PTGER4 prostaglandin E receptor 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PTGER4provided by HGNC
Official Full Name: prostaglandin E receptor 4provided by HGNC
Primary source: HGNC:HGNC:9596
See related: Ensembl:ENSG00000171522 MIM:601586; Vega:OTTHUMG00000094769
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: EP4; EP4R
Summary: The protein encoded by this gene is a member of the G-protein coupled receptor family. This protein is one of four receptors identified for prostaglandin E2 (PGE2). This receptor can activate T-cell factor signaling. It has been shown to mediate PGE2 induced expression of early growth response 1 (EGR1), regulate the level and stability of cyclooxygenase-2 mRNA, and lead to the phosphorylation of glycogen synthase kinase-3. Knockout studies in mice suggest that this receptor may be involved in the neonatal adaptation of circulatory system, osteoporosis, as well as initiation of skin immune responses. [provided by RefSeq, Jul 2008]
Expression: Broad expression in bone marrow (RPKM 30.5), colon (RPKM 12.1) and 18 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 5p13.1

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	5	NC_000005.10 (40679930..40740936)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (40680032..40696962)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Reprogramming of mammary epithelial cells can result from EP4 -mediated stem cell property transfer by extracellular vesicles/exosomes containing caveolae-associated proteins, between mammary basal and luminal epithelial cells.
Title: PGE2 /EP4 Signaling Controls the Transfer of the Mammary Stem Cell State by Lipid Rafts in Extracellular Vesicles.
High PTGER4 methylation is associated with Lung cancer.
Title: Validation of the SHOX2/PTGER4 DNA Methylation Marker Panel for Plasma-Based Discrimination between Patients with Malignant and Nonmalignant Lung Disease.
in breast cancer cells overexpression of S1P3 and its activation by S1P has pro-inflammatory and pro-metastatic potential by inducing COX-2 expression and PGE2 signaling via EP2 and EP4.
Title: Upregulation of the S1P3 receptor in metastatic breast cancer cells increases migration and invasion by induction of PGE2 and EP2/EP4 activation.
These results indicate that the blockage of PGE2-EP4 signaling prevents the bone destruction required for prostate cancer metastases, and that this is, in part due to the abrogation of bone cell responses. The study provides further evidence that an EP4 antagonist is a candidate for the treatment of prostate cancer in the blockade of bone metastasis.
Title: Abrogation of prostaglandin E-EP4 signaling in osteoblasts prevents the bone destruction induced by human prostate cancer metastases.
The results show that stimulation with the selective EP4 agonist CAY10598 or PGE2 promotes invadopodia-mediated degradation of the ECM, as well as the invasion of breast cancer cells in in vitro models.
Title: EP4 receptor promotes invadopodia and invasion in human breast cancer.
EP4 expression can promote the development of resistance to aromatase inhibitor therapy for breast cancer
Title: Epigenetic activation of the prostaglandin receptor EP4 promotes resistance to endocrine therapy for breast cancer.
Findings suggest SUMO-1 protein and PGE2 receptor subtype 4 (EP4) as two potential targets for new therapeutic or prevention strategies for endometrial cancers.
Title: Prostaglandin E2 (PGE2) promotes proliferation and invasion by enhancing SUMO-1 activity via EP4 receptor in endometrial cancer.
GW627368X therefore effectively inhibits cervical cancer survival, motility, proliferation and angiogenesis by blocking EP4/EGFR interactive signaling.
Title: GW627368X inhibits proliferation and induces apoptosis in cervical cancer by interfering with EP4/EGFR interactive signaling.
The cross-talk between SP1 and p65, and the positive feedback regulatory loop of PI3-K/Akt signaling by EP4 contribute to the overall responses of solamargine in this process
Title: Inactivation of PI3-K/Akt and reduction of SP1 and p65 expression increase the effect of solamargine on suppressing EP4 expression in human lung cancer cells.
The PTGER4 gene is a candidate risk factor for radiological progression in rheumatoid arthritis
Title: PTGER4 gene variant rs76523431 is a candidate risk factor for radiological joint damage in rheumatoid arthritis patients: a genetic study of six cohorts.

