| 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. Isgylation of the viral sensor IFIH1/MDA5 promotes IFIH1/MDA5 oligomerization and triggers activation of innate immunity against a range of viruses, including coronaviruses, flaviviruses and picornaviruses. Can also isgylate: RIGI 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 pro-inflammatory cytokines. Protects mice against the consequences of Chikungunya virus infection by down-regulating 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. |
| Protein Name | Ubiquitin-Like Protein Isg15Interferon-Induced 15 Kda ProteinInterferon-Induced 17 Kda ProteinIp17Ubiquitin Cross-Reactive Protein |
| Database Links | Reactome: R-MMU-1169408Reactome: -MMU-5656169Reactome: -MMU-9833482 |
| Cellular Localisation | CytoplasmSecretedExists In Three Distinct States: Free Within The CellReleased Into The Extracellular SpaceOr Conjugated To Target Proteins |
| Alternative Protein Names | Ubiquitin-Like Protein Isg15 proteinInterferon-Induced 15 Kda Protein proteinInterferon-Induced 17 Kda Protein proteinIp17 proteinUbiquitin Cross-Reactive Protein proteinIsg15 proteinG1p2 proteinUcrp protein |
Information sourced from Uniprot.org
