Interferon Induced 17 Kd Protein

Function

ubiquitin-like protein that is conjugated to intracellular target proteins after IFN-alpha or IFN-beta stimulation ( ISGylation)
its enzymatic pathway is partially distinct from that of ubiquitin, differing in substrate specificity & 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, & RIG-1
deconjugated by USP18/UBP43
shows specific chemotactic activity towards neutrophils & activates them to induce release of eosinophil chemotactic factors
may serve as a trans-acting binding factor directing association of ligated target proteins to intermediate filaments
may also be involved in autocrine, paracrine & endocrine mechanisms, as in cell-to-cell signaling, possibly partly by inducing IFN-gamma secretion by monocytes & macrophages. seems to display antiviral activity during viral infections
in response to IFN- tau secreted by the conceptus, may ligate to & regulate proteins involved in the release of prostaglandin F2-alpha ( PGF), & thus prevent lysis of the corpus luteum & maintain the pregnancy ( putative)
interacts with, & is conjugated to its targets by the UBE1L ( E1 enzyme) & UBE2E2 ( E2 enzyme) (probable); interaction with influenza B NS1 protein inhibits this conjugation

cytoplasm, secreted
UCRP conjugates seem to be noncovalently associated with intermediate filaments & distributed in a punctate pattern
also secreted

Entrez gene: 9636
Kegg: [1]
OMIM: 147571
Prosite: [2]
UniProt: [3]

UniProt [4]
Hemelaar J, Borodovsky A, Kessler BM, Reverter D et al Specific and covalent targeting of conjugating and deconjugating enzymes of ubiquitin-like proteins. Mol Cell Biol. 2004 Jan;24(1):84-95. PMID: [5]