InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: BRCC3

Summary

InnateDB Protein

IDBP-92386.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

BRCC3

Protein Name

BRCA1/BRCA2-containing complex, subunit 3

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000328641

InnateDB Gene

IDBG-92384 (BRCC3)

Protein Structure

UniProt Annotation

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, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). In the BRCA1-A complex, it specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX, antagonizing the RNF8-dependent ubiquitination at double- strand breaks (DSBs). Catalytic subunit of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates. Mediates the specific 'Lys-63'- specific deubiquitination associated with the COP9 signalosome complex (CSN), via the interaction of the BRISC complex with the CSN complex. {ECO:0000269PubMed:14636569, ECO:0000269PubMed:16707425, ECO:0000269PubMed:17525341, ECO:0000269PubMed:19202061, ECO:0000269PubMed:19214193, ECO:0000269PubMed:19261746, ECO:0000269PubMed:19261748, ECO:0000269PubMed:19261749}.

Subcellular Localization

Nucleus {ECO:0000269PubMed:18077395, ECO:0000269PubMed:19202061, ECO:0000269PubMed:19261748, ECO:0000269PubMed:19261749}. Note=Localizes at sites of DNA damage at double-strand breaks (DSBs).

Disease Associations

Note=A chromosomal aberration involving BRCC3 is a cause of pro-lymphocytic T-cell leukemia (T-PLL). Translocation t(X;14)(q28;q11) with TCRA.

Tissue Specificity

Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Aberrantly expressed in the vast majority of breast tumors. {ECO:0000269PubMed:16707425}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 66 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	66 [view]
Protein-Protein	66 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004221	ubiquitin thiolesterase activity
GO:0004843	ubiquitin-specific protease activity
GO:0005515	protein binding
GO:0008237	metallopeptidase activity
GO:0030234	enzyme regulator activity
GO:0031593	polyubiquitin binding
GO:0046872	metal ion binding

Biological Process

GO:0006302	double-strand break repair
GO:0006508	proteolysis
GO:0010165	response to X-ray
GO:0010212	response to ionizing radiation
GO:0031572	G2 DNA damage checkpoint
GO:0045739	positive regulation of DNA repair
GO:0050790	regulation of catalytic activity
GO:0070536	protein K63-linked deubiquitination
GO:0070537	histone H2A K63-linked deubiquitination