USP4

Ubiquitin specific protease 4 (USP4) is an enzyme that cleaves ubiquitin from a number of protein substrates. Prior to the standardization of nomenclature USP4 was known as UNP, and was one of the first deubiquitinating enzymes to be identified in mammals. In the mouse and human the USP4 protein is encoded by a gene containing 22 exons.

This protein is a member of cysteine peptidase family C19. As a deubiquitinating enzyme it is unusual in having the capacity to cleave ubiquitin-proline bonds. This property may reflect structural flexibility in the active site of the enzyme, and may explain its ability to cleave ubiquitin chains of various linkages. USP4 has substrates of important function in a number of cell signalling pathways, including the NF-κB, TGF-β, Wnt/β-catenin, p53, and spliceosome pathways. Other substrates include the adenosine A2A receptor and the Ro52 (TRIM21) protein.