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Identification
HMDB Protein ID HMDBP10124
Secondary Accession Numbers
  • 16080
Name Ubiquitin carboxyl-terminal hydrolase 7
Synonyms
  1. Deubiquitinating enzyme 7
  2. Herpesvirus-associated ubiquitin-specific protease
  3. Ubiquitin thioesterase 7
  4. Ubiquitin-specific-processing protease 7
Gene Name USP7
Protein Type Enzyme
Biological Properties
General Function Involved in ubiquitin thiolesterase activity
Specific Function Hydrolase that deubiquitinates target proteins such as FOXO4, TP53, MDM2, PTEN and DAXX. Together with DAXX, prevents MDM2 self-ubiquitination and enhances the E3 ligase activity of MDM2 towards TP53, thereby promoting TP53 ubiquitination and proteasomal degradation. Deubiquitinates TP53 and MDM2 and strongly stabilizes TP53 even in the presence of excess MDM2, and also induces TP53-dependent cell growth repression and apoptosis. Deubiquitination of FOXO4 in presence of hydrogen peroxide is not dependent on TP53 and inhibits FOXO4-induced transcriptional activity. In association with DAXX, is involved in the deubiquitination and translocation of PTEN from the nucleus to the cytoplasm, both processes that are counteracted by PML. Involved in cell proliferation during early embryonic development. Contributes to the overall stabilization and trans-activation capability of the herpesvirus 1 trans-acting transcriptional protein ICP0/VMW110 during HSV-1 infection
Pathways Not Available
Reactions Not Available
GO Classification
Function
hydrolase activity, acting on ester bonds
catalytic activity
hydrolase activity
ubiquitin thiolesterase activity
thiolester hydrolase activity
Process
metabolic process
catabolic process
macromolecule catabolic process
cellular macromolecule catabolic process
modification-dependent macromolecule catabolic process
modification-dependent protein catabolic process
ubiquitin-dependent protein catabolic process
Cellular Location
  1. Nucleus
  2. Nucleus
  3. Cytoplasm
  4. PML body
Gene Properties
Chromosome Location Chromosome:1
Locus 16p13.3
SNPs USP7
Gene Sequence
>3309 bp
ATGAACCACCAGCAGCAGCAGCAGCAGCAGAAAGCGGGCGAGCAGCAGTTGAGCGAGCCC
GAGGACATGGAGATGGAAGCGGGAGATACAGATGACCCACCAAGAATTACTCAGAACCCT
GTGATCAATGGGAATGTGGCCCTGAGTGATGGACACAACACCGCGGAGGAGGACATGGAG
GATGACACCAGTTGGCGCTCCGAGGCAACCTTTCAGTTCACTGTGGAGCGCTTCAGCAGA
CTGAGTGAGTCGGTCCTTAGCCCTCCGTGTTTTGTGCGAAATCTGCCATGGAAGATTATG
GTGATGCCACGCTTTTATCCAGACAGACCACACCAAAAAAGCGTAGGATTCTTTCTCCAG
TGCAATGCTGAATCTGATTCCACGTCATGGTCTTGCCATGCACAAGCAGTGCTGAAGATA
ATAAATTACAGAGATGATGAAAAGTCGTTCAGTCGTCGTATTAGTCATTTGTTCTTCCAT
AAAGAAAATGATTGGGGATTTTCCAATTTTATGGCCTGGAGTGAAGTGACCGATCCTGAG
AAAGGATTTATAGATGATGACAAAGTTACCTTTGAAGTCTTTGTACAGGCGGATGCTCCC
