Genome location: Pf3D7_14_v3:2,460,851..2,463,205(+)
Genome classification: Core
Product Description: ubiquitin carboxyl-terminal hydrolase isozyme L3
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 3.4.19.12 (Ubiquitinyl hydrolase 1)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005737 | cytoplasm |
| Component | GO:0000151 | ubiquitin ligase complex |
| Function | GO:0019784 | NEDD8-specific protease activity |
| Function | GO:0004843 | thiol-dependent deubiquitinase |
| Function | GO:0043130 | ubiquitin binding |
| Process | GO:0000338 | protein deneddylation |
| Process | GO:0016579 | protein deubiquitination |
| Process | GO:0009410 | response to xenobiotic stimulus |
| Process | GO:0006511 | ubiquitin-dependent protein catabolic process |
Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):
| Stage | LR class | MCA mean | MCA prop. zeros |
|---|---|---|---|
| Sporozoite | not expressed | N/A | N/A |
| Ring | expressed | 0.11 | 0.94 |
| Trophozoite | expressed | 0.30 | 0.82 |
| Schizont | expressed | 0.04 | 0.98 |
| Gametocyte | expressed | 0.46 | 0.74 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1460400
Resistome Missense Mutations: None
Resistome Compounds with Missense Mutations: None
Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.652 | MFS: -2.016 | #Insertions: 0
PlasmoGEM Phenotype: N/A
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IKM8
"Best" AlphaFill ligand hit: PHQ (benzyl chlorocarbonate, Local RMSD=0.10) with 4DM9 (Global RMSD=2.32)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 3.4.19.12 | ubiquitinyl hydrolase 1 | KClNEMDTTEDTAEGTARNAisiRNApeptidesAntibodyubiquitinLDN-574442-propenal... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| P15374 | Ubiquitin carboxyl-terminal hydrolase isozyme L3 | Homo sapiens | OMA, OrthoDB | Menadione, 11CHEMBL5193983CHEMBL3407501CHEMBL1241028... |
| Q9JKB1 | Ubiquitin carboxyl-terminal hydrolase isozyme L3 | Mus musculus | OMA, OrthoDB | Menadione, 11 |
| Q9R0P9 | Ubiquitin carboxyl-terminal hydrolase isozyme L1 | Mus musculus | OrthoDB | MLS000849601gerontoxanthone IMLS000728593toxyloxanthone C... |
| P09936 | Ubiquitin carboxyl-terminal hydrolase isozyme L1 | Homo sapiens | OrthoDB | 668467-91-2acs.jmedchem.1c00409_ST.357MangiferinAcetyl Isogambogic Acid... |
Ortholog Group (OrthoMCL): OG6_101218
Most Similar Human Ortholog: D6RE83
TM-align score: 0.92 | RMSD: 1.65
Seq Identity: 0.32 | Length: 205 / 232
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000118939 | ubiquitin C-terminal hydrolase L3 |
| ENSG00000154277 | ubiquitin C-terminal hydrolase L1 |
Protein Length: 232 | Molecular Weight (kDa): 26.899
UniProt ID(s): Q8IKM8
Isoelectric Point: 4.62
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR001578 | Peptidase C12, ubiquitin carboxyl-terminal hydrolase |
| InterPro | IPR038765 | Papain-like cysteine peptidase superfamily |
| PFam | PF01088 | Peptidase C12, ubiquitin carboxyl-terminal hydrolase |
| Superfamily | SSF54001 | Papain-like cysteine peptidase superfamily |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 3 | 14 | 6 | 14 |
| disruptive | 2 | 22 | 17 | 48 |
| missense | 2 | 22 | 17 | 46 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 4 | 28 | 10 | 16 |
| disruptive | 6 | 67 | 42 | 80 |
| missense | 6 | 61 | 37 | 62 |
