BRCC3 Antibody – Mouse Monoclonal

This gene encodes a subunit of the BRCA1-BRCA2-containing complex (BRCC), which is an E3 ubiquitin ligase. This complex plays a role in the DNA damage response, where it is responsible for the stable accumulation of BRCA1 at DNA break sites. The component encoded by this gene can specifically cleave Lys 63-linked polyubiquitin chains, and it regulates the abundance of these polyubiquitin chains in chromatin. The loss of this gene results in abnormal angiogenesis and is associated with syndromic moyamoya, a cerebrovascular angiopathy. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 5. [provided by RefSeq, Jun 2011]

BRCC3: Metalloprotease that specifically cleaves 'Lys-63'- linked polyubiquitin chains. Does not have activity toward 'Lys- 48'-linked polyubiquitin chains. Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). In the BRCA1-A complex, it specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX, antagonizing the RNF8-dependent ubiquitination at double- strand breaks (DSBs). Catalytic subunit of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates. Mediates the specific 'Lys-63'- specific deubiquitination associated with the COP9 signalosome complex (CSN), via the interaction of the BRISC complex with the CSN complex. A chromosomal aberration involving BRCC3 is a cause of pro-lymphocytic T-cell leukemia (T-PLL). Translocation t(X;14)(q28;q11) with TCRA. Belongs to the peptidase M67A family. BRCC36 subfamily. 5 isoforms of the human protein are produced by alternative splicing.

Protein type: Oncoprotein; Ubiquitin conjugating system; Ubiquitin-specific protease; EC 3.4.19.-

Chromosomal Location of Human Ortholog: Xq28

Cellular Component: nucleoplasm; nuclear ubiquitin ligase complex; nucleus; ubiquitin ligase complex

Molecular Function: protein binding; metallopeptidase activity; metal ion binding; ubiquitin-specific protease activity; polyubiquitin binding; enzyme regulator activity

Biological Process: positive regulation of DNA repair; regulation of catalytic activity; double-strand break repair; response to ionizing radiation; G2/M transition DNA damage checkpoint; proteolysis; response to X-ray