BRCC3

BRCC3 Full Name

BRCA1/BRCA2-containing complex, subunit 3

BRCC3 Introduction

BRCC3 (BRCA1/BRCA2-containing complex, subunit 3) is a deubiquitinating enzyme that belongs to the JAMM/MPN+ metalloprotease family and acts as a K63-specific deubiquitinase. It forms part of the BRCA1–BRCA2-containing complex (BRCC) and the BRISC complex, which differ in their association with BRCA1 and confer distinct cellular functions. BRCC3 maps to chromosome Xq28 and is widely expressed, with particularly high levels in testis, brain, and several hormone-responsive tissues.

Figure 1. The structure of BRCC3.

K63-Linked Deubiquitination in DNA Repair and Signaling
BRCC3 removes K63-linked ubiquitin chains from substrates such as H2A, H2AX, and the BRCA1 protein itself, modulating the efficiency of homologous recombination repair. Through the BRISC complex, BRCC3 deubiquitinates NLRP3 and other immune signaling components, restraining inflammasome activation and shaping the innate immune response. The BRCC3 catalytic activity depends on a JAMM-domain zinc-coordinating motif that is conserved across the MPN+ family, and structural studies have shown that BRCC3 integrates into its complexes through an N-terminal helical region that contacts the scaffold subunits ABRAXAS or ABRO1.

DNA Damage Response, Inflammation, and Cancer
BRCC3 hypomorphic variants have been associated with reduced DNA-repair capacity and with increased sensitivity to DNA-damaging agents in patient-derived cells, while complete loss is embryonic lethal in mice. In breast and ovarian cancers, BRCC3 expression correlates with homologous recombination proficiency and with resistance to PARP inhibitors, supporting its role in BRCA1/2-mediated repair. BRCC3 is also implicated in NLRP3 inflammasome regulation, with BRCC3-deficient macrophages showing hyperactive inflammasome signaling, suggesting that BRCC3 modulation could influence inflammatory and autoimmune disease.

Alternate Names for BRCC3

BRCC3; BRCA1/BRCA2-containing complex, subunit 3; C6.1A; BRCC36; CXorf53; lys-63-specific deubiquitinase BRCC36; BRISC complex subunit BRCC36; BRCA1-A complex subunit BRCC36; BRCA1/BRCA2-containing complex subunit 36;