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| Identification |
|---|
| HMDB Protein ID
| HMDBP10134 |
| Secondary Accession Numbers
| |
| Name
| Ubiquitin carboxyl-terminal hydrolase 6 |
| Synonyms
|
- Deubiquitinating enzyme 6
- Proto-oncogene TRE-2
- Ubiquitin thiolesterase 6
- Ubiquitin-specific-processing protease 6
|
| Gene Name
| USP6 |
| Protein Type
| Enzyme |
| Biological Properties |
|---|
| General Function
| Involved in ubiquitin thiolesterase activity |
| Specific Function
| Deubiquitinase with an ATP-independent isopeptidase activity, cleaving at the C-terminus of the ubiquitin moiety. Catalyzes its own deubiquitination. In vitro, isoform 2, but not isoform 3, shows deubiquitinating activity. Promotes plasma membrane localization of ARF6 and selectively regulates ARF6- dependent endocytic protein trafficking. Is able to initiate tumorigenesis by inducing the production of matrix metalloproteinases following NF-kappa-B activation |
| Pathways
|
Not Available
|
| Reactions
| Not Available |
| GO Classification
|
| Component |
| cell part |
| intracellular |
| Function |
| small gtpase regulator activity |
| hydrolase activity, acting on ester bonds |
| catalytic activity |
| hydrolase activity |
| ras gtpase activator activity |
| rab gtpase activator activity |
| enzyme regulator activity |
| ubiquitin thiolesterase activity |
| nucleoside-triphosphatase regulator activity |
| gtpase regulator activity |
| thiolester hydrolase activity |
| Process |
| metabolic process |
| regulation of rab gtpase activity |
| biological regulation |
| regulation of biological process |
| regulation of 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 |
| regulation of cellular metabolic process |
| regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolic process |
| regulation of nucleotide metabolic process |
| regulation of nucleotide catabolic process |
| regulation of purine nucleotide catabolic process |
| regulation of gtp catabolic process |
| regulation of gtpase activity |
| regulation of ras gtpase activity |
|
| Cellular Location
|
- Cell membrane
- Cytoplasm
- Endosome
|
| Gene Properties |
|---|
| Chromosome Location
| Chromosome:1 |
| Locus
| 17p13 |
| SNPs
| USP6 |
| Gene Sequence
|
>4221 bp
ATGGACATGGTAGAGAATGCAGATAGTTTGCAGGCACAGGAGCGGAAGGACATACTTATG
AAGTATGACAAGGGACACCGAGCTGGGCTGCCAGAGGACAAGGGGCCTGAGCCCGTTGGA
ATCAACAGCAGCATTGATCGTTTTGGCATTTTGCATGAGACGGAGCTGCCTCCTGTGACT
GCACGGGAGGCGAAGAAAATTCGGCGGGAGATGACACGAACGAGCAAGTGGATGGAAATG
CTGGGAGAATGGGAGACATATAAGCACAGTAGCAAACTCATAGATCGAGTGTACAAGGGA
ATTCCCATGAACATCCGGGGCCCGGTGTGGTCAGTCCTCCTGAACATTCAGGAAATCAAG
TTGAAAAACCCCGGAAGATACCAGATCATGAAGGAGAGGGGCAAGAGGTCATCTGAACAC
