Homo sapiens Protein: BRCA1
Summary
InnateDB Protein IDBP-52174.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol BRCA1
Protein Name breast cancer 1, early onset
Synonyms BRCAI; BRCC1; BROVCA1; IRIS; PNCA4; PPP1R53; PSCP; RNF53;
Species Homo sapiens
Ensembl Protein ENSP00000350283
InnateDB Gene IDBG-52172 (BRCA1)
Protein Structure
UniProt Annotation
Function 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. {ECO:0000269PubMed:10500182, ECO:0000269PubMed:10724175, ECO:0000269PubMed:11836499, ECO:0000269PubMed:12887909, ECO:0000269PubMed:12890688, ECO:0000269PubMed:14976165, ECO:0000269PubMed:14990569, ECO:0000269PubMed:16326698, ECO:0000269PubMed:16818604, ECO:0000269PubMed:17525340, ECO:0000269PubMed:18056443, ECO:0000269PubMed:19261748, ECO:0000269PubMed:19369211, ECO:0000269PubMed:20351172, ECO:0000269PubMed:20364141}.
Subcellular Localization Nucleus {ECO:0000269PubMed:15133502, ECO:0000269PubMed:17525340, ECO:0000269PubMed:21144835, ECO:0000269PubMed:9528852}. Chromosome {ECO:0000250}. Note=Localizes at sites of DNA damage at double-strand breaks (DSBs); recruitment to DNA damage sites is mediated by the BRCA1-A complex.Isoform 3: Cytoplasm.Isoform 5: Cytoplasm {ECO:0000269PubMed:8972225}.
Disease Associations Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269PubMed:10323242, ECO:0000269PubMed:12442275, ECO:0000269PubMed:12938098, ECO:0000269PubMed:14722926, ECO:0000269PubMed:18285836, ECO:0000269PubMed:7545954, ECO:0000269PubMed:7894491, ECO:0000269PubMed:7894493, ECO:0000269PubMed:7939630, ECO:0000269PubMed:8554067, ECO:0000269PubMed:8723683, ECO:0000269PubMed:8776600, ECO:0000269PubMed:9482581, ECO:0000269PubMed:9609997, ECO:0000269PubMed:9760198}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Mutations in BRCA1 are thought to be responsible for 45% of inherited breast cancer. Moreover, BRCA1 carriers have a 4-fold increased risk of colon cancer, whereas male carriers face a 3- fold increased risk of prostate cancer. Cells lacking BRCA1 show defects in DNA repair by homologous recombination.Breast-ovarian cancer, familial, 1 (BROVCA1) [MIM:604370]: A condition associated with familial predisposition to cancer of the breast and ovaries. Characteristic features in affected families are an early age of onset of breast cancer (often before age 50), increased chance of bilateral cancers (cancer that develop in both breasts, or both ovaries, independently), frequent occurrence of breast cancer among men, increased incidence of tumors of other specific organs, such as the prostate. {ECO:0000269PubMed:12938098, ECO:0000269PubMed:14722926, ECO:0000269PubMed:8968716}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Mutations in BRCA1 are thought to be responsible for more than 80% of inherited breast-ovarian cancer.Ovarian cancer (OC) [MIM:167000]: The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. {ECO:0000269PubMed:10196379, ECO:0000269PubMed:10486320, ECO:0000269PubMed:14746861}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Pancreatic cancer 4 (PNCA4) [MIM:614320]: A malignant neoplasm of the pancreas. Tumors can arise from both the exocrine and endocrine portions of the pancreas, but 95% of them develop from the exocrine portion, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue. {ECO:0000269PubMed:18762988}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
Tissue Specificity Isoform 1 and isoform 3 are widely expressed. Isoform 3 is reduced or absent in several breast and ovarian cancer cell lines.
Comments
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 625 experimentally validated interaction(s) in this database.
They are also associated with 17 interaction(s) predicted by orthology.
