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{{Infobox_gene}}
{{PBB_Controls
'''Ubiquitin specific protease 4''' (USP4) is an [[enzyme]] that cleaves [[ubiquitin]] from a number of protein substrates.<ref>{{cite book | author = Gray D | title = Handbook of Proteolytic Enzymes | year = 2012 | publisher = Elsevier | isbn = 9780123822192 | edition = 3rd | editor = Rawlings & Salvesen | chapter=Chapter 462}}</ref> Prior to the standardization of nomenclature USP4 was known as UNP, and was one of the first deubiquitinating enzymes to be identified in mammals.<ref name="pmid8336951">{{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 | doi =  }}</ref>  In the mouse and human the USP4 protein is encoded by a gene containing 22 [[exon]]s.<ref name="pmid9602026">{{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}}</ref><ref name="pmid12838346">{{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 | pmc = | doi = 10.1038/nrg1111 }}</ref><ref name="entrez">{{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| accessdate = }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
This protein is a member of [[cysteine protease|cysteine peptidase]] family C19.  As a [[deubiquitinating enzyme]] it is unusual in having the capacity to cleave ubiquitin-[[proline]] bonds.<ref name="pmid9405433">{{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}}</ref> 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 signaling pathway|Wnt/β-catenin]], [[p53]], and [[spliceosome]] pathways. Other substrates include the [[adenosine A2A receptor]] and the Ro52 ([[TRIM21]]) protein.
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = Ubiquitin specific peptidase 4 (proto-oncogene)
| HGNCid = 12627
| Symbol = USP4
| AltSymbols =; MGC149848; MGC149849; UNP; Unph
| OMIM = 603486
| ECnumber =
| Homologene = 20716
| MGIid = 98905
| GeneAtlas_image1 = PBB_GE_USP4_211800_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_USP4_202681_at_tn.png
| GeneAtlas_image3 = PBB_GE_USP4_202682_s_at_tn.png
| Function = {{GNF_GO|id=GO:0004197 |text = cysteine-type endopeptidase activity}} {{GNF_GO|id=GO:0004221 |text = ubiquitin thiolesterase activity}} {{GNF_GO|id=GO:0008233 |text = peptidase activity}}
  | Component = {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005764 |text = lysosome}}
| Process = {{GNF_GO|id=GO:0006511 |text = ubiquitin-dependent protein catabolic process}} {{GNF_GO|id=GO:0006512 |text = ubiquitin cycle}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 7375
    | Hs_Ensembl = ENSG00000114316
    | Hs_RefseqProtein = NP_003354
    | Hs_RefseqmRNA = NM_003363
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 3
    | Hs_GenLoc_start = 49290003
    | Hs_GenLoc_end = 49352519
    | Hs_Uniprot = Q13107
    | Mm_EntrezGene = 22258
    | Mm_Ensembl = ENSMUSG00000032612
    | Mm_RefseqmRNA = NM_011678
    | Mm_RefseqProtein = NP_035808
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 9
    | Mm_GenLoc_start = 108205963
    | Mm_GenLoc_end = 108250621
    | Mm_Uniprot = Q3TEX8
  }}
}}
'''Ubiquitin specific peptidase 4 (proto-oncogene)''', also known as '''USP4''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: USP4 ubiquitin specific peptidase 4 (proto-oncogene)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7375| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
==Interactions==
{{PBB_Summary
USP4 has been shown to [[Protein-protein interaction|interact]] with [[Retinoblastoma protein]].<ref name="pmid11571651">{{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 = 5533–7 |date=September 2001 | pmid = 11571651 | doi = 10.1038/sj.onc.1204823 }}</ref>
| section_title =  
| summary_text =  
}}


