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Protein

Breast cancer type 1 susceptibility protein homolog

Gene

BRCA1

Organism
Macaca mulatta (Rhesus macaque)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Protein inferred from homologyi

Functioni

E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for normal cell cycle progression from G2 to mitosis. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Involved in transcriptional regulation of P21 in response to DNA damage. Required for FANCD2 targeting to sites of DNA damage. May function as a transcriptional regulator. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8. Acts as a transcriptional activator (By similarity).By similarity

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri24 – 6542RING-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Ligase

Keywords - Biological processi

Cell cycle, DNA damage, DNA recombination, DNA repair, Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism, Transcription, Transcription regulation, Ubl conjugation pathway

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Breast cancer type 1 susceptibility protein homolog (EC:6.3.2.-)
Gene namesi
Name:BRCA1
OrganismiMacaca mulatta (Rhesus macaque)
Taxonomic identifieri9544 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniCercopithecidaeCercopithecinaeMacaca
Proteomesi
  • UP000006718 Componenti: Unplaced

Subcellular locationi

  • Nucleus By similarity
  • Chromosome By similarity
  • Cytoplasm By similarity

  • Note: Localizes at sites of DNA damage at double-strand breaks (DSBs); recruitment to DNA damage sites is mediated by the BRCA1-A complex. Translocated to the cytoplasm during UV-induced apoptosis.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Cytoplasm, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 18631863Breast cancer type 1 susceptibility protein homologPRO_0000055831Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei114 – 1141PhosphoserineBy similarity
Modified residuei307 – 3071Phosphoserine; by AURKABy similarity
Cross-linki338 – 338Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei394 – 3941PhosphoserineBy similarity
Modified residuei397 – 3971PhosphoserineBy similarity
Modified residuei422 – 4221PhosphoserineBy similarity
Cross-linki442 – 442Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki458 – 458Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki582 – 582Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei693 – 6931PhosphoserineBy similarity
Modified residuei724 – 7241PhosphoserineBy similarity
Cross-linki733 – 733Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki738 – 738Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei752 – 7521PhosphoserineBy similarity
Modified residuei839 – 8391PhosphoserineBy similarity
Modified residuei987 – 9871Phosphoserine; by CHEK2By similarity
Modified residuei1143 – 11431PhosphoserineBy similarity
Modified residuei1211 – 12111PhosphoserineBy similarity
Modified residuei1217 – 12171PhosphoserineBy similarity
Modified residuei1218 – 12181PhosphoserineBy similarity
Modified residuei1280 – 12801PhosphoserineBy similarity
Modified residuei1328 – 13281PhosphoserineBy similarity
Modified residuei1336 – 13361PhosphoserineBy similarity
Modified residuei1342 – 13421PhosphoserineBy similarity
Modified residuei1387 – 13871PhosphoserineBy similarity
Modified residuei1394 – 13941PhosphothreonineBy similarity
Modified residuei1423 – 14231PhosphoserineBy similarity
Modified residuei1457 – 14571PhosphoserineBy similarity
Modified residuei1524 – 15241PhosphoserineBy similarity

Post-translational modificationi

Phosphorylation at Ser-307 by AURKA is required for normal cell cycle progression from G2 to mitosis. Phosphorylated in response to IR, UV, and various stimuli that cause checkpoint activation, probably by ATM or ATR. Phosphorylation at Ser-987 by CHEK2 regulates mitotic spindle assembly (By similarity).By similarity
Autoubiquitinated, undergoes 'Lys-6'-linked polyubiquitination. 'Lys-6'-linked polyubiquitination does not promote degradation (By similarity).By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Interactioni

