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FLASH GENE
Symbol UCHL5 contributors: mct/npt - updated : 31-01-2019
HGNC name ubiquitin carboxyl-terminal hydrolase L5
HGNC id 19678
Location 1q31.2      Physical location : 192.984.899 - 193.028.521
Synonym name
  • ubiquitin C terminal hydrolase 37
  • INO80 complex subunit R
  • ubiquitin thioesterase L5
  • Synonym symbol(s) CGI-70, UCH37, UBL5, INO80R, UCH-L5
    EC.number 3.4.19.12
    DNA
    TYPE functioning gene
    STRUCTURE 47.89 kb     11 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 1703 37 329 - 2017 28198400
    11 - 5254 - 348 - 2017 28198400
    12 - 5335 - 375 - 2017 28198400
    11 - 5484 - 204 - 2017 28198400
    11 - 5487 - 205 - 2017 28198400
    11 - 2435 - 192 - 2017 28198400
    11 - 5129 - 319 - 2017 28198400
    11 - 5132 - 320 - 2017 28198400
    12 - 5302 - 356 - 2017 28198400
    11 - 5218 - 328 - 2017 28198400
    11 - 2244 - 326 - 2017 28198400
    11 - 2169 - 316 - 2017 28198400
    12 - 5299 - 355 - 2017 28198400
    13 - 5374 - 353 - 2017 28198400
    11 - 2253 - 344 - 2017 28198400
    11 - 5087 - 207 - 2017 28198400
    11 - 5090 - 205 - 2017 28198400
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver    
    Nervousbrain    
    Reproductivemale systemprostate   
    Urinarybladder   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a catalytic core domain, (UCH-domain) consisting of about 230 AAs (Nishio 2009)
  • C-terminal tail domain autoinhibitory, containing KEKE motifs, that can mediate interactions with ADRM1( ADRM1 interacts with a base subunit S1 (also known as RPN2), an integral subunit of the 19S RP (Nishio 2009)
  • HOMOLOGY
    interspecies homolog to Drosophila uchl3
    Homologene
    FAMILY
  • peptidase C12 family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • cysteine protease responsible for deubiquination
  • one of the three principal deubiquitinating enzymes and the only ubiquitin carboxy-terminal hydrolase (UCH)-family protease, that is associated with proteasomes
  • deubiquitinating enzyme that could potentially reverse SMURF-mediated ubiquitination
  • catalyze hydrolysis of the isopeptide bond between the C-terminus of ubiquitin and a lysine side chain on the adduct (Nishio 2009)
  • deubiquitylase functioning in two large and very different complexes, the 26S proteasome and the INO80 chromatin remodeler
  • ADMR1 and UCHL5 are implicated in cell cycle progression, providing a rationale for their function in cellular proliferation
  • regulates TCF7 DNA binding for the activation of Wnt signalling
  • UCHL3 and UCHL5 are considered to be tumor promoters, while BAP1 is considered to be a tumor suppressor, and UCH enzymes influence several signaling pathways that play crucial roles in oncogenesis, tumor invasion, and migration
  • suppresses protein degeneration via removing ubiquitin from the distal subunit of the polyubiquitin chain
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • with PSMD8 and TREX2
  • recruited to proteasomes, through ADRM1
  • interacts with SMADs and regulates TGF-beta signalling
  • associated in the nucleus with INO80 chromatin-remodeling complex (Yao 2008)
  • binds proteasome through ADRM1, which in turn is bound to the RPN2 subunit of the 19S complex (Yao 2006)
  • only UCH family protease that interacts with the 19S proteasome regulatory complex and disassembles Lys48-linked poly-ubiquitin from the distal end of the chain (Nishio 2009)
  • can interact with larger adducts such as ubiquitin (Nishio 2009)
  • PI3K-dependent UCHL5 is required for high glucose-induced TGFBR1 protein expression in mesangial cells
  • is also required for high glucose-induced TGFBR1 protein deubiquitination, CDKN1A and fibronectin protein expression and cell hypertrophy
  • UCHL5 is a de-ubiquitinating enzyme that is activated by ADRM1 and involved in the proteasomal degradation of proteins
  • ADMR1 can activate UCHL5 by disrupting dimerization, although physiologically relevant activation likely results from stabilization of a surface competent for ubiquitin binding and modulation of the active-site crossover loop
  • UCHL5 expression is induced by E2F1, and its level rises in G1/S transition and S phase, suggesting a positive feedback loop between UCHL5 and E2F1
  • interacts with TCF7 (formerly named Tcf1) to activate Wnt signalling
  • PSMD1, ubiquitin, and the deubiquitylase UCHL5 bind to ADRM1 with independent energetics
  • UCHL5 could inhibit migration and invasion of glioma cells via down regulating expression of SNRPF
  • UCHL5 is required for both the stabilization and the polymerization of AXIN1 proteins
  • UCHL5 controls CTNNB1 destruction complex function through AXIN1 regulation
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • is a new prognostic marker in both rectal cancer and pancreatic ductal adenocarcinoma
  • is a potential marker in gastric cancer with new prognostic relevance
  • Therapy target
    ANIMAL & CELL MODELS