Human Ubiquitin Specific Peptidase 18,USP18 ELI

Involved in the negative regulation of the inflammatory response triggered by type I interferon (PubMed:28165510, PubMed:27325888).

Upon recruitment by STAT2 to the type I IFN receptor subunit IFNAR2 interferes with the assembly of the ternary interferon-IFNAR1-IFNAR2 complex and acts as a negative regulator of the type I IFN signaling pathway (PubMed:28165510).

Also regulates protein ISGylation.

Can efficiently cleave only ISG15 fusions including native ISG15 conjugates linked via isopeptide bonds.

Necessary to maintain a critical cellular balance of ISG15-conjugated proteins in both healthy and stressed organisms (PubMed:11788588).

{ECO:0000269|PubMed:11788588, ECO:0000269|PubMed:27325888, ECO:0000269|PubMed:28165510}.; [Isoform 2]: Has enzymatic activity similar to isoform 1 and interferes with type I interferon signaling.

Major deISGylation enzyme for nuclear proteins (PubMed:22170061).

{ECO:0000269|PubMed:22170061}.