Ubiquitin carboxy-terminal hydrolase L1 (EC126.96.36.199, ubiquitin C-terminal hydrolase, 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.
Furthermore, a polymorphism (S18Y) in this gene has been found to be associated with a reduced risk for Parkinson's disease.
The gene is also associated with the Alzheimer's disease, and required for normal synaptic and cognitive function. Loss of Uchl1 increases the susceptibility of pancreatic beta-cells to programmed cell death, indicating that this protein plays a protective role in neuroendocrine cells and illustrating a link between diabetes and neurodegenerative diseases.
Human UCH-L1 and the closely related protein UCHL3 have one of the most complicated knot structure yet discovered for a protein, with five knot crossings. It is speculated that a knot structure may increase a protein's resistance to degradation in the proteasome.
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