ID G3V8S5_RAT Unreviewed; 1817 AA.
AC G3V8S5;
DT 16-NOV-2011, integrated into UniProtKB/TrEMBL.
DT 16-NOV-2011, sequence version 1.
DT 27-MAR-2024, entry version 89.
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:ENSRNOP00000028109.3,
GN ECO:0000313|RGD:2218};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116 {ECO:0000313|Ensembl:ENSRNOP00000028109.3, ECO:0000313|Proteomes:UP000002494};
RN [1] {ECO:0000313|Ensembl:ENSRNOP00000028109.3, ECO:0000313|Proteomes:UP000002494}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway {ECO:0000313|Ensembl:ENSRNOP00000028109.3,
RC ECO:0000313|Proteomes:UP000002494};
RX PubMed=15057822; DOI=10.1038/nature02426;
RG Rat Genome Sequencing Project Consortium;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2] {ECO:0000313|Ensembl:ENSRNOP00000028109.3}
RP IDENTIFICATION.
RC STRAIN=Brown Norway {ECO:0000313|Ensembl:ENSRNOP00000028109.3};
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: Chromosome {ECO:0000256|ARBA:ARBA00004286,
CC ECO:0000256|PIRNR:PIRNR001734}. Cytoplasm
CC {ECO:0000256|ARBA:ARBA00004496}. Nucleus
CC {ECO:0000256|PIRNR:PIRNR001734}. 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. {ECO:0000256|PIRNR:PIRNR001734}.
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DR RefSeq; XP_008766314.1; XM_008768092.2.
DR SMR; G3V8S5; -.
DR Ensembl; ENSRNOT00000028109.4; ENSRNOP00000028109.3; ENSRNOG00000020701.5.
DR GeneID; 497672; -.
DR CTD; 672; -.
DR RGD; 2218; Brca1.
DR GeneTree; ENSGT00440000034289; -.
DR OMA; VTECQSS; -.
DR OrthoDB; 5405431at2759; -.
DR TreeFam; TF105060; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000020701; Expressed in thymus and 17 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:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
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: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 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.
PE 4: Predicted;
KW Acetylation {ECO:0000256|ARBA:ARBA00022990};
KW Activator {ECO:0000256|ARBA:ARBA00023159};
KW Cell cycle {ECO:0000256|ARBA:ARBA00023306, ECO:0000256|PIRNR:PIRNR001734};
KW Chromosome {ECO:0000256|ARBA:ARBA00022454, 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|ARBA:ARBA00023125, ECO:0000256|PIRNR:PIRNR001734};
KW Fatty acid biosynthesis {ECO:0000256|ARBA:ARBA00023160};
KW Fatty acid metabolism {ECO:0000256|ARBA:ARBA00022832};
KW Isopeptide bond {ECO:0000256|ARBA:ARBA00022499};
KW Lipid biosynthesis {ECO:0000256|ARBA:ARBA00022516};
KW Lipid metabolism {ECO:0000256|ARBA:ARBA00023098};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723};
KW Nucleus {ECO:0000256|ARBA:ARBA00023242, ECO:0000256|PIRNR:PIRNR001734};
KW Reference proteome {ECO:0000313|Proteomes:UP000002494};
KW Transcription {ECO:0000256|ARBA:ARBA00023163};
KW Transcription regulation {ECO:0000256|ARBA:ARBA00023015};
KW Ubl conjugation {ECO:0000256|ARBA:ARBA00022843};
KW Ubl conjugation pathway {ECO:0000256|ARBA:ARBA00022786,
KW ECO:0000256|PIRNR:PIRNR001734}; Zinc {ECO:0000256|ARBA:ARBA00022833};
KW Zinc-finger {ECO:0000256|ARBA:ARBA00022771}.
