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Ubiquitin-like protein ISG15

UniProtKB accession:  O02741
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Go to UniProtKB:  O02741
UniProtKB description:  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. Exhibits antiviral activity towards both DNA and RNA viruses. The secreted form of ISG15 can: induce natural killer cell proliferation, augment lymphokine-activated-killer (LAK) activity, induce dendritic cell maturation, act as a chemotactic factor for neutrophils and act as a IFN-gamma-inducing cytokine playing an essential role in antimycobacterial immunity (By similarity). 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). In response to IFN-tau secreted by the conceptus, may ligate to and regulate proteins involved in the release of prostaglandin F2-alpha (PGF), and thus prevent lysis of the corpus luteum and maintain the pregnancy (PubMed:9546718).
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