Search
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
General
high-mobility group [HMG] protein
Properties
SIZE: entity length = 165 aa
MW = 18 kD
COMPARTMENT: cytoplasm
MOTIF: Ubiquitin-like 1 {2-78}
Ubiquitin-like 2 {79-157}
MOTIF: Involved in the ligation of specific target proteins {153-157}
binding site
SITE: 153-153
FOR-BINDING-OF: Activating enzyme
Database Correlations
OMIM 147571
UniProt P05161
Pfam PF00240
Entrez Gene 9636
Kegg hsa:9636
References
- UniProt :accession P05161
- 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: 14673145