TISIDB

Summary
Symbol	CES1
Name	carboxylesterase 1
Aliases	HMSE; HMSE1; CES1A1; human monocyte/macrophage serine esterase 1; carboxylesterase 1 (monocyte/macrophage se ......
Chromosomal Location	16q22.2
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	Endoplasmic reticulum lumen
Domain	PF00135 Carboxylesterase family
Function	Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester. Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine. Catalyzes the transesterification of cocaine to form cocaethylene. Displays fatty acid ethyl ester synthase activity, catalyzing the ethyl esterification of oleic acid to ethyloleate.

> Gene Ontology [ TOP ]
Biological Process	GO:0006066 alcohol metabolic process GO:0006631 fatty acid metabolic process GO:0006694 steroid biosynthetic process GO:0006695 cholesterol biosynthetic process GO:0006805 xenobiotic metabolic process GO:0006869 lipid transport GO:0008202 steroid metabolic process GO:0008203 cholesterol metabolic process GO:0009410 response to xenobiotic stimulus GO:0009636 response to toxic substance GO:0010876 lipid localization GO:0015850 organic hydroxy compound transport GO:0015918 sterol transport GO:0016125 sterol metabolic process GO:0016126 sterol biosynthetic process GO:0016482 cytosolic transport GO:0030301 cholesterol transport GO:0032365 intracellular lipid transport GO:0032366 intracellular sterol transport GO:0032367 intracellular cholesterol transport GO:0044283 small molecule biosynthetic process GO:0046165 alcohol biosynthetic process GO:0051791 medium-chain fatty acid metabolic process GO:0071466 cellular response to xenobiotic stimulus GO:0090119 vesicle-mediated cholesterol transport GO:0090122 cholesterol ester hydrolysis involved in cholesterol transport GO:1901615 organic hydroxy compound metabolic process GO:1901617 organic hydroxy compound biosynthetic process GO:1902652 secondary alcohol metabolic process GO:1902653 secondary alcohol biosynthetic process
Molecular Function	GO:0004771 sterol esterase activity GO:0016298 lipase activity GO:0019213 deacetylase activity GO:0047374 methylumbelliferyl-acetate deacetylase activity GO:0052689 carboxylic ester hydrolase activity
Cellular Component	GO:0005788 endoplasmic reticulum lumen

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa00983 Drug metabolism - other enzymes hsa01100 Metabolic pathways
Reactome	R-HSA-211859: Biological oxidations R-HSA-1430728: Metabolism R-HSA-211945: Phase 1 - Functionalization of compounds

Summary
Symbol	CES1
Name	carboxylesterase 1
Aliases	HMSE; HMSE1; CES1A1; human monocyte/macrophage serine esterase 1; carboxylesterase 1 (monocyte/macrophage se ......
Chromosomal Location	16q22.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CES1 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	CES1
Name	carboxylesterase 1
Aliases	HMSE; HMSE1; CES1A1; human monocyte/macrophage serine esterase 1; carboxylesterase 1 (monocyte/macrophage se ......
Chromosomal Location	16q22.2
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 CES1 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	CES1
Name	carboxylesterase 1
Aliases	HMSE; HMSE1; CES1A1; human monocyte/macrophage serine esterase 1; carboxylesterase 1 (monocyte/macrophage se ......
Chromosomal Location	16q22.2
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 CES1 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	0.577	0.488
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.047	0.976
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	1.048	0.369
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.526	0.469
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.153	0.524
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.256	0.898
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.489	0.565
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.123	0.924
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-1.385	0.359
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.05	0.521
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	2.217	0.322
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.938	0.00165

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CES1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	7.1	5.9	1.2	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	7.1	-7.1	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	4.1	-0.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	5.1	-1.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	14.3	0	14.3	0.238
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	15.4	0	15.4	0.482
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	3.7	-1.1	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	7.7	-3.2	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	7.7	-7.7	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	8.3	-8.3	1

