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Identification
HMDB Protein ID HMDBP10136
Secondary Accession Numbers
  • 16092
Name Ubiquitin carboxyl-terminal hydrolase 8
Synonyms
  1. Deubiquitinating enzyme 8
  2. Ubiquitin isopeptidase Y
  3. Ubiquitin thiolesterase 8
  4. Ubiquitin-specific-processing protease 8
  5. hUBPy
Gene Name USP8
Protein Type Enzyme
Biological Properties
General Function Involved in ubiquitin thiolesterase activity
Specific Function Hydrolase that can remove conjugated ubiquitin from proteins and therefore plays an important regulatory role at the level of protein turnover by preventing degradation. Converts both 'Lys-48' an 'Lys-63'-linked ubiquitin chains. Catalytic activity is enhanced in the M phase. Involved in cell proliferation. Required to enter into S phase in response to serum stimulation. May regulate T-cell anergy mediated by RNF128 via the formation of a complex containing RNF128 and OTUB1. Probably regulates the stability of STAM2 and RASGRF1. Regulates endosomal ubiquitin dynamics, cargo sorting, membrane traffic at early endosomes, and maintenance of ESCRT-0 stability. The level of protein ubiquitination on endosomes is essential for maintaining the morphology of the organelle. Deubiquitinates EPS15 and controles tyrosine kinase stability. Removes conjugated ubiquitin from EGFR thus regulating EGFR degradation and downstream MAPK signaling. Involved in acrosome biogenesis through interaction with the spermatid ESCRT-0 complex and microtubules
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. Cell membrane
  2. Nucleus
  3. Cytoplasm
  4. Peripheral membrane protein
  5. Peripheral membrane protein
  6. Endosome membrane
Gene Properties
Chromosome Location Chromosome:1
Locus 15q21.2
SNPs USP8
Gene Sequence
>3357 bp
ATGCCTGCTGTGGCTTCAGTTCCTAAAGAACTCTACCTCAGTTCTTCACTAAAAGACCTT
AATAAGAAGACAGAAGTTAAACCAGAGAAAATAAGCACTAAGAGTTATGTGCACAGTGCC
CTGAAGATCTTTAAGACAGCAGAAGAATGCAGATTAGATCGTGATGAGGAAAGGGCCTAT
GTACTATATATGAAATACGTGACTGTTTATAATCTTATCAAAAAAAGACCTGATTTCAAG
CAACAGCAGGATTATTTCCATTCAATACTTGGACCTGGAAACATCAAAAAAGCTGTCGAA
GAAGCTGAAAGACTCTCTGAAAGCCTTAAATTAAGATATGAAGAAGCTGAAGTCCGGAAA
AAACTTGAGGAAAAAGACAGGCAGGAGGAAGCACAGCGGCTACAACAAAAAAGGCAGGAA
ACAGGAAGAGAGGATGGTGGCACATTGGCTAAAGGCTCTTTGGAGAATGTTTTGGATTCC
AAAGACAAAACCCAAAAGAGCAATGGTGAAAAGAATGAAAAATGTGAGACCAAAGAGAAA
GGAGCAATCACAGCAAAGGAACTATACACAATGATGACGGATAAAAACATCAGCTTGATT
ATAATGGATGCTCGAAGAATGCAGGATTATCAGGATTCCTGTATTTTACATTCTCTCAGT
GTTCCTGAAGAAGCCATCAGTCCAGGAGTCACTGCTAGTTGGATTGAAGCACACCTGCCA
GATGATTCTAAAGACACATGGAAGAAGAGGGGGAATGTGGAGTATGTGGTACTTCTTGAC
TGGTTTAGTTCTGCCAAAGATTTACAGATTGGAACAACTCTCCGGAGTCTGAAAGATGCA
CTTTTCAAGTGGGAAAGTAAAACTGTCCTGCGCAATGAGCCTTTGGTTTTAGAGGGAGGC
TATGAAAACTGGCTCCTTTGTTATCCCCAGTATACAACAAATGCTAAGGTCACTCCACCC
CCACGACGCCAGAATGAAGAGGTGTCTATCTCATTGGATTTTACTTATCCCTCATTGGAA
GAATCAATTCCTTCTAAACCTGCTGCCCAGACGCCACCTGCATCTATAGAAGTAGATGAA
AATATAGAATTGATAAGTGGTCAAAATGAGAGAATGGGACCACTGAATATATCAACTCCA
GTTGAACCAGTTGCTGCTTCTAAATCTGATGTTTCACCCATAATTCAGCCAGTGCCTAGT
