USP18
USP18 (ubiquitin specific peptidase 18, formerly ubiquitin specific protease 18) is a member of the ubiquitin-specific protease family that acts as a major ISG15-specific protease. It also interferes with type I interferon signalling. Browse Assay Genie's current range of USP18 research reagents below, or read on for the biology behind the target.
USP18 belongs to the ubiquitin-specific protease (UBP) family of enzymes, which cleave ubiquitin from ubiquitinated protein substrates, and to the peptidase C19 family. Unlike many relatives, USP18 efficiently cleaves only fusions of ISG15, a ubiquitin-like protein. It is the major deISGylation enzyme for nuclear proteins, removing ISG15 from its conjugates.
The role of USP18 in ISG15 turnover has been shown genetically. Deletion of the gene in mice causes a massive increase of ISG15 conjugates in tissues, identifying the protein as a major ISG15-specific protease. Mice lacking the gene are also hypersensitive to interferon. This points to a second function in downregulating interferon responses that is independent of its isopeptidase activity towards ISG15, and the protein is described as interfering with type I interferon signalling.
The USP18 gene encodes a protein that is highly expressed in liver and thymus and is localised to the nucleus, with UniProt also reporting a cytoplasmic location. HGNC places it in the ubiquitin specific peptidases gene group, and the enzyme carries the EC number 3.4.19.12. The mouse ortholog is Usp18, which has been central to the functional studies above. For researchers, the USP18 gene and protein are a focus for work on ISG15 conjugation and the regulation of interferon signalling.
USP18 is a major ISG15-specific protease, so it is central to studies of how ISG15 conjugates are removed from target proteins.
USP18 interferes with type I interferon signalling, making it relevant to research on how interferon responses are limited.
As the major deISGylation enzyme for nuclear proteins, USP18 is studied in the control of ISG15 modification within the nucleus.
USP18 is a peptidase C19 family member with a narrow ISG15 preference, offering a contrast with ubiquitin-cleaving USP enzymes.
USP18 is a protease that efficiently cleaves ISG15 fusions and is the major deISGylation enzyme for nuclear proteins. It also interferes with type I interferon signalling, and mice lacking the gene are hypersensitive to interferon.
HGNC lists the approved name as ubiquitin specific peptidase 18, with the previous name ubiquitin specific protease 18. UniProt names the protein Ubl carboxyl-terminal hydrolase 18. No alternative gene symbols are recorded.
A mouse ortholog, Usp18, exists, and Usp18-deficient mice show a large increase in ISG15 conjugates and hypersensitivity to interferon. This supports a conserved role in ISG15 processing; check the datasheet of any product for its validated reactivity.
Other ubiquitin specific peptidases with products at Assay Genie, useful for comparison with this ISG15-specific protease.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9UMW8; product specifications from Assay Genie datasheets.