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Protein

Prostaglandin E2 receptor EP4 subtype

Gene

PTGER4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  • prostaglandin E receptor activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-HSA-391908. Prostanoid ligand receptors.
R-HSA-418555. G alpha (s) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Prostaglandin E2 receptor EP4 subtype
Short name:
PGE receptor EP4 subtype
Short name:
PGE2 receptor EP4 subtype
Alternative name(s):
Prostanoid EP4 receptor
Gene namesi
Name:PTGER4
Synonyms:PTGER2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:9596. PTGER4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1919ExtracellularSequence analysisAdd
BLAST
Transmembranei20 – 4324Helical; Name=1Sequence analysisAdd
BLAST
Topological domaini44 – 5512CytoplasmicSequence analysisAdd
BLAST
Transmembranei56 – 7924Helical; Name=2Sequence analysisAdd
BLAST
Topological domaini80 – 9617ExtracellularSequence analysisAdd
BLAST
Transmembranei97 – 11519Helical; Name=3Sequence analysisAdd
BLAST
Topological domaini116 – 13520CytoplasmicSequence analysisAdd
BLAST
Transmembranei136 – 16025Helical; Name=4Sequence analysisAdd
BLAST
Topological domaini161 – 18424ExtracellularSequence analysisAdd
BLAST
Transmembranei185 – 21127Helical; Name=5Sequence analysisAdd
BLAST
Topological domaini212 – 26756CytoplasmicSequence analysisAdd
BLAST
Transmembranei268 – 29528Helical; Name=6Sequence analysisAdd
BLAST
Topological domaini296 – 31217ExtracellularSequence analysisAdd
BLAST
Transmembranei313 – 33220Helical; Name=7Sequence analysisAdd
BLAST
Topological domaini333 – 488156CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA289.

Chemistry

ChEMBLiCHEMBL2363068.
DrugBankiDB00917. Dinoprostone.
DB00929. Misoprostol.
GuidetoPHARMACOLOGYi343.

Polymorphism and mutation databases

BioMutaiPTGER4.
DMDMi548476.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 488488Prostaglandin E2 receptor EP4 subtypePRO_0000070064Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi7 – 71N-linked (GlcNAc...)Sequence analysis
Disulfide bondi92 ↔ 170PROSITE-ProRule annotation
Modified residuei374 – 3741Phosphoserine1 Publication
Modified residuei377 – 3771Phosphoserine1 Publication
Modified residuei379 – 3791Phosphoserine1 Publication
Modified residuei382 – 3821Phosphoserine1 Publication

Post-translational modificationi

Phosphorylation mediates agonist-mediated desensitization by promoting cytoplasmic retention.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP35408.
PaxDbiP35408.
PeptideAtlasiP35408.
PRIDEiP35408.

PTM databases

iPTMnetiP35408.
PhosphoSiteiP35408.

Expressioni

Tissue specificityi

High in intestine and in peripheral blood mononuclear cells; low in lung, kidney, thymus, uterus, vasculature and brain. Not found in liver, heart, retina oe skeletal muscle.

Gene expression databases

BgeeiP35408.
CleanExiHS_PTGER2.
HS_PTGER4.
GenevisibleiP35408. HS.

Organism-specific databases

HPAiHPA011226.
HPA012756.

Interactioni

Subunit structurei

Interacts with FEM1A.1 Publication

Protein-protein interaction databases

BioGridi111706. 3 interactions.
DIPiDIP-61099N.
STRINGi9606.ENSP00000302846.

Chemistry

BindingDBiP35408.

Structurei

3D structure databases

ProteinModelPortaliP35408.
SMRiP35408. Positions 20-156.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi230 – 2345Poly-Ala

