USP4

USP4
Identifiers
Aliases	USP4, UNP, Unph, ubiquitin specific peptidase 4
External IDs	OMIM: 603486; MGI: 98905; GeneCards: USP4
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2Y6E, 5CTR
Enzyme activity
Gene location (Human)
Chr.	Chromosome 3 (human)
End	49,340,712 bp
Gene location (Mouse)
Chr.	Chromosome 9 (mouse)
End	108,269,744 bp
RNA expression pattern
	Top expressed in
	pancreatic ductal cell; ; endothelial cell; ; sural nerve; ; blood; ; epithelium of colon; ; monocyte; ; tonsil; ; nipple; ; sperm; ; pylorus;
	Top expressed in
	spermatid; ; spermatocyte; ; intestinal villus; ; yolk sac; ; Ileal epithelium; ; granulocyte; ; tail of embryo; ; neural layer of retina; ; ventricular zone; ; esophagus;
	More reference expression data
	; ; ; ;
	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
Databases	NCBI: entry; OMA: entry
	7375
	22258
	ENSG00000114316
	ENSMUSG00000032612
	Q13107
	P35123
	NM_199443; NM_001251877; NM_003363
	NM_011678; NM_001311157
	NP_001238806; NP_003354; NP_955475
	NP_001298086; NP_035808
	Wikidata
View/Edit Human	View/Edit Mouse

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.

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. 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.

Interactions

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

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000114316 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000032612 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Gray D (2012). "Chapter 462". In Rawlings S (ed.). Handbook of Proteolytic Enzymes (3rd ed.). Elsevier. ISBN 978-0-12-382219-2.
↑ Gupta K, Copeland NG, Gilbert DJ, Jenkins NA, Gray DA (August 1993). "Unp, a mouse gene related to the tre oncogene". Oncogene. 8 (8): 2307–2310. PMID 8336951.
↑ Di Fruscio M, Gilchrist CA, Baker RT, Gray DA (May 1998). "Genomic structure of Unp, a murine gene encoding a ubiquitin-specific protease". Biochimica et Biophysica Acta. 1398 (1): 9–17. doi:10.1016/s0167-4781(98)00035-9. PMID 9602026.
↑ Puente XS, Sanchez LM, Overall CM, Lopez-Otin C (July 2003). "Human and mouse proteases: a comparative genomic approach". Nature Reviews. Genetics. 4 (7): 544–558. doi:10.1038/nrg1111. PMID 12838346. S2CID 2856065.
↑ "Entrez Gene: USP4 ubiquitin specific peptidase 4 (proto-oncogene)".
↑ Gilchrist CA, Gray DA, Baker RT (December 1997). "A ubiquitin-specific protease that efficiently cleaves the ubiquitin-proline bond". The Journal of Biological Chemistry. 272 (51): 32280–32285. doi:10.1074/jbc.272.51.32280. hdl:2292/60433. PMID 9405433.
1 2 Soboleva TA, Jans DA, Johnson-Saliba M, Baker RT (January 2005). "Nuclear-cytoplasmic shuttling of the oncogenic mouse UNP/USP4 deubiquitylating enzyme". The Journal of Biological Chemistry. 280 (1): 745–752. doi:10.1074/jbc.m401394200. PMID 15494318.
↑ Blanchette P, Gilchrist CA, Baker RT, Gray DA (September 2001). "Association of UNP, a ubiquitin-specific protease, with the pocket proteins pRb, p107 and p130". Oncogene. 20 (39): 5533–5537. doi:10.1038/sj.onc.1204823. PMID 11571651.

External links

Overview of all the structural information available in the PDB for UniProt: Q13107 (Ubiquitin carboxyl-terminal hydrolase 4) at the PDBe-KB.

This article on a gene on human chromosome 3 is a stub. You can help Wikipedia by adding missing information.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000114316 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000032612 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Gray D (2012). "Chapter 462". In Rawlings S (ed.). Handbook of Proteolytic Enzymes (3rd ed.). Elsevier. ISBN 978-0-12-382219-2.

[Gupta_1993-6] Gupta K, Copeland NG, Gilbert DJ, Jenkins NA, Gray DA (August 1993). "Unp, a mouse gene related to the tre oncogene". Oncogene. 8 (8): 2307–2310. PMID 8336951.

[Di_1998-7] Di Fruscio M, Gilchrist CA, Baker RT, Gray DA (May 1998). "Genomic structure of Unp, a murine gene encoding a ubiquitin-specific protease". Biochimica et Biophysica Acta. 1398 (1): 9–17. doi:10.1016/s0167-4781(98)00035-9. PMID 9602026.

[Puente_2003-8] Puente XS, Sanchez LM, Overall CM, Lopez-Otin C (July 2003). "Human and mouse proteases: a comparative genomic approach". Nature Reviews. Genetics. 4 (7): 544–558. doi:10.1038/nrg1111. PMID 12838346. S2CID 2856065.

[entrez-9] "Entrez Gene: USP4 ubiquitin specific peptidase 4 (proto-oncogene)".

[Gilchrist_1997-10] Gilchrist CA, Gray DA, Baker RT (December 1997). "A ubiquitin-specific protease that efficiently cleaves the ubiquitin-proline bond". The Journal of Biological Chemistry. 272 (51): 32280–32285. doi:10.1074/jbc.272.51.32280. hdl:2292/60433. PMID 9405433.

[Soboleva_2005-11] 1 2 Soboleva TA, Jans DA, Johnson-Saliba M, Baker RT (January 2005). "Nuclear-cytoplasmic shuttling of the oncogenic mouse UNP/USP4 deubiquitylating enzyme". The Journal of Biological Chemistry. 280 (1): 745–752. doi:10.1074/jbc.m401394200. PMID 15494318.

[12] Blanchette P, Gilchrist CA, Baker RT, Gray DA (September 2001). "Association of UNP, a ubiquitin-specific protease, with the pocket proteins pRb, p107 and p130". Oncogene. 20 (39): 5533–5537. doi:10.1038/sj.onc.1204823. PMID 11571651.

USP4

Interactions

References

Further reading

External links