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USP6 (ubiquitin specific protease 6 (Tre-2 oncogene))

Written2005-04Andre M Oliveira, Margaret Chou
Department of Pathology, Laboratory Medicine, Mayo Clinic, Mayo Foundation, 200 First Street SW, Rochester, MN 55905, USA

(Note : for Links provided by Atlas : click)

Identity

Other namesTRE2
TRE17
HGNC (Hugo) USP6
LocusID (NCBI) 9098
Atlas_Id 530
Location 17p13.2  [Link to chromosome band 17p13]
Location_base_pair Starts at 5019733 and ends at 5078326 bp from pter ( according to hg19-Feb_2009)  [Mapping USP6.png]
Fusion genes
(updated 2016)
CDH11 (16q21) / USP6 (17p13.2)CENPP (9q22.31) / USP6 (17p13.2)CNBP (3q21.3) / USP6 (17p13.2)
COL1A1 (17q21.33) / USP6 (17p13.2)LOC100130950 (17p13.2) / USP6 (17p13.2)MYH9 (22q12.3) / USP6 (17p13.2)
OMD (9q22.31) / USP6 (17p13.2)SS18 (18q11.2) / USP6 (17p13.2)THRAP3 (1p34.3) / USP6 (17p13.2)
USP6 (17p13.2) / CDH11 (16q21)USP6 (17p13.2) / CNBP (3q21.3)USP6 (17p13.2) / COL1A1 (17q21.33)
USP6 (17p13.2) / OMD (9q22.31)USP6 (17p13.2) / THRAP3 (1p34.3)USP6 (17p13.2) / ZNF9 ()
Note The gene is the result of a recent evolutionary fusion of two other genes - TBC1D3 (PRC17) on chromosome 17q12 and USP32 (NY-REN-60) on chromosome 17q22 (see below).

DNA/RNA

Description 30 exons spanning 47 kb of genomic DNA. Exons 1 to 14 are derived from the TBC1D3 (PRC17), and exons 15 to 30 are derived from the USP32 (NY-REN-60).
Transcription The gene is transcribed from telomere to centromere. The coding region starts on exon 2 but many splicing variants have been identified in the untranslated exon 1. There are at least two major transcripts with an approximate lenght of 8 kb.

Protein

 
Description USP6 encodes for a 1406 aminoacid protein containing two major domains: TBC (from TRE2-Bub2-Cdc16), which encodes a GTPase-activating protein of the Rab family of GTPases, and a UBP domain with a ubiquitin specific protease activity. A USP6 splicing variant, also known as 'onco-TRE17 or TRE17-onco', encodes a 786 aminoacid protein with a truncated UBP domain. See figure 1.
Expression Among normal tissues, USP6 seems to primarily expressed in testes.
Localisation Cytoplasmic protein.
Function USP6 function is still poorly understood but recent evidence has shown that USP6 is involved in endocytic trafficking. USP6 seems to operate in the same pathway controlled by Arf6 GTPase, which has been linked to mitogenic signaling and invasive behavior.
Homology While the N-terminal portion of USP6 is highly homologous to PRC17 (89% identity), the C-terminal end is highly homologous to USP32 (97% identity).

Implicated in

Note
Disease Aneurysmal Bone Cyst or Aneurysmal Bone Tumor
Cytogenetics Rearrangements of 17p13 with different partner chromosomes.
Hybrid/Mutated Gene USP6 fusion genes are formed by juxtaposition of USP6 coding sequences to the promoter regions of several partner genes, which lead to USP6 transcriptional upregulation. There is no fusion protein.
  • THRAP3 -USP6 in t(1;17)(p34;p13)
  • ZNF9 -USP6 in t(3;17)(q21;p13)
  • OMD -USP6 in t(9;17)(q22;p13)
  • CDH11 -USP6 in t(16;17)(q22;p13)
  • COL1A1 -USP6 in t(17;17)(q12;p13)
  •  
      

    Breakpoints

     

