Search Results

Overview

Uniprot IDP09936
Protein NameUbiquitin carboxyl-terminal hydrolase isozyme L1
Gene NameUCHL1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
105 AVANNQDKLGFEDGS
123 QFLSETEKMSPEDRA
195 SSEDTLLKDAAKVCR
221 FSAVALCKAA*****
65 QHENFRKKQIEELKG
71 KKQIEELKGQEVSPK
78 KGQEVSPKVYFMKQT
83 SPKVYFMKQTIGNSC

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)

Protein Sequence

10 MQLKPMEINP 20 EMLNKVLSRL 30 GVAGQWRFVD 40 VLGLEEESLG 50 SVPAPACALL 60 LLFPLTAQHE 70 NFRKKQIEEL 80 KGQEVSPKVY 90 FMKQTIGNSC 100 GTIGLIHAVA 110 NNQDKLGFED 120 GSVLKQFLSE 130 TEKMSPEDRA 140 KCFEKNEAIQ 150 AAHDAVAQEG 160 QCRVDDKVNF 170 HFILFNNVDG 180 HLYELDGRMP 190 FPVNHGASSE 200 DTLLKDAAKV 210 CREFTEREQG 220 EVRFSAVALC KAA

Gene Ontology

Classification GO ID Description
Cellular Component GO:0030424 axon
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0005789 endoplasmic reticulum membrane
Cellular Component GO:0044306 neuron projection terminus
Cellular Component GO:0043025 neuronal cell body
Cellular Component GO:0005654 nucleoplasm
Molecular Function GO:0031694 alpha-2A adrenergic receptor binding
Molecular Function GO:0004843 cysteine-type deubiquitinase activity
Molecular Function GO:0004197 cysteine-type endopeptidase activity
Molecular Function GO:0008242 omega peptidase activity
Molecular Function GO:0043022 ribosome binding
Molecular Function GO:0030547 signaling receptor inhibitor activity
Molecular Function GO:0043130 ubiquitin binding
Molecular Function GO:0031625 ubiquitin protein ligase binding
Biological Process GO:0071466 cellular response to xenobiotic stimulus
Biological Process GO:0043409 negative regulation of MAPK cascade
Biological Process GO:0045821 positive regulation of glycolytic process
Biological Process GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
Biological Process GO:0030163 protein catabolic process
Biological Process GO:0016579 protein deubiquitination
Biological Process GO:0016241 regulation of macroautophagy

Reference

[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.

[2] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.

[3] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.