Browse PTGER4

Summary
SymbolPTGER4
Nameprostaglandin E receptor 4 (subtype EP4)
Aliases EP4; EP4R; PGE receptor EP4 subtype; PGE receptor, EP4 subtype; PGE2 receptor EP4 subtype; prostanoid EP4 re ......
Chromosomal Location5p13.1
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
 
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. Has a relaxing effect on smooth muscle. May play an important role in regulating renal hemodynamics, intestinal epithelial transport, adrenal aldosterone secretion, and uterine function.

> Gene Ontology
 
Biological Process GO:0001501 skeletal system development
GO:0001503 ossification
GO:0001818 negative regulation of cytokine production
GO:0001819 positive regulation of cytokine production
GO:0002237 response to molecule of bacterial origin
GO:0002263 cell activation involved in immune response
GO:0002285 lymphocyte activation involved in immune response
GO:0002286 T cell activation involved in immune response
GO:0002287 alpha-beta T cell activation involved in immune response
GO:0002292 T cell differentiation involved in immune response
GO:0002293 alpha-beta T cell differentiation involved in immune response
GO:0002294 CD4-positive, alpha-beta T cell differentiation involved in immune response
GO:0002366 leukocyte activation involved in immune response
GO:0002521 leukocyte differentiation
GO:0002683 negative regulation of immune system process
GO:0002685 regulation of leukocyte migration
GO:0002686 negative regulation of leukocyte migration
GO:0002691 regulation of cellular extravasation
GO:0002692 negative regulation of cellular extravasation
GO:0006874 cellular calcium ion homeostasis
GO:0006875 cellular metal ion homeostasis
GO:0007015 actin filament organization
GO:0007159 leukocyte cell-cell adhesion
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:0007254 JNK cascade
GO:0009306 protein secretion
GO:0009612 response to mechanical stimulus
GO:0030038 contractile actin filament bundle assembly
GO:0030098 lymphocyte differentiation
GO:0030217 T cell differentiation
GO:0030278 regulation of ossification
GO:0030336 negative regulation of cell migration
GO:0031032 actomyosin structure organization
GO:0031098 stress-activated protein kinase signaling cascade
GO:0031333 negative regulation of protein complex assembly
GO:0031348 negative regulation of defense response
GO:0031349 positive regulation of defense response
GO:0032102 negative regulation of response to external stimulus
GO:0032103 positive regulation of response to external stimulus
GO:0032231 regulation of actin filament bundle assembly
GO:0032496 response to lipopolysaccharide
GO:0032956 regulation of actin cytoskeleton organization
GO:0032970 regulation of actin filament-based process
GO:0033622 integrin activation
GO:0033623 regulation of integrin activation
GO:0033624 negative regulation of integrin activation
GO:0034694 response to prostaglandin
GO:0034695 response to prostaglandin E
GO:0035710 CD4-positive, alpha-beta T cell activation
GO:0040013 negative regulation of locomotion
GO:0042093 T-helper cell differentiation
GO:0042110 T cell activation
GO:0043149 stress fiber assembly
GO:0043254 regulation of protein complex assembly
GO:0043367 CD4-positive, alpha-beta T cell differentiation
GO:0045123 cellular extravasation
GO:0046631 alpha-beta T cell activation
GO:0046632 alpha-beta T cell differentiation
GO:0050663 cytokine secretion
GO:0050707 regulation of cytokine secretion
GO:0050708 regulation of protein secretion
GO:0050709 negative regulation of protein secretion
GO:0050710 negative regulation of cytokine secretion
GO:0050714 positive regulation of protein secretion
GO:0050715 positive regulation of cytokine secretion
GO:0050727 regulation of inflammatory response
GO:0050728 negative regulation of inflammatory response
GO:0050729 positive regulation of inflammatory response
GO:0050900 leukocyte migration
GO:0051017 actin filament bundle assembly
GO:0051047 positive regulation of secretion
GO:0051048 negative regulation of secretion
GO:0051051 negative regulation of transport
GO:0051222 positive regulation of protein transport
GO:0051224 negative regulation of protein transport
GO:0051271 negative regulation of cellular component movement
GO:0051403 stress-activated MAPK cascade
GO:0051480 regulation of cytosolic calcium ion concentration
GO:0051492 regulation of stress fiber assembly
GO:0051493 regulation of cytoskeleton organization
GO:0055074 calcium ion homeostasis
GO:0060348 bone development
GO:0061572 actin filament bundle organization
GO:0070371 ERK1 and ERK2 cascade
GO:0070486 leukocyte aggregation
GO:0070489 T cell aggregation
GO:0071214 cellular response to abiotic stimulus
GO:0071260 cellular response to mechanical stimulus
GO:0071379 cellular response to prostaglandin stimulus
GO:0071380 cellular response to prostaglandin E stimulus
GO:0071496 cellular response to external stimulus
GO:0071593 lymphocyte aggregation
GO:0072503 cellular divalent inorganic cation homeostasis
GO:0072507 divalent inorganic cation homeostasis
GO:0072677 eosinophil migration
GO:0072682 eosinophil extravasation
GO:0097529 myeloid leukocyte migration
GO:0097530 granulocyte migration
GO:1901654 response to ketone
GO:1901655 cellular response to ketone
GO:1903531 negative regulation of secretion by cell
GO:1903532 positive regulation of secretion by cell
GO:1904950 negative regulation of establishment of protein localization
GO:1904951 positive regulation of establishment of protein localization
GO:2000146 negative regulation of cell motility
GO:2000416 regulation of eosinophil migration
GO:2000417 negative regulation of eosinophil migration
GO:2000419 regulation of eosinophil extravasation
GO:2000420 negative regulation of eosinophil extravasation
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
 
