CPLM-002227

Genbank Nucleotide ID

Ubiquitin-like protein ISG15

Protein Synonyms/Alias

Interferon-induced 15 kDa protein; Interferon-induced 17 kDa protein; IP17; Ubiquitin cross-reactive protein; hUCRP

Homo sapiens (Human)

Position	Peptide	Type	References
35	LKAQITQKIGVHAFQ	ubiquitination	[1, 2, 3]

[1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
[2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
[3] Integrated proteomic analysis of post-translational modifications by serial enrichment.
Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]

Functional Description

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.

DOMAIN 2 78 Ubiquitin-like 1.
DOMAIN 79 157 Ubiquitin-like 2.
REGION 153 157 Involved in the ligation of specific
BINDING 153 153 Activating enzyme (By similarity).
CROSSLNK 157 157 Glycyl lysine isopeptide (Gly-Lys)

3D-structure; Antiviral defense; Complete proteome; Cytoplasm; Direct protein sequencing; Host-virus interaction; Isopeptide bond; Polymorphism; Reference proteome; Repeat; Secreted; Ubl conjugation pathway.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005829; C:cytosol; TAS:Reactome.
GO:0005615; C:extracellular space; NAS:UniProtKB.
GO:0031386; F:protein tag; IEA:Compara.
GO:0007267; P:cell-cell signaling; NAS:UniProtKB.
GO:0042742; P:defense response to bacterium; IMP:UniProtKB.
GO:0051607; P:defense response to virus; IMP:UniProtKB.
GO:0032020; P:ISG15-protein conjugation; IDA:UniProtKB.
GO:0019941; P:modification-dependent protein catabolic process; IEA:Compara.
GO:0031397; P:negative regulation of protein ubiquitination; IDA:UniProtKB.
GO:0032480; P:negative regulation of type I interferon production; TAS:Reactome.
GO:0045071; P:negative regulation of viral genome replication; IMP:UniProtKB.
GO:0032649; P:regulation of interferon-gamma production; IMP:UniProtKB.
GO:0060337; P:type I interferon-mediated signaling pathway; TAS:Reactome.
GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW.

IPR000626; Ubiquitin.
IPR019956; Ubiquitin_subgr.
IPR019955; Ubiquitin_supergroup.

PS50053; UBIQUITIN_2