UCHL1 Recombinant Protein

The protein encoded by this 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. This gene is specifically expressed in the neurons and in cells of the diffuse neuroendocrine system. Mutations in this gene may be associated with Parkinson disease.[provided by RefSeq, Sep 2009]

Function: 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. Also binds to free monoubiquitin and may prevent its degradation in lysosomes. The homodimer may have ATP-independent ubiquitin ligase activity. Ref.12 Ref.13 Ref.28

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). Ref.20

Subunit structure: Monomer. Homodimer. Interacts with SNCA

By similarity. Interacts with COPS5. Ref.14 Ref.19

Subcellular location: Cytoplasm. Endoplasmic reticulum membrane; Lipid-anchor. Note: About 30% of total UCHL1 is associated with membranes in brain. Ref.16

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. Ref.5 Ref.12

Post-translational modification: O-glycosylated

By similarity.

Involvement in disease: Parkinson disease 5 (PARK5) [MIM:613643]: 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.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.13 Ref.21 Ref.27

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.

Sequence similarities: Belongs to the peptidase C12 family.

Caution: Ref.8 reports the association of mutation Ile93Met with Parkinson disease. However, according to Ref.27 this association is uncertain and UCHL1 is not a susceptibility gene for Parkinson disease.

Biophysicochemical propertiesKinetic parameters:KM=122 nM for Ub-AMC Ref.8 Ref.11 Ref.21KM=1.20 µM for ubiquitin ethyl esterVmax=0.47 µmol/min/mg enzyme toward Ub-AMCVmax=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.