Chicken Polyclonal Antibody to UCHL1 Cat# CPCA-UCHL1

      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 µg/g wet weight in brain, representing a major protein component of neuronal cytoplasm (1). This has been claimed to represent 1-2% of total brain protein. 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 ubiquitin C-terminal hydrolase 1.
      This is the first of a family of ubiquitin C-terminal hydrolases which have been characterized, and is expressed heavily in neurons in the brain. The ubiquitin C-terminal hydrolases cleave ubiquitin from other molecules. This activity is important to generate mono-ubiquitin from 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. The covalent ubiquitin conjugates may then be degraded in the proteasome.
      Point mutations in the UCHL1 gene are associated with some forms of human Parkinson’s disease (3). Recent studies suggest that UCHL1 also has a ubiqitinyl 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 of UCHL1 in CSF and other bodily fluids can be used as a biomarker.
      UCHL1 was also discovered as a gene mutated in some rare familial forms of Parkinson’s disease. Park5 was characterized as the gene causative of this form of Parkinson’s and on analysis the Park5 gene proved to encode an I93M point mutations in the UCHL1 gene, which reduces the ubiquitin hydrolase activity. Interestingly a common allelic variant of UCHL1, the S18Y polymorphism is actually protective against Parkinson’s disease. For a recent excellent review co-authored by the discoverer of UCHL1/Pgp9.5 see reference 4.

      The antibody has been tested on formalin fixed paraffin embedded sections, and, while it gave weak staining of the expected expression pattern, it is not recommended for this purpose.

1. Doran JF, Jackson P, Kynoch PA, Thompson RJ. Isolation of PGP 9.5, a new human neurone-specific protein detected by high-resolution two-dimensional electrophoresis J Neurochem. 40:1542-7 (1983).
2. Wilkinson KD, et al. The neuron-specific protein PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase. Science 246:670-3 (1989).
3. Kurihara LJ, Kikuchi T, Wada K, Tilghman SM. Loss of Uch-L1 and Uch-L3 leads to neurodegeneration, posterior paralysis and dysphagia. Hum. Mol. Genet. 10:1963-70 (2001).
4. Maraganore DM, et al. UCHL1 is a Parkinson's disease susceptibility gene. Ann Neurol. 55:512-21 (2004).
5. Bilguvar K, et al. Recessive loss of function of the neuronal ubiquitin hydrolase UCHL1 leads to early-onset progressive neurodegeneration. PNAS 110:3489-94 (2013).
6. Liu Y, et al. The UCH-L1 gene encodes two opposing enzymatic activities that affect alpha-synuclein degradation and Parkinson’s disease susceptibility. Cell 111:209-18 (2002).
7. Leroy E, et al. The ubiquitin pathway in Parkinson's disease. Nature 395:451-2 (1998).
8. Day IN, Thompson RJ. UCHL1 (PGP 9.5): Neuronal biomarker and ubiquitin system protein. Prog. Neurobiol. 90:327-62 (2009).
9. Mondello S, et al. Clinical utility of serum levels of ubiquitin C-terminal hydrolase as a biomarker for severe traumatic brain injury. Neurosurgery 70:666-75 (2012).