ID F7BG30_MACMU Unreviewed; 1863 AA.
AC F7BG30;
DT 27-JUL-2011, integrated into UniProtKB/TrEMBL.
DT 30-NOV-2016, sequence version 2.
DT 27-MAR-2024, entry version 72.
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:ENSMMUP00000001777.3,
GN ECO:0000313|VGNC:VGNC:99124};
OS Macaca mulatta (Rhesus macaque).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9544 {ECO:0000313|Ensembl:ENSMMUP00000001777.3, ECO:0000313|Proteomes:UP000006718};
RN [1] {ECO:0000313|Proteomes:UP000006718}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=17573 {ECO:0000313|Proteomes:UP000006718};
RX PubMed=17431167; DOI=10.1126/science.1139247;
RA Gibbs R.A., Rogers J., Katze M.G., Bumgarner R., Weinstock G.M.,
RA Mardis E.R., Remington K.A., Strausberg R.L., Venter J.C., Wilson R.K.,
RA Batzer M.A., Bustamante C.D., Eichler E.E., Hahn M.W., Hardison R.C.,
RA Makova K.D., Miller W., Milosavljevic A., Palermo R.E., Siepel A.,
RA Sikela J.M., Attaway T., Bell S., Bernard K.E., Buhay C.J.,
RA Chandrabose M.N., Dao M., Davis C., Delehaunty K.D., Ding Y., Dinh H.H.,
RA Dugan-Rocha S., Fulton L.A., Gabisi R.A., Garner T.T., Godfrey J.,
RA Hawes A.C., Hernandez J., Hines S., Holder M., Hume J., Jhangiani S.N.,
RA Joshi V., Khan Z.M., Kirkness E.F., Cree A., Fowler R.G., Lee S.,
RA Lewis L.R., Li Z., Liu Y.-S., Moore S.M., Muzny D., Nazareth L.V.,
RA Ngo D.N., Okwuonu G.O., Pai G., Parker D., Paul H.A., Pfannkoch C.,
RA Pohl C.S., Rogers Y.-H.C., Ruiz S.J., Sabo A., Santibanez J.,
RA Schneider B.W., Smith S.M., Sodergren E., Svatek A.F., Utterback T.R.,
RA Vattathil S., Warren W., White C.S., Chinwalla A.T., Feng Y., Halpern A.L.,
RA Hillier L.W., Huang X., Minx P., Nelson J.O., Pepin K.H., Qin X.,
RA Sutton G.G., Venter E., Walenz B.P., Wallis J.W., Worley K.C., Yang S.-P.,
RA Jones S.M., Marra M.A., Rocchi M., Schein J.E., Baertsch R., Clarke L.,
RA Csuros M., Glasscock J., Harris R.A., Havlak P., Jackson A.R., Jiang H.,
RA Liu Y., Messina D.N., Shen Y., Song H.X.-Z., Wylie T., Zhang L., Birney E.,
RA Han K., Konkel M.K., Lee J., Smit A.F.A., Ullmer B., Wang H., Xing J.,
RA Burhans R., Cheng Z., Karro J.E., Ma J., Raney B., She X., Cox M.J.,
RA Demuth J.P., Dumas L.J., Han S.-G., Hopkins J., Karimpour-Fard A.,
RA Kim Y.H., Pollack J.R., Vinar T., Addo-Quaye C., Degenhardt J., Denby A.,
RA Hubisz M.J., Indap A., Kosiol C., Lahn B.T., Lawson H.A., Marklein A.,
RA Nielsen R., Vallender E.J., Clark A.G., Ferguson B., Hernandez R.D.,
RA Hirani K., Kehrer-Sawatzki H., Kolb J., Patil S., Pu L.-L., Ren Y.,
RA Smith D.G., Wheeler D.A., Schenck I., Ball E.V., Chen R., Cooper D.N.,
RA Giardine B., Hsu F., Kent W.J., Lesk A., Nelson D.L., O'brien W.E.,
RA Pruefer K., Stenson P.D., Wallace J.C., Ke H., Liu X.-M., Wang P.,
RA Xiang A.P., Yang F., Barber G.P., Haussler D., Karolchik D., Kern A.D.,
RA Kuhn R.M., Smith K.E., Zwieg A.S.;
RT "Evolutionary and biomedical insights from the rhesus macaque genome.";
RL Science 316:222-234(2007).
RN [2] {ECO:0000313|Ensembl:ENSMMUP00000001777.3}
RP IDENTIFICATION.
RC STRAIN=17573 {ECO:0000313|Ensembl:ENSMMUP00000001777.3};
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_014975230.1; XM_015119744.1.
DR RefSeq; XP_014975231.1; XM_015119745.1.
DR SMR; F7BG30; -.
DR Ensembl; ENSMMUT00000001882.4; ENSMMUP00000001777.3; ENSMMUG00000001329.4.
DR GeneID; 712634; -.
DR CTD; 672; -.
DR VEuPathDB; HostDB:ENSMMUG00000001329; -.
DR VGNC; VGNC:99124; BRCA1.
DR GeneTree; ENSGT00440000034289; -.
DR OrthoDB; 5405431at2759; -.
DR Proteomes; UP000006718; Chromosome 16.
DR Bgee; ENSMMUG00000001329; Expressed in spermatid and 20 other cell types or tissues.
DR ExpressionAtlas; F7BG30; baseline.
DR GO; GO:0031436; C:BRCA1-BARD1 complex; IEA:UniProtKB-UniRule.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
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: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:0051865; P:protein autoubiquitination; IEA:UniProtKB-UniRule.