Subunit structurei

Heterodimer with BARD1. Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the MRE11-RAD50-NBN protein (MRN) complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Component of the BRCA1-A complex, at least composed of BRCA1, BARD1, UIMC1/RAP80, FAM175A/Abraxas, BRCC3/BRCC36, BRE/BRCC45 and BABAM1/NBA1. Interacts (via the BRCT domains) with FAM175A (phosphorylated form); this is important for recruitment to sites of DNA damage. Can form a heterotetramer with two molecules of FAM175A (phosphorylated form). Component of the BRCA1-RBBP8 complex. Interacts (via the BRCT domains) with RBBP8 ('Ser-327' phosphorylated form); the interaction ubiquitinates RBBP8, regulates CHEK1 activation, and involves RBBP8 in BRCA1-dependent G2/M checkpoint control on DNA damage. Associates with RNA polymerase II holoenzyme. Interacts with SMC1A, COBRA1, DCLRE1C, CLSPN. CHEK1, CHEK2, BAP1, BRCC3, AURKA, UBXN1 and KIAA0101/PAF15. Interacts (via BRCT domains) with BRIP1 (phosphorylated form). Interacts with FANCD2 (ubiquitinated form). Interacts with H2AFX (phosphorylated on 'Ser-140'). Interacts (via the BRCT domains) with ACACA (phosphorylated form); the interaction prevents dephosphorylation of ACACA. Part of a BRCA complex containing BRCA1, BRCA2 and PALB2. Interacts directly with PALB2; the interaction is essential for its function in HRR. Interacts directly with BRCA2; the interaction occurs only in the presence of PALB2 which serves as the bridging protein. Interacts (via the BRCT domains) with LMO4; the interaction represses the transcriptional activity of BRCA1. Interacts (via the BRCT domains) with CCAR2 (via N-terminus); the interaction represses the transcriptional activator activity of BRCA1 (By similarity). Interacts with EXD2 (By similarity).By similarity

Protein-protein interaction databases

STRINGi9544.ENSMMUP00000034386.

Structurei

3D structure databases

ProteinModelPortaliQ6J6I9.
SMRiQ6J6I9. Positions 1-103, 1649-1859.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1642 – 173695BRCT 1PROSITE-ProRule annotationAdd
BLAST
Domaini1756 – 1855100BRCT 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1397 – 142428Interaction with PALB2By similarityAdd
BLAST

Domaini

The BRCT domains recognize and bind phosphorylated pSXXF motif on proteins. The interaction with the phosphorylated pSXXF motif of FAM175A/Abraxas, recruits BRCA1 at DNA damage sites (By similarity).By similarity
The RING-type zinc finger domain interacts with BAP1.By similarity

