TISIDB

Summary
Symbol	UCHL1
Name	ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase)
Aliases	PGP9.5; Uch-L1; PARK5; HEL-117; NDGOA; PGP 9.5; PGP95; neuron cytoplasmic protein 9.5; ubiquitin C-terminal ......
Chromosomal Location	4p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Cytoplasm Endoplasmic reticulum membrane Lipid-anchor Note=About 30% of total UCHL1 is associated with membranes in brain.
Domain	PF01088 Ubiquitin carboxyl-terminal hydrolase
Function	Ubiquitin-protein hydrolase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins. This enzyme is a thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin. Also binds to free monoubiquitin and may prevent its degradation in lysosomes. The homodimer may have ATP-independent ubiquitin ligase activity.

> Gene Ontology [ TOP ]
Biological Process	GO:0001933 negative regulation of protein phosphorylation GO:0002931 response to ischemia GO:0006469 negative regulation of protein kinase activity GO:0006914 autophagy GO:0007018 microtubule-based movement GO:0007409 axonogenesis GO:0007412 axon target recognition GO:0007626 locomotory behavior GO:0007628 adult walking behavior GO:0007631 feeding behavior GO:0008088 axo-dendritic transport GO:0008344 adult locomotory behavior GO:0010498 proteasomal protein catabolic process GO:0010506 regulation of autophagy GO:0010970 transport along microtubule GO:0016236 macroautophagy GO:0016241 regulation of macroautophagy GO:0016579 protein deubiquitination GO:0019233 sensory perception of pain GO:0019896 axonal transport of mitochondrion GO:0030534 adult behavior GO:0030705 cytoskeleton-dependent intracellular transport GO:0033673 negative regulation of kinase activity GO:0034643 establishment of mitochondrion localization, microtubule-mediated GO:0042326 negative regulation of phosphorylation GO:0042692 muscle cell differentiation GO:0042755 eating behavior GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0043405 regulation of MAP kinase activity GO:0043407 negative regulation of MAP kinase activity GO:0043409 negative regulation of MAPK cascade GO:0044708 single-organism behavior GO:0047497 mitochondrion transport along microtubule GO:0048667 cell morphogenesis involved in neuron differentiation GO:0048747 muscle fiber development GO:0050905 neuromuscular process GO:0051146 striated muscle cell differentiation GO:0051348 negative regulation of transferase activity GO:0051640 organelle localization GO:0051646 mitochondrion localization GO:0051654 establishment of mitochondrion localization GO:0051656 establishment of organelle localization GO:0055001 muscle cell development GO:0055002 striated muscle cell development GO:0061564 axon development GO:0070646 protein modification by small protein removal GO:0071900 regulation of protein serine/threonine kinase activity GO:0071901 negative regulation of protein serine/threonine kinase activity GO:0072384 organelle transport along microtubule GO:0090659 walking behavior GO:0098930 axonal transport GO:1902532 negative regulation of intracellular signal transduction
Molecular Function	GO:0001664 G-protein coupled receptor binding GO:0004175 endopeptidase activity GO:0004197 cysteine-type endopeptidase activity GO:0004843 thiol-dependent ubiquitin-specific protease activity GO:0008234 cysteine-type peptidase activity GO:0008238 exopeptidase activity GO:0008242 omega peptidase activity GO:0016874 ligase activity GO:0019783 ubiquitin-like protein-specific protease activity GO:0031625 ubiquitin protein ligase binding GO:0031690 adrenergic receptor binding GO:0031694 alpha-2A adrenergic receptor binding GO:0032182 ubiquitin-like protein binding GO:0036459 thiol-dependent ubiquitinyl hydrolase activity GO:0043130 ubiquitin binding GO:0044389 ubiquitin-like protein ligase binding GO:0101005 ubiquitinyl hydrolase activity
Cellular Component	GO:0030424 axon GO:0032838 cell projection cytoplasm GO:0033267 axon part GO:0043025 neuronal cell body GO:0043209 myelin sheath GO:0044297 cell body GO:0044306 neuron projection terminus GO:0099568 cytoplasmic region GO:1904115 axon cytoplasm

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-5688426: Deubiquitination R-HSA-392499: Metabolism of proteins R-HSA-597592: Post-translational protein modification R-HSA-5689603: UCH proteinases

Summary
Symbol	UCHL1
Name	ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase)
Aliases	PGP9.5; Uch-L1; PARK5; HEL-117; NDGOA; PGP 9.5; PGP95; neuron cytoplasmic protein 9.5; ubiquitin C-terminal ......
Chromosomal Location	4p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between UCHL1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining [ TOP ]
There is no record.

Summary
Symbol	UCHL1
Name	ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase)
Aliases	PGP9.5; Uch-L1; PARK5; HEL-117; NDGOA; PGP 9.5; PGP95; neuron cytoplasmic protein 9.5; ubiquitin C-terminal ......
Chromosomal Location	4p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of UCHL1 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	UCHL1
Name	ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase)
Aliases	PGP9.5; Uch-L1; PARK5; HEL-117; NDGOA; PGP 9.5; PGP95; neuron cytoplasmic protein 9.5; ubiquitin C-terminal ......
Chromosomal Location	4p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of UCHL1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-1.598	0.0287
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-2.453	0.0911
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.984	0.446
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.262	0.65
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.304	0.805
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.973	0.525
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.7	0.253
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.501	0.638
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-1.064	0.395
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.009	0.997
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	-1.308	0.706
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.277	0.319

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of UCHL1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	1.4	-1.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	7.1	-7.1	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	UCHL1
Name	ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase)
Aliases	PGP9.5; Uch-L1; PARK5; HEL-117; NDGOA; PGP 9.5; PGP95; neuron cytoplasmic protein 9.5; ubiquitin C-terminal ......
Chromosomal Location	4p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of UCHL1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	UCHL1
Name	ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase)
Aliases	PGP9.5; Uch-L1; PARK5; HEL-117; NDGOA; PGP 9.5; PGP95; neuron cytoplasmic protein 9.5; ubiquitin C-terminal ......
Chromosomal Location	4p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of UCHL1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by UCHL1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	UCHL1
Name	ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase)
Aliases	PGP9.5; Uch-L1; PARK5; HEL-117; NDGOA; PGP 9.5; PGP95; neuron cytoplasmic protein 9.5; ubiquitin C-terminal ......
Chromosomal Location	4p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of UCHL1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	UCHL1
Name	ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase)
Aliases	PGP9.5; Uch-L1; PARK5; HEL-117; NDGOA; PGP 9.5; PGP95; neuron cytoplasmic protein 9.5; ubiquitin C-terminal ......
Chromosomal Location	4p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of UCHL1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	UCHL1
Name	ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase)
Aliases	PGP9.5; Uch-L1; PARK5; HEL-117; NDGOA; PGP 9.5; PGP95; neuron cytoplasmic protein 9.5; ubiquitin C-terminal ......
Chromosomal Location	4p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between UCHL1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	UCHL1
Name	ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase)
Aliases	PGP9.5; Uch-L1; PARK5; HEL-117; NDGOA; PGP 9.5; PGP95; neuron cytoplasmic protein 9.5; ubiquitin C-terminal ......
Chromosomal Location	4p13
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting UCHL1 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting UCHL1.

ID	Name	Drug Type	Targets	#Targets
DB12695	Phenethyl Isothiocyanate	Small Molecule	ACTA2, ACTB, ATP5B, ATP5I, ATP5L, CYB5B, DIABLO, FBXO41, HNRNPF, H ......	45

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