SQ SEQUENCE 1817 AA; 200090 MW; 433449AE4C9CA1DF CRC64;
MDLSAVRIQE VQNVLHAMQK ILECPICLEL IKEPVSTKCD HIFCKFCMLK LLNQKKGPSQ
CPLCKNEITK RSLQGSARFS QLVEELLKII DAFELDTGMQ CANGFSFSKK KNSSSELLNE
DASIIQSVGY RNRVKKLRQI ESGSATLKDS LSVQLSNLGI VRSMKKNRQT QPQNKSVYIA
LESDSSEERV NAPDGCSVRD QELFQIAPGG AGDEGKLNSA KKAACDFSEG IRNIEHHQCS
DKDLNPTENH ATERHPEKCP RISVANVHVE PCGTDARASS LQRGTRSLLF TEDRLDAEKA
EFCDRSKQSG AAVSQQSRWA DSKETCNGRP VPRTEGKADP NVDSLCGRKQ WNHPKSLCPE
NSGATTDVPW ITLNSSIQKV NEWFSRTGEM LTSDNASDRR PASNAEAAVV LEVSNEVDGC
FSSSKKIDLV APDSDNAVMC TSGRDFSKPV ENIINDKIFG KTYQRKGSRP HLNHVTEIIG
TFTTEPQIIQ EQPFTNKLKR KRSTCLHPED FIKKADLTVV QRISENLNQG TDQMEPNDQA
MSITSNGQEN RATGNDLQRG RNAHPIESLR KEPAFTAKAK SISNSISDLE VELNVHSSKA
PKKNRLRRKS TRCVLPLEPI SRNPSPPTCA ELQIESCGSS EETKKNNSNQ TPAGHIREPQ
LIEDTEPAAD AKKNEPNEHI RKRSASDAFP EEKLMNKAGL LTSCSSPRKP QGPVNPSPER
KGIEQLEMCQ MPDNNKELGD LVLGGEPSGK PTEPSEESTS VSLVPDTDYD TQNSVSILEA
NTVRYARTGS VQCMTQFVAS ENPKELVHGS NNAGSGSECF KHPLRHELNH NQETIEMEDS
ELDTQYLQNT FQVSKRQSFA LFSKLRSPQK DCTLVGARSV PSREPSPKVT SRGEQKERQG
QEESEISHVQ AVTVTVGLPV PCQEGKPGAV TMCADVSRLC PSSHYRSCEN GLNTTDKSGI
SQNSHFRQSV SPLRSSIKTD NRKTLTEGRF EKHTERGMGN ETAVQSTIHT ISQNNRGDAC
QEASSGSVIE VHSTGENVQG QLDRNRGPTV NTVSLLDSTQ PGVSKQSAPV SDKYLEIKQE
SKAVSADFSP CLFSDHLEKP MRSDKIFQVC SETPDDLLDD VEIQENASFG EGGITEKSAI
FNGSVLRRES SRIPSPVTHA SKSRSLHRGS RKLEFSEESD STEDEDLPCF QHLLSRVSST
PELTRCSSVV TQRVPEKAKG TQAPRKSSIS DCNNEVILVE ASQEYQFSED AKCSGSMFSS
QHSAALGSPA NALSQDPDFN PPSKQRRHQA ENEEAFLSDK ELISDHEDMA ACLEEASDQE
EDSIIPDSVA SGYESEANLS EDCSQSDILT TQQRATMKDN LIKLQQEMAQ LEAVLEQHGS
QPSGHPPCLP ADPCALEDLP DPEQNRSGTA ILTSKNINEN PVSQNPKRAC DDKSQPQPPD
GLPSGDKESG MRRPSPFKSP LTSRRCSARG HSRSLQNRNS TSQEELLQPV ELEKSCEPHN
LTGRSCLPRQ DLEGTPYLES GISLFSSRDP DSESPKVPAL VCTAPASTSA LKISQGQVAG
SCRSPAAGGA DTAVVEIVSK IKPEVTSSKE RAERDISMVV SGLTPKEVMI VQKFAEKYRL
ALTDVITEET THVIIKTDAE FVCERTLKYF LGIAGGKWIV SYSWVIKSIQ ERKLLSVHEF
EVKGDVVTGS NHQGPRRSRE SQEKLFEGLQ IYCCEPFTNM PKDELERMLQ LCGASVVKEL
PLLTRDTGAH PIVLVQPSAW TEDNDCPDIG QLCKGRLVMW DWVLDSISVY RCRDLDAYLV
QNITCGRDGS EPQDSND
//
