background:
The two ubiquitin SLCterminal hydrolase (UCH) enzymes, UCHL1 and UCHL3, deubiquitinate ubiquitin-protein conjugates and control the cellular balance of ubiquitin. UCHL1 and UCHL3 are both small proteins of ~220 amino acids that share more than 40% amino acid sequence identity. UCHL3 is universally expressed in all tissues, while UCHL1 is expressed exclusively in neuronal tissue, testis and ovary. The activity of UCHL3 is more than 200 fold higher than UCHL1 when a fluorogenic ubiquitin substrate is used. UCHL1 associates with monoubiquitin and UCHL3 binds to Nedd8, ubiquitin-like protein. UCHL1 and UCHL3 play a role in the regulation of neuronal development and spermatogenesis. UCHL1 is involved in the pathogenesis of Parkinson’s disease (PD) and Alzheimer’s disease (AD).
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 SLCterminal glycine of ubiquitin. Also binds to free monoubiquitin and may prevent its degradation in lysosomes. The homodimer may have ATP-independent ubiquitin ligase activity.
Subunit:
Monomer. Homodimer. Interacts with SNCA (By similarity). 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.
Post-translational modifications:
O-glycosylated
DISEASE:
Defects in UCHL1 are the cause of Parkinson disease type 5 (PARK5) [MIM:613643]; 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.
Similarity:
Belongs to the peptidase C12 family.
Database links:
Entrez Gene: 7345 Human
Entrez Gene: 22223 Mouse
Entrez Gene: 396637 Pig
Entrez Gene: 29545 Rat
Entrez Gene: 101117250 Sheep
Omim: 191342 Human
SwissProt: P09936 Human
SwissProt: Q9R0P9 Mouse
SwissProt: Q6SEG5 Pig
SwissProt: Q00981 Rat
Unigene: 518731 Human
Unigene: 5967 Mouse
Unigene: 107213 Rat
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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