PE2R4_HUMAN
ID PE2R4_HUMAN Reviewed; 488 AA.
AC P35408; Q3MJ87;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Prostaglandin E2 receptor EP4 subtype;
DE Short=PGE receptor EP4 subtype;
DE Short=PGE2 receptor EP4 subtype;
DE AltName: Full=Prostanoid EP4 receptor;
GN Name=PTGER4; Synonyms=PTGER2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lung;
RX PubMed=8163486; DOI=10.1016/s0021-9258(17)32654-6;
RA Bastien L., Sawyer N., Grygorczyk R., Metters K.M., Adam M.;
RT "Cloning, functional expression, and characterization of the human
RT prostaglandin E2 receptor EP2 subtype.";
RL J. Biol. Chem. 269:11873-11877(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lung;
RX PubMed=8250933; DOI=10.1006/bbrc.1993.2470;
RA An S., Yang J., Xia M., Goetzl E.J.;
RT "Cloning and expression of the EP2 subtype of human receptors for
RT prostaglandin E2.";
RL Biochem. Biophys. Res. Commun. 197:263-270(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8661119; DOI=10.1006/geno.1996.0337;
RA Foord S.M., Marks B., Stolz M., Bufflier E., Fraser N.J., Lee M.G.;
RT "The structure of the prostaglandin EP4 receptor gene and related
RT pseudogenes.";
RL Genomics 35:182-188(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lung;
RX PubMed=8862514; DOI=10.1007/bf00207510;
RA Mori K., Tanaka I., Kotani M., Miyaoka F., Sando T., Muro S., Sasaki Y.,
RA Nakagawa O., Ogawa Y., Usui T., Ozaki S., Ichikawa A., Narumiya S.,
RA Nakao K.;
RT "Gene expression of the human prostaglandin E receptor EP4 subtype:
RT differential regulation in monocytoid and lymphoid lineage cells by phorbol
RT ester.";
RL J. Mol. Med. 74:333-336(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RA Kopatz S.A., Aronstam R.S., Sharma S.V.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG SeattleSNPs variation discovery resource;
RL Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PHOSPHORYLATION.
RX PubMed=11597569; DOI=10.1016/s0006-2952(01)00742-0;
RA Slipetz D., Buchanan S., Mackereth C., Brewer N., Pellow V., Hao C.,
RA Adam M., Abramovitz M., Metters K.M.;
RT "Sequestration and phosphorylation of the prostaglandin E2 EP4 receptor:
RT dependence on the C-terminal tail.";
RL Biochem. Pharmacol. 62:997-1012(2001).
RN [9]
RP PHOSPHORYLATION AT SER-374; SER-377; SER-379 AND SER-382.
RX PubMed=14709160; DOI=10.1042/bj20031820;
RA Neuschafer-Rube F., Hermosilla R., Rehwald M., Ronnstrand L., Schulein R.,
RA Wernstedt C., Puschel G.P.;
RT "Identification of a Ser/Thr cluster in the C-terminal domain of the human
RT prostaglandin receptor EP4 that is essential for agonist-induced beta-
RT arrestin1 recruitment but differs from the apparent principal
RT phosphorylation site.";
RL Biochem. J. 379:573-585(2004).
RN [10]
RP INTERACTION WITH FEM1A.
RX PubMed=16424369; DOI=10.1161/01.res.0000204451.88147.96;
RA Takayama K., Sukhova G.K., Chin M.T., Libby P.;
RT "A novel prostaglandin E receptor 4-associated protein participates in
RT antiinflammatory signaling.";
RL Circ. Res. 98:499-504(2006).
CC -!- FUNCTION: Receptor for prostaglandin E2 (PGE2). The activity of this
CC receptor is mediated by G(s) proteins that stimulate adenylate cyclase.
CC Has a relaxing effect on smooth muscle. May play an important role in
CC regulating renal hemodynamics, intestinal epithelial transport, adrenal
CC aldosterone secretion, and uterine function.
CC -!- SUBUNIT: Interacts with FEM1A. {ECO:0000269|PubMed:16424369}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: High in intestine and in peripheral blood
CC mononuclear cells; low in lung, kidney, thymus, uterus, vasculature and
CC brain. Not found in liver, heart, retina oe skeletal muscle.
CC -!- PTM: Phosphorylation mediates agonist-mediated desensitization by
CC promoting cytoplasmic retention. {ECO:0000269|PubMed:11597569,
CC ECO:0000269|PubMed:14709160}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- CAUTION: Was originally designated as the EP2 subtype. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/ptger4/";
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DR EMBL; L28175; AAA36434.1; -; mRNA.
DR EMBL; L25124; AAA36438.1; -; mRNA.
DR EMBL; X97873; CAA66463.1; -; Genomic_DNA.
