TISIDB

Summary
Symbol	PTGER3
Name	prostaglandin E receptor 3 (subtype EP3)
Aliases	EP3; EP3-I; EP3-II; EP3-III; EP3-IV; EP3-VI; EP3e; PGE2-R; PGE receptor, EP3 subtype; PGE2 receptor EP3 subt ......
Chromosomal Location	1p31.2
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	Cell membrane; Multi-pass membrane protein.
Domain	PF00001 7 transmembrane receptor (rhodopsin family)
Function	Receptor for prostaglandin E2 (PGE2); the EP3 receptor may be involved in inhibition of gastric acid secretion, modulation of neurotransmitter release in central and peripheral neurons, inhibition of sodium and water reabsorption in kidney tubulus and contraction in uterine smooth muscle. The activity of this receptor can couple to both the inhibition of adenylate cyclase mediated by G-I proteins, and to an elevation of intracellular calcium. The various isoforms have identical ligand binding properties but can interact with different second messenger systems (By similarity).

> Gene Ontology [ TOP ]
Biological Process	GO:0001659 temperature homeostasis GO:0001660 fever generation GO:0001696 gastric acid secretion GO:0002526 acute inflammatory response GO:0002673 regulation of acute inflammatory response GO:0002675 positive regulation of acute inflammatory response GO:0003012 muscle system process GO:0006874 cellular calcium ion homeostasis GO:0006875 cellular metal ion homeostasis GO:0006936 muscle contraction GO:0006939 smooth muscle contraction GO:0006953 acute-phase response GO:0007200 phospholipase C-activating G-protein coupled receptor signaling pathway GO:0007204 positive regulation of cytosolic calcium ion concentration GO:0007586 digestion GO:0014821 phasic smooth muscle contraction GO:0014827 intestine smooth muscle contraction GO:0014831 gastro-intestinal system smooth muscle contraction GO:0022600 digestive system process GO:0031349 positive regulation of defense response GO:0031620 regulation of fever generation GO:0031622 positive regulation of fever generation GO:0031649 heat generation GO:0031650 regulation of heat generation GO:0031652 positive regulation of heat generation GO:0032103 positive regulation of response to external stimulus GO:0032844 regulation of homeostatic process GO:0032846 positive regulation of homeostatic process GO:0044057 regulation of system process GO:0044058 regulation of digestive system process GO:0046717 acid secretion GO:0048871 multicellular organismal homeostasis GO:0050727 regulation of inflammatory response GO:0050729 positive regulation of inflammatory response GO:0051048 negative regulation of secretion GO:0051051 negative regulation of transport GO:0051480 regulation of cytosolic calcium ion concentration GO:0055074 calcium ion homeostasis GO:0060453 regulation of gastric acid secretion GO:0060455 negative regulation of gastric acid secretion GO:0060457 negative regulation of digestive system process GO:0072503 cellular divalent inorganic cation homeostasis GO:0072507 divalent inorganic cation homeostasis
Molecular Function	GO:0004953 icosanoid receptor activity GO:0004954 prostanoid receptor activity GO:0004955 prostaglandin receptor activity GO:0004957 prostaglandin E receptor activity
Cellular Component	GO:0005635 nuclear envelope

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04020 Calcium signaling pathway hsa04024 cAMP signaling pathway hsa04080 Neuroactive ligand-receptor interaction
Reactome	R-HSA-373076: Class A/1 (Rhodopsin-like receptors) R-HSA-391903: Eicosanoid ligand-binding receptors R-HSA-418594: G alpha (i) signalling events R-HSA-388396: GPCR downstream signaling R-HSA-500792: GPCR ligand binding R-HSA-391908: Prostanoid ligand receptors R-HSA-162582: Signal Transduction R-HSA-372790: Signaling by GPCR

Summary
Symbol	PTGER3
Name	prostaglandin E receptor 3 (subtype EP3)
Aliases	EP3; EP3-I; EP3-II; EP3-III; EP3-IV; EP3-VI; EP3e; PGE2-R; PGE receptor, EP3 subtype; PGE2 receptor EP3 subt ......
Chromosomal Location	1p31.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between PTGER3 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

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Literatures describing the relation between PTGER3 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
23390011	Colon Carcinoma	Promote immunity	PGE2 signals through four different receptors (EP1-EP4) and targeting individual receptor(s) may avoid these side effects, while retaining significant anticancer benefits. This antitumor effect was associated with reduced Fas ligand expression and attenuated tumor-induced immune suppression. In particular, tumor infiltration by CD4(+) CD25(+) Foxp3(+) regulatory T cells was decreased, whereas the cytotoxic activity of isolated splenocytes against CT26 cells was increased.

