interferon-induced 17 kD protein; contains: ubiquitin cross-reactive protein; hUCRP; interferon-induced 15 kD protein (IFP17, ISG15, G1P2, UCRP)

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

Structure

• contains 2 ubiquitin-like domains

Compartment

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

Expression

• detected in lymphoid cells, striated & smooth muscle, several epithelia & neurons
• induced by interferon type 1

More general terms

• high-mobility group [HMG] protein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=9636
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:9636
• OMIM: https://mirror.omim.org/entry/147571
• UniProt: http://www.uniprot.org/uniprot/P05161.html