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Protein

Breast cancer type 1 susceptibility protein homolog

Gene

BRCA1

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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

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
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 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 – 18491849Breast cancer type 1 susceptibility protein homologPRO_0000055827Add
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-linki457 – 457Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei691 – 6911PhosphoserineBy similarity
Modified residuei711 – 7111PhosphoserineBy similarity
Modified residuei720 – 7201PhosphoserineBy similarity
Modified residuei982 – 9821Phosphoserine; by CHEK2By similarity
Modified residuei1138 – 11381PhosphoserineBy similarity
Modified residuei1211 – 12111PhosphoserineBy similarity
Modified residuei1212 – 12121PhosphoserineBy similarity
Modified residuei1274 – 12741PhosphoserineBy similarity
Modified residuei1323 – 13231PhosphoserineBy similarity
Modified residuei1330 – 13301PhosphoserineBy similarity
Modified residuei1336 – 13361PhosphoserineBy similarity
Modified residuei1382 – 13821PhosphoserineBy similarity
Modified residuei1389 – 13891PhosphothreonineBy similarity
Modified residuei1418 – 14181PhosphoserineBy similarity
Modified residuei1452 – 14521PhosphoserineBy similarity
Modified residuei1518 – 15181PhosphoserineBy 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-982 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

PaxDbiQ864U1.
PRIDEiQ864U1.

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 similarity1 Publication

Protein-protein interaction databases

BioGridi160259. 2 interactions.
STRINGi9913.ENSBTAP00000011616.

Structurei

3D structure databases

ProteinModelPortaliQ864U1.
SMRiQ864U1. Positions 1-103, 1642-1849.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1642 – 172988BRCT 1PROSITE-ProRule annotationAdd
BLAST
Domaini1749 – 1848100BRCT 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1392 – 141928Interaction with PALB2By similarityAdd
BLAST

Domaini

The RING-type zinc finger domain interacts with BAP1.By similarity
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

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.
InParanoidiQ864U1.
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.