Experimentally validated
Total 625 [view]
Protein-Protein 603 [view]
Protein-DNA 15 [view]
Protein-RNA 0
DNA-DNA 7 [view]
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 17 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0003677 DNA binding
GO:0003713 transcription coactivator activity
GO:0003723 RNA binding
GO:0004842 ubiquitin-protein transferase activity
GO:0005515 protein binding
GO:0008270 zinc ion binding
GO:0015631 tubulin binding
GO:0016874 ligase activity
GO:0019899 enzyme binding
GO:0031625 ubiquitin protein ligase binding
GO:0044212 transcription regulatory region DNA binding
GO:0046872 metal ion binding
GO:0050681 androgen receptor binding
Biological Process
GO:0000724 double-strand break repair via homologous recombination
GO:0006281 DNA repair
GO:0006301 postreplication repair
GO:0006302 double-strand break repair
GO:0006357 regulation of transcription from RNA polymerase II promoter
GO:0006359 regulation of transcription from RNA polymerase III promoter
GO:0006633 fatty acid biosynthetic process
GO:0006915 apoptotic process
GO:0006974 cellular response to DNA damage stimulus
GO:0006978 DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator
GO:0007059 chromosome segregation
GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage
GO:0010212 response to ionizing radiation
GO:0016567 protein ubiquitination
GO:0030521 androgen receptor signaling pathway
GO:0031398 positive regulation of protein ubiquitination
GO:0031572 G2 DNA damage checkpoint
GO:0034446 substrate adhesion-dependent cell spreading
GO:0035066 positive regulation of histone acetylation
GO:0042127 regulation of cell proliferation
GO:0042981 regulation of apoptotic process
GO:0043627 response to estrogen
GO:0045717 negative regulation of fatty acid biosynthetic process
GO:0045739 positive regulation of DNA repair
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0046600 negative regulation of centriole replication
GO:0051571 positive regulation of histone H3-K4 methylation
GO:0051573 negative regulation of histone H3-K9 methylation
GO:0051865 protein autoubiquitination
GO:0070512 positive regulation of histone H4-K20 methylation
GO:0071158 positive regulation of cell cycle arrest
GO:0071681 cellular response to indole-3-methanol
GO:0085020 protein K6-linked ubiquitination
GO:2000145 regulation of cell motility
GO:2000617 positive regulation of histone H3-K9 acetylation
GO:2000620 positive regulation of histone H4-K16 acetylation
Cellular Component
GO:0000151 ubiquitin ligase complex
GO:0001726 ruffle
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005694 chromosome
GO:0005737 cytoplasm
GO:0005886 plasma membrane
GO:0005925 focal adhesion
GO:0008274 gamma-tubulin ring complex
GO:0030529 ribonucleoprotein complex
GO:0031436 BRCA1-BARD1 complex
GO:0031941 filamentous actin
GO:0043234 protein complex
GO:0070531 BRCA1-A complex
Protein Structure and Domains
PDB ID
InterPro IPR001357 BRCT domain
IPR001841 Zinc finger, RING-type
IPR011364 Breast cancer type 1 susceptibility protein (BRCA1)
IPR018957 Zinc finger, C3HC4 RING-type
PFAM PF00533
PF12738
PF13639
PF14634
PF00097
PRINTS PR00493
PIRSF PIRSF001734
SMART SM00292
SM00184
TIGRFAMs
Post-translational Modifications
Modification
Cross-References
SwissProt P38398
PhosphoSite PhosphoSite-P38398
TrEMBL Q9UE29
UniProt Splice Variant
Entrez Gene 672
UniGene Hs.622171
RefSeq NP_009225
HUGO HGNC:1100
OMIM 113705
CCDS CCDS11453
HPRD 00218
IMGT
EMBL AB621825 AC060780 AC135721 AF005068 AF284812 AF507076 AF507078 AY093485 AY093486 AY093487 AY093489 AY093490 AY093493 AY273801 BC072418 BC106745 DQ116737 DQ145822 DQ145825 DQ145826 DQ190450 DQ190451 DQ190452 DQ190453 DQ190454 DQ190455 DQ190456 DQ190457 DQ299305 DQ299306 DQ299307 DQ299308 DQ299309 DQ299310 DQ299311 DQ299312 DQ299313 DQ299314 DQ299315 DQ299321 DQ299322 DQ299323 DQ299324 DQ299325 DQ299326 DQ299327 DQ299328 DQ299329 DQ299330 DQ299331 DQ478408 FJ940752 HE600032 HE600033 HE600034 HE600035 HE600036 HE600037 HE600038 JX480460 JX480462 JX480466 L78833 U14680 U37574 U61268 U64805 U68041 Y08757
GenPept AAA73985 AAB08105 AAB40910 AAB61673 AAC00049 AAC37594 AAC50330 AAF97939 AAH72418 AAI06746 AAM18219 AAM18220 AAM18221 AAM18222 AAM18223 AAM18226 AAN61423 AAN61425 AAP12647 AAZ16492 AAZ79406 AAZ79409 AAZ79410 ABA29208 ABA29211 ABA29214 ABA29217 ABA29220 ABA29223 ABA29226 ABA29229 ABB87053 ABB87054 ABB87055 ABB87056 ABB87057 ABB87058 ABB87059 ABB87060 ABB87061 ABB87062 ABB87063 ABB87069 ABB87070 ABB87071 ABB87072 ABB87073 ABB87074 ABB87075 ABB87076 ABB87077 ABB87078 ABB87079 ABF14462 ACR33809 AFU88802 AFU88804 AFU88808 BAK64160 CAA70003 CCD57768 CCD57769 CCD57770 CCD57771 CCD57772 CCD57773 CCD57774