DR EMBL; X97874; CAA66463.1; JOINED; Genomic_DNA.
DR EMBL; D28472; BAA05834.1; -; mRNA.
DR EMBL; AY429109; AAR07904.1; -; mRNA.
DR EMBL; DQ400918; ABD48960.1; -; Genomic_DNA.
DR EMBL; BC101534; AAI01535.1; -; mRNA.
DR EMBL; BC113523; AAI13524.1; -; mRNA.
DR CCDS; CCDS3930.1; -.
DR PIR; A53572; A53572.
DR RefSeq; NP_000949.1; NM_000958.2.
DR PDB; 5YHL; X-ray; 4.20 A; A=4-366.
DR PDB; 5YWY; X-ray; 3.20 A; A=4-366.
DR PDB; 7D7M; EM; 3.30 A; A=4-366.
DR PDBsum; 5YHL; -.
DR PDBsum; 5YWY; -.
DR PDBsum; 7D7M; -.
DR AlphaFoldDB; P35408; -.
DR SMR; P35408; -.
DR BioGRID; 111706; 47.
DR DIP; DIP-61099N; -.
DR IntAct; P35408; 43.
DR MINT; P35408; -.
DR STRING; 9606.ENSP00000302846; -.
DR BindingDB; P35408; -.
DR ChEMBL; CHEMBL1836; -.
DR DrugBank; DB11113; Castor oil.
DR DrugBank; DB00917; Dinoprostone.
DR DrugBank; DB12836; Grapiprant.
DR DrugBank; DB09211; Limaprost.
DR DrugBank; DB00929; Misoprostol.
DR DrugCentral; P35408; -.
DR GuidetoPHARMACOLOGY; 343; -.
DR GlyGen; P35408; 1 site.
DR iPTMnet; P35408; -.
DR PhosphoSitePlus; P35408; -.
DR BioMuta; PTGER4; -.
DR DMDM; 548476; -.
DR jPOST; P35408; -.
DR MassIVE; P35408; -.
DR MaxQB; P35408; -.
DR PaxDb; P35408; -.
DR PeptideAtlas; P35408; -.
DR PRIDE; P35408; -.
DR ProteomicsDB; 55059; -.
DR ABCD; P35408; 2 sequenced antibodies.
DR Antibodypedia; 2762; 379 antibodies from 36 providers.
DR DNASU; 5734; -.
DR Ensembl; ENST00000302472.4; ENSP00000302846.3; ENSG00000171522.6.
DR GeneID; 5734; -.
DR KEGG; hsa:5734; -.
DR MANE-Select; ENST00000302472.4; ENSP00000302846.3; NM_000958.3; NP_000949.1.
DR UCSC; uc003jlz.5; human.
DR CTD; 5734; -.
DR DisGeNET; 5734; -.
DR GeneCards; PTGER4; -.
DR HGNC; HGNC:9596; PTGER4.
DR HPA; ENSG00000171522; Tissue enhanced (bone marrow, pancreas).
DR MIM; 601586; gene.
DR neXtProt; NX_P35408; -.
DR OpenTargets; ENSG00000171522; -.
DR PharmGKB; PA289; -.
DR VEuPathDB; HostDB:ENSG00000171522; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01050000244902; -.
DR HOGENOM; CLU_045991_0_2_1; -.
DR InParanoid; P35408; -.
DR OMA; PTIPTVM; -.
DR OrthoDB; 972015at2759; -.
DR PhylomeDB; P35408; -.
DR TreeFam; TF324982; -.
DR PathwayCommons; P35408; -.
DR Reactome; R-HSA-391908; Prostanoid ligand receptors.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SABIO-RK; P35408; -.
DR SignaLink; P35408; -.
DR SIGNOR; P35408; -.
DR BioGRID-ORCS; 5734; 11 hits in 1080 CRISPR screens.
DR ChiTaRS; PTGER4; human.
DR GeneWiki; EP4_receptor; -.
DR GenomeRNAi; 5734; -.
DR Pharos; P35408; Tclin.
DR PRO; PR:P35408; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P35408; protein.
DR Bgee; ENSG00000171522; Expressed in palpebral conjunctiva and 192 other tissues.
DR Genevisible; P35408; HS.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0004957; F:prostaglandin E receptor activity; IDA:UniProtKB.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0060348; P:bone development; ISS:UniProtKB.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; ISS:UniProtKB.
DR GO; GO:0071380; P:cellular response to prostaglandin E stimulus; IBA:GO_Central.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0006955; P:immune response; IEP:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0007254; P:JNK cascade; ISS:UniProtKB.
DR GO; GO:0001818; P:negative regulation of cytokine production; ISS:UniProtKB.
DR GO; GO:2000420; P:negative regulation of eosinophil extravasation; IDA:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IDA:UniProtKB.
