BRCC36 Protein, Human (His-SUMO)

BRCC36, identified as a metalloprotease, exhibits specificity in cleaving 'Lys-63'-linked polyubiquitin chains while displaying no activity toward 'Lys-48'-linked polyubiquitin chains. As a crucial component of the BRCA1-A complex, BRCC36 participates in DNA damage response by recognizing 'Lys-63'-linked ubiquitinated histones H2A and H2AX at sites of double-strand breaks. Within this complex, BRCC36 selectively removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX, opposing the RNF8-dependent ubiquitination at double-strand breaks. Additionally, BRCC36 serves as the catalytic subunit of the BRISC complex, another multiprotein assembly dedicated to cleaving 'Lys-63'-linked ubiquitin in various substrates. The BRISC complex's involvement in mitotic spindle assembly and microtubule attachment to kinetochores, mediated by the deubiquitination of NUMA1, underscores its regulatory role in cell division. BRCC36 also contributes to interferon signaling through deubiquitination of the interferon receptor IFNAR1, enhancing its stability and cell surface expression. Furthermore, BRCC36 plays a role in regulating the NLRP3 inflammasome by mediating deubiquitination of NLRP3, leading to inflammasome assembly, and down-regulates the response to bacterial lipopolysaccharide by participating in IFNAR1 deubiquitination. In its repertoire, BRCC36 deubiquitinates HDAC1 and PWWP2B, contributing to their stabilization.