The deubiquitylating enzymes (DUBs) regulate ubiquitin dependent signaling pathways. The activities of the DUBs include the generation of free ubiquitin from precursor molecules, the recycling of ubiquitin following substrate degradation to maintain cellular ubiquitin homeostasis and the removal of ubiquitin or ubiquitin-like protein (UBL) modifications through chain editing to rescue proteins from proteasomal degradation or to influence cell signalling events (Komander et al., 2009). There are two main classes of DUB enzyme the cysteine proteases and metalloproteases. UCHL1 is a cysteine protease and member of the UCH family of ubiquitin C-terminal hydrolases. Cloning of the human UCHL1 gene was first described by Day and Thompson (1987). UCHL1 contains a catalytic triad consisting of a cysteine (Cys90), a histidine (His161), and an aspartate (Asp176) residue. The overall structure of UCHL1 is very similar to that of its nearest UCH relative UCHL3, with which it shares 51% sequence identity (Das et al., 2006). UCHL1 is expressed predominantly in neurons, testis and ovary (Osaka et al., 2003). In vivo UCHL1 has been shown to be involved in the regulation of the ubiquitin pool, apoptosis, learning and memory, and its absence in mice because of spontaneous intragenic deletions yields phenotypes with neurological defects (Saigoh et al., 1999). Mutations in UCHL1 have been implicated in Parkinson disease (PD); a point mutation near the active site that changes Ile93 to Met (I93M) has been linked to an increased risk of developing an autosomal-dominant form of PD (Leroy et al., 1998).
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