UCHL1
GeneName
UCHL1
Summary
UCHL1, also known as UCH L1, PGP9.5, or UCHL-1, is a 25kDa cysteine-type deubiquitinase predominantly expressed in the nervous system, particularly in neurons. It is localised in various cellular compartments, including the cytoplasm, endoplasmic reticulum membrane, and neuronal cell body. UCHL1 plays a critical role in the regulation of protein degradation and turnover through its deubiquitination activity, which is essential for maintaining cellular homeostasis. Additionally, it is involved in processes such as axonal transport, cellular responses to xenobiotic stimuli, and the regulation of metabolic pathways, including glycolysis and macroautophagy.
Importance
UCHL1 is relevant to: - Neurodegenerative diseases, where its dysfunction may contribute to protein aggregation and neuronal loss - Synaptic plasticity and memory formation due to its role in protein turnover - Cancer biology, as it may influence cell proliferation and survival through its involvement in ubiquitin-mediated pathways - Developmental processes, particularly in muscle cell development and male germ cell proliferation
Top Products
For researchers investigating UCHL1, we recommend two excellent primary antibodies that have garnered significant attention in the field. The first is the well-cited Anti-PGP9.5 antibody [13C4 / I3C4] (ab8189), a monoclonal antibody that has been validated in knockout models and is suitable for immunohistochemistry (IHC), western blotting (WB), and immunocytochemistry (ICC). With 151 citations, it demonstrates a strong reputation among researchers.Additionally, we offer the recombinant Anti-PGP9.5 antibody [EPR4118] (ab108986), which also shows impressive versatility across multiple applications, including IHC, WB, immunocytochemistry (ICC), immunoprecipitation (IP), and flow cytometry (FC). This recombinant antibody has been validated in knockout models as well and has received 142 citations, highlighting its reliability and effectiveness in UCHL1 research. Together, these antibodies provide robust options for accurate and consistent detection of UCHL1 in various experimental settings. The Recombinant human PGP9.5 protein ELISA Kit (ab198431) is an excellent option for researchers looking to measure UCHL1 in their experiments.
Abcam Product Citation Summary
The data indicates that UCHL1 antibodies have been effectively used in various applications, including immunohistochemistry (IHC) and western blot (WB), across different species such as mice and rats. The studies focus on contexts like gastrointestinal dysfunction, highlighting the relevance of UCHL1 in these biological processes.
Abcam Product Citation Table
Function
Deubiquitinase that plays a role in the regulation of several processes such as maintenance of synaptic function, cardiac function, inflammatory response or osteoclastogenesis (PubMed:22212137, PubMed:23359680). Abrogates the ubiquitination of multiple proteins including WWTR1/TAZ, EGFR, HIF1A and beta-site amyloid precursor protein cleaving enzyme 1/BACE1 (PubMed:22212137, PubMed:25615526). In addition, recognizes and hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin to maintain a stable pool of monoubiquitin that is a key requirement for the ubiquitin-proteasome and the autophagy-lysosome pathways (PubMed:12408865, PubMed:8639624, PubMed:9774100). Regulates amyloid precursor protein/APP processing by promoting BACE1 degradation resulting in decreased amyloid beta production (PubMed:22212137). Plays a role in the immune response by regulating the ability of MHC I molecules to reach cross-presentation compartments competent for generating Ag-MHC I complexes (By similarity). Mediates the 'Lys-48'-linked deubiquitination of the transcriptional coactivator WWTR1/TAZ leading to its stabilization and inhibition of osteoclastogenesis (By similarity). Deubiquitinates and stabilizes epidermal growth factor receptor EGFR to prevent its degradation and to activate its downstream mediators (By similarity). Modulates oxidative activity in skeletal muscle by regulating key mitochondrial oxidative proteins (By similarity). Enhances the activity of hypoxia-inducible factor 1-alpha/HIF1A by abrogateing its VHL E3 ligase-mediated ubiquitination and consequently inhibiting its degradation (PubMed:25615526).
Involvement in disease
Parkinson disease 5
PARK5
A complex neurodegenerative disorder with manifestations ranging from typical Parkinson disease to dementia with Lewy bodies. Clinical features include parkinsonian symptoms (resting tremor, rigidity, postural instability and bradykinesia), dementia, diffuse Lewy body pathology, autonomic dysfunction, hallucinations and paranoia.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Spastic paraplegia 79A, autosomal dominant, with ataxia
SPG79A
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG79A is a slowly progressive form characterized by late-onset spastic ataxia, neuropathy, and often optic atrophy.
None
The disease is caused by variants affecting the gene represented in this entry.
Spastic paraplegia 79B, autosomal recessive
SPG79B
A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG79B is characterized by childhood onset blindness, cerebellar ataxia, nystagmus, dorsal column dysfunction, and spasticity with upper motor neuron dysfunction.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
O-glycosylated.
Sequence Similarities
Belongs to the peptidase C12 family.
Tissue Specificity
Found in neuronal cell bodies and processes throughout the neocortex (at protein level). Expressed in neurons and cells of the diffuse neuroendocrine system and their tumors. Weakly expressed in ovary. Down-regulated in brains from Parkinson disease and Alzheimer disease patients.
Cellular localization
- Cytoplasm
- Endoplasmic reticulum membrane
- Lipid-anchor
- About 30% of total UCHL1 is associated with membranes in brain. Localizes near and/or within mitochondria to potentially interact with mitochondrial proteins.
Alternative names
Ubiquitin carboxyl-terminal hydrolase isozyme L1, UCH-L1, Neuron cytoplasmic protein 9.5, PGP 9.5, Ubiquitin thioesterase L1, PGP9.5, UCHL1