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000119188.
HOGENOMiHOG000251595.
HOVERGENiHBG053556.
InParanoidiP35408.
KOiK04261.
OMAiIDWRTNV.
OrthoDBiEOG72VH6G.
PhylomeDBiP35408.
TreeFamiTF324982.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR001758. Prost_EP4_rcpt.
IPR008365. Prostanoid_rcpt.
IPR001244. Prostglndn_DP_rcpt.
[Graphical view]
PANTHERiPTHR11866. PTHR11866. 2 hits.
PTHR11866:SF6. PTHR11866:SF6. 2 hits.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR00428. PROSTAGLNDNR.
PR01788. PROSTANOIDR.
PR00586. PRSTNOIDEP4R.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P35408-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSTPGVNSSA SLSPDRLNSP VTIPAVMFIF GVVGNLVAIV VLCKSRKEQK
60 70 80 90 100
ETTFYTLVCG LAVTDLLGTL LVSPVTIATY MKGQWPGGQP LCEYSTFILL
110 120 130 140 150
FFSLSGLSII CAMSVERYLA INHAYFYSHY VDKRLAGLTL FAVYASNVLF
160 170 180 190 200
CALPNMGLGS SRLQYPDTWC FIDWTTNVTA HAAYSYMYAG FSSFLILATV
210 220 230 240 250
LCNVLVCGAL LRMHRQFMRR TSLGTEQHHA AAAASVASRG HPAASPALPR
260 270 280 290 300
LSDFRRRRSF RRIAGAEIQM VILLIATSLV VLICSIPLVV RVFVNQLYQP
310 320 330 340 350
SLEREVSKNP DLQAIRIASV NPILDPWIYI LLRKTVLSKA IEKIKCLFCR
360 370 380 390 400
IGGSRRERSG QHCSDSQRTS SAMSGHSRSF ISRELKEISS TSQTLLPDLS
410 420 430 440 450
LPDLSENGLG GRNLLPGVPG MGLAQEDTTS LRTLRISETS DSSQGQDSES
460 470 480
VLLVDEAGGS GRAGPAPKGS SLQVTFPSET LNLSEKCI
Length:488
Mass (Da):53,119
Last modified:June 1, 1994 - v1
Checksum:iD028478CD72C85EE
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti464 – 4663GPA → WAC in AAA36438 (PubMed:8250933).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L28175 mRNA. Translation: AAA36434.1.
L25124 mRNA. Translation: AAA36438.1.
X97873, X97874 Genomic DNA. Translation: CAA66463.1.
D28472 mRNA. Translation: BAA05834.1.
AY429109 mRNA. Translation: AAR07904.1.
DQ400918 Genomic DNA. Translation: ABD48960.1.
BC101534 mRNA. Translation: AAI01535.1.
BC113523 mRNA. Translation: AAI13524.1.
CCDSiCCDS3930.1.
PIRiA53572.
RefSeqiNP_000949.1. NM_000958.2.
UniGeneiHs.199248.

Genome annotation databases

EnsembliENST00000302472; ENSP00000302846; ENSG00000171522.
GeneIDi5734.
KEGGihsa:5734.
UCSCiuc003jlz.5. human.

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L28175 mRNA. Translation: AAA36434.1.
L25124 mRNA. Translation: AAA36438.1.
X97873, X97874 Genomic DNA. Translation: CAA66463.1.
D28472 mRNA. Translation: BAA05834.1.
AY429109 mRNA. Translation: AAR07904.1.
DQ400918 Genomic DNA. Translation: ABD48960.1.
BC101534 mRNA. Translation: AAI01535.1.
BC113523 mRNA. Translation: AAI13524.1.
CCDSiCCDS3930.1.
PIRiA53572.
RefSeqiNP_000949.1. NM_000958.2.
UniGeneiHs.199248.

3D structure databases

ProteinModelPortaliP35408.
SMRiP35408. Positions 20-156.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111706. 3 interactions.
DIPiDIP-61099N.
STRINGi9606.ENSP00000302846.

Chemistry

BindingDBiP35408.
ChEMBLiCHEMBL2363068.
DrugBankiDB00917. Dinoprostone.
DB00929. Misoprostol.
GuidetoPHARMACOLOGYi343.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP35408.
PhosphoSiteiP35408.

Polymorphism and mutation databases

BioMutaiPTGER4.
DMDMi548476.

Proteomic databases

MaxQBiP35408.
PaxDbiP35408.
PeptideAtlasiP35408.
PRIDEiP35408.

Protocols and materials databases

DNASUi5734.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000302472; ENSP00000302846; ENSG00000171522.
GeneIDi5734.
KEGGihsa:5734.
UCSCiuc003jlz.5. human.

