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ISG15 antiviral mechanism

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-1169408

PubChem

R-HSA-1169408

Description

Interferon-stimulated gene 15 (ISG15) is a member of the ubiquitin-like (Ubl) family. It is strongly induced upon exposure to type I Interferons (IFNs), viruses, bacterial LPS, and other stresses. Once released the mature ISG15 conjugates with an array of target proteins, a process termed ISGylation. ISGylation utilizes a mechanism similar to ubiquitination, requiring a three-step enzymatic cascade. UBE1L is the ISG15 E1 activating enzyme which specifically activates ISG15 at the expense of ATP. ISG15 is then transfered from E1 to the E2 conjugating enzyme UBCH8 and then to the target protein with the aid of an ISG15 E3 ligase, such as HERC5 and EFP. Hundreds of target proteins for ISGylation have been identified. Several proteins that are part of antiviral signaling pathways, such as RIG-I, MDA5, Mx1, PKR, filamin B, STAT1, IRF3 and JAK1, have been identified as targets for ISGylation. ISG15 also conjugates some viral proteins, inhibiting viral budding and release. ISGylation appears to act either by disrupting the activity of a target protein and/or by altering its localization within the cell.

Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.

SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying entries **1 - 10** of 41 in total

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UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
A8CG34	Nuclear envelope pore membrane protein POM 121C	POM121C	view
O15504	Nucleoporin NUP42	CG1 NUP42 NUPL2	view
O43432	Eukaryotic translation initiation factor 4 gamma 3	EIF4G3	view
O75369	Filamin-B	FLN1L FLN3 FLNB TABP TAP	view
O75694	Nuclear pore complex protein Nup155	KIAA0791 NUP155	view
O95786	Antiviral innate immune response receptor RIG-I	DDX58 RIGI	view
P06730	Eukaryotic translation initiation factor 4E	EIF4E EIF4EL1 EIF4F	view
P12270	Nucleoprotein TPR	TPR	view
P19174	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	PLC1 PLCG1	view
P19525	Interferon-induced, double-stranded RNA-activated protein kinase	EIF2AK2 PKR PRKR	view

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