TISIDB

Summary
Symbol	PTGER2
Name	prostaglandin E receptor 2 (subtype EP2), 53kDa
Aliases	prostaglandin E receptor 2 (subtype EP2), 53kD; PGE receptor EP2 subtype; PGE2 receptor EP2 subtype; prostan ......
Chromosomal Location	14q22
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 activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. The subsequent raise in intracellular cAMP is responsible for the relaxing effect of this receptor on smooth muscle.

> Gene Ontology [ TOP ]
Biological Process	GO:0002237 response to molecule of bacterial origin GO:0006874 cellular calcium ion homeostasis GO:0006875 cellular metal ion homeostasis GO:0007187 G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger GO:0007188 adenylate cyclase-modulating G-protein coupled receptor signaling pathway GO:0007189 adenylate cyclase-activating G-protein coupled receptor signaling pathway GO:0007204 positive regulation of cytosolic calcium ion concentration GO:0032496 response to lipopolysaccharide GO:0032570 response to progesterone GO:0034694 response to prostaglandin GO:0034695 response to prostaglandin E GO:0048545 response to steroid hormone GO:0051480 regulation of cytosolic calcium ion concentration GO:0055074 calcium ion homeostasis GO:0071379 cellular response to prostaglandin stimulus GO:0071380 cellular response to prostaglandin E stimulus GO:0072503 cellular divalent inorganic cation homeostasis GO:0072507 divalent inorganic cation homeostasis GO:1901654 response to ketone GO:1901655 cellular response to ketone
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	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04024 cAMP signaling pathway hsa04080 Neuroactive ligand-receptor interaction hsa04750 Inflammatory mediator regulation of TRP channels
Reactome	R-HSA-373076: Class A/1 (Rhodopsin-like receptors) R-HSA-391903: Eicosanoid ligand-binding receptors R-HSA-418555: G alpha (s) 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	PTGER2
Name	prostaglandin E receptor 2 (subtype EP2), 53kDa
Aliases	prostaglandin E receptor 2 (subtype EP2), 53kD; PGE receptor EP2 subtype; PGE2 receptor EP2 subtype; prostan ......
Chromosomal Location	14q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between PTGER2 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 PTGER2 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
23390011	Colon Carcinoma	Inhibit immunity (infiltration)	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.
19197941	Lymphoma	Inhibit immunity (T cell function)	By analyzing freshly isolated TCRVgamma9Vdelta2(+) lymphocytes and primary cell lines stimulated with synthetic phosphoantigen or B-cell lymphoma cell lines in the presence of MSC, we demonstrated that MSC were potent suppressors of gammadelta-cell proliferation, cytokine production and cytolytic responses in vitro. This inhibition was mediated by the COX-2-dependent production of prostaglandin E2 (PGE(2)) and by MSC through EP2 and EP4 inhibitory receptors expressed by Vgamma9Vdelta2 T lymphocytes.
21972293	ovarian carcinoma	Inhibit immunity	The disruption of COX2-PGE(2) feedback using COX2 inhibitors or EP2 and EP4 antagonists suppresses the production of MDSC-associated suppressive factors and the CTL-inhibitory function of fully developed MDSCs from cancer patients.

Summary
Symbol	PTGER2
Name	prostaglandin E receptor 2 (subtype EP2), 53kDa
Aliases	prostaglandin E receptor 2 (subtype EP2), 53kD; PGE receptor EP2 subtype; PGE2 receptor EP2 subtype; prostan ......
Chromosomal Location	14q22
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 PTGER2 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	PTGER2
Name	prostaglandin E receptor 2 (subtype EP2), 53kDa
Aliases	prostaglandin E receptor 2 (subtype EP2), 53kD; PGE receptor EP2 subtype; PGE2 receptor EP2 subtype; prostan ......
Chromosomal Location	14q22
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 PTGER2 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	-0.746	0.0556
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-1.067	0.114
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.517	0.394
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.754	0.259
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.005	0.997
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1.723	0.322
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.433	0.476
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.09	0.229
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.337	0.732
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.942	0.0248
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	2.555	0.0344
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.43	0.0279

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of PTGER2 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	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	2.7	-2.7	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	7.1	-7.1	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	1.7	-1.7	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	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	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	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	PTGER2
Name	prostaglandin E receptor 2 (subtype EP2), 53kDa
Aliases	prostaglandin E receptor 2 (subtype EP2), 53kD; PGE receptor EP2 subtype; PGE2 receptor EP2 subtype; prostan ......
Chromosomal Location	14q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PTGER2. 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	PTGER2
Name	prostaglandin E receptor 2 (subtype EP2), 53kDa
Aliases	prostaglandin E receptor 2 (subtype EP2), 53kD; PGE receptor EP2 subtype; PGE2 receptor EP2 subtype; prostan ......
Chromosomal Location	14q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PTGER2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PTGER2. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PTGER2
Name	prostaglandin E receptor 2 (subtype EP2), 53kDa
Aliases	prostaglandin E receptor 2 (subtype EP2), 53kD; PGE receptor EP2 subtype; PGE2 receptor EP2 subtype; prostan ......
Chromosomal Location	14q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PTGER2. 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	PTGER2
Name	prostaglandin E receptor 2 (subtype EP2), 53kDa
Aliases	prostaglandin E receptor 2 (subtype EP2), 53kD; PGE receptor EP2 subtype; PGE2 receptor EP2 subtype; prostan ......
Chromosomal Location	14q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PTGER2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PTGER2
Name	prostaglandin E receptor 2 (subtype EP2), 53kDa
Aliases	prostaglandin E receptor 2 (subtype EP2), 53kD; PGE receptor EP2 subtype; PGE2 receptor EP2 subtype; prostan ......
Chromosomal Location	14q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PTGER2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PTGER2
Name	prostaglandin E receptor 2 (subtype EP2), 53kDa
Aliases	prostaglandin E receptor 2 (subtype EP2), 53kD; PGE receptor EP2 subtype; PGE2 receptor EP2 subtype; prostan ......
Chromosomal Location	14q22
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PTGER2 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting PTGER2.

ID	Name	Drug Type	Targets	#Targets
DB00770	Alprostadil	Small Molecule	PTGDR2, PTGER1, PTGER2	3
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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