AlphaFold predicted structure
UCHL1 · P09936
Mean pLDDT
93.6/ 100
Very high
223 residues
Confidence breakdown
- Very high(≥ 90)80%
- Confident(70–90)18%
- Low(50–70)2%
- Very low(< 50)0%
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AlphaFold (Jumper et al., 2021) · CC BY 4.0
UCHL1
Chr 4p13ubiquitin C-terminal hydrolase L1
- Aliases:
- PGP9.5, Uch-L1, UCHL-1
- MANE:
- ENST00000284440.9
Annotations refreshed 1 month ago.
Predicted protein structure
Clinical relevance (Genomics England PanelApp)
Diagnostic Grade (Green)
Adult onset hereditary spastic paraplegia
BOTH monoallelic and biallelic, autosomal or pseudoautosomalAtaxia and cerebellar anomalies - narrow panel
BOTH monoallelic and biallelic, autosomal or pseudoautosomalChildhood onset hereditary spastic paraplegia
BOTH monoallelic and biallelic, autosomal or pseudoautosomalHereditary ataxia
BOTH monoallelic and biallelic, autosomal or pseudoautosomalHereditary ataxia with onset in adulthood
BOTH monoallelic and biallelic, autosomal or pseudoautosomalHereditary neuropathy or pain disorder
BOTH monoallelic and biallelic, autosomal or pseudoautosomalOptic neuropathy
BOTH monoallelic and biallelic, autosomal or pseudoautosomalAdult onset dystonia, chorea or related movement disorder
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
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Disease associations (Open Targets)
early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome
0.80Early-onset progressive neurodegeneration - blindness - ataxia - spasticity
0.77spastic paraplegia 79A, autosomal dominant, with ataxia
0.70Spastic paraplegia
0.50Young adult-onset Parkinsonism
0.49hereditary spastic paraplegia
0.42Optic neuropathy
0.34glomerulonephritis
0.33hereditary disease
0.19neoplasm
0.13
Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.
Protein function (UniProt)
Ubiquitin carboxyl-terminal hydrolase isozyme L1
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)
Diseases associated with UCHL1
Curated MONDO disease pages that list UCHL1 among their top associated genes.