Uchl1
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:31492742, PubMed:32494592, PubMed:37215988). Abrogates the ubiquitination of multiple proteins including WWTR1/TAZ, EGFR, HIF1A and beta-site amyloid precursor protein cleaving enzyme 1/BACE1. 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 (By similarity). Regulates amyloid precursor protein/APP processing by promoting BACE1 degradation resulting in decreased amyloid beta production (By similarity). 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 (PubMed:31492742). Mediates the 'Lys-48'-linked deubiquitination of the transcriptional coactivator WWTR1/TAZ leading to its stabilization and inhibition of osteoclastogenesis (PubMed:37215988). Deubiquitinates and stabilizes epidermal growth factor receptor EGFR to prevent its degradation and to activate its downstream mediators (PubMed:32494592). Modulates oxidative activity in skeletal muscle by regulating key mitochondrial oxidative proteins (PubMed:33137160). Enhances the activity of hypoxia-inducible factor 1-alpha/HIF1A by abrogateing its VHL E3 ligase-mediated ubiquitination and consequently inhibiting its degradation (By similarity).
Post-translational modifications
O-glycosylated.
Sequence Similarities
Belongs to the peptidase C12 family.
Tissue Specificity
Expressed in brain, where it is found in neurons but not in oligodendrocytes or astrocytes. Found in the ganglion cell layer and the inner nuclear layer of the retina (at protein level). Expressed in brain and testis. In the brain, expression is at its lowest in replaceable neurons of hippocampus and olfactory bulb. Highly expressed in senescent pituitary. In skeletal muscle, primarily expressed in oxidative muscle fibers (PubMed:33137160).
Cellular localization
- Cytoplasm
- Endoplasmic reticulum membrane
- Lipid-anchor
- 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