UCH-L1
UCH-L1 (ubiquitin C-terminal hydrolase L1, also known as PGP9.5, Uch-L1, UCHL-1 and PARK5) is a thiol protease and deubiquitinase of the peptidase C12 family. It cleaves ubiquitin at its C-terminal glycine, maintaining the monoubiquitin pool that cells depend on. Browse Assay Genie's current range of UCH-L1 research reagents below, or read on for the biology behind the target.
UCH-L1 is a deubiquitinase that recognises and hydrolyses a peptide bond at the C-terminal glycine of ubiquitin. This activity maintains a stable pool of monoubiquitin, a key requirement for both the ubiquitin-proteasome and the autophagy-lysosome pathways. It also removes ubiquitin from specific substrates, including WWTR1/TAZ, EGFR, HIF1A and BACE1, and so protects or alters their fate. Deubiquitination of WWTR1/TAZ through 'Lys-48'-linked chains stabilises it and inhibits osteoclastogenesis. Stabilising EGFR prevents its degradation and activates downstream mediators. By blocking VHL E3 ligase-mediated ubiquitination of HIF1A, UCH-L1 enhances hypoxia-inducible factor 1-alpha activity.
The enzyme also regulates amyloid precursor protein (APP) processing. It promotes BACE1 degradation, which decreases amyloid beta production. In the immune response, it influences the ability of MHC I molecules to reach cross-presentation compartments that can generate Ag-MHC I complexes. Further roles include maintenance of synaptic function, cardiac function and inflammatory response, and modulation of oxidative activity in skeletal muscle through key mitochondrial oxidative proteins. UCH-L1 localises to the cytoplasm and the endoplasmic reticulum membrane.
The UCH-L1 gene encodes a member of the peptidase C12 family and belongs to the HGNC group of ubiquitin C-terminal hydrolases. Its previous name was ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase). According to NCBI, the gene is specifically expressed in neurons and in cells of the diffuse neuroendocrine system. Mutations in the gene may be associated with Parkinson disease, which accounts for the PARK5 alias. Mouse and rat both carry an ortholog named Uchl1.
UCH-L1 is neuron-specific, and mutations in its gene may be associated with Parkinson disease, making it a focus for studies of neuronal protein turnover.
By cleaving ubiquitin at its C-terminal glycine, UCH-L1 maintains the monoubiquitin pool needed by the proteasome and autophagy-lysosome pathways.
UCH-L1 promotes BACE1 degradation, decreasing amyloid beta production, so it is relevant to studies of APP processing.
UCH-L1 deubiquitinates and stabilises HIF1A and EGFR, linking it to hypoxia responses and growth factor receptor signalling.
UCH-L1 is a deubiquitinase that hydrolyses a peptide bond at the C-terminal glycine of ubiquitin, maintaining the monoubiquitin pool. It also stabilises substrates such as WWTR1/TAZ, EGFR, HIF1A and BACE1 by removing ubiquitin, and it contributes to synaptic function, inflammatory response and osteoclastogenesis.
The gene symbol is UCHL1. Aliases include PGP9.5, Uch-L1, UCHL-1 and PARK5, and the previous name was ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase). UniProt lists the protein as ubiquitin carboxyl-terminal hydrolase isozyme L1.
NCBI reports that mutations in the UCH-L1 gene may be associated with Parkinson disease, and the PARK5 alias reflects this. Mouse and rat have an ortholog named Uchl1. Check the datasheet of any product for its validated reactivity.
Other ubiquitin C-terminal hydrolases that are related to UCH-L1.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P09936; product specifications from Assay Genie datasheets.