Q864U1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDLSADHVEE VQNVLNAMQK ILECPICLEL IKEPVSTKCD HIFCKFCMLK
60 70 80 90 100
LLNQKKGPSQ CPLCKNDITK RSLQESTRFS QLVEELLKII HAFELDTGLQ
110 120 130 140 150
FANSYNFSRK EDNSPEHLKE EVSIIQSMGY RNRAKRLWQS EPENPTLQET
160 170 180 190 200
SLTVELSNLG IVRSLRTKQQ TQSQNKSVYI ELGSDSSEDT VNKASYFSVG
210 220 230 240 250
DHELLEITPQ GAKAKTNLNP AEKAACEFSE KDITNTEHHQ LSIKDLITTQ
260 270 280 290 300
KHATETHPEK YQGISVSDFH VEPCGTDTHA SSLQHENSSL LLTENRLNVE
310 320 330 340 350
KAEFCNKSKQ PVLVKSQQSR WAESKGTCKD RQIPSTEKKI VLNTDPLYRR
360 370 380 390 400
KELRKQKPAC PDSPGDSQDV PWVTLNNSIQ KVNDWFSRSD EILTSDDSCD
410 420 430 440 450
GGSESNNEVA GAVEIPNKVD GYSGSSEKIN LMASDPHGTL IHERVHSKPV
460 470 480 490 500
ESNIEDKIFG KTYRRKSSLP NFSHIAEDLI LGAFTVEPQI TQEQPLTNKL
510 520 530 540 550
KCKRRGTSGL QPEDFIKKVD LTIVPKTPEK MTEGTDQTEQ KCHGMNITSD
560 570 580 590 600
GHENKTKRDY VQKEQNANPA ESLEKESVFR TEAEPISISI SNMELELNIH
610 620 630 640 650
RSKAPKNRLK RKSSTRKIPE LELVVSRNPS LPNHTELPID SSSSNEEMKK
660 670 680 690 700
KHSSQMPVRQ SQKLQLIGDK ELTAGAKNNK TYEQINKRLA SDAFPELKLT
710 720 730 740 750
NTPGYFTNCS SKPEEFVHPS LQREENLGTI QVSNSTKDPK DLILREGKAL
760 770 780 790 800
QIERSVESTN ISLVPDTDYS TQDSISLLEA KTPEKAKTAP NPCVSLCTAT
810 820 830 840 850
KNLKELIHRD FKDTKNNTEG FQDLLGHDIN YVIQETSREM EDSELDTQYL
860 870 880 890 900
QNTFKASKRQ TFALFSNPGN PQKECATVFA HSGSLRDQSP RDPLKCRQKE
910 920 930 940 950
DSQGKSESKS QHVQAICTTV HFPVADQQDR TPGDDAKCSA KEVTRVCQSS
960 970 980 990 1000
QLRGHKTELV FANKQGVSEK PNLIPSLSPI KSSVKTICKK SPSEKFEEPV
1010 1020 1030 1040 1050
TSPEKTLGSE SIIQSAVSTI SQNNIQESTF KEVSSNSVNE VGSSTNEVGS
1060 1070 1080 1090 1100
SVNEVGSSGE NIQAEPGRNR EPKLRALLGL GLTQPEVYKQ SLPVSNCHHP
1110 1120 1130 1140 1150
EIKRQGENED MPQAVKADFS PCLISDNLEQ PTGSRHASQV CSETPDNLLN
1160 1170 1180 1190 1200
DDEIKENSHF AESDIKERSA VFSESVQKGE FRGSPGPFTH THLAQGHQRG
1210 1220 1230 1240 1250
AGKLESEETV SSEDEELPCF QQLLFGKVTS TLSPSTGCNT VATEGLSKET
1260 1270 1280 1290 1300
EGNLESLKSG LNDCSGQVTS AKVSQEHHLN EEARCSGSLF SSQCSAMEDL
1310 1320 1330 1340 1350
TTNTNTQDPF LMFERPSKQV YQSESEEVLS DKELVSDDEE RETGLEEDSC
1360 1370 1380 1390 1400
QEEQSVDSDL GEAVSDHVSE TSLSEDGVGL SSQSDILTTQ QRDTMQDNLL
1410 1420 1430 1440 1450
KLQQEMAELE AVLERHGSQP SHSSASLTAD SRGPEHLLNL EQDTSERAIL
1460 1470 1480 1490 1500
TSEKSRDYSR SQNPESLSAD KFPVSLDSST NKNKEPGMER SSASKFQLSY
1510 1520 1530 1540 1550
NRWYMHSSRS LQDRNCPSQK EPINVADMEE QQLAKREAQD LMGSFLPRQD
1560 1570 1580 1590 1600
QEGTPYLKSG ISLFSHEPES DPSEDRAAEP AHVHSMPPSA SALKLSQFRV
1610 1620 1630 1640 1650
EESTKNPAAA HIANTTRCNL REESMSKEKP EVISSTERSK KRLSMVASGL
1660 1670 1680 1690 1700
TPKELMLVQK FARKHHVTLT NLITEETTHV IMKTDPEFVC ERTLKYFLGI
1710 1720 1730 1740 1750
AGGKWVVSYF WVTQSIKEGK MLDEHDFEVR GDVVNGRNHQ GPKRARESRD
1760 1770 1780 1790 1800
KKIFKGLEIC CYGPFTNMPT DQLEWMVQLC GASVVKEPSS FTPDQGTHPV
1810 1820 1830 1840
VVVQPDAWTE DAGFHVIGQM CEAPVVTREW VLDSVALYQC QELDTYLVP
Length:1,849
Mass (Da):206,279
Last modified:June 1, 2003 - v1
Checksum:i66354C5D0BAFE8A8
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY077732 mRNA. Translation: AAL76094.1.
RefSeqiNP_848668.1. NM_178573.1.
UniGeneiBt.14026.

Genome annotation databases

GeneIDi353120.
KEGGibta:353120.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY077732 mRNA. Translation: AAL76094.1.
RefSeqiNP_848668.1. NM_178573.1.
UniGeneiBt.14026.

3D structure databases

ProteinModelPortaliQ864U1.
SMRiQ864U1. Positions 1-103, 1642-1849.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi160259. 2 interactions.
STRINGi9913.ENSBTAP00000011616.

Proteomic databases

PaxDbiQ864U1.
PRIDEiQ864U1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi353120.
KEGGibta:353120.

Organism-specific databases

CTDi672.

Phylogenomic databases

eggNOGiENOG410ITQ6. Eukaryota.
ENOG4111WR7. LUCA.
HOGENOMiHOG000230969.
HOVERGENiHBG050730.
InParanoidiQ864U1.
KOiK10605.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

NextBioi20812700.

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. "Bovine BRCA1 shows classic responses to genotoxic stress but low in vitro transcriptional activation activity."
    Krum S.A., Womack J.E., Lane T.F.
    Oncogene 22:6032-6044(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH RNA POLYMERASE II.

Entry informationi

Entry nameiBRCA1_BOVIN
AccessioniPrimary (citable) accession number: Q864U1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 23, 2004
Last sequence update: June 1, 2003
Last modified: May 11, 2016
This is version 99 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.