Mouse Ubiquitin-like Protein Isg15, ISG15 ELI

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, IRF3 which inhibits its ubiquitination and degradation as well as 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.

The secreted form acts through the integrin ITGAL/ITGB2 receptor to initiate activation of SRC family tyrosine kinases including LYN, HCK and FGR which leads to secretion of IFNG and IL10; the interaction is mediated by ITGAL (By similarity).