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FLASH GENE
Symbol USP15 contributors: mct/shn - updated : 25-06-2017
HGNC name ubiquitin specific peptidase 15
HGNC id 12613
Location 12q14.1      Physical location : 62.654.186 - 62.799.898
Synonym name
  • deubiquitinating enzyme
  • ubiquitin specific protease 15
  • ubiquitin carboxyl-terminal hydrolase 15
  • ubiquitin thioesterase 15
  • ubiquitin thiolesterase 15
  • ubiquitin-specific-processing protease 15
    • Synonym symbol(s) KIAA0529, UNPH4, MGC74854, MGC131982, MGC149838, UNPH-2
    EC.number 3.1.2.15/3.4.19.12
    DNA
    TYPE functioning gene
    STRUCTURE 149.38 kb     21 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status provisional
    Map cen - D12S334 - D12S1726 - USP15 - D12S329 - D12S1022 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    21 - 8280 109 952 - 2006 16298993
    22 - 8367 - 981 - 2006 16298993
    7 - 2286 - 235 - 2006 16298993
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately Homo sapiensAdult
    Digestiveintestinesmall intestine  lowly Homo sapiensAdult
     liver   lowly Homo sapiensAdult
    Lymphoid/Immunethymus   lowly Homo sapiensAdult
    Nervousbrain   lowly Homo sapiensAdult
    Reproductivefemale systemplacenta  lowly Homo sapiensAdult
     female systemovary  lowly Homo sapiensAdult
     male systemprostate  lowly Homo sapiensAdult
     male systemtestis  lowly Homo sapiensAdult
    Respiratorylung   lowly Homo sapiensAdult
    Urinarykidney   lowly Homo sapiensAdult
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal moderately Homo sapiensAdult
    cell lineage
    cell lines
    fluid/secretion highly in blood
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal "domain present in ubiquitin specific proteases" (DUSP)
  • five highly conserved domains, domain I, II and III containing the expected catalytic triad Cys, Asp, His which defines cysteine proteases
  • "ubiquitin-like" (UBL) domains (DU subfamily)
    • HOMOLOGY
    interspecies ortholog to Usp15, Rattus norvegicus
    ortholog to Usp15, Mus musculus
    ortholog to USP15, Pan troglodytes
    intraspecies paralog to ubiquitin carboxy-terminal hydrolaser (UCH)
    Homologene
    FAMILY
  • deubiquitin family
  • peptidase C19 family
    • CATEGORY enzyme , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    basic FUNCTION
  • acting as an ubiquitin specific protease
  • play a critical role in dorsoventral patterning through the BMP pathway
  • involved in the regulation of hypertrophic responses in cardiac muscle through transcriptional and post-translational modulation of FHL1
  • functions in COP9 signalosome mediated regulation of protein degradation and cellular signaling through catalyzing the ubiquitin deconjugation reaction of a discrete number of substrates
  • required for TGFB1 and BMP responses in mammalian cells
  • critical for the occupancy of endogenous target promoters by the SMAD complex
  • a key component of the TGF-beta signaling pathway, and in glioblastoma pathogenesis as well
  • USP4 and USP15 extend the life of activated receptors against the negative pressure of receptor-ubiquitinating complexes, but through distinct modes of action
  • a key regulator of cellular RE1-silencing transcription factor, REST
  • specifically deubiquitinates Keap1
  • removes ubiquitin chains from target proteins and maintains protein stability
    • CELLULAR PROCESS protein, ubiquitin dependent proteolysis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism protein
    signaling
  • Ubl conjugation pathway
    • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • COP9 signalosome (CSN) protein complex
  • HPV16 E6
  • skeletal muscle LIM protein 1, LIM1
  • E3 ligase BRAP
  • Tsc22d3
  • specifically deubiquitinates KEAP1, which suppresses the NFE2L2 pathway
  • USP15 interacted with RORC, removed ubiquitin from K446, and stimulated RORC activity by enhancing coactivator SRC recruitment (positive role for USP15-mediated deubiquitination of RORC in Th17 differentiation)
  • USP15 could interact with EIF4A1, thereby promoting translational efficacy in keratinocytes, which is essential for keratinocyte proliferation and migration
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • may be a candidate diagnostic marker and therapeutic target for Paclitaxel-resistant cancers
    • Therapy target
    ANIMAL & CELL MODELS
  • lack of USP15 causes Paclitaxel resistance
  • USP15-siRNA enhances chemoresistance of cells through upregulation of Nrf2