USP18
Function
Interferon-induced ISG15-specific protease that plays a crucial role for maintaining a proper balance of ISG15-conjugated proteins in cells (PubMed:11788588). Regulates protein ISGylation by efficiently cleaving ISG15 conjugates linked via isopeptide bonds. Regulates T-cell activation and T-helper 17 (Th17) cell differentiation by deubiquitinating TAK1, likely to keep TAK1-TAB complexes in steady conditions (PubMed:23825189). In turn, restricts activation of NF-kappa-B, NFAT, and JNK as well as expression of IL2 in T-cells after TCR activation (PubMed:23825189). Acts as a molecular adapter with USP20 to promote innate antiviral response through deubiquitinating STING1 (PubMed:27801882). Involved also in the negative regulation of the inflammatory response triggered by type I interferon (PubMed:27325888, PubMed:28165510). Upon recruitment by STAT2 to the type I interferon receptor subunit IFNAR2 interferes with the assembly of the ternary interferon-IFNAR1-IFNAR2 complex and acts as a negative regulator of the type I interferon signaling pathway (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).
Involvement in disease
Pseudo-TORCH syndrome 2
PTORCH2
An autosomal recessive multisystem disorder characterized by antenatal onset of intracranial hemorrhage, calcification, brain malformations, liver dysfunction, and often thrombocytopenia. Affected individuals tend to have respiratory insufficiency and seizures, and die in infancy. The phenotype resembles the sequelae of intrauterine infection, but there is no evidence of an infectious agent.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the peptidase C19 family.
Cellular localization
- Isoform 1
- Cytoplasm
- Isoform 2
- Nucleus
- Cytoplasm
Alternative names
ISG43, USP18, Ubl carboxyl-terminal hydrolase 18, 43 kDa ISG15-specific protease, ISG15-specific-processing protease, Ubl thioesterase 18, hUBP43