InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Otub1

Summary

InnateDB Protein

IDBP-138321.6

Last Modified

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

Gene Symbol

Otub1

Protein Name

OTU domain, ubiquitin aldehyde binding 1

Synonyms

AI850305;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000025679

InnateDB Gene

IDBG-138319 (Otub1)

Protein Structure

UniProt Annotation

Function

Hydrolase that can specifically remove compared to 'Lys- 48'-linked conjugated ubiquitin from proteins and plays an important regulatory role at the level of protein turnover by preventing degradation. Regulator of T-cell anergy, a phenomenon that occurs when T-cells are rendered unresponsive to antigen rechallenge and no longer respond to their cognate antigen. Acts via its interaction with RNF128/GRAIL. Surprisingly, it regulates RNF128-mediated ubiquitination, but does not deubiquitinate polyubiquitinated RNF128. Deubiquitinates estrogen receptor alpha (ESR1). Mediates deubiquitination of 'Lys-48'-linked polyubiquitin chains, but not 'Lys-63'-linked polyubiquitin chains. Not able to cleave di-ubiquitin. Also capable of removing NEDD8 from NEDD8 conjugates, but with a much lower preference compared to 'Lys-48'- linked ubiquitin. {ECO:0000269PubMed:14661020}.Plays a key non-catalytic role in DNA repair regulation by inhibiting activity of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites. Inhibits RNF168 independently of ubiquitin thioesterase activity by binding and inhibiting UBE2N/UBC13, the E2 partner of RNF168, thereby limiting spreading of 'Lys-63'- linked histone H2A and H2AX marks. Inhibition occurs by binding to free ubiquitin: free ubiquitin acts as an allosteric regulator that increases affinity for UBE2N/UBC13 and disrupts interaction with UBE2V1. The OTUB1-UBE2N/UBC13-free ubiquitin complex adopts a configuration that mimics a cleaved 'Lys48'-linked di-ubiquitin chain (By similarity). {ECO:0000250}.

Subcellular Localization

Cytoplasm {ECO:0000250}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 6 experimentally validated interaction(s) in this database.
They are also associated with 61 interaction(s) predicted by orthology.

Experimentally validated
Total	6 [view]
Protein-Protein	6 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	61 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004843	ubiquitin-specific protease activity
GO:0005515	protein binding
GO:0008242	omega peptidase activity
GO:0019784	NEDD8-specific protease activity
GO:0031625	ubiquitin protein ligase binding
GO:0043130	ubiquitin binding

Biological Process

GO:0002376	immune system process
GO:0006281	DNA repair
GO:0006508	proteolysis
GO:0006974	cellular response to DNA damage stimulus
GO:0019538	protein metabolic process
GO:0071108	protein K48-linked deubiquitination
GO:1901315	negative regulation of histone H2A K63-linked ubiquitination
GO:2000780	negative regulation of double-strand break repair