UCHL1, UCHL3 cleave ubiquitin adducts

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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).

Literature References
PubMed ID Title Journal Year
9790970 Cleavage of the C-terminus of NEDD8 by UCH-L3

Kamitani, T, Wada, H, Yeh, ET, Caskey, LS, Kito, K

Biochem. Biophys. Res. Commun. 1998
2530630 The neuron-specific protein PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase

Pohl, J, Boss, JM, Wilkinson, KD, Duerksen-Hughes, P, Deshpande, S, Lee, KM

Science 1989
Catalyst Activity

cysteine-type deubiquitinase activity of UCHL1,UCHL3:Ub-Lys [cytosol]

Orthologous Events
Cite Us!