USP4
Description
The USP4 (ubiquitin specific peptidase 4) is a protein-coding gene located on chromosome 3.
USP4 is an enzyme that cleaves ubiquitin from a number of protein substrates. It was originally known as UNP and was one of the first deubiquitinating enzymes to be identified in mammals. The USP4 protein is encoded by a gene containing 22 exons. USP4 is a member of cysteine peptidase family C19. 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. USP4 is a nucleocytoplasmic shuttling protein that bears a functional nuclear localization signal (NLS) 766QPQKKKK772 and a nuclear export signal (NES) 133VEVYLLELKL142. Those signals initiate the translocation of USP4 to the nucleus from the cytoplasm and vice versa, respectively.
USP4 is a deubiquitinating enzyme that removes ubiquitin from target proteins. It has been shown to deubiquitinate a variety of proteins, including PDPK1, TRIM21, ADORA2A, HAS2, and RHEB. USP4 may regulate mRNA splicing through deubiquitination of the U4 spliceosomal protein PRPF3. This may prevent its recognition by the U5 component PRPF8 thereby destabilizing interactions within the U4/U6.U5 snRNP. USP4 may also play a role in the regulation of quality control in the ER.
USP4 is also known as UNP, Unph.