    Bibliography

    A rearranged transforming gene, tre, is made up of human sequences derived from chromosome regions 5q, 17q and 18q.
    Huebner K, Cannizzaro LA, Nakamura T, Hillova J, Mariage-Samson R, Hecht F, Hill M, Croce CM
    Oncogene. 1988 ; 3 (4) : 449-455.
    PMID 3274085
     
    The TBC (Tre-2/Bub2/Cdc16) domain protein TRE17 regulates plasma membrane-endosomal trafficking through activation of Arf6.
    Martinu L, Masuda-Robens JM, Robertson SE, Santy LC, Casanova JE, Chou MM
    Molecular and cellular biology. 2004 ; 24 (22) : 9752-9762.
    PMID 15509780
     
    Endocytosis of epidermal growth factor receptor regulated by Grb2-mediated recruitment of the Rab5 GTPase-activating protein RN-tre.
    Martinu L, Santiago-Walker A, Qi H, Chou MM
    The Journal of biological chemistry. 2002 ; 277 (52) : 50996-51002.
    PMID 12399475
     
    The TRE17 oncogene encodes a component of a novel effector pathway for Rho GTPases Cdc42 and Rac1 and stimulates actin remodeling.
    Masuda-Robens JM, Kutney SN, Qi H, Chou MM
    Molecular and cellular biology. 2003 ; 23 (6) : 2151-2161.
    PMID 12612085
     
    A novel transcriptional unit of the tre oncogene widely expressed in human cancer cells.
    Nakamura T, Hillova J, Mariage-Samson R, Onno M, Huebner K, Cannizzaro LA, Boghosian-Sell L, Croce CM, Hill M
    Oncogene. 1992 ; 7 (4) : 733-741.
    PMID 1565468
     
    Aneurysmal bone cyst variant translocations upregulate USP6 transcription by promoter swapping with the ZNF9, COL1A1, TRAP150, and OMD genes.
    Oliveira AM, Perez-Atayde AR, Dal Cin P, Gebhardt MC, Chen CJ, Neff JR, Demetri GD, Rosenberg AE, Bridge JA, Fletcher JA
    Oncogene. 2005 ; 24 (21) : 3419-3426.
    PMID 15735689
     
    The Tre2 (USP6) oncogene is a hominoid-specific gene.
    Paulding CA, Ruvolo M, Haber DA
    Proceedings of the National Academy of Sciences of the United States of America. 2003 ; 100 (5) : 2507-2511.
    PMID 12604796
     

    Citation

    This paper should be referenced as such :
    Oliveira, AM ; Chou, M
    USP6 (ubiquitin specific protease 6 (Tre-2 oncogene))
    Atlas Genet Cytogenet Oncol Haematol. 2005;9(3):222-223.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Genes/USP6ID530ch17p13.html


    Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 7 ]
      Bone: Aneurysmal bone cysts
    Bone tumors: an overview
    Soft tissue tumors: an overview
    Bone: Aneurysmal bone cyst with t(1;17)(p34;p13) THRAP3/USP6
    Bone: Aneurysmal bone cyst with t(3;17)(q21;p13) CNBP/USP6
    Bone: Aneurysmal bone cyst with t(9;17)(q22;p13) OMD/USP6
    Bone: Aneurysmal bone cyst with t(16;17)(q22;p13) CDH11/USP6
    Bone: Aneurysmal bone cyst with t(17;17)(p13;q21) COL1A1/USP6