ATAAAGAATGTTCCACAGATTGATCGTACTAAAAAACCAGCAGTCAAATTGCCTGAAGAG
CATAGAATAAAATCTGAAAGTACAAACCATGAGCAACAATCTCCTCAGAGTGGAAAAGTT
ATTCCTGATCGTTCCACCAAGCCAGTAGTTTTTTCTCCAACTCTCATGTTAACAGATGAA
GAAAAGGCTCGTATTCATGCAGAAACTGCTCTTCTAATGGAAAAAAACAAACAAGAAAAA
GAACTTCGGGAAAGGCAGCAAGAGGAACAGAAAGAGAAACTGAGGAAGGAAGAACAAGAA
CAAAAAGCCAAAAAGAAACAAGAAGCTGAAGAAAATGAAATTACAGAGAAGCAACAAAAA
GCAAAAGAAGAAATGGAGAAGAAAGAAAGTGAACAGGCCAAGAAAGAAGATAAAGAAACC
TCAGCAAAGAGGGGCAAAGAAATAACAGGAGTAAAAAGACAAAGTAAAAGTGAACATGAA
ACTTCTGATGCCAAGAAATCTGTAGAAGATAGGGGGAAAAGGTGTCCAACCCCAGAAATA
CAGAAAAAGTCAACAGGAGATGTGCCCCATACATCTGTGACAGGGGATTCAGGTTCAGGC
AAGCCATTTAAGATTAAAGGACAACCAGAAAGTGGAATTCTAAGGACAGGAACTTTTAGA
GAGGATACAGACGATACCGAAAGAAATAAAGCTCAACGAGAACCTTTGACAAGAGCACGA
AGTGAAGAAATGGGGAGGATCGTACCAGGACTGCCTTCAGGCTGGGCCAAGTTTCTTGAC
CCAATCACTGGAACCTTTCGTTATTATCATTCACCCACCAACACTGTTCATATGTACCCA
CCGGAAATGGCTCCTTCATCTGCACCTCCTTCCACCCCTCCAACTCATAAAGCCAAGCCA
CAGATTCCTGCTGAGCGGGATAGGGAACCTTCCAAACTGAAGCGCTCCTACTCCTCCCCA
GATATAACCCAGGCTATTCAAGAGGAAGAGAAGAGGAAGCCAACAGTAACTCCAACAGTT
AATCGGGAAAACAAGCCAACATGTTATCCTAAAGCTGAGATCTCAAGGCTTTCTGCTTCT
CAGATTCGGAACCTCAATCCTGTTTTTGGAGGTTCTGGACCAGCTCTTACTGGACTTCGT
AACTTAGGAAATACTTGTTATATGAACTCAATATTGCAGTGCCTATGTAACGCTCCACAT
TTGGCTGATTATTTCAACCGAAACTGTTATCAGGATGATATTAACAGGTCAAATTTGTTG
GGGCATAAAGGTGAAGTGGCAGAAGAATTTGGTATAATCATGAAAGCCCTGTGGACAGGA
CAGTATAGATATATCAGTCCAAAGGACTTTAAAATCACCATTGGGAAGATCAATGACCAG
TTTGCAGGATACAGTCAGCAAGATTCACAAGAATTGCTTCTGTTCCTAATGGATGGTCTC
CATGAAGATCTAAATAAAGCTGATAATCGGAAGAGATATAAAGAAGAAAATAATGATCAT
CTCGATGACTTTAAAGCTGCAGAACATGCCTGGCAGAAACACAAGCAGCTCAATGAGTCT
ATTATTGTTGCACTTTTTCAGGGTCAATTCAAATCTACAGTACAGTGCCTCACATGTCAC
AAAAAGTCTAGGACATTTGAGGCCTTCATGTATTTGTCTCTACCACTAGCATCCACAAGT
AAATGTACATTACAGGATTGCCTTAGATTATTTTCCAAAGAAGAAAAACTCACAGATAAC
AACAGATTTTACTGCAGTCATTGCAGAGCTCGACGGGATTCTCTAAAAAAGATAGAAATC
TGGAAGTTACCACCTGTGCTTTTAGTGCATCTGAAACGTTTTTCCTACGATGGCAGGTGG
AAACAAAAATTACAGACATCTGTGGACTTCCCGTTAGAAAATCTTGACTTGTCACAGTAT
GTTATTGGTCCAAAGAACAATTTGAAGAAATATAATTTGTTTTCTGTTTCAAATCACTAC
GGTGGGCTGGATGGAGGCCACTACACAGCCTATTGTAAAAATGCAGCAAGACAACGGTGG
TTTAAGTTTGATGATCATGAAGTTTCTGATATCTCCGTTTCTTCTGTGAAATCTTCAGCA
GCTTATATCCTCTTTTATACTTCATTGGGACCACGAGTAACTGATGTAGCCACATAA
Protein Properties
Number of Residues 1118
Molecular Weight 127522.2
Theoretical pI 8.75
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Ubiquitin carboxyl-terminal hydrolase 8
MPAVASVPKELYLSSSLKDLNKKTEVKPEKISTKSYVHSALKIFKTAEECRLDRDEERAY
VLYMKYVTVYNLIKKRPDFKQQQDYFHSILGPGNIKKAVEEAERLSESLKLRYEEAEVRK
KLEEKDRQEEAQRLQQKRQETGREDGGTLAKGSLENVLDSKDKTQKSNGEKNEKCETKEK
GAITAKELYTMMTDKNISLIIMDARRMQDYQDSCILHSLSVPEEAISPGVTASWIEAHLP
DDSKDTWKKRGNVEYVVLLDWFSSAKDLQIGTTLRSLKDALFKWESKTVLRNEPLVLEGG
YENWLLCYPQYTTNAKVTPPPRRQNEEVSISLDFTYPSLEESIPSKPAAQTPPASIEVDE
NIELISGQNERMGPLNISTPVEPVAASKSDVSPIIQPVPSIKNVPQIDRTKKPAVKLPEE
HRIKSESTNHEQQSPQSGKVIPDRSTKPVVFSPTLMLTDEEKARIHAETALLMEKNKQEK
ELRERQQEEQKEKLRKEEQEQKAKKKQEAEENEITEKQQKAKEEMEKKESEQAKKEDKET
SAKRGKEITGVKRQSKSEHETSDAKKSVEDRGKRCPTPEIQKKSTGDVPHTSVTGDSGSG
