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Symbol UCHL1 contributors: mct/npt/pgu - updated : 11-04-2016
HGNC name ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase)
HGNC id 12513
Corresponding disease
NDGOA Neurodegeneration with optic atrophy, childhood onset
PARK5 Parkinson disease 5
SPG79 spastic paraplegia 79, autosomal recessive
Location 4p13      Physical location : 41.258.897 - 41.270.445
Synonym name
  • neuron cytoplasmic protein 9.5
  • ubiquitin thioesterase L1
  • ubiquitin C-terminal hydrolase
  • Synonym symbol(s) PGP9.5, MSY1, UBL1, UCH-L1, PGP95
    TYPE like-sequence
    STRUCTURE 11.52 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence
    text structure a bifunctional regulatory element contributing to neuron restricted transcription
    MAPPING cloned Y linked N status provisional
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 1141 - 223 - 1991 1840236
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinepancreas     Homo sapiens
    Nervousbrain   predominantly Homo sapiens
     nervecranial nerve  highly Homo sapiens
     nervespinal nerve   
    Reproductivemale systemprostate  moderately
    Urinarykidney   moderately
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    SystemCellPubmedSpeciesStageRna symbol
    Endocrineislet cell (alpha,beta...) Homo sapiens
    Nervousdopaminergic neuron Homo sapiens
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    at STAGE
  • ubiquitin carboxyl-terminal hydrolase domain
    interspecies homolog to murine Uchl1
  • ubiquitin carboxyl-terminal hydrolase family 1 (peptidase family C12)
  • CATEGORY enzyme , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    basic FUNCTION
  • having ubiquitin hydrolase and ligase activities
  • involved in proteasomal degradation, a critical process for neuronal health
  • significant role in synaptic remodeling, most likely by modulating free monomeric ubiquitin levels in an activity-dependent manner
  • catalyzing its own deubiquitination in an intramolecular manner
  • functions in maintaining normal synaptic structure in hippocampal neurons
  • plays a role in regulating principal pathways involved in oncogenesis
  • de-ubiquitinating enzyme with important functions in recycling of ubiquitin
  • negatively regulates TNFalpha-mediated vascular smooth muscle cell proliferation via suppressing ERK activation
  • required for the maintenance of the structure and function of the neuromuscular junctions and the loss of normal activity may result in neurodegeneration in the peripheral nervous system
  • plays a critical role in the maintenance of normal neuromuscular synaptic transmission
  • essential role of maternal UCHL1 and UCHL3 in fertilization and preimplantation embryo development
  • has dual functions, such as hydrolase activity on the chemical bonds formed by the C-terminal Gly of Ub and dimerization-dependent ubiquitin ligase activity
  • HTRA2-mediated cleavage of UCHL1 may play important roles in regulating the fine balance between cell growth and cell death
  • UCHL1 and HTRA2 pair may play important roles in regulating the balance between cell death and cell survival
  • is a neuron-restricted protein that acts as a deubiquitinating enzyme, ubiquitin ligase or monoubiquitin stabilizer (PMId: 23064229)
  • neuron-specific de-ubiquitinating enzyme and plays an important role in ubiquitin turnover through its C-terminal hydrolytic activity
  • is a novel regulator of the kinase activities of CDKs
  • is involved in podocyte injury and proteinuria
  • de-ubiquitinating enzyme that cleaves ubiquitin at its carboxyl terminal
  • may delay Alzheimer progression by regulating APP degradation in a long-term fashion
  • CELLULAR PROCESS cell cycle
    nucleotide, transcription
    protein, ubiquitin dependent proteolysis
    a component
    small molecule
  • potentially contributing to CDKN1B degradation via its interaction and nuclear translocation with COPS5 (JAB1)
  • degradation of SNCA
  • physically interacts with LAMP2
  • is a natural substrate for the serine protease HTRA2 in the apoptotic pathway
  • has essential functional and anti-apoptotic roles in beta cells under stress conditions associated with lipotoxicity
  • stabilizes focal adhesion signaling in the absence of adhesion, as assessed by reduced caspase-dependent cleavage of PTK2 following cell detachment and sustained activity of the AKT1 signaling pathway
  • UCHL1 is a novel interaction partner of both NCAM1 isoforms (NCAM140, NCAM180) that regulates their ubiquitination and intracellular trafficking
  • UCH1LAS regulates UCHL1 expression at a post-transcriptional level
  • is a key regulator of the dichotomy between MTOR and CRTC2 signaling
  • UCHL1, is the major regulator of neuronal ubiquitin homeostasis, and indirectly modulates the turnover of SLC6A5
  • physically interacts with CDK1, CDK4, and CDK5, enhancing their kinase activity
  • UCHL1 interacts with APP and regulates Abeta production
  • cell & other
    repressed by oestradiol
    Other mono-Ub may regulate the enzymatic functions of UCHL1
    corresponding disease(s) PARK5 , NDGOA , SPG79
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in non-small cell lung cancer
    tumoral     --low  
    in cervical tumor (by hypermethylation)
    constitutional     --low  
    in Huntington diseaseand Alzheimer disease, and in replaceable neurons of hippocampus and olfactory bulb
    constitutional     --over  
    robustly increased in spinal muscular atrophy (SMA) patient fibroblasts
    constitutional       loss of function
    defective UCHL1 function may be an early contributor to vulnerability of pancreatic beta-cells for protein misfolding and proteotoxicity, hallmark defects in islets of T2DM
  • to Parkinson disease
  • to Alzheimer disease (AD)
  • Variant & Polymorphism other
  • S18Y polymorphism influencing the variability in age-onset of Huntington disease
  • carbonyl modification and subsequent abnormal interactions of carbonyl-modified UCHL1 with multiple proteins, including tubulin, constitute one of the causes of sporadic Parkinson disease
  • not protective effect of the UCHL1 S18Y polymorphism against AD
  • Candidate gene
  • role of GFAP and UCHL1 as candidate biomarkers for pediatric traumatic brain injury (TBI)
  • Marker
  • reliable and potential biomarker of neuronal damage after acute neurologic insults, such as ischemic stroke, subarachnoid hemorrhage, and traumatic brain injury
  • Therapy target
    neurologyneurodegenerativeParkinson/dementia Parkinsonism
    potential target for Parkinson-modifying therapies
    overexpression of UCHL1 may be a safe and effective disease-modifying strategy to treat AD
    miscelleaneousurinarychronic kidney disease
    NFKB1-UCH-L1 interaction could be a novel therapeutic strategy for the treatment of podocyte lesions and proteinuria
  • gracile axonal dystrophic mouse (gad) which arbors a deletion of Uchl1
  • pharmacological inhibition of Uchl1 exacerbates rather than ameliorates disease symptoms in a mouse model of SMA
  • Uchl1 knockout mice should serve as a useful model of gut aging