BRCC3
Description
The BRCC3 (BRCA1/BRCA2-containing complex subunit 3) is a protein-coding gene located on chromosome X.
BRCC3 is a gene that encodes a subunit of the BRCA1-BRCA2-containing complex (BRCC), which is an E3 ubiquitin ligase. This protein is also involved in the cellular response to ionizing radiation and progression through the G2/M checkpoint. BRCC3 is a deubiquitinating enzyme, specifically removing 'Lys-63'-linked ubiquitin chains from various substrates. It functions in DNA repair, interferon signaling, and inflammasome assembly. BRCC3 interacts with several other proteins, including BRCA1, BRCA2, BARD1, ABRAXAS1, ABRAXAS2, NUMA1, HDAC1, and PWWP2B.
BRCC3 is a metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains but does not cleave 'Lys-48'-linked polyubiquitin chains. It is a component of the BRCA1-A complex, which recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions, targeting the BRCA1-BARD1 heterodimer to DNA damage sites at double-strand breaks (DSBs). BRCC3 removes 'Lys-63'-linked ubiquitin from histones H2A and H2AX within the BRCA1-A complex, counteracting RNF8-dependent ubiquitination at DSBs. As the catalytic subunit of the BRISC complex, a multiprotein complex, BRCC3 specifically cleaves 'Lys-63'-linked ubiquitin in various substrates. It mediates 'Lys-63'-specific deubiquitination associated with the COP9 signalosome complex (CSN) through the interaction of the BRISC complex with the CSN complex. The BRISC complex is essential for normal mitotic spindle assembly and microtubule attachment to kinetochores by deubiquitinating NUMA1. BRCC3 plays a role in interferon signaling by deubiquitinating the interferon receptor IFNAR1, enhancing IFNAR1 activity by increasing its stability and cell surface expression. It regulates the NLRP3 inflammasome by mediating deubiquitination of NLRP3, leading to NLRP3 inflammasome assembly. BRCC3 downregulates the response to bacterial lipopolysaccharide (LPS) through its role in IFNAR1 deubiquitination. It deubiquitinates HDAC1 and PWWP2B, stabilizing these proteins. BRCC3 is a component of the ARISC complex, composed of UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2, and BABAM1/NBA1. It is also a component of the BRCA1-A complex, interacting directly with ABRAXAS1 and babam2. BRCC3 is a component of the BRISC complex, interacting directly with ABRAXAS2. It is found in a complex with ABRAXAS2 and NUMA1. The BRISC complex interacts with the CSN complex. BRCC3 is a component of the BRCA1/BRCA2-containing complex (BRCC), which includes BRCA1, BRCA2, BARD1, BABAM2, and RAD51. The BRCC complex is a ubiquitin E3 ligase that enhances cellular survival following DNA damage. BRCC3 interacts with BRCA1, binds polyubiquitin, and interacts with PWWP2B and HDAC1, with this interaction being enhanced in the presence of PWWP2B.
BRCC3 is also known as BRCC36, C6.1A, CXorf53.