KEGG 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
SymbolPTGER4
Nameprostaglandin E receptor 4 (subtype EP4)
Aliases EP4; EP4R; PGE receptor EP4 subtype; PGE receptor, EP4 subtype; PGE2 receptor EP4 subtype; prostanoid EP4 re ......
Chromosomal Location5p13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between PTGER4 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
 
  Literatures describing the relation between PTGER4 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
23390011Colon CarcinomaInhibit 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.
19197941LymphomaInhibit 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.
21972293ovarian carcinomaInhibit immunityThe 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
SymbolPTGER4
Nameprostaglandin E receptor 4 (subtype EP4)
Aliases EP4; EP4R; PGE receptor EP4 subtype; PGE receptor, EP4 subtype; PGE2 receptor EP4 subtype; prostanoid EP4 re ......
Chromosomal Location5p13.1
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
  Statistical results of PTGER4 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen Total # shRNA with >= 4-fold: 1 Resistant to T-cell proliferation
24476824shRNAmelanomaB16Secondary screen Total # shRNA with >= 4-fold: 2 Resistant to T-cell proliferation
Summary
SymbolPTGER4
Nameprostaglandin E receptor 4 (subtype EP4)
Aliases EP4; EP4R; PGE receptor EP4 subtype; PGE receptor, EP4 subtype; PGE2 receptor EP4 subtype; prostanoid EP4 re ......
Chromosomal Location5p13.1
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
 
Points in the above scatter plot represent the expression difference of PTGER4 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.3620.391
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.3690.745
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.3540.675
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.6820.0311
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.7190.679
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.6440.787
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.220.647
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.8740.474
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.4970.711
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 481.3580.141
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.550.285
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.240.0954
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of PTGER4 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 141705.9-5.91
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 41407.1-7.11
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277301.4-1.41
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275901.7-1.71
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211705.9-5.90.447
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)86016.7-16.70.429
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91606.2-6.21
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47014.3-14.31
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolPTGER4
Nameprostaglandin E receptor 4 (subtype EP4)
Aliases EP4; EP4R; PGE receptor EP4 subtype; PGE receptor, EP4 subtype; PGE2 receptor EP4 subtype; prostanoid EP4 re ......
Chromosomal Location5p13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PTGER4. 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
 
Summary
SymbolPTGER4
Nameprostaglandin E receptor 4 (subtype EP4)
Aliases EP4; EP4R; PGE receptor EP4 subtype; PGE receptor, EP4 subtype; PGE2 receptor EP4 subtype; prostanoid EP4 re ......
Chromosomal Location5p13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PTGER4. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PTGER4.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolPTGER4
Nameprostaglandin E receptor 4 (subtype EP4)
Aliases EP4; EP4R; PGE receptor EP4 subtype; PGE receptor, EP4 subtype; PGE2 receptor EP4 subtype; prostanoid EP4 re ......
Chromosomal Location5p13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PTGER4. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolPTGER4
Nameprostaglandin E receptor 4 (subtype EP4)
Aliases EP4; EP4R; PGE receptor EP4 subtype; PGE receptor, EP4 subtype; PGE2 receptor EP4 subtype; prostanoid EP4 re ......
Chromosomal Location5p13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of PTGER4 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolPTGER4
Nameprostaglandin E receptor 4 (subtype EP4)
Aliases EP4; EP4R; PGE receptor EP4 subtype; PGE receptor, EP4 subtype; PGE2 receptor EP4 subtype; prostanoid EP4 re ......
Chromosomal Location5p13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between PTGER4 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolPTGER4
Nameprostaglandin E receptor 4 (subtype EP4)
Aliases EP4; EP4R; PGE receptor EP4 subtype; PGE receptor, EP4 subtype; PGE2 receptor EP4 subtype; prostanoid EP4 re ......
Chromosomal Location5p13.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting PTGER4 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting PTGER4.
ID Name Drug Type Targets #Targets
DB00917DinoprostoneSmall MoleculePTGDR2, PTGER1, PTGER2, PTGER3, PTGER45
DB00929MisoprostolSmall MoleculePTGER2, PTGER3, PTGER43
DB09211LimaprostSmall MoleculePTGER1, PTGER2, PTGER3, PTGER44