Submit: New GeneRIF Correction See all GeneRIFs (112)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

Description
A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
A genome-wide association study identifies new susceptibility loci for non-cardia gastric cancer at 3q13.31 and 5p13.1. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
A genome-wide association study on a southern European population identifies a new Crohn's disease susceptibility locus at RBX1-EP300. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
A genome-wide scan of Ashkenazi Jewish Crohn's disease suggests novel susceptibility loci. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association study of multiple sclerosis confirms a novel locus at 5p13.1. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Systematic association mapping identifies NELL1 as a novel IBD disease gene. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
capsid	gag	Prostaglandin E2 downregulates HIV-1 CA/p24 production through the EP2 and EP4 receptors	PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

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Class A/1 (Rhodopsin-like receptors), organism-specific biosystem (from REACTOME)
Class A/1 (Rhodopsin-like receptors), organism-specific biosystemRhodopsin-like receptors (class A/1) are the largest group of GPCRs and are the best studied group from a functional and structural point of view. They show great diversity at the sequence level and ...
Eicosanoid ligand-binding receptors, organism-specific biosystem (from REACTOME)
Eicosanoid ligand-binding receptors, organism-specific biosystemEicosanoids, derived from polyunsaturated 20-carbon fatty acids, are paracrine and autocrine regulators of inflammation, smooth muscle contraction, and blood coagulation. The actions of eicosanoids a...
G alpha (s) signalling events, organism-specific biosystem (from REACTOME)
G alpha (s) signalling events, organism-specific biosystemThe general function of the G alpha (s) subunit (Gs) is to activate adenylate cyclase, which in turn produces cAMP, leading to the activation of cAMP-dependent protein kinases (often referred to col...
GPCR downstream signaling, organism-specific biosystem (from REACTOME)
GPCR downstream signaling, organism-specific biosystemG protein-coupled receptors (GPCRs) are classically defined as the receptor, G-protein and downstream effectors, the alpha subunit of the G-protein being the primary signaling molecule. However, it h...
GPCR ligand binding, organism-specific biosystem (from REACTOME)
GPCR ligand binding, organism-specific biosystemThere are more than 800 G-protein coupled receptor (GPCRs) in the human genome, making it the largest receptor superfamily. GPCRs are also the largest class of drug targets, involved in virtually all...
GPCRs, Class A Rhodopsin-like, organism-specific biosystem (from WikiPathways)
GPCRs, Class A Rhodopsin-like, organism-specific biosystemThis pathway was created using the GPCRDB (Horn et al., 1998), http://www.gpcr.org/7tm/ (originally at http://www.cmbi.kun.nl/7tm/). The groupings are based on the GPCR phylogenetic tree available fr...
Inflammatory mediator regulation of TRP channels, organism-specific biosystem (from KEGG)
Inflammatory mediator regulation of TRP channels, organism-specific biosystemThe TRP channels that exhibit a unique response to temperature have been given the name thermo-TRPs. Among all thermo- TRP channels, TRPV1-4, TRPM8, and TRPA1 are expressed in subsets of nociceptive...
Inflammatory mediator regulation of TRP channels, conserved biosystem (from KEGG)
Inflammatory mediator regulation of TRP channels, conserved biosystemThe TRP channels that exhibit a unique response to temperature have been given the name thermo-TRPs. Among all thermo- TRP channels, TRPV1-4, TRPM8, and TRPA1 are expressed in subsets of nociceptive...
Neuroactive ligand-receptor interaction, organism-specific biosystem (from KEGG)
Neuroactive ligand-receptor interaction, organism-specific biosystem
Neuroactive ligand-receptor interaction
Neuroactive ligand-receptor interaction, conserved biosystem (from KEGG)
Neuroactive ligand-receptor interaction, conserved biosystem
Neuroactive ligand-receptor interaction
Pathways in cancer, organism-specific biosystem (from KEGG)
Pathways in cancer, organism-specific biosystem
Pathways in cancer
Prostaglandin Synthesis and Regulation, organism-specific biosystem (from WikiPathways)
Prostaglandin Synthesis and Regulation, organism-specific biosystemA prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon ato...
Prostanoid ligand receptors, organism-specific biosystem (from REACTOME)
Prostanoid ligand receptors, organism-specific biosystemFatty acid cyclo-oxygenase (COX) converts arachidonic acid to prostaglandin H2 (PGH2) from which the prostanoids PGD2, PGE2, PGF2alpha, PGI2 (prostacyclin) and thromboxane A2 (TXA2) are derived. Base...
Renin secretion, organism-specific biosystem (from KEGG)
Renin secretion, organism-specific biosystemThe aspartyl-protease renin is the key regulator of the renin-angiotensin-aldosterone system, which is critically involved in extracellular fluid volume and blood pressure homeostasis of the body. R...
Renin secretion, conserved biosystem (from KEGG)
Renin secretion, conserved biosystemThe aspartyl-protease renin is the key regulator of the renin-angiotensin-aldosterone system, which is critically involved in extracellular fluid volume and blood pressure homeostasis of the body. R...
Signal Transduction, organism-specific biosystem (from REACTOME)
Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
Signaling by GPCR, organism-specific biosystem (from REACTOME)
Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...
Small Ligand GPCRs, organism-specific biosystem (from WikiPathways)
Small Ligand GPCRs, organism-specific biosystem
Small Ligand GPCRs

