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FLASH GENE
Symbol USP5 contributors: mct - updated : 15-04-2021
HGNC name ubiquitin specific protease 5 (isopeptidase T)
HGNC id 12628
Location 12p13.31      Physical location : 6.961.284 - 6.975.793
Synonym name
  • isopeptidase T
  • Synonym symbol(s) UCH2, ISOT1, ISOT
    EC.number 3.1.2.15/ 3.4.19.12
    DNA
    TYPE functioning gene
    STRUCTURE 14.00 kb     20 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    regionally located close to CD4
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    20 - 3162 - 858 - 2019 31455361
  • ISOT-L
  • insertion of 23 amino-acids
  • one Zn2+-binding site of high-affinity, which is part of a cryptic nitrilo-triacetate-resistant pocket (site 1)
  • 20 splicing 3093 95 835 - 2019 31455361
  • ISOT-S
  • alternative splicing exon 15, two AA+ substitutions
  • one Zn2+-binding site of high-affinity, which is part of a cryptic nitrilo-triacetate-resistant pocket (site 1)
  • 19 - 3139 - 789 - 2019 31455361
    19 - 3036 - 816 - 2019 31455361
    20 - 3090 - 834 - 2019 31455361
    19 - 2967 - 793 - 2019 31455361
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   lowly
    Digestivesalivary gland   highly
    Nervousbrain    
    Respiratorylung   lowly
    Skin/Tegumentskin   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion lymph
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • one zinc biding site
  • a catalytic site resembling that of other cysteine proteases, containing one Cys, one Asp and one His
  • a cryptic ZnF-UBP domain (residues 1-156), which was tightly bound to the catalytic core and was indispensable for catalytic activity
  • HOMOLOGY
    intraspecies paralog to ubiquitin C terminal hydrolases ucl+
    Homologene
    FAMILY deubiquitin family
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,lysosome
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • zinc-binding deubiquitinating enzyme, clearing bonds between UB and unfolded polypeptide or UB and small substituents, also disassembling branched polyubiquitin chains
  • recycles ubiquitin by hydrolyzing isopeptide bonds in a variety of unanchored polyubiquitin substrates
  • deubiquitinating enzyme, involved in the elimination of the ubiquitin signal from damaged sites and required for efficient DNA double-strand break (DSB) repair
  • disassembly of polyubiquitin chains by USP5 at sites of damage is important for efficient DSB repair
  • USP5 contributed to hepatocarcinogenesis by acting as an oncogene
  • USP5 regulates the assembly and disassembly of heat-induced stress granules by mediating the hydrolysis of unanchored ubiquitin chains while USP13 regulates stress granules through deubiquitylating protein-conjugated ubiquitin chains
  • CELLULAR PROCESS protein, ubiquitin dependent proteolysis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
    zinc required for its catalytic activity
    protein
  • USP5 uses multiple ZnF-UBP domains for substrate targeting and core catalytic function
  • USP5 and UBE1, are interacting partners of UBTD2
  • critical for the production of Tumor Necrosis Factor-alpha (TNF), a pivotal mediator for inflammatory responses
  • E3 ligase SMURF1 regulates USP5 protein stability and USP5-mediated TNF production through the ubiquitin proteasome pathway
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       gain of function
    in hepatocellular carcinoma (HCC) cells
    constitutional     --other  
    dysregulation of USP5 SUMOylation after peripheral nerve injury may contribute to the well described alteration in CACNA1H activity during neuropathic pain states
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • may serve as a novel prognostic biomarker in non-small cell lung cancer (NSCLC)
  • Therapy target
    SystemTypeDisorderPubmed
    miscelleaneouspain 
    enhancement of CACNA1H currents in afferent neurons is mediated by deubiquitination of the channels by the deubiquitinase USP5, and disrupting USP5/CACNA1H interactions protected from inflammatory and neuropathic pain
    cancerlung 
    potential target for the treatment of metastasis in NSCLC
    ANIMAL & CELL MODELS