USP4
{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
Ubiquitin specific protease 4 (USP4) is an enzyme that cleaves ubiquitin from a number of protein substrates.{{cite book | author = Gray D | title = Handbook of Proteolytic Enzymes | year = 2012 | publisher = Elsevier | isbn = 9780123822192 | edition = 3rd | editor = Rawlings & Salvesen | chapter=Chapter 462}} Prior to the standardization of nomenclature USP4 was known as UNP, and was one of the first deubiquitinating enzymes to be identified in mammals.{{cite journal |vauthors=Gupta K, Copeland NG, Gilbert DJ, Jenkins NA, Gray DA | title = Unp, a mouse gene related to the tre oncogene | journal = Oncogene | volume = 8 | issue = 8 | pages = 2307–10 |date=August 1993 | pmid = 8336951 }} In the mouse and human the USP4 protein is encoded by a gene containing 22 exons.{{cite journal |vauthors=Di Fruscio M, Gilchrist CA, Baker RT, Gray DA | title = Genomic structure of Unp, a murine gene encoding a ubiquitin-specific protease | journal = Biochim. Biophys. Acta | volume = 1398 | issue = 1 | pages = 9–17 |date=May 1998 | pmid = 9602026 | doi = 10.1016/s0167-4781(98)00035-9}}{{cite journal |vauthors=Puente XS, Sanchez LM, Overall CM, Lopez-Otin C | title = Human and mouse proteases: a comparative genomic approach | journal = Nat Rev Genet | volume = 4 | issue = 7 | pages = 544–558 |date=July 2003 | pmid = 12838346 | doi = 10.1038/nrg1111 | s2cid = 2856065 }}{{cite web | title = Entrez Gene: USP4 ubiquitin specific peptidase 4 (proto-oncogene)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7375}}
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.{{cite journal |vauthors=Gilchrist CA, Gray DA, Baker RT | title = A ubiquitin-specific protease that efficiently cleaves the ubiquitin-proline bond | journal = J. Biol. Chem. | volume = 272 | issue = 51 | pages = 32280–5 |date=December 1997 | pmid = 9405433 | doi = 10.1074/jbc.272.51.32280| doi-access = free | hdl = 2292/60433 | hdl-access = free }} 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.{{Cite journal|last1=Soboleva|first1=Tatiana A.|last2=Jans|first2=David A.|last3=Johnson-Saliba|first3=Melanie|last4=Baker|first4=Rohan T.|date=2004-10-18|title=Nuclear-Cytoplasmic Shuttling of the Oncogenic Mouse UNP/USP4 Deubiquitylating Enzyme|journal=Journal of Biological Chemistry|volume=280|issue=1|pages=745–752|doi=10.1074/jbc.m401394200|pmid=15494318|issn=0021-9258|doi-access=free}} 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.{{Cite journal|last1=Blanchette|first1=Paola|last2=Gilchrist|first2=Catherine A|last3=Baker|first3=Rohan T|last4=Gray|first4=Douglas A|date=September 2001|title=Association of UNP, a ubiquitin-specific protease, with the pocket proteins pRb, p107 and p130|journal=Oncogene|volume=20|issue=39|pages=5533–5537|doi=10.1038/sj.onc.1204823|pmid=11571651|issn=0950-9232|doi-access=free}}
References
{{Reflist}}
Further reading
{{Refbegin | 2}}
- {{cite journal |vauthors=D'Andrea A, Pellman D |title=Deubiquitinating enzymes: a new class of biological regulators |journal=Crit. Rev. Biochem. Mol. Biol. |volume=33 |issue= 5 |pages= 337–352 |year= 1999 |pmid= 9827704 |doi=10.1080/10409239891204251 }}
- {{cite journal | author=Gray DA |title=Elevated expression of Unph, a proto-oncogene at 3p21.3, in human lung tumors |journal=Oncogene |volume=10 |issue= 11 |pages= 2179–83 |year= 1995 |pmid= 7784062 |name-list-style=vanc| author2=Inazawa J | author3=Gupta K | display-authors=3 | last4=Wong | first4=A | last5=Ueda | first5=R | last6=Takahashi | first6=T }}
