USP4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2Y6E, 5CTR
Identifiers
Aliases	USP4, UNP, Unph, ubiquitin specific peptidase 4
External IDs	OMIM: 603486 MGI: 98905 HomoloGene: 20716 GeneCards: USP4
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3p21.31 Start 49,277,144 bp[1] End 49,340,712 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9 F2|9 59.25 cM Start 108,225,052 bp[2] End 108,269,744 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in pancreatic ductal cell endothelial cell sural nerve blood monocyte thymus nipple sperm pylorus visceral pleura Top expressed in spermatid spermatocyte intestinal villus yolk sac esophagus superior frontal gyrus lip corneal stroma masseter muscle plantaris muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function peptidase activity adenosine receptor binding hydrolase activity thiol-dependent deubiquitinase metal ion binding cysteine-type peptidase activity identical protein binding protein binding Cellular component nucleus lysosome plasma membrane cytoplasm cytosol Biological process ubiquitin-dependent protein catabolic process spliceosomal tri-snRNP complex assembly regulation of protein stability proteolysis negative regulation of protein ubiquitination protein localization to cell surface protein deubiquitination Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7375 22258 Ensembl ENSG00000114316 ENSMUSG00000032612 UniProt Q13107 P35123 RefSeq (mRNA) NM_199443 NM_001251877 NM_003363 NM_011678 NM_001311157 RefSeq (protein) NP_001238806 NP_003354 NP_955475 NP_001298086 NP_035808 Location (UCSC) Chr 3: 49.28 – 49.34 Mb Chr 9: 108.23 – 108.27 Mb PubMed search [3] [4]
Wikidata
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Ubiquitin specific protease 4 (USP4) is an enzyme that cleaves ubiquitin from a number of protein substrates.^[5] Prior to the standardization of nomenclature USP4 was known as UNP, and was one of the first deubiquitinating enzymes to be identified in mammals.^[6] In the mouse and human the USP4 protein is encoded by a gene containing 22 exons.^[7][8][9]

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.^[10] 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.^[11] Those signals initiate the translocation of USP4 to the nucleus from the cytoplasm and vice versa, respectively. The proportion of cytoplasmic to nuclear USP4 pool varies depending on the cell type, the phase of cell cycle and the level of protein expression.^[11]

Interactions

USP4 has been shown to interact with the tumor suppressor pRb protein and the pocket-related proteins p107 and p130.^[12]