Ubiquitin-like protein ISG15 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. It is secreted from monocytes in response to type I interferons and causes natural killer (NK)-cell proliferation and an augmentation of non-MCH (major histocompatibility complex)-restricted cytotoxicity. Synthesis is stimulated by IFN-alpha or IFN-beta or IFN-omega, but not IFN-gamma. ISG15 expression is also induced by overexpression of interferon regulatory factors that participate in transcriptional regulation of IFN genes, and by influenza B virus. ISG15 is secreted by cell lines of monocyte, T-lymphocyte, B-lymphocyte, human fibroblasts, and epithelial origins. Enhancement of NK cell proliferation, augmentation of non-major histocompatibility complex-restricted cytotoxicity, and induction of IFN-gamma from T cells identify ISG15 as a member of the cytokine cascade and suggest that it may be responsible for amplifying and directing some of the immunomodulatory effects of IFN-alpha or IFN-beta. ISG15 has has also been shown to function intracellularly as a ubiquitin homolog. Mutations affecting the gene can result in Immunodeficiency 38, with basal ganglia calcification (IMD38).
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Protein Aliases: hUCRP; interferon, alpha-inducible protein (clone IFI-15K); Interferon-induced 15 kDa protein; Interferon-induced 17 kDa protein; interferon-induced 17-kDa/15-kDa protein; interferon-stimulated protein, 15 kDa; IP17; Ubiquitin cross-reactive protein; Ubiquitin-like protein ISG15
Gene Aliases: G1P2; hUCRP; IFI15; IMD38; IP17; ISG15; UCRP
UniProt ID: (Human) P05161
Entrez Gene ID: (Human) 9636