PlasmoDB Total SNPs: 124
Non-coding: 110 | Synonymous: 9 | Nonsynonymous: 4 | Stop Codon: 1
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 20042598 | Characterization and structural studies of the Plasmodium falciparum ubiquitinand Nedd8 hydrolase UCHL3. | Artavanis-Tsakonas K, Weihofen WA, ..., Ploegh HL | 10.1074/jbc.M109.072405 |
| 31658303 | Nedd8 hydrolysis by UCH proteases in Plasmodium parasites. | Karpiyevich M, Adjalley S, ..., Artavanis-Tsakonas K | 10.1371/journal.ppat.1008086 |
| 35042884 | Repurposing the Pathogen Box compounds for identification of potentanti-malarials against blood stages of Plasmodium falciparum with PfUCHL3inhibitory activity. | Bharti H, Singal A, ..., Nag A | 10.1038/s41598-021-04619-4 |
| 37712884 | Native Semisynthesis of Isopeptide-Linked Substrates for Specificity Analysis of Deubiquitinases and Ubl Proteases | Zhao Z, O'Dea R, ..., Gersch M | 10.1021/jacs.3c04062 |
| 37524875 | The deubiquitinase UCHL3 mediates p300-dependent chemokine signaling in alveolartype II cells to promote pulmonary fibrosis | Lee SY, Park SY, ..., Yoon HG | 10.1038/s12276-023-01066-1 |
| 38092274 | UCHL3 inhibits ferroptosis by stabilizing beta-catenin and maintains stem-likeproperties of hepatocellular carcinoma cells | Long G, Wu Z, ..., Tang J | 10.1016/j.freeradbiomed.2023.11.030 |
| 37634761 | Identification of covalent fragment inhibitors for Plasmodium falciparum UCHL3with anti-malarial efficacy | Imhoff RD, Rosenthal MR, ..., Flaherty DP | 10.1016/j.bmcl.2023.129458 |
| 36527747 | UCHL3 promotes cervical cancer development and metastasis by stabilizing NRF2 viadeubiquitination | Zhang Y, Liu JB, ..., Zhang J | 10.1016/j.bbrc.2022.11.065 |
| 37460253 | Stem Cell Properties of Gastric Cancer Stem-Like Cells under Stress Conditions Are Regulated via the c-Fos/UCH-L3/beta-Catenin Axis | Lee JH, Park SA, ..., Lee JM | 10.14348/molcells.2023.0011 |
| 37740194 | Activation of CTNNB1 by deubiquitinase UCHL3-mediated stabilization facilitates bladder cancer progression | Liu T, Fan MQ, ..., Li SZ | 10.1186/s12967-023-04311-3 |
| 37012254 | Farrerol directly activates the deubiqutinase UCHL3 to promote DNA repair andreprogramming when mediated by somatic cell nuclear transfer | Zhang W, Wang M, ..., Jiang Y | 10.1038/s41467-023-37576-9 |
| 38187053 | Porphyromonas gingivalis induced UCHL3 to promote colon cancer progression | Lu Y, Huang R, ..., Xu Y | https://pubmed.ncbi.nlm.nih.gov/38187053/ |
| 36446970 | Strategies for Monitoring "Ubiquitin C-Terminal Hydrolase 1" (Yuh1) Activity | Saad S, Berda E, ..., Pick E | 10.1007/978-1-0716-2859-1_8 |
| 38266402 | UCHL-3 as a potential biomarker of ovarian cancer | Yang Q, Peng X, ..., Yi T | 10.1016/j.ygyno.2023.12.031 |
| 36813921 | The deubiquitinating enzyme UCHL3 promotes anaplastic thyroid cancer progressionand metastasis through Hippo signaling pathway | Tang J, Yang Q, ..., Tao Y | 10.1038/s41418-023-01134-z |
| 36969045 | UCHL3 promotes hepatocellular carcinoma cell migration by de-ubiquitinating andstabilizing Vimentin | Ma Q, Lu Q, ..., Huang D | 10.3389/fonc.2023.1088475 |
| 36915132 | Mechanical force induces macrophage-derived exosomal UCHL3 promoting bone marrow mesenchymal stem cell osteogenesis by targeting SMAD1 | Pu P, Wu S, ..., Yan B | 10.1186/s12951-023-01836-z |