ISG15: Ubiquitin-like protein that is conjugated to intracellular target proteins after IFN-alpha or IFN-beta stimulation. Its enzymatic pathway is partially distinct from that of ubiquitin, differing in substrate specificity and interaction with ligating enzymes. ISG15 conjugation pathway uses a dedicated E1 enzyme, but seems to converge with the Ub conjugation pathway at the level of a specific E2 enzyme. Targets include STAT1, SERPINA3G/SPI2A, JAK1, MAPK3/ERK1, PLCG1, EIF2AK2/PKR, MX1/MxA, and RIG-1. Deconjugated by USP18/UBP43. Shows specific chemotactic activity towards neutrophils and activates them to induce release of eosinophil chemotactic factors. May serve as a trans-acting binding factor directing the association of ligated target proteins to intermediate filaments. May also be involved in autocrine, paracrine and endocrine mechanisms, as in cell-to-cell signaling, possibly partly by inducing IFN-gamma secretion by monocytes and macrophages. Seems to display antiviral activity during viral infections. Interacts with, and is conjugated to its targets by the UBE1L (E1 enzyme) and UBE2E2 (E2 enzyme) (Probable). Interaction with influenza B NS1 protein inhibits this conjugation. By type I interferons. Detected in lymphoid cells, striated and smooth muscle, several epithelia and neurons.
Protein type: Ubiquitin-like modifier
Chromosomal Location of Human Ortholog: 1p36.33
Cellular Component: cytosol; extracellular region; nucleoplasm
Molecular Function: protein binding; protein tag
Biological Process: bypass DNA synthesis; cytokine and chemokine mediated signaling pathway; defense response to bacterium; defense response to virus; DNA repair; innate immune response; ISG15-protein conjugation; modification-dependent protein catabolic process; negative regulation of interferon type I production; negative regulation of protein ubiquitination; negative regulation of viral genome replication; positive regulation of erythrocyte differentiation; regulation of interferon-gamma production; viral reproduction
Disease: Immunodeficiency 38
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