The Immunogen: Ubiquitin C-terminal hydrolase 1 (UCHL1) has several other names, such as ubiquitin carboxyl esterase L1, ubiquitin thiolesterase, neuron-specific protein PGP9.5 and Park5. It was originally identified as a major component of the neuronal cytoplasm from 2-dimensional gel analysis of brain tissues, and was given the name PGP9.5 (1). The protein is extremely abundant, and was estimated to be present at a concentration of 200-500 micrograms/g wet weight, representing a major protein component of neuronal cytoplasm (1). This has been claimed to represent 1-2% of total brain protein (2). It was later found that a ubiquitin C-terminal hydrolase enzyme activity was associated with the PGP9.5 protein, resulting in the renaming of PGP9.5 to UCHL1. This is the first of a family of ubiquitin C-terminal hydrolases which have been characterized, many of which also have rigid cell type specific expression patterns. The ubiquitin C-terminal hydrolases cleave ubiquitin from other molecules. This activity is important to generate mono-ubiquitin from the several genes which encode polyubiquitin chains or ubiquitin fused to other proteins. The activity is also important to remove ubiquitin from partially degraded proteins, allowing the ubiquitin monomer to be recycled. Regulation of the ubiquitin pathway is very important and many disease states are associated with defects in this pathway. For example the Park5 gene causes one form of human Parkinson's disease, and proves to be a point mutations in the UCHL1 gene producing a I93M form of the UCHL1 protein which has reduced ubiquitin hydrolase activity (3). Interestingly a common allelic variant of UCHL1, the S18Y polymorphism is actually protective against Parkinson's disease. Recent studies suggest that UCHL1 also has a ubiqutinyl ligase activity, being able to couple ubiquitin monomers by linking the C-terminus of one with lysine 63 of the other (3). Since UCHL1 is heavily expressed in neurons, antibodies to UCHL1 can be used to identify neurons in histological sections and in tissue culture. The great abundance of this protein in neurons means that it is released from neurons in large amounts following injury or degeneration, so the detection of UCHL1 in CSF and other bodily fluids can be used as a biomarker of neuronal injury or degeneration. The HGNC name for this protein is UCHL1.

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