Sequence similaritiesi

Contains 2 BRCT domains.PROSITE-ProRule annotation
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri24 – 6542RING-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410ITQ6. Eukaryota.
ENOG4111WR7. LUCA.
HOGENOMiHOG000230969.
HOVERGENiHBG050730.
InParanoidiQ6J6I9.
KOiK10605.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
3.40.50.10190. 2 hits.
InterProiIPR011364. BRCA1.
IPR031099. BRCA1-associated.
IPR025994. BRCA1_serine_dom.
IPR001357. BRCT_dom.
IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PANTHERiPTHR13763. PTHR13763. 1 hit.
PTHR13763:SF0. PTHR13763:SF0. 1 hit.
PfamiPF00533. BRCT. 2 hits.
PF12820. BRCT_assoc. 1 hit.
PF00097. zf-C3HC4. 1 hit.
[Graphical view]
PIRSFiPIRSF001734. BRCA1. 1 hit.
PRINTSiPR00493. BRSTCANCERI.
SMARTiSM00292. BRCT. 2 hits.
SM00184. RING. 1 hit.
[Graphical view]
SUPFAMiSSF52113. SSF52113. 2 hits.
PROSITEiPS50172. BRCT. 2 hits.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q6J6I9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDLSAVRVEE VQNVINAMQK ILECPICLEL IKEPVSTKCD HIFCRFCMLK
60 70 80 90 100
LLNQKKGPSQ CPLCKNDITK RSLQESTRFS QLVEELLKII HAFQLDTGLQ
110 120 130 140 150
FANSYNFAKK ENHSPEHLKD EVSIIQSMGY RNRAKRLLQS EPENPSLQET
160 170 180 190 200
SLSVPLSNLG IVRTLRTKQQ IQPQKKSVYI ELGSDSSEDT VNKATYCSVG
210 220 230 240 250
DQELLQITPQ GTRDETSLDS AKKAACEFSE KDITNTEHHQ SSNNDLNTTE
260 270 280 290 300
KHATERHPEK YQGSSVSNLH VEPCGTNTHA SSLQHENSLL LTKDRMNVEK
310 320 330 340 350
AEFCNKSKQP GLARSQHNRW TGSKETCNDR QTPSTEKKVD LNANALYERK
360 370 380 390 400
EWNKQKLPCS ENPRDAEDVP WITLNSSIQK VNEWFSRSDE LLSSDDSHDG
410 420 430 440 450
GSESNAKVAD VLDVLNEVDE YSGSSEKIDL LASDPHEPLI CKSERVHSSS
460 470 480 490 500
VESNIKDKIF GKTYRRKANL PNLSHVTENL IIGALVTESQ IMQERPLTNK
510 520 530 540 550
LKRKRRTTSG LHPEDFIKKA DLAVQKTPEI INQGTNQMEQ NGQVMNITNS
560 570 580 590 600
AHENKTKGDS IQNEKNPNAI ESLEEESAFK TKAEPISSSI NNMELELNIH
610 620 630 640 650
NSKAPKKNRL RRKSSTRHIH ALELVVSRNL SPPNCTELQI DSCSSSEEIK
660 670 680 690 700
KKNYNQMPVR HSRNLQLMED KESATGAKKS NKPNEQTSKR HASDTFPELK
710 720 730 740 750
LTKVPGSFTN CSNTSELKEF VNPSLSREEK EEKLETVKVS NNAKDPKDLM
760 770 780 790 800
LSGERVLQTE RSVESSSISL VPDTDYGTQE SISLLEVSTL GKAKTERNKC
810 820 830 840 850
MSQCAAFENP KELIHGCSED TRNDTEGFKY PLGSEVNHSQ ETSIEIEESE
860 870 880 890 900
LDTQYLQNTF KVSKRQSFAL FSNPGNPEEE CATFSAHSRS LKKQSPKVTS
910 920 930 940 950
ECEQKEENQG KKESNIKPVQ TVNITAGFSV VCQKDKPVDN AKCSIKGGSR
960 970 980 990 1000
FCLSSQFRGN ETGLITPNKH GLLQNPYHIP PLFPVKSFVK TKCNKNLLEE
1010 1020 1030 1040 1050
NSEEHSVSPE RAVGNENIIP STVSTISHNN IRENAFKEAS SSNINEVGSS
1060 1070 1080 1090 1100
TNEVGSSINE VGPSDENIQA ELGRNRGPKL NAVLRLGLLQ PEVCKQSLPI
1110 1120 1130 1140 1150
SNCKHPEIKK QEHEELVQTV NTDFSPCLIS DNLEQPMGSS HASEVCSETP
1160 1170 1180 1190 1200
DDLLDDGEIK EDTSFAANDI KESSAVFSKS IQRGELSRSP SPFTHTHLAQ
1210 1220 1230 1240 1250
GYQKEAKKLE SSEENLSSED EELPCFQHLL FGKVSNIPSQ TTRHSTVATE
1260 1270 1280 1290 1300
CLSKNTEENL LSLKNSLTDC SNQVILAKAS QEHHLSEETK CSGSLFSSQC
1310 1320 1330 1340 1350
SELEDLTANT NTQDPFLIGS SKRMRHQSES QGVGLSDKEL VSDDEERGTG
1360 1370 1380 1390 1400
LEEDNQEEQS VDSNLGEAAS GYESETSVSE DCSRLSSQSE ILTTQQRDTM
1410 1420 1430 1440 1450
QDNLIKLQQE MAELEAVLEQ HGSQPSNSYP SIITDSSALE DLRNPEQSTS
1460 1470 1480 1490 1500
EKAVLTSQKS SEYPINQNPE GLSADKFEVS ADSSTSKNKE PGVERSSPSK
1510 1520 1530 1540 1550
CQSLEDRWYV HSSSGSLQNG NYPSQEELIK VVDVETQQLE KSGPHDLMEP
1560 1570 1580 1590 1600
SYLPRQDLDG TPYLESGISL FSDDPESDPS EDRAPESAHV GSIPSSTSAL
1610 1620 1630 1640 1650
KVPQWQVAES AQSPAAAHNT NTAGYNAMEE SVSRENPKLT ASTERVNKRM
1660 1670 1680 1690 1700
SLVVSGLTPE EFMLVYKFAR RYHIALTNLI SEETTHVVMK TDAEFVCERT
1710 1720 1730 1740 1750
LKYFLGIAGG KWVVSYFWVT QSIKERKMLN EHDFEVRGDV VNGRNHQGPK
1760 1770 1780 1790 1800
RARESPDRKI FRGLEICCYG PFTNMPTDQL EWMVQLCGAS VVKELSSFTL
1810 1820 1830 1840 1850
GTGFHPIVVV QPDAWTEDNG FHAIGQMCEA PVVTREWVLD SVALYQCQEL
1860
DTYLIPQIPH SHY
Length:1,863
Mass (Da):207,790
Last modified:July 5, 2004 - v1
Checksum:i6AA0DE2AA9A983BC
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti366 – 3661A → T in AAC39586 (PubMed:9462745).Curated
Sequence conflicti569 – 5691A → P in AAC39586 (PubMed:9462745).Curated
Sequence conflicti717 – 7171Missing in AAC39586 (PubMed:9462745).Curated
Sequence conflicti750 – 7501M → I in AAC39586 (PubMed:9462745).Curated
Sequence conflicti773 – 7731D → G in AAC39586 (PubMed:9462745).Curated
Sequence conflicti913 – 9131E → Q in AAC39586 (PubMed:9462745).Curated
Sequence conflicti1016 – 10161E → K in AAC39586 (PubMed:9462745).Curated
Sequence conflicti1063 – 10631P → S in AAC39586 (PubMed:9462745).Curated
Sequence conflicti1167 – 11671A → E in AAC39586 (PubMed:9462745).Curated
Sequence conflicti1203 – 12031Q → R in AAC39586 (PubMed:9462745).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY589041 Genomic DNA. Translation: AAT44833.1.
AF019078 Genomic DNA. Translation: AAC39586.1.
U44730 Genomic DNA. Translation: AAB03212.1.
PIRiG02999.
RefSeqiNP_001108421.1. NM_001114949.1.
UniGeneiMmu.17471.
Mmu.30604.