Organism-specific databases

CTDi5734.
GeneCardsiPTGER4.
H-InvDBHIX0032033.
HGNCiHGNC:9596. PTGER4.
HPAiHPA011226.
HPA012756.
MIMi601586. gene.
neXtProtiNX_P35408.
PharmGKBiPA289.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000119188.
HOGENOMiHOG000251595.
HOVERGENiHBG053556.
InParanoidiP35408.
KOiK04261.
OMAiIDWRTNV.
OrthoDBiEOG72VH6G.
PhylomeDBiP35408.
TreeFamiTF324982.

Enzyme and pathway databases

ReactomeiR-HSA-391908. Prostanoid ligand receptors.
R-HSA-418555. G alpha (s) signalling events.

Miscellaneous databases

GeneWikiiEP4_receptor.
GenomeRNAii5734.
PROiP35408.
SOURCEiSearch...

Gene expression databases

BgeeiP35408.
CleanExiHS_PTGER2.
HS_PTGER4.
GenevisibleiP35408. HS.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR001758. Prost_EP4_rcpt.
IPR008365. Prostanoid_rcpt.
IPR001244. Prostglndn_DP_rcpt.
[Graphical view]
PANTHERiPTHR11866. PTHR11866. 2 hits.
PTHR11866:SF6. PTHR11866:SF6. 2 hits.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR00428. PROSTAGLNDNR.
PR01788. PROSTANOIDR.
PR00586. PRSTNOIDEP4R.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning, functional expression, and characterization of the human prostaglandin E2 receptor EP2 subtype."
    Bastien L., Sawyer N., Grygorczyk R., Metters K.M., Adam M.
    J. Biol. Chem. 269:11873-11877(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Lung.
  2. "Cloning and expression of the EP2 subtype of human receptors for prostaglandin E2."
    An S., Yang J., Xia M., Goetzl E.J.
    Biochem. Biophys. Res. Commun. 197:263-270(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Lung.
  3. "The structure of the prostaglandin EP4 receptor gene and related pseudogenes."
    Foord S.M., Marks B., Stolz M., Bufflier E., Fraser N.J., Lee M.G.
    Genomics 35:182-188(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  4. "Gene expression of the human prostaglandin E receptor EP4 subtype: differential regulation in monocytoid and lymphoid lineage cells by phorbol ester."
    Mori K., Tanaka I., Kotani M., Miyaoka F., Sando T., Muro S., Sasaki Y., Nakagawa O., Ogawa Y., Usui T., Ozaki S., Ichikawa A., Narumiya S., Nakao K.
    J. Mol. Med. 74:333-336(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Lung.
  5. "cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
    Kopatz S.A., Aronstam R.S., Sharma S.V.
    Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Lung.
  6. SeattleSNPs variation discovery resource
    Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  8. "Sequestration and phosphorylation of the prostaglandin E2 EP4 receptor: dependence on the C-terminal tail."
    Slipetz D., Buchanan S., Mackereth C., Brewer N., Pellow V., Hao C., Adam M., Abramovitz M., Metters K.M.
    Biochem. Pharmacol. 62:997-1012(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION.
  9. "Identification of a Ser/Thr cluster in the C-terminal domain of the human prostaglandin receptor EP4 that is essential for agonist-induced beta-arrestin1 recruitment but differs from the apparent principal phosphorylation site."
    Neuschafer-Rube F., Hermosilla R., Rehwald M., Ronnstrand L., Schulein R., Wernstedt C., Puschel G.P.
    Biochem. J. 379:573-585(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-374; SER-377; SER-379 AND SER-382.
  10. "A novel prostaglandin E receptor 4-associated protein participates in antiinflammatory signaling."
    Takayama K., Sukhova G.K., Chin M.T., Libby P.
    Circ. Res. 98:499-504(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FEM1A.

Entry informationi

Entry nameiPE2R4_HUMAN
AccessioniPrimary (citable) accession number: P35408
Secondary accession number(s): Q3MJ87
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: June 1, 1994
Last modified: July 6, 2016
This is version 156 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Caution

Was originally designated as the EP2 subtype.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.