ID A0A286ZS33_PIG Unreviewed; 1845 AA.
AC A0A286ZS33;
DT 22-NOV-2017, integrated into UniProtKB/TrEMBL.
DT 14-DEC-2022, sequence version 2.
DT 27-MAR-2024, entry version 41.
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:ENSSSCP00000034439.2,
GN ECO:0000313|VGNC:VGNC:85869};
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823 {ECO:0000313|Ensembl:ENSSSCP00000034439.2, ECO:0000313|Proteomes:UP000008227};
RN [1] {ECO:0000313|Ensembl:ENSSSCP00000034439.2, ECO:0000313|Proteomes:UP000008227}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Duroc {ECO:0000313|Ensembl:ENSSSCP00000034439.2,
RC ECO:0000313|Proteomes:UP000008227};
RG Porcine genome sequencing project;
RL Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0000313|Ensembl:ENSSSCP00000034439.2}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (NOV-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; 9823.ENSSSCP00000034439; -.
DR PaxDb; 9823-ENSSSCP00000019934; -.
DR Ensembl; ENSSSCT00000057335.3; ENSSSCP00000034439.2; ENSSSCG00000022101.4.
DR VGNC; VGNC:85869; BRCA1.
DR eggNOG; KOG4362; Eukaryota.
DR GeneTree; ENSGT00440000034289; -.
DR InParanoid; A0A286ZS33; -.
DR OrthoDB; 5405431at2759; -.
DR Reactome; R-SSC-5685938; HDR through Single Strand Annealing (SSA).
DR Reactome; R-SSC-5685942; HDR through Homologous Recombination (HRR).
DR Reactome; R-SSC-5689901; Metalloprotease DUBs.
DR Reactome; R-SSC-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-SSC-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR Reactome; R-SSC-5693571; Nonhomologous End-Joining (NHEJ).
DR Reactome; R-SSC-5693579; Homologous DNA Pairing and Strand Exchange.
DR Reactome; R-SSC-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-SSC-5693616; Presynaptic phase of homologous DNA pairing and strand exchange.
DR Reactome; R-SSC-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-SSC-69473; G2/M DNA damage checkpoint.
DR Proteomes; UP000008227; Chromosome 12.
DR ExpressionAtlas; A0A286ZS33; baseline and differential.
DR GO; GO:0070531; C:BRCA1-A complex; IBA:GO_Central.
DR GO; GO:0070532; C:BRCA1-B complex; IEA:Ensembl.
DR GO; GO:0031436; C:BRCA1-BARD1 complex; IBA:GO_Central.
DR GO; GO:0070533; C:BRCA1-C complex; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
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; IBA:GO_Central.
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; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0007059; P:chromosome segregation; IEA:Ensembl.
DR GO; GO:0009048; P:dosage compensation by inactivation of X chromosome; IBA:GO_Central.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0044027; P:negative regulation of gene expression via CpG island methylation; IEA:Ensembl.
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; 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:0035066; P:positive regulation of histone acetylation; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
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 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; 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 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 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 Nucleus {ECO:0000256|ARBA:ARBA00023242, ECO:0000256|PIRNR:PIRNR001734};
KW Reference proteome {ECO:0000313|Proteomes:UP000008227};
KW Ubl conjugation pathway {ECO:0000256|ARBA:ARBA00022786,
KW ECO:0000256|PIRNR:PIRNR001734}.