CATGGAGTTGCGTGGGATTCAAAGAAGCACACAGGCTACGTCGGCTTAAAGAATCAGGGA
GCGACTTGTTACATGAACAGCCTGCTACAGACGTTATTTTTCACGAATCAGCTACGAAAG
GCTGTGTACATGATGCCAACCGAGGGGGATGATTCGTCTAAAAGCGTCCCTTTAGCATTA
CAAAGAGTGTTCTATGAATTACAGCATAGTGATAAACCTGTAGGAACAAAAAAGTTAACA
AAGTCATTTGGGTGGGAAACTTTAGATAGCTTCATGCAACATGATGTTCAGGAGCTTTGT
CGAGTGTTGCTCGATAATGTGGAAAATAAGATGAAAGGCACCTGTGTAGAGGGCACCATA
CCCAAATTATTCCGCGGCAAAATGGTGTCCTATATCCAGTGTAAAGAAGTAGACTATCGG
TCTGATAGAAGAGAAGATTATTATGATATCCAGCTAAGTATCAAAGGAAAGAAAAATATA
TTTGAATCATTTGTGGATTATGTGGCAGTAGAACAGCTCGATGGGGACAATAAATACGAC
GCTGGGGAACATGGCTTACAGGAAGCAGAGAAAGGTGTGAAATTCCTAACATTGCCACCA
GTGTTACATCTACAACTGATGAGATTTATGTATGACCCTCAGACGGACCAAAATATCAAG
ATCAATGATAGGTTTGAATTCCCAGAGCAGTTACCACTTGATGAATTTTTGCAAAAAACA
GATCCTAAGGACCCTGCAAATTATATTCTTCATGCAGTCCTGGTTCATAGTGGAGATAAT
CATGGTGGACATTATGTGGTTTATCTAAACCCCAAAGGGGATGGCAAATGGTGTAAATTT
GATGACGACGTGGTGTCAAGGTGTACTAAAGAGGAAGCAATTGAGCACAATTATGGGGGT
CACGATGACGACCTGTCTGTTCGACACTGCACTAATGCTTACATGTTAGTCTACATCAGG
GAATCAAAACTGAGTGAAGTTTTACAGGCGGTCACCGACCATGATATTCCTCAGCAGTTG
GTGGAGCGATTACAAGAAGAGAAAAGGATCGAGGCTCAGAAGCGGAAGGAGCGGCAGGAA
GCCCATCTCTATATGCAAGTGCAGATAGTCGCAGAGGACCAGTTTTGTGGCCACCAAGGG
AATGACATGTACGATGAAGAAAAAGTGAAATACACTGTGTTCAAAGTATTGAAGAACTCC
TCGCTTGCTGAGTTTGTTCAGAGCCTCTCTCAGACCATGGGATTTCCACAAGATCAAATT
CGATTGTGGCCCATGCAAGCAAGGAGTAATGGAACAAAACGACCAGCAATGTTAGATAAT
GAAGCCGACGGCAATAAAACAATGATTGAGCTCAGTGATAATGAAAACCCTTGGACAATA
TTCCTGGAAACAGTTGATCCCGAGCTGGCTGCTAGTGGAGCGACCTTACCCAAGTTTGAT
AAAGATCATGATGTAATGTTATTTTTGAAGATGTATGATCCCAAAACGCGGAGCTTGAAT
TACTGTGGGCATATCTACACACCAATATCCTGTAAAATACGTGACTTGCTCCCAGTTATG
TGTGACAGAGCAGGATTTATTCAAGATACTAGCCTTATCCTCTATGAGGAAGTTAAACCG
AATTTAACAGAGAGAATTCAGGACTATGACGTGTCTCTTGATAAAGCCCTTGATGAACTA
ATGGATGGTGACATCATAGTATTTCAGAAGGATGACCCTGAAAATGATAACAGTGAATTA
CCCACCGCAAAGGAGTATTTCCGAGATCTCTACCACCGCGTTGATGTCATTTTCTGTGAT
AAAACAATCCCTAATGATCCTGGATTTGTGGTTACGTTATCAAATAGAATGAATTATTTT
CAGGTTGCAAAGACAGTTGCACAGAGGCTCAACACAGATCCAATGTTGCTGCAGTTTTTC
AAGTCTCAAGGTTATAGGGATGGCCCAGGTAATCCTCTTAGACATAATTATGAAGGTACT
TTAAGAGATCTTCTACAGTTCTTCAAGCCTAGACAACCTAAGAAACTTTACTATCAGCAG
CTTAAGATGAAAATCACAGACTTTGAGAACAGGCGAAGTTTTAAATGTATATGGTTAAAC
AGCCAATTTAGGGAAGAGGAAATAACACTATATCCAGACAAGCATGGGTGTGTCCGGGAC
CTGTTAGAAGAATGTAAAAAGGCCGTGGAGCTTGGGGAGAAAGCATCAGGGAAACTTAGG
CTGCTAGAAATTGTAAGCTACAAAATCATTGGTGTTCATCAAGAAGATGAACTATTAGAA
TGTTTATCTCCTGCAACGAGCCGGACGTTTCGAATAGAGGAAATCCCTTTGGACCAGGTG
GACATAGACAAAGAGAATGAGATGCTTGTCACAGTGGCGCATTTCCACAAAGAGGTCTTC
GGAACGTTCGGAATCCCGTTTTTGCTGAGGATACACCAGGGCGAGCATTTTCGAGAAGTG
ATGAAGCGAATCCAGAGCCTGCTGGACATCCAGGAGAAGGAGTTTGAGAAGTTTAAATTT
GCAATTGTAATGATGGGCCGACACCAGTACATAAATGAAGACGAGTATGAAGTAAATTTG
AAAGACTTTGAGCCACAGCCCGGTAATATGTCTCATCCTCGGCCTTGGCTAGGGCTCGAC
CACTTCAACAAAGCCCCAAAGAGGAGTCGCTACACTTACCTTGAAAAGGCCATTAAAATC