- {{cite journal |vauthors=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides |journal=Gene |volume=138 |issue= 1–2 |pages= 171–174 |year= 1994 |pmid= 8125298 |doi=10.1016/0378-1119(94)90802-8 }}
- {{cite journal |vauthors=Gupta K, Chevrette M, Gray DA |title=The Unp proto-oncogene encodes a nuclear protein |journal=Oncogene |volume=9 |issue= 6 |pages= 1729–31 |year= 1994 |pmid= 8183569 }}
- {{cite journal | author=Suzuki Y |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library |journal=Gene |volume=200 |issue= 1–2 |pages= 149–156 |year= 1997 |pmid= 9373149 |doi=10.1016/S0378-1119(97)00411-3 |name-list-style=vanc| author2=Yoshitomo-Nakagawa K | author3=Maruyama K | display-authors=3 | last4=Suyama | first4=A | last5=Sugano | first5=S }}
- {{cite journal | author=Di Donato F |title=Interaction between 52 kDa SSA/Ro and deubiquitinating enzyme UnpEL: a clue to function |journal=Int. J. Biochem. Cell Biol. |volume=33 |issue= 9 |pages= 924–934 |year= 2001 |pmid= 11461834 |doi=10.1016/S1357-2725(01)00055-3 |name-list-style=vanc| author2=Chan EK | author3=Askanase AD | display-authors=3 | last4=Miranda-Carus | first4=Maria-Eugenia | last5=Buyon | first5=Jill P }}
- {{cite journal |vauthors=Blanchette P, Gilchrist CA, Baker RT, Gray DA |title=Association of UNP, a ubiquitin-specific protease, with the pocket proteins pRb, p107 and p130 |journal=Oncogene |volume=20 |issue= 39 |pages= 5533–5537 |year= 2001 |pmid= 11571651 |doi= 10.1038/sj.onc.1204823 |doi-access= free }}
- {{cite journal | author=DeSalle LM |title=The de-ubiquitinating enzyme Unp interacts with the retinoblastoma protein |journal=Oncogene |volume=20 |issue= 39 |pages= 5538–5542 |year= 2001 |pmid= 11571652 |doi= 10.1038/sj.onc.1204824 |name-list-style=vanc| author2=Latres E | author3=Lin D | display-authors=3 | last4=Graner | first4=Edgard | last5=Montagnoli | first5=Alessia | last6=Baker | first6=Rohan T | last7=Pagano | first7=Michele | last8=Loda | first8=Massimo | doi-access=free }}
- {{cite journal | author=Strausberg RL |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–16903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |name-list-style=vanc| author2=Feingold EA | author3=Grouse LH | display-authors=3 | last4=Derge | first4=JG | last5=Klausner | first5=RD | last6=Collins | first6=FS | last7=Wagner | first7=L | last8=Shenmen | first8=CM | last9=Schuler | first9=GD |bibcode=2002PNAS...9916899M |doi-access=free }}
- {{cite journal | author=Gerhard DS |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–2127 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 |name-list-style=vanc| author2=Wagner L | author3=Feingold EA | display-authors=3 | last4=Shenmen | first4=CM | last5=Grouse | first5=LH | last6=Schuler | first6=G | last7=Klein | first7=SL | last8=Old | first8=S | last9=Rasooly | first9=R }}
- {{cite journal |vauthors=Wada K, Tanji K, Kamitani T |title=Oncogenic protein UnpEL/Usp4 deubiquitinates Ro52 by its isopeptidase activity |journal=Biochem. Biophys. Res. Commun. |volume=339 |issue= 3 |pages= 731–736 |year= 2006 |pmid= 16316627 |doi= 10.1016/j.bbrc.2005.11.076 }}
- {{cite journal |vauthors=Wada K, Kamitani T |title=UnpEL/Usp4 is ubiquitinated by Ro52 and deubiquitinated by itself |journal=Biochem. Biophys. Res. Commun. |volume=342 |issue= 1 |pages= 253–258 |year= 2006 |pmid= 16472766 |doi= 10.1016/j.bbrc.2006.01.144 }}
{{Refend}}
External links
- {{PDBe-KB2|Q13107|Ubiquitin carboxyl-terminal hydrolase 4}}
{{Gene-3-stub}}