Summary
Symbol	PTGER3
Name	prostaglandin E receptor 3 (subtype EP3)
Aliases	EP3; EP3-I; EP3-II; EP3-III; EP3-IV; EP3-VI; EP3e; PGE2-R; PGE receptor, EP3 subtype; PGE2 receptor EP3 subt ......
Chromosomal Location	1p31.2
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 PTGER3 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	PTGER3
Name	prostaglandin E receptor 3 (subtype EP3)
Aliases	EP3; EP3-I; EP3-II; EP3-III; EP3-IV; EP3-VI; EP3e; PGE2-R; PGE receptor, EP3 subtype; PGE2 receptor EP3 subt ......
Chromosomal Location	1p31.2
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 PTGER3 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	-0.437	0.375
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.531	0.531
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.342	0.576
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.425	0.414
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.569	0.764
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.254	0.905
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.391	0.552
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.931	0.367
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.115	0.914
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.28	0.394
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	1.241	0.54
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.539	0.0549

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of PTGER3 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	21.4	0	21.4	0.081
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	20	0	20	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	25	0	25	0.222
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	7.4	4.1	3.3	0.61
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	7.4	5.1	2.3	0.647
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	11.8	-11.8	0.193
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	16.7	-16.7	0.429
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	9.1	-9.1	0.458
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	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	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	0	0	1

Summary
Symbol	PTGER3
Name	prostaglandin E receptor 3 (subtype EP3)
Aliases	EP3; EP3-I; EP3-II; EP3-III; EP3-IV; EP3-VI; EP3e; PGE2-R; PGE receptor, EP3 subtype; PGE2 receptor EP3 subt ......
Chromosomal Location	1p31.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PTGER3. 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	PTGER3
Name	prostaglandin E receptor 3 (subtype EP3)
Aliases	EP3; EP3-I; EP3-II; EP3-III; EP3-IV; EP3-VI; EP3e; PGE2-R; PGE receptor, EP3 subtype; PGE2 receptor EP3 subt ......
Chromosomal Location	1p31.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PTGER3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PTGER3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PTGER3
Name	prostaglandin E receptor 3 (subtype EP3)
Aliases	EP3; EP3-I; EP3-II; EP3-III; EP3-IV; EP3-VI; EP3e; PGE2-R; PGE receptor, EP3 subtype; PGE2 receptor EP3 subt ......
Chromosomal Location	1p31.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PTGER3. 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	PTGER3
Name	prostaglandin E receptor 3 (subtype EP3)
Aliases	EP3; EP3-I; EP3-II; EP3-III; EP3-IV; EP3-VI; EP3e; PGE2-R; PGE receptor, EP3 subtype; PGE2 receptor EP3 subt ......
Chromosomal Location	1p31.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PTGER3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PTGER3
Name	prostaglandin E receptor 3 (subtype EP3)
Aliases	EP3; EP3-I; EP3-II; EP3-III; EP3-IV; EP3-VI; EP3e; PGE2-R; PGE receptor, EP3 subtype; PGE2 receptor EP3 subt ......
Chromosomal Location	1p31.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PTGER3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PTGER3
Name	prostaglandin E receptor 3 (subtype EP3)
Aliases	EP3; EP3-I; EP3-II; EP3-III; EP3-IV; EP3-VI; EP3e; PGE2-R; PGE receptor, EP3 subtype; PGE2 receptor EP3 subt ......
Chromosomal Location	1p31.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PTGER3 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting PTGER3.

ID	Name	Drug Type	Targets	#Targets
DB00905	Bimatoprost	Small Molecule	AKR1C3, PTGER1, PTGER3, PTGFR	4
DB00917	Dinoprostone	Small Molecule	PTGDR2, PTGER1, PTGER2, PTGER3, PTGER4	5
DB00929	Misoprostol	Small Molecule	PTGER2, PTGER3, PTGER4	3
DB08964	Gemeprost	Small Molecule	PTGER2, PTGER3	2
DB09211	Limaprost	Small Molecule	PTGER1, PTGER2, PTGER3, PTGER4	4

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