Recombinant Mouse Lys-63-specific deubiquitinase BRCC36 (Brcc3)

Function

Metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains (PubMed:23246432, PubMed:34180153). Does not have activity toward 'Lys-48'-linked polyubiquitin chains (By similarity). 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) (By similarity). 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) (By similarity). Catalytic subunit of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates (By similarity). 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 (By similarity). The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1 (By similarity). Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activity by enhancing its stability and cell surface expression (By similarity). Acts as a regulator of the NLRP3 inflammasome by mediating deubiquitination of NLRP3, leading to NLRP3 inflammasome assembly (PubMed:23246432, PubMed:28943315). Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (By similarity). Deubiquitinates HDAC1 and PWWP2B leading to their stabilization (PubMed:34180153)

Subcellular Location

Nucleus; Cytoplasm; Cytoplasm, cytoskeleton, spindle pole

Subunit

Component of the ARISC complex, at least composed of UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Component of the BRCA1-A complex, at least composed of BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. In the BRCA1-A complex, interacts directly with ABRAXAS1 and BABAM2. Component of the BRISC complex, at least composed of ABRAXAS2, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Identified in a complex with SHMT2 and the other subunits of the BRISC complex. In the BRISC complex, interacts directly with ABRAXAS2. Identified in a complex with ABRAXAS2 and NUMA1. The BRISC complex interacts with the CSN complex. Component of the BRCA1/BRCA2 containing complex (BRCC), which also contains BRCA1, BRCA2, BARD1, BABAM2 and RAD51. BRCC is a ubiquitin E3 ligase complex that enhances cellular survival following DNA damage. Interacts with BRCA1. Binds polyubiquitin (By similarity). Interacts with PWWP2B (PubMed:34180153). Interacts with HDAC1; this interaction is enhanced in the presence of PWWP2B (PubMed:34180153)

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