UBP43, also known as Ubiquitin Specific Peptidase 18 (USP18), is a member of the peptidase C19 family of deubiquitinating enzymes. It is a nuclear protein highly expressed in the liver, thymus, and peritoneal macrophages, as well as in monocyte-derived cell lines. UBP43/USP18 is 372 amino acids (aa) in length with a predicted molecular weight of 43 kDa.
Human UBP43/USP18 shares 72% and 73% aa sequence identity with the mouse and rat orthologs, respectively. UBP43/USP18 is an Interferon-stimulated Gene 15 (ISG15)-specific protease. ISG15 is a Ubiquitin-like modifier whose expression is strongly induced in response to type I Interferons (IFNs) and lipopolysaccharide treatment. UBP43/USP18 removes ISG15 from ISGylated proteins and thus regulates the levels of IGS15-conjugated proteins in cells.
UBP43/USP18 is believed to have a role in innate immune responses to infections by pathogenic organisms. It has been shown that mice deficient in UBP43/USP18 are resistant to viral infections. UBP43/USP18 also negatively regulates type I IFN signaling by binding to the IFNAR2 subunit of the type I IFN receptor and blocking its association with JAK. UBP43/USP18 is also thought to be involved in cancer cell survival.
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