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Lys-63-specific deubiquitinase BRCC36; BRCA1-A complex subunit BRCC36; BRISC complex subunit BRCC36; BRCA1/BRCA2-containing complex subunit 3; BRCA1/BRCA2-containing complex subunit 36 (BRCC3, BRCC36, C61A, CXorf53)
Function:
- metalloprotease that specifically cleaves Lys-63-linked polyubiquitin chains
- does not have activity toward Lys-48-linked polyubiquitin chains
- component of the BRCA1-A complex
- in the BRCA1-A complex
a) specifically removes Lys-63-linked ubiquitin on histones H2A & H2AX, antagonizing the RNF8-dependent u biquitination at double-strand breaks
b) interacts directly with FAM175A/Abraxas & BRE/BRCC45
- catalytic subunit of the BRISC complex
- mediates Lys-63-specific deubiquitination associated with the COP9 signalosome complex, via the interaction of the BRISC complex with the COP9 signalosome complex
- component of the BRCC complex
- interacts with BRCA1
- binds polyubiquitin
Structure:
- belongs to the peptidase M67A family, BRCC36 subfamily
- contains 1 MPN (JAB/Mov34) domain
- has sequence homology to poh1/pad1 subunit of 26S proteasome & subunit 5 (jab1) of COP9 signalosome
Compartment:
- nucleus
- localizes at sites of DNA damage at double-strand breaks
Alternative splicing: named isoforms=5
Expression:
- heart, brain, placenta, lung, liver, skeletal muscle, kidney & pancreas
Pathology:
- aberrantly expressed in the vast majority of breast cancers
- chromosomal translocation t(X;14)(q28;q11) involving BRCC3 with TCRA is a cause of pro-lymphocytic T-cell leukemia
General
metalloprotease
nuclear protein
Properties
SIZE: entity length = 316 aa
MW = 36 kD
COMPARTMENT: cell nucleus
MOTIF: acetylation site
SITE: N-TERMINUS
EFFECTOR-BOUND: acetyl
peptide motif {122-135}
MOTIF: Zn+2-binding site
SITE: 122-122
Zn+2-binding site
SITE: 124-124
Zn+2-binding site
SITE: 135-135
Database Correlations
OMIM 300617
UniProt P46736
Pfam PF01398
Entrez Gene 79184
Kegg hsa:79184
ENZYME 3.1.2.15
References
- UniProt :accession P46736
- Dong Y, Hakimi MA, Chen X, Kumaraswamy E, Cooch NS,
Godwin AK, Shiekhattar R.
Regulation of BRCC, a holoenzyme complex containing BRCA1 and
BRCA2, by a signalosome-like subunit and its role in DNA repair.
Mol Cell. 2003 Nov;12(5):1087-99.
PMID: 14636569
Component-of
BRCA1-A complex