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Protein

Breast cancer type 1 susceptibility protein homolog

Gene

BRCA1

Organism
Pan troglodytes (Chimpanzee)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

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

Regions

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

GO - Molecular functioni

  • DNA binding Source: UniProtKB-KW
  • ligase activity Source: UniProtKB-KW
  • tubulin binding Source: UniProtKB
  • ubiquitin-protein transferase activity Source: UniProtKB
  • zinc ion binding Source: InterPro

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

Names & Taxonomyi

Protein namesi
Recommended name:
Breast cancer type 1 susceptibility protein homolog (EC:6.3.2.-)
Gene namesi
Name:BRCA1
OrganismiPan troglodytes (Chimpanzee)
Taxonomic identifieri9598 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaePan
Proteomesi
  • UP000002277 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

  • BRCA1-A complex Source: GO_Central
  • BRCA1-BARD1 complex Source: UniProtKB
  • chromosome Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • gamma-tubulin ring complex Source: UniProtKB
  • nucleus Source: UniProtKB
  • plasma membrane Source: GO_Central
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_0000055833Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei114 – 1141PhosphoserineBy similarity
Modified residuei308 – 3081Phosphoserine; by AURKABy similarity
Cross-linki339 – 339Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei395 – 3951PhosphoserineBy similarity
Modified residuei398 – 3981PhosphoserineBy similarity
Modified residuei423 – 4231PhosphoserineBy similarity
Cross-linki443 – 443Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki459 – 459Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki583 – 583Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki654 – 654Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei694 – 6941PhosphoserineBy similarity
Modified residuei725 – 7251PhosphoserineBy similarity
Cross-linki734 – 734Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki739 – 739Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei753 – 7531PhosphoserineBy similarity
Modified residuei840 – 8401PhosphoserineBy similarity
Modified residuei988 – 9881Phosphoserine; 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-308 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-988 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

Proteomic databases

PaxDbiQ9GKK8.

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

GO - Molecular functioni

  • tubulin binding Source: UniProtKB

Protein-protein interaction databases

STRINGi9598.ENSPTRP00000015727.

Structurei

3D structure databases

ProteinModelPortaliQ9GKK8.
SMRiQ9GKK8. 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

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi651 – 6544Poly-Lys

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.
InParanoidiQ9GKK8.
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.