Genome annotation databases

GeneIDi712634.
KEGGimcc:712634.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY589041 Genomic DNA. Translation: AAT44833.1.
AF019078 Genomic DNA. Translation: AAC39586.1.
U44730 Genomic DNA. Translation: AAB03212.1.
PIRiG02999.
RefSeqiNP_001108421.1. NM_001114949.1.
UniGeneiMmu.17471.
Mmu.30604.

3D structure databases

ProteinModelPortaliQ6J6I9.
SMRiQ6J6I9. Positions 1-103, 1649-1859.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9544.ENSMMUP00000034386.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi712634.
KEGGimcc:712634.

Organism-specific databases

CTDi672.

Phylogenomic databases

eggNOGiENOG410ITQ6. Eukaryota.
ENOG4111WR7. LUCA.
HOGENOMiHOG000230969.
HOVERGENiHBG050730.
InParanoidiQ6J6I9.
KOiK10605.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

NextBioi19972539.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
3.40.50.10190. 2 hits.
InterProiIPR011364. BRCA1.
IPR031099. BRCA1-associated.
IPR025994. BRCA1_serine_dom.
IPR001357. BRCT_dom.
IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PANTHERiPTHR13763. PTHR13763. 1 hit.
PTHR13763:SF0. PTHR13763:SF0. 1 hit.
PfamiPF00533. BRCT. 2 hits.
PF12820. BRCT_assoc. 1 hit.
PF00097. zf-C3HC4. 1 hit.
[Graphical view]
PIRSFiPIRSF001734. BRCA1. 1 hit.
PRINTSiPR00493. BRSTCANCERI.
SMARTiSM00292. BRCT. 2 hits.
SM00184. RING. 1 hit.
[Graphical view]
SUPFAMiSSF52113. SSF52113. 2 hits.
PROSITEiPS50172. BRCT. 2 hits.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Evolution of the tumor suppressor BRCA1 locus in primates: implications for cancer predisposition."
    Pavlicek A., Noskov V.N., Kouprina N., Barrett J.C., Jurka J., Larionov V.
    Hum. Mol. Genet. 13:2737-2751(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "Evolutionary sequence comparisons using high-density oligonucleotide arrays."
    Hacia J.G., Makalowski W., Edgemon K., Erdos M.R., Robbins C.M., Fodor S.P.A., Brody L.C., Collins F.S.
    Nat. Genet. 18:155-158(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 225-1365.
  3. Thompson M.E., Holt J.T.
    Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1189-1253.

Entry informationi

Entry nameiBRCA1_MACMU
AccessioniPrimary (citable) accession number: Q6J6I9
Secondary accession number(s): O46487, Q28525
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 23, 2004
Last sequence update: July 5, 2004
Last modified: May 11, 2016
This is version 94 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.