UCHL1

Ubiquitin-protein hydrolase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins. This enzyme is a thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin. UCHL1 also binds to free monoubiquitin and may prevent its degradation in lysosomes. The homodimer may have ATP-independent ubiquitin ligase activity.

UCHL1 Related Areas

Neuroscience>>Neurodegenerative Disease>>Ubiquitin-proteasome pathway>>UCHL1

UCHL1 Alternative Names

UCHL1, Uch-L1, PARK5, PGP 9.5, PGP9.5, PGP95 [Homo sapiens]

Uchl1, UCH-L1, AW822034, C88048, PGP9.5, R75593, gad, PGP 9.5 [Mus musculus]

Summaries for UCHL1

Entrez Gene summary for UCHL1:

The protein encoded by UCHL1 gene belongs to the peptidase C12 family. This enzyme is a thiol protease that hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin. UCHL1 gene is specifically expressed in the neurons and in cells of the diffuse neuroendocrine system. Mutations in UCHL1 gene may be associated with Parkinson disease.[provided by RefSeq, Sep 2009]

OMIM - description for UCHL1:

UCHL1 is a member of a gene family whose products hydrolyze small C-terminal adducts of ubiquitin to generate the ubiquitin monomer. Expression of UCHL1 is highly specific to neurons and to cells of the diffuse neuroendocrine system and their tumors. It is present in all neurons (Doran et al., 1983).

Wikipedia summary for UCHL1:

Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) is a deubiquitinating enzyme. UCHL1 is a member of a gene family whose products hydrolyze small C-terminal adducts of ubiquitin to generate the ubiquitin monomer. Expression of UCHL1 is highly specific to neurons and to cells of the diffuse neuroendocrine system and their tumors. It is present in all neurons.

Human UCHL1 Protein General Information

 

• Protein names: Ubiquitin carboxyl-terminal hydrolase isozyme L1
  Short name=UCHL1
• Sequence length: 223 AA.
• Catalytic activity: Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).
• Sequence similarities: Belongs to the peptidase C12 family.
• Post-translational modification: O-glycosylated .
• Subunit structure: Monomer. Homodimer. Interacts with SNCA . Interacts with COPS5.
• Subcellular location: Cytoplasm. Endoplasmic reticulum membrane; Lipid-anchor. Note: About 30% of total UCHL1 is associated with membranes in brain.
• Tissue specificity: Found in neuronal cell bodies and processes throughout the neocortex (at protein level). Expressed in neurons and cells of the diffuse neuroendocrine system and their tumors. Weakly expressed in ovary. Down-regulated in brains from Parkinson disease and Alzheimer disease patients.
• Involvement in disease: Defects in UCHL1 are the cause of Parkinson disease type 5 (PARK5) ; also known as Parkinson disease autosomal dominant 5. PARK5 is a complex neurodegenerative disorder with manifestations ranging from typical Parkinson disease to dementia with Lewy bodies. Clinical features include parkinsonian symptoms (resting tremor, rigidity, postural instability and bradykinesia), dementia, diffuse Lewy body pathology, autonomic dysfunction, hallucinations and paranoia.
• Miscellaneous: Oxidation of Met-1, Met-6, Met-12, Met-124 and Met-179 to methionine sulfoxide, and oxidation of Cys-220 to cysteine sulfonic acid have been observed in brains from Alzheimer disease (AD) and Parkinson disease (PD) patients. In AD, UCHL1 was found to be associated with neurofibrillary tangles. In contrast to UCHL3, does not hydrolyze a peptide bond at the C-terminal glycine of NEDD8.
• Caution: reports the association of mutation Ile93Met with Parkinson disease. However, according to this association is uncertain and UCHL1 is not a susceptibility gene for Parkinson disease.
• Biophysicochemical properties: Kinetic parameters:
  K_M=122 nM for Ub-AMC
  K_M=1.20 µM for ubiquitin ethyl ester
  V_max=0.47 µmol/min/mg enzyme toward Ub-AMC
  V_max=25 µmol/min/mg enzyme toward ubiquitin ethyl ester
• Sequence caution: The sequence CAA28443.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

General information above from UniProt

Function for UCHL1 Protein

UniProtKB:

Ubiquitin-protein hydrolase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins. This enzyme is a thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin. UCHL1 also binds to free monoubiquitin and may prevent its degradation in lysosomes. The homodimer may have ATP-independent ubiquitin ligase activity.

Genatlas:

• UCHL1 has ubiquitin hydrolase and ligase activities
• UCHL1 is involved in proteasomal degradation, a critical process for neuronal health
• UCHL1 plays significant role in synaptic remodeling, most likely by modulating free monomeric ubiquitin levels in an activity-dependent manner
• UCHL1 catalyzes its own deubiquitination in an intramolecular manner
• UCHL1 functions in maintaining normal synaptic structure in hippocampal neurons
• UCHL1 plays a role in regulating principal pathways involved in oncogenesis
• UCHL1 is de-ubiquitinating enzyme with important functions in recycling of ubiquitin
• UCHL1 negatively regulates TNFalpha-mediated vascular smooth muscle cell proliferation via suppressing ERK activation
• UCHL1 is 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
• UCHL1 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

Homology for human UCHL1

• homolog to murine Uchl1

Phenotype Information for UCHL1

• Gene/Locus: UCHL1, PARK5
• Phenotype: {Parkinson disease 5, susceptibility to}

Phenotype Information for UCHL1 from OMIM (Online Mendelian Inheritance in Man)