USP4

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]

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 108,347,853 bp[2] End 108,392,545 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • peptidase activity • adenosine receptor binding • hydrolase activity • thiol-dependent ubiquitin-specific protease activity • metal ion binding • cysteine-type peptidase activity • identical protein binding • GO:0001948 protein binding Cellular component • cell nucleus • lysosome • cell 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: 108.35 – 108.39 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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]