CATAACTGA
Protein Properties
Number of Residues 1102
Molecular Weight 128301.3
Theoretical pI 5.24
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Ubiquitin carboxyl-terminal hydrolase 7
MNHQQQQQQQKAGEQQLSEPEDMEMEAGDTDDPPRITQNPVINGNVALSDGHNTAEEDME
DDTSWRSEATFQFTVERFSRLSESVLSPPCFVRNLPWKIMVMPRFYPDRPHQKSVGFFLQ
CNAESDSTSWSCHAQAVLKIINYRDDEKSFSRRISHLFFHKENDWGFSNFMAWSEVTDPE
KGFIDDDKVTFEVFVQADAPHGVAWDSKKHTGYVGLKNQGATCYMNSLLQTLFFTNQLRK
AVYMMPTEGDDSSKSVPLALQRVFYELQHSDKPVGTKKLTKSFGWETLDSFMQHDVQELC
RVLLDNVENKMKGTCVEGTIPKLFRGKMVSYIQCKEVDYRSDRREDYYDIQLSIKGKKNI
FESFVDYVAVEQLDGDNKYDAGEHGLQEAEKGVKFLTLPPVLHLQLMRFMYDPQTDQNIK
INDRFEFPEQLPLDEFLQKTDPKDPANYILHAVLVHSGDNHGGHYVVYLNPKGDGKWCKF
DDDVVSRCTKEEAIEHNYGGHDDDLSVRHCTNAYMLVYIRESKLSEVLQAVTDHDIPQQL
VERLQEEKRIEAQKRKERQEAHLYMQVQIVAEDQFCGHQGNDMYDEEKVKYTVFKVLKNS
SLAEFVQSLSQTMGFPQDQIRLWPMQARSNGTKRPAMLDNEADGNKTMIELSDNENPWTI
FLETVDPELAASGATLPKFDKDHDVMLFLKMYDPKTRSLNYCGHIYTPISCKIRDLLPVM
CDRAGFIQDTSLILYEEVKPNLTERIQDYDVSLDKALDELMDGDIIVFQKDDPENDNSEL
PTAKEYFRDLYHRVDVIFCDKTIPNDPGFVVTLSNRMNYFQVAKTVAQRLNTDPMLLQFF
KSQGYRDGPGNPLRHNYEGTLRDLLQFFKPRQPKKLYYQQLKMKITDFENRRSFKCIWLN
SQFREEEITLYPDKHGCVRDLLEECKKAVELGEKASGKLRLLEIVSYKIIGVHQEDELLE
CLSPATSRTFRIEEIPLDQVDIDKENEMLVTVAHFHKEVFGTFGIPFLLRIHQGEHFREV
MKRIQSLLDIQEKEFEKFKFAIVMMGRHQYINEDEYEVNLKDFEPQPGNMSHPRPWLGLD
HFNKAPKRSRYTYLEKAIKIHN
GenBank ID Protein 150378533
UniProtKB/Swiss-Prot ID Q93009
UniProtKB/Swiss-Prot Entry Name UBP7_HUMAN
PDB IDs
GenBank Gene ID NM_003470.2
GeneCard ID USP7
GenAtlas ID USP7
HGNC ID HGNC:12630
References
General References
  1. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  2. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  3. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332 ]
  4. Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villen J, Li J, Cohn MA, Cantley LC, Gygi SP: Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12130-5. Epub 2004 Aug 9. [PubMed:15302935 ]
  5. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330 ]
  6. Martin J, Han C, Gordon LA, Terry A, Prabhakar S, She X, Xie G, Hellsten U, Chan YM, Altherr M, Couronne O, Aerts A, Bajorek E, Black S, Blumer H, Branscomb E, Brown NC, Bruno WJ, Buckingham JM, Callen DF, Campbell CS, Campbell ML, Campbell EW, Caoile C, Challacombe JF, Chasteen LA, Chertkov O, Chi HC, Christensen M, Clark LM, Cohn JD, Denys M, Detter JC, Dickson M, Dimitrijevic-Bussod M, Escobar J, Fawcett JJ, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Goodwin LA, Grady DL, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Hildebrand CE, Huang W, Israni S, Jett J, Jewett PB, Kadner K, Kimball H, Kobayashi A, Krawczyk MC, Leyba T, Longmire JL, Lopez F, Lou Y, Lowry S, Ludeman T, Manohar