InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: OTUB1

Summary

InnateDB Protein

IDBP-377022.5

Last Modified

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

Gene Symbol

OTUB1

Protein Name

OTU domain, ubiquitin aldehyde binding 1

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000402551

InnateDB Gene

IDBG-52992 (OTUB1)

Protein Structure

UniProt Annotation

Function

Hydrolase that can specifically remove '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, a crucial inductor of CD4 T-cell anergy. Isoform 1 destabilizes RNF128, leading to prevent anergy. In contrast, isoform 2 stabilizes RNF128 and promotes anergy. 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.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.

Subcellular Localization

Cytoplasm {ECO:0000250}.

Disease Associations

Tissue Specificity

Isoform 1 is ubiquitous. Isoform 2 is expressed only in lymphoid tissues such as tonsils, lymph nodes and spleen, as well as peripheral blood mononuclear cells. {ECO:0000269PubMed:12704427, ECO:0000269PubMed:14661020}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 103 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	103 [view]
Protein-Protein	102 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [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:0045087	innate immune response (InnateDB)
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