BRCA1 - Breast cancer type 1 susceptibility protein - human protein (Function)
 
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BRCA1 »  Breast cancer type 1 susceptibility protein   [ EC 6.3.2.- ]
 
Protein also known as:  RING finger protein 53.
Gene name:  BRCA1
Entry whose protein(s) existence is based on evidence at protein level
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1 241 8
GENE REF ISO

Function

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Overview 
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.  
16
  • UniProtKB
GO molecular function 
Androgen receptor bindingdefinition[GO:0050681]  
1
  • UniProtKB
Damaged DNA bindingdefinition[GO:0003684] silver  
1
  • Ortholog Compara
DNA bindingdefinition[GO:0003677]  
1
  • PINC
Enzyme bindingdefinition[GO:0019899]  
1
  • UniProtKB
Ligase activitydefinition[GO:0016874]  
1
  • UniProtKB KW
Protein bindingdefinition[GO:0005515]  
45
  • IntAct
  • UniProtKB
RNA bindingdefinition[GO:0003723]  
1
  • MGI
Transcription coactivator activitydefinition[GO:0003713]  
1
  • UniProtKB
Transcription regulatory region DNA bindingdefinition[GO:0044212]  
1
  • BHF-UCL
Tubulin bindingdefinition[GO:0015631]  
1
  • UniProtKB
Ubiquitin protein ligase bindingdefinition[GO:0031625]  
1
  • UniProtKB
Contributes to ubiquitin-protein transferase activitydefinition[GO:0004842]  
4
  • UniProtKB
  • BHF-UCL
Zinc ion bindingdefinition[GO:0008270] silver  
1
  • InterPro 2 GO
GO biological process 
Androgen receptor signaling pathwaydefinition[GO:0030521]  
1
  • UniProtKB
Apoptotic processdefinition[GO:0006915]  
1
  • UniProtKB
Cellular response to DNA damage stimulusdefinition[GO:0006974]  
1
  • PINC
Cellular response to indole-3-methanoldefinition[GO:0071681]  
1
  • UniProtKB
Cellular response to tumor necrosis factordefinition[GO:0071356]  
1
  • BHF-UCL
Centrosome cycledefinition[GO:0007098] silver  
1
  • Ortholog Compara
Chordate embryonic developmentdefinition[GO:0043009]  
1
  • RefGenome
Chromosome segregationdefinition[GO:0007059]  
1
  • UniProtKB
DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediatordefinition[GO:0006978]  
1
  • UniProtKB
DNA replicationdefinition[GO:0006260] silver  
1
  • Ortholog Compara
Dosage compensation by inactivation of X chromosomedefinition[GO:0009048]  
1
  • RefGenome
Double-strand break repairdefinition[GO:0006302]  
4
  • CACAO
  • UniProtKB
Double-strand break repair via homologous recombinationdefinition[GO:0000724]  
1
  • HGNC
Fatty acid biosynthetic processdefinition[GO:0006633]  
1
  • UniProtKB KW
G2 DNA damage checkpointdefinition[GO:0031572]  
3
  • UniProtKB
Intrinsic apoptotic signaling pathway in response to DNA damagedefinition[GO:0008630]  
1
  • MGI
Negative regulation of centriole replicationdefinition[GO:0046600]  
1
  • UniProtKB
Negative regulation of extrinsic apoptotic signaling pathway via death domain receptorsdefinition[GO:1902042]  
1
  • BHF-UCL
Negative regulation of fatty acid biosynthetic processdefinition[GO:0045717]  
1
  • UniProtKB
Negative regulation of histone acetylationdefinition[GO:0035067]  
1
  • RefGenome
Negative regulation of histone H3-K4 methylationdefinition[GO:0051572] silver  
1
  • Ortholog Compara
Negative regulation of histone H3-K9 methylationdefinition[GO:0051573]  
1
  • BHF-UCL
Negative regulation of reactive oxygen species metabolic processdefinition[GO:2000378]  
1
  • BHF-UCL
Negative regulation of transcription, DNA-templateddefinition[GO:0045892]  
1
  • UniProtKB