CF, Mark GA, McMurray KL, Meincke LJ, Morgan J, Moyzis RK, Mundt MO, Munk AC, Nandkeshwar RD, Pitluck S, Pollard M, Predki P, Parson-Quintana B, Ramirez L, Rash S, Retterer J, Ricke DO, Robinson DL, Rodriguez A, Salamov A, Saunders EH, Scott D, Shough T, Stallings RL, Stalvey M, Sutherland RD, Tapia R, Tesmer JG, Thayer N, Thompson LS, Tice H, Torney DC, Tran-Gyamfi M, Tsai M, Ulanovsky LE, Ustaszewska A, Vo N, White PS, Williams AL, Wills PL, Wu JR, Wu K, Yang J, Dejong P, Bruce D, Doggett NA, Deaven L, Schmutz J, Grimwood J, Richardson P, Rokhsar DS, Eichler EE, Gilna P, Lucas SM, Myers RM, Rubin EM, Pennacchio LA: The sequence and analysis of duplication-rich human chromosome 16. Nature. 2004 Dec 23;432(7020):988-94. [PubMed:15616553 ]
  7. Song MS, Salmena L, Carracedo A, Egia A, Lo-Coco F, Teruya-Feldstein J, Pandolfi PP: The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network. Nature. 2008 Oct 9;455(7214):813-7. doi: 10.1038/nature07290. Epub 2008 Aug 20. [PubMed:18716620 ]
  8. Song MS, Song SJ, Kim SY, Oh HJ, Lim DS: The tumour suppressor RASSF1A promotes MDM2 self-ubiquitination by disrupting the MDM2-DAXX-HAUSP complex. EMBO J. 2008 Jul 9;27(13):1863-74. doi: 10.1038/emboj.2008.115. Epub 2008 Jun 19. [PubMed:18566590 ]
  9. Li M, Brooks CL, Kon N, Gu W: A dynamic role of HAUSP in the p53-Mdm2 pathway. Mol Cell. 2004 Mar 26;13(6):879-86. [PubMed:15053880 ]
  10. Tang J, Qu LK, Zhang J, Wang W, Michaelson JS, Degenhardt YY, El-Deiry WS, Yang X: Critical role for Daxx in regulating Mdm2. Nat Cell Biol. 2006 Aug;8(8):855-62. Epub 2006 Jul 16. [PubMed:16845383 ]
  11. Zweitzig DR, Shcherbik N, Haines DS: Retraction for D. R. Zweitzig, N. Shcherbik, and D. S. Haines: AAA ATPase P97 and adaptor UBXD1 suppress MDM2 ubiquitination and degradation and promote constitutive P53 turnover. Mol Biol Cell. 2008 Nov;19(11):5029. doi: 10.1091/mbc.E08-01-0067. Epub 2008 Sep 3. [PubMed:18768758 ]
  12. Hu M, Gu L, Li M, Jeffrey PD, Gu W, Shi Y: Structural basis of competitive recognition of p53 and MDM2 by HAUSP/USP7: implications for the regulation of the p53-MDM2 pathway. PLoS Biol. 2006 Feb;4(2):e27. Epub 2006 Jan 17. [PubMed:16402859 ]
  13. Sheng Y, Saridakis V, Sarkari F, Duan S, Wu T, Arrowsmith CH, Frappier L: Molecular recognition of p53 and MDM2 by USP7/HAUSP. Nat Struct Mol Biol. 2006 Mar;13(3):285-91. Epub 2006 Feb 12. [PubMed:16474402 ]
  14. Hu M, Li P, Li M, Li W, Yao T, Wu JW, Gu W, Cohen RE, Shi Y: Crystal structure of a UBP-family deubiquitinating enzyme in isolation and in complex with ubiquitin aldehyde. Cell. 2002 Dec 27;111(7):1041-54. [PubMed:12507430 ]