FT DOMAIN 1627..1714
FT /note="BRCT"
FT /evidence="ECO:0000259|PROSITE:PS50172"
FT DOMAIN 1734..1833
FT /note="BRCT"
FT /evidence="ECO:0000259|PROSITE:PS50172"
FT REGION 206..231
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 293..315
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 330..349
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 367..432
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 505..552
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 622..672
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 855..894
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 988..1054
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1158..1198
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1395..1502
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1542..1567
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1588..1619
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 333..349
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 414..432
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 516..548
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 622..669
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 857..894
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 990..1040
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1421..1464
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1473..1502
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1591..1607
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 1845 AA; 204734 MW; 931756D5D7C79B18 CRC64;
MDLSVDHIEE VQNVLNAMQK ILECPIFCML KLLNQKKGPS QCPLCKNDIT KRSLQESTRF
SQLVEELLKI IHAFELDTGL QFANNYNFSK KTENNSPEHL KEEVSIIQSM GYRNRAKRLR
QSDPEDPTLQ ETSLSAQLSN LGIVKPLRTQ QQIQPQNKSV YIELGSDSSE DTVNKANYCS
GGDHGLLETT PQGAKAEAKK DACQFSEKDI TNTEHHHSSN KDLTATEKHA TEKHPEKYEG
ISVSNLHVEP CGTDTHASSL QHENSSLLLT KDRMNVEKAE FCNKSKQPVL AKSQQSRWAE
SKGTCNDRQT PNTEKKVVLN TDLLYGRNEL NKQKPACSDS PRDSQDVPWI TLNSSIQKVN
EWFSRSDEML TSDDSQDRRS ESNTGVAGAA EVPNEADGHL GSSEKIDLMA SDPHGALIRE
RERGHSKPAE SNIEDKIFGK TYRRKASLPN LSHVIEDLIL GASAVEPQIT QERPLTNKLK
RKRRGTSGLD PEDFIKRADS AVVPKTPEKT IEGTDETEQN GQGMNITSKG HENETKSGNV
QKEKNVNPTA SLGKEPAFRA RAEPISSSIS NMELELNIHG SKAPKNRLRR KSSTRQIHAL
ELVVNRNPSP PSHTELQIDS CSSSEEMKKR NSDQVPVRHS KKLHLRGDKE PTTGAKKNNR
PHEQVNKRPI SDAFPELNLT NVPVSITNCS NSNKLQESVS PNLQREENLG TIQVSNSNKD
PKDVMLSGGK GFQIERSVEN TSISLVPDTD YGTQDSISLL ETDTLGKAKT TPNQHVRLCA
ATENPKELSL GCSKGVRNDT GDFKDPLAHD VNHTQEASIE VEENELDTQY LQSMFKVSKR
QTFALFSNPA NPEKECTTVH AHSKSLREQS PKVTHEGGQK DENQGKSESK VKHGQSVHTT
VDFLVVGQKD KKPSDFAKCG AKGVTGLYQT SQFRGHKTEF INANKPGISQ NPYVIPSLSP
IRSSVKTICK KNLSEEKFEE PKMSPERTMG NESIIPNTES TVSQNNIQER TFKEGSSGSP
NEVGSSTNEV GSSINEVGSS GENVRAEPGR NRGPKLSAML RLGLMQPEVY KQSLPVSNCN
HTEIKRQGEN EGIFQAVNAD FSPYLISDNP EQPMGSSHAS QICSETPDDL LNDDKIKENL
NFAESDVKER SAVFSKSAQE GEFKRSPSPL AHRRLAQGHQ RWARKLESSE ESGSSEDEEL
PCFQHLLFGK VTNTPSPSTR HNAVAAEGLS KEAGESLVSL KNSLNDCSDQ VTSAKASQEH
HLSEDVRCSG SLFSSQCSAL EDSAANTNSQ DPFLMFDPPS KQVEHQSENQ EVLSDKELVS
EDDERETGLE EDNCQEEQIV DSDLGETAFE YESETSFSED CSGLSSQSAI LTTQQRDTMQ
DNLLKLQQEM AELEAVLEQH GSQPSHSSPS LIADSCAPED LLNPEQNTSE KVLTSEKSSD
YPITQNPESL SADKFQVSLD RSTSKNKESG MERSSTSKSQ LSDSRWYMHS PSRSLQNRSC
PSQEELIPVI DLEEQQLTTS EAQDSVKQSY LPRQDLEGTP YLKSGISLFS DDPESDPSEN
RAPESAHVFS TPLSTSALKL PQFQVKESAK SPAAAHTTNT AGYNVRQESM SRKKPEVISS
TKTNSRRISI VASGLTPKEY TLVQKFARKH YITLTNLITE ETTHVIMKTD AEFVCERTLK
YFLGIAGGKW VVSYFWVTQS IKEGKMLDEH DFEVRGDVVN GRNHRGPKRA RESQDRKIFK
GLEICCCGPF TNMPTDQLEW MVLLCGASVV KDPSSFTFRQ GTRPVVVVQP DAWPEDSGFH
VIGQMCEAPV VTREWVLDSV ALYQCQELDT YLIPQVPQSC CRPCT
//