ATCCACCACATCGACCTGGACGTGAGGACGACTCTCCGGAACCATGTCTTCTTTAGGGAT
CGATATGGAGCCAAGCAGAGGGAACTATTCTACATCCTCCTGGCCTATTCGGAGTATAAC
CCGGAGGTGGGCTACTGCAGGGACCTGAGCCACATCACCGCCTTGTTCCTCCTTTATCTG
CCTGAGGAGGACGCATTCTGGGCACTGGTGCAGCTGCTGGCCAGTGAGAGGCACTCCCTG
CCAGGATTCCACAGCCCAAATGGTGGGACAGTCCAGGGGCTCCAAGACCAACAGGAGCAT
GTGGTACCCAAGTCACAACCCAAGACCATGTGGCATCAGGACAAGGAAGGTCTATGCGGG
CAGTGTGCCTCGTTAGGCTGCCTTCTCCGGAACCTGATTGACGGGATCTCTCTCGGGCTC
ACCCTGCGCCTGTGGGACGTGTATTTGGTGGAAGGAGAACAGGTGTTGATGCCAATAACC
AGCATTGCTCTTAAGGTTCAGCAGAAGCGCCTCATGAAGACATCCAGGTGTGGCCTGTGG
GCACGTCTGCGGAACCAATTCTTCGATACCTGGGCCATGAACGATGACACCGTGCTCAAG
CATCTTAGGGCCTCTACGAAGAAACTAACAAGGAAGCAAGGGGACCTGCCACCCCCAGCC
AAACGCGAGCAAGGGTCCTTGGCACCCAGGCCTGTGCCGGCTTCACGTGGTGGGAAGACC
CTCTGCAAGGGGTATAGGCAGGCCCCTCCAGGCCCACCAGCCCAGTTCCAGCGGCCCATT
TGCTCAGCTTCCCCGCCATGGGCATCTCGTTTTTCCACGCCCTGTCCTGGTGGGGCTGTC
CGGGAAGACACGTACCCTGTGGGCACTCAGGGTGTGCCCAGCCTGGCCCTGGCTCAGGGA
GGACCTCAGGGTTCCTGGAGATTCCTGGAGTGGAAGTCAATGCCCCGGCTCCCAACGGAC
CTGGATATAGGGGGCCCTTGGTTCCCCCATTATGATTTTGAATGGAGCTGCTGGGTCCGT
GCCATATCCCAGGAGGACCAGCTGGCCACCTGCTGGCAGGCTGAACACTGCGGAGAGGTT
CACAACAAAGATATGAGTTGGCCTGAGGAGATGTCTTTTACAGCAAATAGTAGTAAAATA
GATAGACAAAAGGTTCCCACAGAAAAGGGAGCCACAGGTCTAAGCAACCTGGGAAACACA
TGCTTCATGAACTCAAGCATCCAGTGCGTTAGTAACACACAGCCACTGACACAGTATTTT
ATCTCAGGGAGACATCTTTATGAACTCAACAGGACAAATCCCATTGGTATGAAGGGGCAT
ATGGCTAAATGCTATGGTGATTTAGTGCAGGAACTCTGGAGTGGAACTCAGAAGAGTGTT
GCCCCATTAAAGCTTCGGCGGACCATAGCAAAATATGCTCCCAAGTTTGATGGGTTTCAG
CAACAAGACTCCCAAGAACTTCTGGCTTTTCTCTTGGATGGTCTTCATGAAGATCTCAAC
CGAGTCCATGAAAAGCCATATGTGGAACTGAAGGACAGTGATGGCCGACCAGACTGGGAA
GTAGCTGCAGAGGCCTGGGACAACCATCTAAGAAGAAATAGATCAATTATTGTGGATTTG
TTCCATGGGCAGCTAAGATCTCAAGTCAAATGCAAGACATGTGGGCATATAAGTGTCCGA
TTTGACCCTTTCAATTTTTTGTCTTTGCCACTACCAATGGACAGTTACATGGACTTAGAA
ATAACAGTGATTAAGTTAGATGGTACTACCCCTGTACGGTATGGACTAAGACTGAATATG
GATGAAAAGTACACAGGTTTAAAAAAACAGCTGAGGGATCTCTGTGGACTTAATTCAGAA
CAAATCCTACTAGCAGAAGTACATGATTCCAACATAAAGAACTTTCCTCAGGATAACCAA
AAAGTACAACTCTCAGTGAGCGGATTTTTGTGTGCATTTGAAATTCCTGTCCCTTCATCT
CCAATTTCAGCTTCTAGTCCAACACAAATAGATTTCTCCTCTTCACCATCTACAAATGGA
ATGTTCACCCTAACTACCAATGGGGACCTACCCAAACCAATATTCATCCCCAATGGAATG
CCAAACACTGTTGTGCCATGTGGAACTGAGAAGAACTTCACAAATGGAATGGTTAATGGT
CACATGCCATCTCTTCCTGACAGCCCCTTTACAGGTTACATCATTGCAGTCCACCGAAAA
ATGATGAGGACAGAACTGTATTTCCTGTCACCTCAGGAGAATCGCCCCAGCCTCTTTGGA
ATGCCATTGATTGTTCCATGCACTGTGCATACCCGGAAGAAAGACCTATATGATGCGGTT
TGGATTCAAGTATCCTGGTTAGCAAGACCACTCCCACCTCAGGAAGCTAGTATTCATGCC
CAGGATCGTGATAACTGTATGGGCTATCAATATCCATTCACTCTACGAGTTGTGCAGAAA
GATGGGAACTCCTGTGCTTGGTGCCCACAGTATAGATTTTGCAGAGGCTGTAAAATTGAT
TGTGGGGAAGACAGAGCTTTCATTGGAAATGCCTATATTGCTGTGGATTGGCACCCCACA
GCCCTTCACCTTCGCTATCAAACATCCCAGGAAAGGGTTGTAGATAAGCATGAGAGTGTG
