Search results for UCHL1

Showing 6 results out of 6

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Protein (1 results from a total of 1)

Identifier: R-HSA-5660679
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: UCHL1: P09936

Set (1 results from a total of 1)

Identifier: R-HSA-5690768
Species: Homo sapiens
Compartment: cytosol

Complex (2 results from a total of 2)

Identifier: R-HSA-6782592
Species: Homo sapiens
Compartment: cytosol
Identifier: R-HSA-6782633
Species: Homo sapiens
Compartment: cytosol

Reaction (2 results from a total of 2)

Identifier: R-HSA-5690319
Species: Homo sapiens
Compartment: cytosol
UCHL1 and UCHL3 can hydrolyze several short C-terminal ubiquitin adducts to generate ubiquitin monomers (Wilkinson et al. 1989, Wada et al. 1998, Larsen et al. 1998). This liberates small molecule nucleophiles that may have inadvertently reacted with Ub C-terminal thiolesters. Because these enzymes can cleave small peptides from the C-terminus of Ub, they could also function in recycling Ub from incomplete proteasomal or lysosomal protein degradation. UCHL3, but not UCHL1, is able to cleave the C-terminus of Neural precursor cell expressed developmentally downregulated protein 8 (NEDD8), a ubiquitin-like protein that activates the largest ubiquitin E3 ligase family, the cullin-RING ligases (Wada et al. 1998, Enchev et al. 2015). UCHL1 and 3 are specifically expressed in neurons, cells of the diffuse neuroendocrine system and their tumors. A polymorphism (S18Y) in UCHL1 is associated with a reduced risk for Parkinson's disease (Wang et al. 2002) and its overexpression is protective in models of Alzheimer's disease (Gong et al. 2006). UCHL1 has been shown to interact with alpha-synuclein, but as a ubiquitin ligase rather than as a ubiquitin hydrolase (Liu et al. 2002). It is K63-polyubiquitinated by Parkin in cooperation with the Ubc13/Uev1a E2 ubiquitin-conjugating enzyme complex, promoting UCH-L1 degradation by the autophagy-lysosome pathway (McKeon et al. 2015).
Identifier: R-HSA-5658496
Species: Homo sapiens
Compartment: cytosol
Seven in absentia homolog 1 (SIAH1) and 2 (SIAH2) are E3 ubiquitin-protein ligases that mediates ubiquitination of a number of target proteins including Synphilin-1 (SNCAIP) (Nagano et al. 2003) and alpha-synuclein (SNCA) (Liani et al. 2004, Lee et al. 2008). Ubiquitination of SNCA by SIAH1 is disrupted by the Parkinson's Disease (PD)-linked A30P mutation but not by the A53T mutation. SIAH1 binds the E2 ubiquitin-conjugating enzyme UBE2L6 (UBCH8) (Lee et al. 2008). This facilitates the mono- and di-ubiquitination of SNCA in vivo, but does not target SNCA for proteasomal degradation, rather it promotes SNCA aggregation and enhances toxicity (Lee et al. 2008). Monoubiquitinated SNCA may work as a seed for aggregation (Engelender 2008) and recruit other PD-related proteins, such as SNCAIP and UCHL1.
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