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PTGER4_1066 (e-PCR)
- UniSTS:277621

D5S1920 (e-PCR)
- UniSTS:58504

SHGC-64757 (e-PCR)
- UniSTS:184204

STS-L25124 (e-PCR)
- UniSTS:20119

STS-N92884 (e-PCR)
- UniSTS:56223

PMC311006P6 (e-PCR)
- UniSTS:272833

STS-N31927 (e-PCR)
- UniSTS:44493

NoName (e-PCR)
- UniSTS:484328

Homology

Homologs of the PTGER4 gene: The PTGER4 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 201 organisms have orthologs with human gene PTGER4
The Hierarchical Catalog of Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
G-protein coupled receptor activity	IBA Inferred from Biological aspect of Ancestor more info
prostaglandin E receptor activity	IBA Inferred from Biological aspect of Ancestor more info
prostaglandin E receptor activity	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
ERK1 and ERK2 cascade	ISS Inferred from Sequence or Structural Similarity more info
G-protein coupled receptor signaling pathway	TAS Traceable Author Statement more info
JNK cascade	ISS Inferred from Sequence or Structural Similarity more info
T-helper cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
adenylate cyclase-activating G-protein coupled receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
adenylate cyclase-modulating G-protein coupled receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
bone development	ISS Inferred from Sequence or Structural Similarity more info
cellular response to mechanical stimulus	ISS Inferred from Sequence or Structural Similarity more info
cellular response to prostaglandin E stimulus	IBA Inferred from Biological aspect of Ancestor more info
immune response	IEP Inferred from Expression Pattern more info	PubMed
inflammatory response	IBA Inferred from Biological aspect of Ancestor more info
negative regulation of cytokine secretion	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of eosinophil extravasation	IDA Inferred from Direct Assay more info	PubMed
negative regulation of inflammatory response	IDA Inferred from Direct Assay more info	PubMed
negative regulation of integrin activation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cytokine secretion	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of cytosolic calcium ion concentration	IBA Inferred from Biological aspect of Ancestor more info
positive regulation of inflammatory response	ISS Inferred from Sequence or Structural Similarity more info
regulation of ossification	IEA Inferred from Electronic Annotation more info
regulation of stress fiber assembly	ISS Inferred from Sequence or Structural Similarity more info
response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
response to mechanical stimulus	IEP Inferred from Expression Pattern more info	PubMed

Component	Evidence Code	Pubs
integral component of membrane	NAS Non-traceable Author Statement more info	PubMed
intracellular	IEA Inferred from Electronic Annotation more info
plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: prostaglandin E2 receptor EP4 subtype

Names: PGE receptor, EP4 subtype; PGE2 receptor EP4 subtype; prostaglandin E receptor 4 (subtype EP4); prostanoid EP4 receptor

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_047000.1 RefSeqGene

Range

5433..19238

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000958.2 → NP_000949.1 prostaglandin E2 receptor EP4 subtype

See identical proteins and their annotated locations for NP_000949.1

Status: REVIEWED

Source sequence(s)

BC027934, BM312677, BQ029720, CD000197, L28175

Consensus CDS

CCDS3930.1

UniProtKB/Swiss-Prot

P35408

UniProtKB/TrEMBL

A0PJF5

Related

ENSP00000302846.3, OTTHUMP00000119996, ENST00000302472.3, OTTHUMT00000211578

Conserved Domains (1) summary

cd15142
Location:18 → 341

7tmA_PGE2_EP4; prostaglandin E2 receptor EP4 subtype, member of the class A family of seven-transmembrane G protein-coupled receptors

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000005.10 Reference GRCh38.p12 Primary Assembly

Range

40679930..40740936

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017009659.2 → XP_016865148.1 prostaglandin E2 receptor EP4 subtype isoform X4

Conserved Domains (2) summary

pfam00001
Location:34 → 222

7tm_1; 7 transmembrane receptor (rhodopsin family)

cl21561
Location:29 → 216

7tm_4; Olfactory receptor
XM_017009656.2 → XP_016865145.1 prostaglandin E2 receptor EP4 subtype isoform X1

Conserved Domains (2) summary

pfam00001
Location:34 → 222

7tm_1; 7 transmembrane receptor (rhodopsin family)

cl21561
Location:29 → 216

7tm_4; Olfactory receptor
XM_017009657.1 → XP_016865146.1 prostaglandin E2 receptor EP4 subtype isoform X2

Conserved Domains (2) summary

pfam00001
Location:34 → 222

7tm_1; 7 transmembrane receptor (rhodopsin family)

cl21561
Location:29 → 216

7tm_4; Olfactory receptor
XM_017009658.1 → XP_016865147.1 prostaglandin E2 receptor EP4 subtype isoform X3