GAGCAGAGTCGGCGAGCGCAAGCCGAGCCCATCAACCTGGACAGCTGTCTCCGTGCTTTC
ACCAGTGAGGAAGAGCTAGGGGAAAGTGAGATGTACTACTGTTCCAAGTGTAAGACCCAC
TGCTTAGCAACAAAGAAGCTGGATCTCTGGAGGCTTCCACCCTTCCTGATTATTCACCTT
AAGCGATTTCAATTTGTAAATGATCAGTGGATAAAATCACAGAAAATTGTCAGATTTCTT
CGGGAAAGTTTTGATCCGAGTGCTTTTTTGGTACCACGAGACCCGGCCCTCTGCCAGCAT
AAACCACTCACACCCCAGGGGGATGAGCTCTCCAAGCCCAGGATTCTGGCAAGAGAGGTG
AAGAAAGTGGATGCGCAGAGTTCGGCTGGAAAAGAGGACATGCTCCTAAGCAAAAGCCCA
TCCTCACTCAGCGCTAACATCAGCAGCAGCCCAAAAGGTTCTCCTTCTTCATCAAGAAAA
AGTGGAACCAGCTGTCCCTCCAGCAAAAACAGCAGCCCTAATAGCAGCCCACGGACTTTG
GGGAGGAGCAAAGGGAGGCTCCGGCTGCCCCAGATTGGCAGCAAAAATAAGCCGTCAAGT
AGTAAGAAGAACTTGGATGCCAGCAAAGAGAATGGGGCTGGGCAGATCTGTGAGCTGGCT
GACGCCTTGAGCCGAGGGCATATGCGGGGGGGCAGCCAACCAGAGCTGGTCACTCCTCAG
GACCATGAGGTAGCTTTGGCCAATGGATTCCTTTATGAGCATGAAGCATGTGGCAATGGC
TGTGGCGATGGCTACAGCAATGGTCAGCTTGGAAACCACAGTGAAGAAGACAGCACTGAT
GACCAAAGAGAAGACACTCATATTAAGCCTATTTATAATCTATATGCAATTTCATGCCAT
TCAGGAATTCTGAGTGGGGGCCATTACATCACTTATGCCAAAAACCCAAACTGCAAGTGG
TACTGTTATAATGACAGCAGCTGTGAGGAACTTCACCCTGATGAAATTGACACCGACTCT
GCCTACATTCTTTTCTATGAGCAGCAGGGGATAGACTACGCACAATTTCTGCCAAAGATT
GATGGCAAAAAGATGGCAGACACAAGCAGTACGGATGAAGACTCTGAGTCTGATTACGAA
AAGTACTCTATGTTACAGTAA
|
| Protein Properties |
|---|
| Number of Residues
| 1406 |
| Molecular Weight
| 158656.8 |
| Theoretical pI
| 7.75 |
| Pfam Domain Function
|
|
| Signals
|
|
|
Transmembrane Regions
|
|
| Protein Sequence
|
>Ubiquitin carboxyl-terminal hydrolase 6
MDMVENADSLQAQERKDILMKYDKGHRAGLPEDKGPEPVGINSSIDRFGILHETELPPVT
AREAKKIRREMTRTSKWMEMLGEWETYKHSSKLIDRVYKGIPMNIRGPVWSVLLNIQEIK
LKNPGRYQIMKERGKRSSEHIHHIDLDVRTTLRNHVFFRDRYGAKQRELFYILLAYSEYN
PEVGYCRDLSHITALFLLYLPEEDAFWALVQLLASERHSLPGFHSPNGGTVQGLQDQQEH
VVPKSQPKTMWHQDKEGLCGQCASLGCLLRNLIDGISLGLTLRLWDVYLVEGEQVLMPIT
SIALKVQQKRLMKTSRCGLWARLRNQFFDTWAMNDDTVLKHLRASTKKLTRKQGDLPPPA
KREQGSLAPRPVPASRGGKTLCKGYRQAPPGPPAQFQRPICSASPPWASRFSTPCPGGAV
REDTYPVGTQGVPSLALAQGGPQGSWRFLEWKSMPRLPTDLDIGGPWFPHYDFEWSCWVR
AISQEDQLATCWQAEHCGEVHNKDMSWPEEMSFTANSSKIDRQKVPTEKGATGLSNLGNT
CFMNSSIQCVSNTQPLTQYFISGRHLYELNRTNPIGMKGHMAKCYGDLVQELWSGTQKSV
APLKLRRTIAKYAPKFDGFQQQDSQELLAFLLDGLHEDLNRVHEKPYVELKDSDGRPDWE
VAAEAWDNHLRRNRSIIVDLFHGQLRSQVKCKTCGHISVRFDPFNFLSLPLPMDSYMDLE
ITVIKLDGTTPVRYGLRLNMDEKYTGLKKQLRDLCGLNSEQILLAEVHDSNIKNFPQDNQ
KVQLSVSGFLCAFEIPVPSSPISASSPTQIDFSSSPSTNGMFTLTTNGDLPKPIFIPNGM
PNTVVPCGTEKNFTNGMVNGHMPSLPDSPFTGYIIAVHRKMMRTELYFLSPQENRPSLFG
MPLIVPCTVHTRKKDLYDAVWIQVSWLARPLPPQEASIHAQDRDNCMGYQYPFTLRVVQK
DGNSCAWCPQYRFCRGCKIDCGEDRAFIGNAYIAVDWHPTALHLRYQTSQERVVDKHESV
EQSRRAQAEPINLDSCLRAFTSEEELGESEMYYCSKCKTHCLATKKLDLWRLPPFLIIHL
KRFQFVNDQWIKSQKIVRFLRESFDPSAFLVPRDPALCQHKPLTPQGDELSKPRILAREV
KKVDAQSSAGKEDMLLSKSPSSLSANISSSPKGSPSSSRKSGTSCPSSKNSSPNSSPRTL
GRSKGRLRLPQIGSKNKPSSSKKNLDASKENGAGQICELADALSRGHMRGGSQPELVTPQ
