWTE DAGFHVIGQM CEAPVVTREW VLDSVALYQC QELDTYLVP
