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FLASH GENE
Symbol USP6 contributors: mct/pgu - updated : 09-02-2015
HGNC name ubiquitin specific protease 6 (Tre-2 oncogene)
HGNC id 12629
DNA
TYPE functioning gene
STRUCTURE 46.64 kb     30 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Physical map
LOC390758 17 similar to 40S RIBOSOMAL PROTEIN S12 ARRB2 17p13 arrestin, beta 2 CXCL16 17p13 chemokine (C-X-C motif) ligand 16 LOC388322 17 similar to HSPC296 ZMYND15 17p13.3 zinc finger, MYND domain containing 15 TM4SF5 17p13.3 transmembrane 4 superfamily member 5 LOC284013 17p13.3 secretory protein LOC284013 LOC388323 17 similar to RIKEN cDNA C730027E14 PSMB6 17p13 proteasome (prosome, macropain) subunit, beta type, 6 PLD2 17p13.1 phospholipase D2 LOC284015 17p13.3 similar to Vacuolar ATP synthase 16 kDa proteolipid subunit MINK 17p13 similar to Vacuolar ATP synthase 16 kDa proteolipid subunit CHRNE 17p13.1 cholinergic receptor, nicotinic, epsilon polypeptide GP1BA 17pter-p12 glycoprotein Ib (platelet), alpha polypeptide SLC25A11 17p13.3 solute carrier family 25 (mitochondrial carrier; oxoglutarate carrier), member 11 DKFZP566H073 17p13.3 DKFZP566H073 protein PFN1 17p13.3 profilin 1 ENO3 17pter-p12 enolase 3, (beta, muscle) SPAG7 17p13.2 sperm associated antigen 7 CAMTA2 17p13.3 calmodulin binding transcription activator 2 LOC388324 17 LOC388324 KIF1C 17p13 kinesin family member 1C FLJ10060 17p13.3 putative G-protein coupled receptor GPCR42 FLJ30726 17p13.3 hypothetical protein FLJ30726 ZNF232 17p13-p12 zinc finger protein 232 USP6 17q11 ubiquitin specific protease 6 (Tre-2 oncogene) KIAA1871 17p13 KIAA1871 protein LOC388325 17 similar to DTFT5783 RABEP1 17p13.1 rabaptin, RAB GTPase binding effector protein 1 NUP88 17p13.2-p13.1 nucleoporin 88kDa MGC4189 17p13.3 hypothetical protein MGC4189 C1QBP 17p13.3 complement component 1, q subcomponent binding protein DHX33 17p13.2 DEAH (Asp-Glu-Ala-His) box polypeptide 33 F-LANa  carcinoma related gene MIS12 17p13.3 homolog of yeast Mis12
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
30 - 7971 158.5 1406 - 1993 8471161
- - 8524 - 1406 - -
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • at its N terminus a TBC domain,(Tre-2/Bub2/Cdc16) domain predicted to encode GTPase-activating proteins (GAPs) for Rab family G proteins that mediates binding to the ARF6 GTPase
  • a ubiquitin-specific protease at its C terminus
  • HOMOLOGY
    Homologene
    FAMILY
  • peptidase C19 family
  • TBC family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,organelle,lysosome
    basic FUNCTION
  • regulator of the ARF6-regulated plasma membrane recycling system through TBC domains
  • ubiquitin specific protease, clearing bonds between UB and an unfolded polypeptide or UB and small substituents
  • ubiquitin-specific protease (USP), with a TBC domain that mediates binding to the Arf6 GTPase
  • sufficient to induce expression of MMP9 and MMP10, in a manner requiring its USP activity, but not its ability to bind Arf6
  • sufficient to initiate tumorigenesis, and MMPs are novel TRE17 effectors that likely contribute to ABC (aneurysmal bone cyst) pathogenesis
  • role in dysregulation of autocrine bone morphogenetic protein (BMP) signaling is an important mechanism by which USP6 arrests osteoblastic maturation
  • appears to simultaneously inhibit osteoblast maturation and stimulate osteoclast activity
  • critical role for NFKB1 in USP6-mediated tumorigenesis, suggesting that NFKB1 inhibitors may function as effective therapeutic agents in the treatment of aneurysmal bone cyst (ABC)
  • implicated as a key etiological factor in aneurysmal bone cyst (ABC), a locally recurrent pediatric bone tumor,
  • regulator of both cell migration and division
  • ubiquitylation of clathrin-independent endocytosis (CIE) cargo proteins by MARCH8 was reversed by USP6, suggesting that USP6 leads to deubiquitylation of CIE cargo proteins
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • targets the Arf family GTPase ARF6, which regulates plasma membrane-endosome trafficking
  • ubiquitous calcium (Ca2+)-binding protein calmodulin (CALM) is a novel binding partner (CALM1 bound directly to USP in a Ca2+-dependent manner, and regulates ubiquitination)
  • induces transcription of MMP9 through activation of nuclear factor-KB (NF-KB), mediated in part by the GTPase RhoA and its effector kinase, ROCK
  • first de-ubiquitinating enzyme to activate NFKB1
  • oncogenic potential of USP6 is linked to its ability to integrate cell migration and cytokinesis by regulating ARF6/ACAP1
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   translocation    
    translocated at high frequency in aneurysmal bone cyst (ABC), a pediatric osseous neoplasm
    tumoral fusion      
    t(16;17)(q22;p13) the most frequent chromosomal aberration with translocation generating a CDH11-USP6 fusion gene in aneurysmal bone cyst
    tumoral   translocation    
    t(17;17) resulting in a COL1A1-USP6 chimeric gene in aneurysmal bone cyst
    tumoral     --over  
    attenuated osteoblast maturation caused by USP6 overexpression may contribute to the bone loss/destruction observed in aneurysmal bone cyst
    tumoral fusion      
    rearrangements of both USP6 and SS18, but histologic features were consistent with aneurysmal bone cyst throughout the lesion
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS