Tchem BRCA1 Breast cancer type 1 susceptibility protein

Protein Summary

Description

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 (PubMed:20160719). This gene encodes a nuclear phosphoprotein that plays a role in maintaining genomic stability, and it also acts as a tumor suppressor. The encoded protein combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC). This gene product associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. This protein thus plays a role in transcription, DNA repair of double-stranded breaks, and recombination. Mutations in this gene are responsible for approximately 40% of inherited breast cancers and more than 80% of inherited breast and ovarian cancers. Alternative splicing plays a role in modulating the subcellular localization and physiological function of this gene. Many alternatively spliced transcript variants, some of which are disease-associated mutations, have been described for this gene, but the full-length natures of only some of these variants has been described. A related pseudogene, which is also located on chromosome 17, has been identified. [provided by RefSeq, May 2009]

Uniprot Accession IDs

• P38398
• E9PFZ0
• O15129
• Q1RMC1
• Q3LRJ0
• Q3LRJ6
• Q6IN79
• Q7KYU9

Gene Name

• BRCA1

Ensembl ID

• ENST00000352993
• ENSP00000312236
• ENSG00000012048
• ENST00000357654
• ENSP00000350283
• ENST00000461221
• ENSP00000418548
• ENST00000461798
• ENSP00000417988
• ENST00000468300
• ENSP00000417148
• ENST00000471181
• ENSP00000418960
• ENST00000491747
• ENSP00000420705
• ENST00000493795
• ENSP00000418775

Symbol

• RNF53
• IRIS
• PSCP
• BRCAI
• BRCC1
• FANCS
• PNCA4
• RNF53
• BROVCA1
• PPP1R53

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
hub protein	1
co-expressed gene	0.99
kinase	0.99
molecular function	0.98

Protein Classes

PANTHER Classes

Protein / ... / Ubiquitin-protein Ligase / Breast Cancer Type 1 Susceptibility Protein

DTO Classes

Protein / Enzyme / Ligase / Ubiquitin-protein Ligase / Breast Cancer Type 1 Susceptibility Protein

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 11366.24   (req: < 5)

Gene RIFs: 2569   (req: <= 3)

Antibodies: 2084   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 11366.24   (req: >= 5)

Gene RIFs: 2569   (req: > 3)

Antibodies: 2084   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 69

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 4

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0