Summary
Symbol	CES1
Name	carboxylesterase 1
Aliases	HMSE; HMSE1; CES1A1; human monocyte/macrophage serine esterase 1; carboxylesterase 1 (monocyte/macrophage se ......
Chromosomal Location	16q22.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CES1. 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	CES1
Name	carboxylesterase 1
Aliases	HMSE; HMSE1; CES1A1; human monocyte/macrophage serine esterase 1; carboxylesterase 1 (monocyte/macrophage se ......
Chromosomal Location	16q22.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CES1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CES1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CES1
Name	carboxylesterase 1
Aliases	HMSE; HMSE1; CES1A1; human monocyte/macrophage serine esterase 1; carboxylesterase 1 (monocyte/macrophage se ......
Chromosomal Location	16q22.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CES1. 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	CES1
Name	carboxylesterase 1
Aliases	HMSE; HMSE1; CES1A1; human monocyte/macrophage serine esterase 1; carboxylesterase 1 (monocyte/macrophage se ......
Chromosomal Location	16q22.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CES1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CES1
Name	carboxylesterase 1
Aliases	HMSE; HMSE1; CES1A1; human monocyte/macrophage serine esterase 1; carboxylesterase 1 (monocyte/macrophage se ......
Chromosomal Location	16q22.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CES1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CES1
Name	carboxylesterase 1
Aliases	HMSE; HMSE1; CES1A1; human monocyte/macrophage serine esterase 1; carboxylesterase 1 (monocyte/macrophage se ......
Chromosomal Location	16q22.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CES1 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting CES1.

ID	Name	Drug Type	Targets	#Targets
DB00198	Oseltamivir	Small Molecule	CES1, NEU1, NEU2	3
DB00382	Tacrine	Small Molecule	ACHE, BCHE, CES1	3
DB00454	Pethidine	Small Molecule	CES1, CHRM1, CHRM2, CHRM3, CHRM4, CHRM5, GRIN1, GRIN2A, GRIN2B, GR ......	16
DB00583	L-Carnitine	Small Molecule	CES1, CPT1A, CPT2, CRAT, CROT, MPO, SLC22A4, SLC22A5, SLC25A20, SL ......	11
DB00647	Dextropropoxyphene	Small Molecule	CES1, OPRD1, OPRK1, OPRM1	4
DB00907	Cocaine	Small Molecule	CES1, CHRM1, CHRM2, SCN10A, SCN11A, SCN5A, SIGMAR1, SLC6A2, SLC6A3 ......	10
DB01183	Naloxone	Small Molecule	CES1, CREB1, ESR1, OPRD1, OPRK1, OPRM1, TLR4	7
DB01452	Heroin	Small Molecule	CES1, OPRD1, OPRK1, OPRM1	4
DB01599	Probucol	Small Molecule	ABCA1, CES1	2
DB02161	Hydroxy-Phenyl-Acetic Acid 8-Methyl-8-Aza-Bicyclo[3.2.1]Oct-3-Yl Ester	Small Molecule	CES1	1
DB02659	Cholic Acid	Small Molecule	ADH1C, CES1, COX4I1, COX5A, COX5B, COX6A2, COX6B1, COX6C, COX7A1, ......	21
DB03056	4-Piperidino-Piperidine	Small Molecule	CES1	1
DB03721	N-acetyl-alpha-neuraminic acid	Small Molecule	AZGP1, CES1, MBL2, REG1A, SELE, SELP, SIGLEC1	7
DB04509	N-Methylnaloxonium	Small Molecule	CES1	1
DB04795	Thenoyltrifluoroacetone	Small Molecule	CES1, SDHA	2
DB04838	Cyclandelate	Small Molecule	CACNA2D1, CES1	2
DB06442	Avasimibe	Small Molecule	CES1	1
DB07821	(1R)-1,2,2-trimethylpropyl (R)-methylphosphinate	Small Molecule	CES1, PAFAH1B3, PLA2G7	3
DB08224	(1S,7S,8S,8AR)-1,2,3,7,8,8A-HEXAHYDRO-7-METHYL-8-[2-[(2R,4R)-TETRAHYDRO-4-HY DROXY-6-OXO-2H-PYRAN-2-YL]ETHYL]-1-NAPHTHALENOL	Small Molecule	CES1	1
DB11181	Homatropine	Small Molecule	CES1	1

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