InterPro domain: IPR033860

BRCC36 (BRCA1-A complex subunit BRCC36; BRCA1/BRCA2-containing complex subunit 36; BRCA1/BRCA2-containing complex subunit 3; BRCC3; BRISC complex subunit BRCC36; BRCC36 isopeptidase complex; Lys-63-specific deubiquitinase BRCC36; MEROPS identifier M67.004) and BRCC36-like proteins are JAMM/MPN+ deubiquitinases (DUBs), possibly with Zn ²⁺ -dependent ubiquitin isopeptidase activity. BRCC36 specifically cleaves Lys 63-linked polyubiquitin chains [ 1 ].

BRCC36 is part of the BRCA1/BRCA2/BARD1-containing nuclear complex that displays an E3 ubiquitin ligase activity [ 2 ]. It is targeted to DNA damage foci after irradiation; RAP80 recruits the Abraxas-BRCC36-BRCA1-BARD1 complex to DNA double strand breaks (DSBs) for DNA repair through specific recognition of Lys 63-linked polyubiquitinated proteins by its tandem ubiquitin-interacting motifs [ 3 , 4 ]. BRCC36 exists in at least two distinct complexes, the RAP80 complex (also called the BRCA1-A complex) and the BRCC36 isopeptidase complex (BRISC) [ 5 , 5 , 6 ].

1. The Lys63-specific deubiquitinating enzyme BRCC36 is regulated by two scaffold proteins localizing in different subcellular compartments. J. Biol. Chem. 285, 30982-8
2. Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair. Mol. Cell 12, 1087-99
3. The Rap80-BRCC36 de-ubiquitinating enzyme complex antagonizes RNF8-Ubc13-dependent ubiquitination events at DNA double strand breaks. Proc. Natl. Acad. Sci. U.S.A. 106, 3166-71
4. RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage sites. Science 316, 1198-202
5. NBA1/MERIT40 and BRE interaction is required for the integrity of two distinct deubiquitinating enzyme BRCC36-containing complexes. J. Biol. Chem. 286, 11734-45
6. The deubiquitinating enzyme complex BRISC is required for proper mitotic spindle assembly in mammalian cells. J. Cell Biol. 210, 209-24