DHEVALANGFLYEHEACGNGCGDGYSNGQLGNHSEEDSTDDQREDTHIKPIYNLYAISCH
SGILSGGHYITYAKNPNCKWYCYNDSSCEELHPDEIDTDSAYILFYEQQGIDYAQFLPKI
DGKKMADTSSTDEDSESDYEKYSMLQ
|
| External Links |
|---|
| GenBank ID Protein
| 24474450 |
| UniProtKB/Swiss-Prot ID
| P35125 |
| UniProtKB/Swiss-Prot Entry Name
| UBP6_HUMAN |
| PDB IDs
|
Not Available |
| GenBank Gene ID
| AY143550 |
| GeneCard ID
| USP6 |
| GenAtlas ID
| USP6 |
| HGNC ID
| HGNC:12629 |
| References |
|---|
| General References
| - Shen C, Ye Y, Robertson SE, Lau AW, Mak DO, Chou MM: Calcium/calmodulin regulates ubiquitination of the ubiquitin-specific protease TRE17/USP6. J Biol Chem. 2005 Oct 28;280(43):35967-73. Epub 2005 Aug 26. [PubMed:16127172 ]
- Masuda-Robens JM, Kutney SN, Qi H, Chou MM: The TRE17 oncogene encodes a component of a novel effector pathway for Rho GTPases Cdc42 and Rac1 and stimulates actin remodeling. Mol Cell Biol. 2003 Mar;23(6):2151-61. [PubMed:12612085 ]
- Oliveira AM, Hsi BL, Weremowicz S, Rosenberg AE, Dal Cin P, Joseph N, Bridge JA, Perez-Atayde AR, Fletcher JA: USP6 (Tre2) fusion oncogenes in aneurysmal bone cyst. Cancer Res. 2004 Mar 15;64(6):1920-3. [PubMed:15026324 ]
- Martinu L, Masuda-Robens JM, Robertson SE, Santy LC, Casanova JE, Chou MM: The TBC (Tre-2/Bub2/Cdc16) domain protein TRE17 regulates plasma membrane-endosomal trafficking through activation of Arf6. Mol Cell Biol. 2004 Nov;24(22):9752-62. [PubMed:15509780 ]
- Paulding CA, Ruvolo M, Haber DA: The Tre2 (USP6) oncogene is a hominoid-specific gene. Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2507-11. Epub 2003 Feb 25. [PubMed:12604796 ]
- Nakamura T, Hillova J, Mariage-Samson R, Onno M, Huebner K, Cannizzaro LA, Boghosian-Sell L, Croce CM, Hill M: A novel transcriptional unit of the tre oncogene widely expressed in human cancer cells. Oncogene. 1992 Apr;7(4):733-41. [PubMed:1565468 ]
- Papa FR, Hochstrasser M: The yeast DOA4 gene encodes a deubiquitinating enzyme related to a product of the human tre-2 oncogene. Nature. 1993 Nov 25;366(6453):313-9. [PubMed:8247125 ]
- Bizimungu C, De Neve N, Burny A, Bach S, Bontemps F, Portetelle D, Vandenbol M: Expression in a RabGAP yeast mutant of two human homologues, one of which is an oncogene. Biochem Biophys Res Commun. 2003 Oct 17;310(2):498-504. [PubMed:14521938 ]
- Ye Y, Pringle LM, Lau AW, Riquelme DN, Wang H, Jiang T, Lev D, Welman A, Blobel GA, Oliveira AM, Chou MM: TRE17/USP6 oncogene translocated in aneurysmal bone cyst induces matrix metalloproteinase production via activation of NF-kappaB. Oncogene. 2010 Jun 24;29(25):3619-29. doi: 10.1038/onc.2010.116. Epub 2010 Apr 26. [PubMed:20418905 ]
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