DR GO; GO:0085020; P:protein K6-linked ubiquitination; IEA:UniProtKB-UniRule.
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 Coiled coil {ECO:0000256|SAM:Coils};
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:UP000006718};
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, ECO:0000256|PROSITE-
KW ProRule:PRU00175}.
FT DOMAIN 24..65
FT /note="RING-type"
FT /evidence="ECO:0000259|PROSITE:PS50089"
FT DOMAIN 1642..1736
FT /note="BRCT"
FT /evidence="ECO:0000259|PROSITE:PS50172"
FT DOMAIN 1756..1855
FT /note="BRCT"
FT /evidence="ECO:0000259|PROSITE:PS50172"
FT REGION 231..266
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 305..336
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 653..699
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 886..914
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1323..1397
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1440..1501
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1540..1618
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1397..1424
FT /evidence="ECO:0000256|SAM:Coils"
FT COMPBIAS 309..329
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 664..697
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 894..913
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1346..1360
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1361..1397
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1440..1468
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1478..1501
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1590..1618
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 1863 AA; 207780 MW; 14B921E248329ED8 CRC64;
MDLSAVRVEE VQNVINAMQK ILECPICLEL IKEPVSTKCD HIFCRFCMLK LLNQKKGPSQ
CPLCKNDITK RSLQESTRFS QLVEELLKII HAFQLDTGLQ FANSYNFAKK ENHSPEHLKD
EVSIIQSMGY RNRAKRLLQS EPENPSLQET SLSVPLSNLG IVRTLRTKQQ IQPQKKSVYI
ELGSDSSEDT VNKATYCSVG DQELLQITPQ GTRDETSLDS AKKAACEFSE KDITNTEHHQ
SSNNDLNTTE KHATERHPEK YQGSSVSNLH VEPCGTNTHA SSLQHENSLL LTKDRMNVEK
AEFCNKSKQP GLARSQHNRW TGSKETCNDR QTPSTEKKVD LNANALYERK EWNKQKLPCS
ENPRDAEDVP WITLNSSIQK VNEWFSRSDE LLSSDDSHDG GSESNAKVAD VLDVLNEVDE
YSGSSEKIDL LASDPHEPLI CKSERVHSSS VESNIKDKIF GKTYRRKANL PNLSHVTENL
IIGALVTESQ IMQERPLTNK LKRKRRTTSG LHPEDFIKKA DLAVQKTPEI INQGTNQMEQ
NGQVMNITNS AHENKTKGDS IQNEKNPNAI ESLEEESAFK TKAEPISSSI NNMELELNIH
NSKAPKKNRL RRKSSTRHIH ALELVVSRNL SPPNCTELQI DSCSSSEEIK KKNYNQMPVR
HSRNLQLMED KESATGAKKS NKPNEQTSKR HASDTFPELK LTKVPGSFTN CSNTSELKEF
VNPSLSREEK EEKLETVKVS NNAKDPKDLM LSGERVLQTE RSVESSSISL VPDTDYGTQE
SISLLEVSTL GKAKTERNKC MSQCAAFENP KELIHGCSED TRNDTEGFKY PLGSEVNHSQ
ETSIEIEESE LDTQYLQNTF KVSKRQSFAL FSNPGNPEEE CATFSAHSRS LKKQSPKVTS
ECEQKEENQG KKESNIKPVQ TVNITAGFSV VCQKDKPVDN AKCSIKGGSR FCLSSQFRGN
ETGLITPNKH GLLQNPYHIP PLFPVKSFVK TKCNKNLLEE NSEEHSVSPE RAVGNENIIP
STVSTISHNN IRENAFKEAS SSNINEVGSS TNEVGSSINE VGSSDENIQA ELGRNRGPKL
NAVLRLGLLQ PEVCKQSLPI SNCKHPEIKK QEHEELVQTV NTDFSPCLIS DNLEQPMGSS
HASEVCSETP DDLLDDGEIK EDTSFAANDI KESSAVFSKS IQRGELSRSP SPFTHTHLAQ
GYQKEAKKLE SSEENLSSED EELPCFQHLL FGKVSNIPSQ TTRHSTVATE CLSKNTEENL
LSLKNSLTDC SNQVILAKAS QEHHLSEETK CSGSLFSSQC SELEDLTANT NTQDPFLIGS
SKRMRHQSES QGVGLSDKEL VSDDEERGTG LEEDNQEEQS VDSNLGEAAS GYESETSVSE
DCSRLSSQSE ILTTQQRDTM QDNLIKLQQE MAELEAVLEQ HGSQPSNSYP SIITDSSALE
DLRNPEQSTS EKAVLTSQKS SEYPINQNPE GLSADKFEVS ADSSTSKNKE PGVERSSPSK
CQSLEDRWYV HSSSGSLQNG NYPSQEELIK VVDVETQQLE KSGPHDLMEP SYLPRQDLDG
TPYLESGISL FSDDPESDPS EDRAPESAHV GSIPSSTSAL KVPQWQVAES AQSPAAAHNT
NTAGYNAMEE SVSRENPKLT ASTERVNKRM SLVVSGLTPE EFMLVYKFAR RYHIALTNLI
SEETTHVVMK TDAEFVCERT LKYFLGIAGG KWVVSYFWVT QSIKERKMLN EHDFEVRGDV
VNGRNHQGPK RARESPDRKI FRGLEICCYG PFTNMPTDQL EWMVQLCGAS VVKELSSFTL
GTGFHPIVVV QPDAWTEDNG FHAIGQMCEA PVVTREWVLD SVALYQCQEL DTYLIPQIPH
SHY
//