  15. van der Horst A, de Vries-Smits AM, Brenkman AB, van Triest MH, van den Broek N, Colland F, Maurice MM, Burgering BM: FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP. Nat Cell Biol. 2006 Oct;8(10):1064-73. Epub 2006 Sep 10. [PubMed:16964248 ]
  16. Everett RD, Meredith M, Orr A, Cross A, Kathoria M, Parkinson J: A novel ubiquitin-specific protease is dynamically associated with the PML nuclear domain and binds to a herpesvirus regulatory protein. EMBO J. 1997 Feb 3;16(3):566-77. [PubMed:9034339 ]
  17. Everett RD, Meredith M, Orr A, Cross A, Kathoria M, Parkinson J: A novel ubiquitin-specific protease is dynamically associated with the PML nuclear domain and binds to a herpesvirus regulatory protein. EMBO J. 1997 Apr 1;16(7):1519-30. [PubMed:9130697 ]
  18. Hong S, Kim SJ, Ka S, Choi I, Kang S: USP7, a ubiquitin-specific protease, interacts with ataxin-1, the SCA1 gene product. Mol Cell Neurosci. 2002 Jun;20(2):298-306. [PubMed:12093161 ]
  19. Li M, Chen D, Shiloh A, Luo J, Nikolaev AY, Qin J, Gu W: Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization. Nature. 2002 Apr 11;416(6881):648-53. Epub 2002 Mar 31. [PubMed:11923872 ]
  20. Holowaty MN, Sheng Y, Nguyen T, Arrowsmith C, Frappier L: Protein interaction domains of the ubiquitin-specific protease, USP7/HAUSP. J Biol Chem. 2003 Nov 28;278(48):47753-61. Epub 2003 Sep 23. [PubMed:14506283 ]
  21. Boutell C, Canning M, Orr A, Everett RD: Reciprocal activities between herpes simplex virus type 1 regulatory protein ICP0, a ubiquitin E3 ligase, and ubiquitin-specific protease USP7. J Virol. 2005 Oct;79(19):12342-54. [PubMed:16160161 ]
  22. Fernandez-Montalvan A, Bouwmeester T, Joberty G, Mader R, Mahnke M, Pierrat B, Schlaeppi JM, Worpenberg S, Gerhartz B: Biochemical characterization of USP7 reveals post-translational modification sites and structural requirements for substrate processing and subcellular localization. FEBS J. 2007 Aug;274(16):4256-70. Epub 2007 Jul 25. [PubMed:17651432 ]
  23. Antrobus R, Boutell C: Identification of a novel higher molecular weight isoform of USP7/HAUSP that interacts with the Herpes simplex virus type-1 immediate early protein ICP0. Virus Res. 2008 Oct;137(1):64-71. doi: 10.1016/j.virusres.2008.05.017. Epub 2008 Jul 17. [PubMed:18590780 ]
  24. Tang J, Qu L, Pang M, Yang X: Daxx is reciprocally regulated by Mdm2 and Hausp. Biochem Biophys Res Commun. 2010 Mar 12;393(3):542-5. doi: 10.1016/j.bbrc.2010.02.051. Epub 2010 Feb 12. [PubMed:20153724 ]
  25. Saridakis V, Sheng Y, Sarkari F, Holowaty MN, Shire K, Nguyen T, Zhang RG, Liao J, Lee W, Edwards AM, Arrowsmith CH, Frappier L: Structure of the p53 binding domain of HAUSP/USP7 bound to Epstein-Barr nuclear antigen 1 implications for EBV-mediated immortalization. Mol Cell. 2005 Apr 1;18(1):25-36. [PubMed:15808506 ]