KPFKIKGQPESGILRTGTFREDTDDTERNKAQREPLTRARSEEMGRIVPGLPSGWAKFLD
PITGTFRYYHSPTNTVHMYPPEMAPSSAPPSTPPTHKAKPQIPAERDREPSKLKRSYSSP
DITQAIQEEEKRKPTVTPTVNRENKPTCYPKAEISRLSASQIRNLNPVFGGSGPALTGLR
NLGNTCYMNSILQCLCNAPHLADYFNRNCYQDDINRSNLLGHKGEVAEEFGIIMKALWTG
QYRYISPKDFKITIGKINDQFAGYSQQDSQELLLFLMDGLHEDLNKADNRKRYKEENNDH
LDDFKAAEHAWQKHKQLNESIIVALFQGQFKSTVQCLTCHKKSRTFEAFMYLSLPLASTS
KCTLQDCLRLFSKEEKLTDNNRFYCSHCRARRDSLKKIEIWKLPPVLLVHLKRFSYDGRW
KQKLQTSVDFPLENLDLSQYVIGPKNNLKKYNLFSVSNHYGGLDGGHYTAYCKNAARQRW
FKFDDHEVSDISVSSVKSSAAYILFYTSLGPRVTDVAT
GenBank ID Protein 83405557
UniProtKB/Swiss-Prot ID P40818
UniProtKB/Swiss-Prot Entry Name UBP8_HUMAN
PDB IDs
GenBank Gene ID BC110590
GeneCard ID USP8
GenAtlas ID USP8
HGNC ID HGNC:12631
References
General References
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  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. Yu LR, Zhu Z, Chan KC, Issaq HJ, Dimitrov DS, Veenstra TD: Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra. J Proteome Res. 2007 Nov;6(11):4150-62. Epub 2007 Oct 9. [PubMed:17924679 ]
  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. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [PubMed:17974005 ]
  7. Nomura N, Nagase T, Miyajima N, Sazuka T, Tanaka A, Sato S, Seki N, Kawarabayasi Y, Ishikawa K, Tabata S: Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1. DNA Res. 1994;1(5):223-9. [PubMed:7584044 ]
  8. Naviglio S, Mattecucci C, Matoskova B, Nagase T, Nomura N, Di Fiore PP, Draetta GF: UBPY: a growth-regulated human ubiquitin isopeptidase. EMBO J. 1998 Jun 15;17(12):3241-50. [PubMed:9628861 ]
  9. Row PE, Prior IA, McCullough J, Clague MJ, Urbe S: The ubiquitin isopeptidase UBPY regulates endosomal ubiquitin dynamics and is essential for receptor down-regulation. J Biol Chem. 2006 May 5;281(18):12618-24. Epub 2006 Mar 6. [PubMed:16520378 ]
  10. Row PE, Liu H, Hayes S, Welchman R, Charalabous P, Hofmann K, Clague MJ, Sanderson CM, Urbe S: The MIT domain of UBPY constitutes a CHMP binding and endosomal localization signal required for efficient epidermal growth factor receptor degradation. J Biol Chem. 2007 Oct 19;282(42):30929-37. Epub 2007 Aug 21. [PubMed:17711858 ]
  11. Waters S, Marchbank K, Solomon E, Whitehouse C, Gautel M: Interactions with LC3 and polyubiquitin chains link nbr1 to autophagic protein turnover. FEBS Lett. 2009 Jun 18;583(12):1846-52. doi: 10.1016/j.febslet.2009.04.049. Epub 2009 May 8. [PubMed:19427866 ]
  12. Agromayor M, Carlton JG, Phelan JP, Matthews DR, Carlin LM, Ameer-Beg S, Bowers K, Martin-Serrano J: Essential role of hIST1 in cytokinesis. Mol Biol Cell. 2009 Mar;20(5):1374-87. doi: 10.1091/mbc.E08-05-0474. Epub 2009 Jan 7. [PubMed:19129480 ]
  13. Avvakumov GV, Walker JR, Xue S, Finerty PJ Jr, Mackenzie F, Newman EM, Dhe-Paganon S: Amino-terminal dimerization, NRDP1-rhodanese interaction, and inhibited catalytic domain conformation of the ubiquitin-specific protease 8 (USP8). J Biol Chem. 2006 Dec 8;281(49):38061-70. Epub 2006 Oct 11. [PubMed:17035239 ]