    External links

    Nomenclature
    HGNC (Hugo)USP6   12629
    Cards
    AtlasUSP6ID530ch17p13
    Entrez_Gene (NCBI)USP6  9098  ubiquitin specific peptidase 6
    AliasesHRP1; TRE17; TRE2; TRESMCR; 
    Tre-2; USP6-short
    GeneCards (Weizmann)USP6
    Ensembl hg19 (Hinxton)ENSG00000129204 [Gene_View]  chr17:5019733-5078326 [Contig_View]  USP6 [Vega]
    Ensembl hg38 (Hinxton)ENSG00000129204 [Gene_View]  chr17:5019733-5078326 [Contig_View]  USP6 [Vega]
    ICGC DataPortalENSG00000129204
    TCGA cBioPortalUSP6
    AceView (NCBI)USP6
    Genatlas (Paris)USP6
    WikiGenes9098
    SOURCE (Princeton)USP6
    Genomic and cartography
    GoldenPath hg19 (UCSC)USP6  -     chr17:5019733-5078326 +  17p13   [Description]    (hg19-Feb_2009)
    GoldenPath hg38 (UCSC)USP6  -     17p13   [Description]    (hg38-Dec_2013)
    EnsemblUSP6 - 17p13 [CytoView hg19]  USP6 - 17p13 [CytoView hg38]
    Mapping of homologs : NCBIUSP6 [Mapview hg19]  USP6 [Mapview hg38]
    OMIM604334   
    Gene and transcription
    Genbank (Entrez)AB449915 AY143550 BC029495 BC169209 BX647719
    RefSeq transcript (Entrez)NM_001304284 NM_004505 NM_005152
    RefSeq genomic (Entrez)NC_000017 NC_018928 NT_010718 NW_004929405
    Consensus coding sequences : CCDS (NCBI)USP6
    Cluster EST : UnigeneHs.448851 [ NCBI ]
    CGAP (NCI)Hs.448851
    Alternative Splicing GalleryENSG00000129204
    Gene ExpressionUSP6 [ NCBI-GEO ]   USP6 [ EBI - ARRAY_EXPRESS ]   USP6 [ SEEK ]   USP6 [ MEM ]
    Gene Expression Viewer (FireBrowse)USP6 [ Firebrowse - Broad ]
    SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
    GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
    BioGPS (Tissue expression)9098
    GTEX Portal (Tissue expression)USP6
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtP35125 (Uniprot)
    NextProtP35125  [Sequence]  [Exons]  [Medical]  [Publications]
    With graphics : InterProP35125
    Splice isoforms : SwissVarP35125 (Swissvar)
    Catalytic activity : Enzyme3.4.19.12 [ Enzyme-Expasy ]   3.4.19.123.4.19.12 [ IntEnz-EBI ]   3.4.19.12 [ BRENDA ]   3.4.19.12 [ KEGG ]   
    PhosPhoSitePlusP35125
    Domaine pattern : Prosite (Expaxy)TBC_RABGAP (PS50086)    USP_1 (PS00972)    USP_2 (PS00973)    USP_3 (PS50235)   
    Domains : Interpro (EBI)Peptidase_C19_UCH    Rab-GTPase-TBC_dom    USP_CS    USP_dom   
    Domain families : Pfam (Sanger)RabGAP-TBC (PF00566)    UCH (PF00443)   
    Domain families : Pfam (NCBI)pfam00566    pfam00443   
    Domain families : Smart (EMBL)TBC (SM00164)  
    DMDM Disease mutations9098
    Blocks (Seattle)USP6
    SuperfamilyP35125
    Human Protein AtlasENSG00000129204
    Peptide AtlasP35125
    HPRD06827
    IPIIPI00423562   IPI00423563   IPI00423565   IPI01014191   IPI00815911   
    Protein Interaction databases
    DIP (DOE-UCLA)P35125
    IntAct (EBI)P35125
    FunCoupENSG00000129204
    BioGRIDUSP6
    STRING (EMBL)USP6
    ZODIACUSP6
    Ontologies - Pathways
    QuickGOP35125
    Ontology : AmiGOnucleic acid binding  cysteine-type endopeptidase activity  thiol-dependent ubiquitin-specific protease activity  protein binding  calmodulin binding  cytoplasm  lysosome  plasma membrane  cellular protein modification process  ubiquitin-dependent protein catabolic process  protein deubiquitination  recycling endosome  regulation of vesicle-mediated transport  