Positive regulation of angiogenesisdefinition[GO:0045766]  
1
  • BHF-UCL
Positive regulation of cell cycle arrestdefinition[GO:0071158]  
1
  • BHF-UCL
Positive regulation of DNA repairdefinition[GO:0045739]  
3
  • UniProtKB
Positive regulation of gene expressiondefinition[GO:0010628]  
1
  • BHF-UCL
Positive regulation of histone acetylationdefinition[GO:0035066]  
1
  • BHF-UCL
Positive regulation of histone H3-K4 methylationdefinition[GO:0051571]  
1
  • BHF-UCL
Positive regulation of histone H3-K9 acetylationdefinition[GO:2000617]  
1
  • BHF-UCL
Positive regulation of histone H3-K9 methylationdefinition[GO:0051574] silver  
1
  • Ortholog Compara
Positive regulation of histone H4-K16 acetylationdefinition[GO:2000620]  
1
  • BHF-UCL
Positive regulation of histone H4-K20 methylationdefinition[GO:0070512]  
1
  • BHF-UCL
Positive regulation of protein ubiquitinationdefinition[GO:0031398]  
1
  • UniProtKB
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]  
2
  • BHF-UCL
  • UniProtKB
Positive regulation of transcription, DNA-templateddefinition[GO:0045893]  
2
  • UniProtKB
Positive regulation of vascular endothelial growth factor productiondefinition[GO:0010575]  
1
  • BHF-UCL
Postreplication repairdefinition[GO:0006301]  
1
  • HGNC
Protein autoubiquitinationdefinition[GO:0051865]  
2
  • UniProtKB
Protein K6-linked ubiquitinationdefinition[GO:0085020]  
2
  • UniProtKB
Protein ubiquitinationdefinition[GO:0016567]  
1
  • HGNC
Regulation of apoptotic processdefinition[GO:0042981]  
1
  • UniProtKB
Regulation of cell proliferationdefinition[GO:0042127]  
1
  • UniProtKB
Regulation of DNA methylationdefinition[GO:0044030] silver  
1
  • Ortholog Compara
Regulation of gene expression by genetic imprintingdefinition[GO:0006349] silver  
1
  • Ortholog Compara
Regulation of transcription from RNA polymerase II promoterdefinition[GO:0006357]  
1
  • PINC
Regulation of transcription from RNA polymerase III promoterdefinition[GO:0006359]  
1
  • UniProtKB
Response to estrogendefinition[GO:0043627]  
1
  • UniProtKB
Response to ionizing radiationdefinition[GO:0010212]  
3
  • UniProtKB
Enzymatic activity 
It is regulated in the following manner
The E3 ubiquitin-protein ligase activity is inhibited by phosphorylation by AURKA. Activity is increased by phosphatase treatment.  
2
  • UniProtKB
 
More information is available from:
Pathways 
This protein is involved in the following pathway
Protein modification; protein ubiquitination  
1
  • UniProtKB
According to KEGG, this protein belongs to the following pathways:
Fanconi anemia pathway  hsa03460+672  
Ubiquitin mediated proteolysis  hsa04120+672  
According to Reactome, this protein belongs to the following pathways:
ATM mediated phosphorylation of repair proteins  REACT_1924  
Fanconi Anemia pathway  REACT_18410  
Meiotic recombination  REACT_27271  
Meiotic synapsis  REACT_75792  
Recruitment of repair and signaling proteins to double-strand breaks  REACT_97  
 

Keywords

Biological process 
Cell cycle  definition   [KW-0131]
DNA damage  definition   [KW-0227]
DNA recombination  definition   [KW-0233]
DNA repair  definition   [KW-0234]
Fatty acid biosynthesis  definition   [KW-0275]
Fatty acid metabolism  definition   [KW-0276]
Lipid biosynthesis  definition   [KW-0444]
Lipid metabolism  definition   [KW-0443]
Ubl conjugation pathway  definition   [KW-0833]
Molecular function 
Ligase  definition   [KW-0436]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: BRCA1
GenomeRNAi: 672
PRO: PR:P38398