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 chotactic factor for neutrophils and act as a IFN-gamma-inducing cytokine playing an essential role in antimycobacterial immunity
Identification of a ubiquitin family protein as a novel neutrophil chemotactic factor.Owhashi M., Taoka Y., Ishii K., Nakazawa S., Uemura H., Kambara H.Biochem. Biophys. Res. Commun. 309:533-539(2003)
Research Topic:Immunology