==References==
==References==
{{reflist|2}}
{{Reflist}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{Refbegin | 2}}
{{PBB_Further_reading
*{{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  }}
| citations =
*{{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 |doi= |name-list-format=vanc| author2=Inazawa J  | author3=Gupta K  | display-authors=3  | last4=Wong  | first4=A  | last5=Ueda  | first5=R  | last6=Takahashi  | first6=T }}
*{{cite journal  | author=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= 337-52 |year= 1999 |pmid= 9827704 |doi=  }}
*{{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  | author=Puente XS, Sánchez LM, Overall CM, López-Otín C |title=Human and mouse proteases: a comparative genomic approach. |journal=Nat. Rev. Genet. |volume=4 |issue= 7 |pages= 544-58 |year= 2003 |pmid= 12838346 |doi= 10.1038/nrg1111 }}
*{{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 |doi=  }}
*{{cite journal  | author=Gray DA, Inazawa J, Gupta K, ''et al.'' |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 |doi=  }}
*{{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-format=vanc| author2=Yoshitomo-Nakagawa K  | author3=Maruyama K  | display-authors=3  | last4=Suyama  | first4=A  | last5=Sugano  | first5=S  }}
*{{cite journal  | author=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= 171-4 |year= 1994 |pmid= 8125298 |doi=  }}
*{{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-format=vanc| author2=Chan EK  | author3=Askanase AD  | display-authors=3  | last4=Miranda-Carus  | first4=Maria-Eugenia  | last5=Buyon  | first5=Jill P }}
*{{cite journal  | author=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 |doi=  }}
*{{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 }}
*{{cite journal  | author=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, ''et al.'' |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1-2 |pages= 149-56 |year= 1997 |pmid= 9373149 |doi= }}
*{{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-format=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 }}
*{{cite journal | author=Frederick A, Rolfe M, Chiu MI |title=The human UNP locus at 3p21.31 encodes two tissue-selective, cytoplasmic isoforms with deubiquitinating activity that have reduced expression in small cell lung carcinoma cell lines. |journal=Oncogene |volume=16 |issue= 2 |pages= 153-65 |year= 1998 |pmid= 9464533 |doi= 10.1038/sj.onc.1201537 }}
*{{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-format=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 }}
*{{cite journal  | author=Di Donato F, Chan EK, Askanase AD, ''et al.'' |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= 924-34 |year= 2001 |pmid= 11461834 |doi=  }}
*{{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-format=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  | author=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= 5533-7 |year= 2001 |pmid= 11571651 |doi= 10.1038/sj.onc.1204823 }}
*{{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  | author=DeSalle LM, Latres E, Lin D, ''et al.'' |title=The de-ubiquitinating enzyme Unp interacts with the retinoblastoma protein. |journal=Oncogene |volume=20 |issue= 39 |pages= 5538-42 |year= 2001 |pmid= 11571652 |doi= 10.1038/sj.onc.1204824 }}
*{{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 }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |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= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
{{Refend}}
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |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= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
 
*{{cite journal  | author=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= 731-6 |year= 2006 |pmid= 16316627 |doi= 10.1016/j.bbrc.2005.11.076 }}
*{{cite journal  | author=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= 253-8 |year= 2006 |pmid= 16472766 |doi= 10.1016/j.bbrc.2006.01.144 }}
}}
{{refend}}


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Latest revision as of 10:04, 17 September 2017

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Orthologs
SpeciesHumanMouse
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Ubiquitin specific protease 4 (USP4) is an enzyme that cleaves ubiquitin from a number of protein substrates.[1] Prior to the standardization of nomenclature USP4 was known as UNP, and was one of the first deubiquitinating enzymes to be identified in mammals.[2] In the mouse and human the USP4 protein is encoded by a gene containing 22 exons.[3][4][5]

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.[6] 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.

Interactions

USP4 has been shown to interact with Retinoblastoma protein.[7]

References

  1. ↑ Gray D (2012). "Chapter 462". In Rawlings & Salvesen. Handbook of Proteolytic Enzymes (3rd ed.). Elsevier. ISBN 9780123822192.
  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): 2307–10. PMID 8336951.
  3. ↑ Di Fruscio M, Gilchrist CA, Baker RT, Gray DA (May 1998). "Genomic structure of Unp, a murine gene encoding a ubiquitin-specific protease". Biochim. Biophys. Acta. 1398 (1): 9–17. doi:10.1016/s0167-4781(98)00035-9. PMID 9602026.
  4. ↑ Puente XS, Sanchez LM, Overall CM, Lopez-Otin C (July 2003). "Human and mouse proteases: a comparative genomic approach". Nat Rev Genet. 4 (7): 544–558. doi:10.1038/nrg1111. PMID 12838346.
  5. ↑ "Entrez Gene: USP4 ubiquitin specific peptidase 4 (proto-oncogene)".
  6. ↑ Gilchrist CA, Gray DA, Baker RT (December 1997). "A ubiquitin-specific protease that efficiently cleaves the ubiquitin-proline bond". J. Biol. Chem. 272 (51): 32280–5. doi:10.1074/jbc.272.51.32280. PMID 9405433.
  7. ↑ 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): 5533–7. doi:10.1038/sj.onc.1204823. PMID 11571651.

Further reading


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