Q9GKK8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDLSALRVEE VQNVINAMQK ILECPICLEL IKEPVSTKCD HIFCKFCMLK
60 70 80 90 100
LLNQKKGPSQ CPLCKNDITK RSLQESTRFS QLVEELLKII CAFQLDTGLE
110 120 130 140 150
YANSYNFAKK ENNSPEHLKD EVSIIQSMGY RNRAKRLLQS EPENPSLQET
160 170 180 190 200
SLSVQLSNLG TVRTLRTKQR IQPQKKSVYI ELGSDSSEDT VNKATYCSVG
210 220 230 240 250
DQELLQITPQ GTRDEISLDS AKKAACEFSE TDVTNTEHHQ PSNNDLNTTE
260 270 280 290 300
KRATERHPEK YQGSSVSNLH VEPCGTNTHA SSLQHENSSL LLTKDRMNVE
310 320 330 340 350
KAEFCNKSKQ PGLARSQHNR WAGSKETCND RRTPSTEKKV DLNADPLCER
360 370 380 390 400
KEWNKQKLPC SENPRDTEDV PWITLNSSIQ KVNEWFSRSD ELLGSDDSHD
410 420 430 440 450
GGSESNAKVA DVLDVLNEVD EYSGSSEKID LLASDPHEAL ICKSERVHSK
460 470 480 490 500
SVESNTEDKI FGKTYRRKAS LPNLSHVTEN LIIGAFVTEP QIIQERPLTN
510 520 530 540 550
KLKRKRRATS GLHPEDFIKK ADLAVQKTPE MINQGTNQME QNGQVMNITN
560 570 580 590 600
SGHENKTKGD SIQNEKNPNP IESLEKESAF KTKAEPISSS ISNMELELNI
610 620 630 640 650
HNSKAPKKNR LRRKSSTRHI HALELVVSRN LSPPNCTELQ IDSCSSSEEI
660 670 680 690 700
KKKKYNQMPV RHSRNLQLME DKEPATGVKK SNKPNEQTSK RHDSDTFPEL
710 720 730 740 750
KLTNAPGSFT NCSNTSELKE FVNPSLPREE KEEKLETVKV SNNAEDPKDL
760 770 780 790 800
MLSGERVLQT ERSVESSSIS LVPGTDYGTQ ESISLLEVST LGKAKTEPNK
810 820 830 840 850
CVSQCAAFEN PKGLIHGCSK DTRNDTEGFK YPLGHEVNHS RETSIEMEES
860 870 880 890 900
ELDAQYLQNT FKVSKRQSFA LFSNPGNPEE ECATFSAHCR SLKKQSPKVT
910 920 930 940 950
FEREQKEQNQ GKNESNIKPV QTVNITAGFP VVCQKDKPVD YAKCSIKGGS
960 970 980 990 1000
RFCLSSQFRG NETGLITPNK HGLLQNPYHI PPLFPIKSFV KTKCKKNLLE
1010 1020 1030 1040 1050
ENFEEHSMSP EREMGNENIP STVSTISRNN IRENVFKEAS SSNINEVGSS
1060 1070 1080 1090 1100
TNEVGSSINE VGSSDENIQA ELGRNRGPKL NAMLRLGVLQ PEVYKQSLPG
1110 1120 1130 1140 1150
SNCKHPEIKK QEYEEVVQTV NTDFSPCLIS DNLEQPMGSS HASQVCSETP
1160 1170 1180 1190 1200
DDLLDDGEIK EDTSFAENDI KESSAVFSKS VQRGELSRSP SPFTHTHLAQ
1210 1220 1230 1240 1250
GYRRGAKKLE SSEENLSSED EELPCFQHLL FGKVSNIPSQ STRHSTVATE
1260 1270 1280 1290 1300
CLSKNTEENL LSLKNSLNDC SNQVILAKAS QEHHLSEETK CSASLFSSQC
1310 1320 1330 1340 1350
SELEDLTANT NTQDPFLIGS SKQMRHQSES QGVGLSDKEL VSDDEERGTG
1360 1370 1380 1390 1400
LEENNQEEQS MDSNLGEAAS GCESETSVSE DCSGLSSQSD ILTTQQRDTM
1410 1420 1430 1440 1450
QDNLIKLQQE MAELEAVLEQ HGSQPSNSYP SIISDSSALE DLQNPEQSTS
1460 1470 1480 1490 1500
EKAVLTSQKS SEYPISQNPE GLSADKFEVS ADSSTSKNKE PGVERSSPSK
1510 1520 1530 1540 1550
CPSLDDRWYM HSCSGSLQNR NYPSQEELIK VVDVEEQQLE ESGPHDLTET
1560 1570 1580 1590 1600
SYLPRQDLEG TPYLESGISL FSDDPESDPS EDKAPESAHV GNIPSSTSAL
1610 1620 1630 1640 1650
KVPQLKVAES AQSPAAAHTT NTAGYNAMEE SVSREKPELT ASTERVNKRM
1660 1670 1680 1690 1700
SMVVSGLTPE EFMLVYKFAR KHHITLTNLI TEETTHVVMK TDAEFVCERT
1710 1720 1730 1740 1750
LKYFLGIAGG KWVVSYFWVT QSIKERKMLN EHDFEVRGDV VNGRNHQGPK
1760 1770 1780 1790 1800
RARESQDRKI FRGLEICCYG PFTNMPTDQL EWMVQLCGAS VVKELSSFTL
1810 1820 1830 1840 1850
GTGVHPIVVV QPDAWTEDNG FHAIGQMCEA PVVTREWVLD SVALYQCQEL
1860
DTYLIPQIPH SHY
Length:1,863
Mass (Da):207,899
Last modified:November 21, 2003 - v2
Checksum:i49673829CCFA756E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti427 – 4271E → K in AAR04849 (PubMed:15385441).Curated
Sequence conflicti925 – 9251I → T in AAR04849 (PubMed:15385441).Curated
Sequence conflicti1520 – 15201R → T in AAG43492 (Ref. 1) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti309 – 3091K → E.1 Publication
VAR_018712
Natural varianti590 – 5901S → G.1 Publication
VAR_018713
Natural varianti731 – 7311K → E.2 Publications
VAR_018714
Natural varianti1100 – 11001G → E.2 Publications
VAR_018715

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF207822 mRNA. Translation: AAG43492.1.
AY365046 Genomic DNA. Translation: AAR04849.1.
AF019075 Genomic DNA. Translation: AAC39583.1.
RefSeqiNP_001038958.1. NM_001045493.1.
UniGeneiPtr.6298.

Genome annotation databases

GeneIDi449497.
KEGGiptr:449497.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF207822 mRNA. Translation: AAG43492.1.
AY365046 Genomic DNA. Translation: AAR04849.1.
AF019075 Genomic DNA. Translation: AAC39583.1.
RefSeqiNP_001038958.1. NM_001045493.1.
UniGeneiPtr.6298.

3D structure databases

ProteinModelPortaliQ9GKK8.
SMRiQ9GKK8. Positions 1-103, 1649-1859.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9598.ENSPTRP00000015727.

Proteomic databases

PaxDbiQ9GKK8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi449497.
KEGGiptr:449497.

Organism-specific databases

CTDi672.

Phylogenomic databases

eggNOGiENOG410ITQ6. Eukaryota.
ENOG4111WR7. LUCA.
HOGENOMiHOG000230969.
HOVERGENiHBG050730.
InParanoidiQ9GKK8.
KOiK10605.

Miscellaneous databases

NextBioi20832624.

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. "Positive selection on the human BRCA1 gene may have resulted from pressure for prolonged care for infants."
    Takeda R., Hink R.L., Jogodka C., Walter N.A.R., Messier W.
    Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS GLU-309; GLY-590; GLU-731 AND GLU-1100.
    Tissue: Blood.
  2. "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].
  3. "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, VARIANTS GLU-731 AND GLU-1100.

Entry informationi

Entry nameiBRCA1_PANTR
AccessioniPrimary (citable) accession number: Q9GKK8
Secondary accession number(s): O46484
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 21, 2003
Last sequence update: November 21, 2003
Last modified: May 11, 2016
This is version 121 of the entry and version 2 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. 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.