DR GO; GO:0033624; P:negative regulation of integrin activation; IDA:UniProtKB.
DR GO; GO:0001819; P:positive regulation of cytokine production; ISS:UniProtKB.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IBA:GO_Central.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0030278; P:regulation of ossification; IEA:Ensembl.
DR GO; GO:0051492; P:regulation of stress fiber assembly; ISS:UniProtKB.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0009612; P:response to mechanical stimulus; IEP:UniProtKB.
DR GO; GO:0009624; P:response to nematode; IEA:Ensembl.
DR GO; GO:0042093; P:T-helper cell differentiation; ISS:UniProtKB.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR001758; Prost_EP4_rcpt.
DR InterPro; IPR008365; Prostanoid_rcpt.
DR InterPro; IPR001244; Prostglndn_DP_rcpt.
DR PANTHER; PTHR11866; PTHR11866; 1.
DR PANTHER; PTHR11866:SF6; PTHR11866:SF6; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR00428; PROSTAGLNDNR.
DR PRINTS; PR01788; PROSTANOIDR.
DR PRINTS; PR00586; PRSTNOIDEP4R.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Disulfide bond; G-protein coupled receptor;
KW Glycoprotein; Membrane; Phosphoprotein; Receptor; Reference proteome;
KW Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..488
FT /note="Prostaglandin E2 receptor EP4 subtype"
FT /id="PRO_0000070064"
FT TOPO_DOM 1..19
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 20..43
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 44..55
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 56..79
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 80..96
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 97..115
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 116..135
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 136..160
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 161..184
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 185..211
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 212..267
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 268..295
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 296..312
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 313..332
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 333..488
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 356..376
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 437..475
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 374
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:14709160"
FT MOD_RES 377
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:14709160"
FT MOD_RES 379
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:14709160"
FT MOD_RES 382
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:14709160"
FT CARBOHYD 7
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 92..170
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT CONFLICT 464..466
FT /note="GPA -> WAC (in Ref. 2; AAA36438)"
FT /evidence="ECO:0000305"
FT HELIX 19..41
FT /evidence="ECO:0007829|PDB:5YWY"
FT STRAND 44..46
FT /evidence="ECO:0007829|PDB:5YWY"
FT HELIX 52..82
FT /evidence="ECO:0007829|PDB:5YWY"
FT HELIX 89..122
FT /evidence="ECO:0007829|PDB:5YWY"
FT HELIX 125..128
FT /evidence="ECO:0007829|PDB:5YWY"
FT HELIX 134..152
FT /evidence="ECO:0007829|PDB:5YWY"
FT TURN 153..156
FT /evidence="ECO:0007829|PDB:5YWY"
FT STRAND 161..163
FT /evidence="ECO:0007829|PDB:5YWY"
FT TURN 165..167
FT /evidence="ECO:0007829|PDB:5YWY"
FT STRAND 170..172
FT /evidence="ECO:0007829|PDB:5YWY"
FT HELIX 179..213
FT /evidence="ECO:0007829|PDB:5YWY"
FT HELIX 267..283
FT /evidence="ECO:0007829|PDB:5YWY"
FT HELIX 286..297
FT /evidence="ECO:0007829|PDB:5YWY"
FT TURN 306..308
FT /evidence="ECO:0007829|PDB:5YWY"
FT HELIX 310..319
FT /evidence="ECO:0007829|PDB:5YWY"
FT HELIX 321..331
FT /evidence="ECO:0007829|PDB:5YWY"
FT HELIX 334..343
FT /evidence="ECO:0007829|PDB:5YWY"
SQ SEQUENCE 488 AA; 53119 MW; D028478CD72C85EE CRC64;
MSTPGVNSSA SLSPDRLNSP VTIPAVMFIF GVVGNLVAIV VLCKSRKEQK ETTFYTLVCG
LAVTDLLGTL LVSPVTIATY MKGQWPGGQP LCEYSTFILL FFSLSGLSII CAMSVERYLA
INHAYFYSHY VDKRLAGLTL FAVYASNVLF CALPNMGLGS SRLQYPDTWC FIDWTTNVTA
HAAYSYMYAG FSSFLILATV LCNVLVCGAL LRMHRQFMRR TSLGTEQHHA AAAASVASRG
HPAASPALPR LSDFRRRRSF RRIAGAEIQM VILLIATSLV VLICSIPLVV RVFVNQLYQP
SLEREVSKNP DLQAIRIASV NPILDPWIYI LLRKTVLSKA IEKIKCLFCR IGGSRRERSG
QHCSDSQRTS SAMSGHSRSF ISRELKEISS TSQTLLPDLS LPDLSENGLG GRNLLPGVPG
MGLAQEDTTS LRTLRISETS DSSQGQDSES VLLVDEAGGS GRAGPAPKGS SLQVTFPSET
LNLSEKCI
