InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Isg15

Summary

InnateDB Protein

IDBP-137566.6

Last Modified

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

Gene Symbol

Isg15

Protein Name

ISG15 ubiquitin-like modifier

Synonyms

Species

Mus musculus

Ensembl Protein

ENSMUSP00000082548

InnateDB Gene

IDBG-137564 (Isg15)

Protein Structure

UniProt Annotation

Function

Ubiquitin-like protein which plays a key role in the innate immune response to viral infection either via its conjugation to a target protein (ISGylation) or via its action as a free or unconjugated protein. ISGylation involves a cascade of enzymatic reactions involving E1, E2, and E3 enzymes which catalyze the conjugation of ISG15 to a lysine residue in the target protein. Its target proteins include SERPINA3G/SPI2A, JAK1, MAPK3/ERK1, PLCG1, TRIM25, STAT5A, MAPK1/ERK2 and globin. Can also isgylate: DDX58/RIG-I which inhibits its function in antiviral signaling response and EIF4E2 which enhances its cap structure- binding activity and translation-inhibition activity. Exhibits antiviral activity towards both DNA and RNA viruses, including influenza A and B virus, sindbis virus (SV) and herpes simplex type-1 (HHV-1). Plays a significant role in the control of neonatal Chikungunya virus (CHIKV) infection by acting as a putative immunomodulator of proinflammatory cytokines. Protects mice against the consequences of Chikungunya virus infection by downregulating the pathogenic cytokine response, often denoted as the cytokine storm. Plays a role in erythroid differentiation. The secreted form of ISG15 can: induce natural killer cell proliferation, act as a chemotactic factor for neutrophils and act as a IFN-gamma-inducing cytokine playing an essential role in antimycobacterial immunity. {ECO:0000269PubMed:16254333, ECO:0000269PubMed:17222803, ECO:0000269PubMed:17227866, ECO:0000269PubMed:17289916, ECO:0000269PubMed:18057259, ECO:0000269PubMed:22022510, ECO:0000269PubMed:22028657, ECO:0000269PubMed:22859821}.

Subcellular Localization

Cytoplasm. Secreted {ECO:0000250}. Note=Exists in three distinct states: free within the cell, released into the extracellular space, or conjugated to target proteins. {ECO:0000250}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 23 experimentally validated interaction(s) in this database.
They are also associated with 184 interaction(s) predicted by orthology.

Experimentally validated
Total	23 [view]
Protein-Protein	19 [view]
Protein-DNA	4 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	184 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding
GO:0031386	protein tag

Biological Process

GO:0019941	modification-dependent protein catabolic process
GO:0031397	negative regulation of protein ubiquitination
GO:0032020	ISG15-protein conjugation
GO:0032649	regulation of interferon-gamma production
GO:0034340	response to type I interferon
GO:0042742	defense response to bacterium
GO:0045071	negative regulation of viral genome replication
GO:0045087	innate immune response (InnateDB)
GO:0045648	positive regulation of erythrocyte differentiation
GO:0051607	defense response to virus