    Ontology : EGO-EBInucleic acid binding  cysteine-type endopeptidase activity  thiol-dependent ubiquitin-specific protease activity  protein binding  calmodulin binding  cytoplasm  lysosome  plasma membrane  cellular protein modification process  ubiquitin-dependent protein catabolic process  protein deubiquitination  recycling endosome  regulation of vesicle-mediated transport  
    NDEx NetworkUSP6
    Atlas of Cancer Signalling NetworkUSP6
    Wikipedia pathwaysUSP6
    Orthology - Evolution
    OrthoDB9098
    GeneTree (enSembl)ENSG00000129204
    Phylogenetic Trees/Animal Genes : TreeFamUSP6
    Homologs : HomoloGeneUSP6
    Homology/Alignments : Family Browser (UCSC)USP6
    Gene fusions - Rearrangements
    Fusion : MitelmanCDH11/USP6 [16q21/17p13.2]  [t(16;17)(q21;p13)]  
    Fusion : MitelmanCNBP/USP6 [3q21.3/17p13.2]  [t(3;7)(q21;p13)]  
    Fusion : MitelmanCOL1A1/USP6 [17q21.33/17p13.2]  [t(17;17)(p13;q21)]  
    Fusion : MitelmanMYH9/USP6 [22q12.3/17p13.2]  [t(17;22)(p13;q12)]  
    Fusion : MitelmanOMD/USP6 [9q22.31/17p13.2]  [t(9;17)(q22;p13)]  
    Fusion : MitelmanTHRAP3/USP6 [1p34.3/17p13.2]  [t(1;17)(p34;p13)]  
    Fusion : MitelmanUSP6/COL1A1 [17p13.2/17q21.33]  [t(17;17)(p13;q21)]  
    Fusion : COSMICTHRAP3 [1p34.3]  -  USP6 [17p13.2]  [fusion_1410]  [fusion_1411]  
    Fusion : TICdbCNBP [3q21.3]  -  USP6 [17p13.2]
    Fusion : TICdbCOL1A1 [17q21.33]  -  USP6 [17p13.2]
    Fusion : TICdbTHRAP3 [1p34.3]  -  USP6 [17p13.2]
    Polymorphisms : SNP, variants
    NCBI Variation ViewerUSP6 [hg38]
    dbSNP Single Nucleotide Polymorphism (NCBI)USP6
    dbVarUSP6
    ClinVarUSP6
    1000_GenomesUSP6 
    Exome Variant ServerUSP6
    ExAC (Exome Aggregation Consortium)USP6 (select the gene name)
    Genetic variants : HAPMAP9098
    Genomic Variants (DGV)USP6 [DGVbeta]
    Mutations
    ICGC Data PortalUSP6 
    TCGA Data PortalUSP6 
    Broad Tumor PortalUSP6
    OASIS PortalUSP6 [ Somatic mutations - Copy number]
    Cancer Gene: CensusUSP6 
    Somatic Mutations in Cancer : COSMICUSP6 
    intOGen PortalUSP6
    LOVD (Leiden Open Variation Database)Whole genome datasets
    LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
    LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
    BioMutasearch USP6
    DgiDB (Drug Gene Interaction Database)USP6
    DoCM (Curated mutations)USP6 (select the gene name)
    CIViC (Clinical Interpretations of Variants in Cancer)USP6 (select a term)
    intoGenUSP6
    Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
    Diseases
    DECIPHER (Syndromes)17:5019733-5078326  ENSG00000129204
    CONAN: Copy Number AnalysisUSP6 
    Mutations and Diseases : HGMDUSP6
    OMIM604334   
    MedgenUSP6
    Genetic Testing Registry USP6
    NextProtP35125 [Medical]
    TSGene9098
    GENETestsUSP6
    Huge Navigator USP6 [HugePedia]
    snp3D : Map Gene to Disease9098
    BioCentury BCIQUSP6
    ClinGenUSP6
    Clinical trials, drugs, therapy
    Chemical/Protein Interactions : CTD9098
    Chemical/Pharm GKB GenePA37254
    Clinical trialUSP6
    Miscellaneous
    canSAR (ICR)USP6 (select the gene name)
    Probes
    Litterature
    PubMed36 Pubmed reference(s) in Entrez
    GeneRIFsGene References Into Functions (Entrez)
    CoreMineUSP6
    EVEXUSP6
    GoPubMedUSP6
    iHOPUSP6
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

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    indexed on : Mon Sep 19 19:35:12 CEST 2016

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