Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
Symbol UCHL1 contributors: mct/npt/pgu - updated : 11-04-2015
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
    Physical map
    TLR6 4p16.1 toll-like receptor 6 LOC92689 4p14 hypothetical protein BC001096 FLJ23235 4p14 hypothetical protein FLJ23235 KLHL5 4p15.1-p13 kelch-like 5 (Drosophila) PWDMP 4p14 WD repeat membrane protein PWDMP RFC1 4p14-p13 replication factor C (activator 1) 1, 145kDa LOC152831 4p14 klotho beta like RPL9 4p13 ribosomal protein L9 LIAS 4p14 lipoic acid synthetase LOC391645 4 similar to WD repeat domain 5; Bmp2-induced gene UGDH 4p15.1 UDP-glucose dehydrogenase LOC201895 4p14 hypothetical protein LOC201895 HIP2 4p14 huntingtin interacting protein 2 LOC391646 4 similar to chromosome 6 open reading frame 46; Em:AF134726.1 KIAA0648 4p15.1-p11 similar to chromosome 6 open reading frame 46; Em:AF134726.1 PABPCP1 4p14 poly(A) binding protein, cytoplasmic, pseudogene 1 LOC391647 4 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) LOC344967 4p14 similar to cytosolic acyl coenzyme A thioester hydrolase N4BP2 4p14 Nedd4 binding protein 2 ARHH 4p13 ras homolog gene family, member H LOC339997 4p14 hypothetical LOC339997 CHRNA9 4p15.1-p14 cholinergic receptor, nicotinic, alpha polypeptide 9 FLJ20273 4p13-p12 RNA-binding protein FLJ14001 4p14 hypothetical protein FLJ14001 APBB2 4p15.1-p14 amyloid beta (A4) precursor protein-binding, family B, member 2 (Fe65-like) UCHL1 4p15.1-p14 ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) KIAA1102 4p13-p11 ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) PHOX2B 4p12 paired-like homeobox 2b FLJ10525 4p14 hypothetical protein FLJ10525 LOC285429 4p14 hypothetical protein LOC285429 SLC30A9 4p13-p12 solute carrier family 30 (zinc transporter), member 9 ATP1BL1 4p15-q13 ATPase, Na+/K+ transporting, beta polypeptide-like 1 LOC389206 4 hypothetical gene supported by AK125953 ATP8A1 4p14-p12 ATPase, aminophospholipid transporter (APLT), Class I, type 8A, member 1 LOC389207 4 similar to ENSANGP00000012385 LOC345302 4p13 similar to ribosomal protein S2; 40S ribosomal protein S2
    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
  • 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