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
  • specifically removes Lys-63-linked ubiquitin on histones H2A & H2AX, antagonizing the RNF8-dependent u biquitination at double-strand breaks
  • 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

More general terms

• metalloprotease
• nuclear protein

Component of

• BRISC complex
• BRCC holoenzyme complex
• BRCA1-A complex

Database

• UniProt: http://www.uniprot.org/uniprot/P46736.html
• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=79184
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:79184
• OMIM: https://mirror.omim.org/entry/300617