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 02-SEP-2026, entry version 213. 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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_000958.3. 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 PDB; 8GCM; EM; 3.50 A; R=1-488. DR PDB; 8GCP; EM; 3.10 A; R=1-488. DR PDB; 8GD9; EM; 3.20 A; R=1-488. DR PDB; 8GDA; EM; 3.30 A; R=1-488. DR PDB; 8GDB; EM; 3.10 A; R=1-488. DR PDB; 9JQY; EM; 2.92 A; A=2-366. DR PDB; 9JQZ; EM; 2.65 A; A=2-366. DR AlphaFoldDB; P35408; -. DR EMDB; EMD-29935; -. DR EMDB; EMD-29940; -. DR EMDB; EMD-29943; -. DR EMDB; EMD-29944; -. DR EMDB; EMD-29945; -. DR EMDB; EMD-30608; -. DR EMDB; EMD-61743; -. DR EMDB; EMD-61744; -. DR MDRepo; P35408; -. DR SMR; P35408; -. DR BioGRID; 111706; 47. DR CORUM; P35408; -. DR DIP; DIP-61099N; -. DR FunCoup; P35408; 1431. DR IntAct; P35408; 43. DR MINT; P35408; -. DR NDEx; IQUERY-CP-PTGER4; 7 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000302846; -. DR BindingDB; P35408; -. DR ChEMBL; CHEMBL1836; -. DR DrugBank; DB00770; Alprostadil. DR DrugBank; DB11113; Castor oil. DR DrugBank; DB20983; Cicaprost. DR DrugBank; DB12789; Dinoprost. DR DrugBank; DB00917; Dinoprostone. DR DrugBank; DB12836; Grapiprant. DR DrugBank; DB09211; Limaprost. DR DrugBank; DB00929; Misoprostol. DR DrugBank; DB21421; Palupiprant. DR DrugBank; DB02056; Prostaglandin D2. DR DrugBank; DB16315; Rivenprost. DR DrugBank; DB04297; Trichostatin A. DR DrugCentral; P35408; -. DR GuidetoPHARMACOLOGY; 343; -. DR GlyCosmos; P35408; 1 site, No reported glycans. DR GlyGen; P35408; 1 site. DR iPTMnet; P35408; -. DR PhosphoSitePlus; P35408; -. DR BioMuta; PTGER4; -. DR DMDM; 548476; -. DR jPOST; P35408; -. DR MassIVE; P35408; -. DR PaxDb; 9606-ENSP00000302846; -. DR PeptideAtlas; P35408; -. DR ProteomicsDB; 55059; -. DR ABCD; P35408; 2 sequenced antibodies. DR Antibodypedia; 2762; 373 antibodies from 36 providers. DR DNASU; 5734; -. DR Ensembl; ENST00000302472.4; ENSP00000302846.3; ENSG00000171522.7. 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 AGR; HGNC:9596; -. DR ClinPGx; PA289; -. 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 OpenTargets; ENSG00000171522; -. DR VEuPathDB; HostDB:ENSG00000171522; -. DR eggNOG; KOG3656; Eukaryota. DR GeneTree; ENSGT01050000244902; -. DR HOGENOM; CLU_045991_0_2_1; -. DR InParanoid; P35408; -. DR OMA; VGHVVWR; -. DR OrthoDB; 5959154at2759; -. DR PAN-GO; P35408; 7 GO annotations based on evolutionary models. DR PhylomeDB; P35408; -. DR PathwayCommons; P35408; -. DR Reactome; R-HSA-391908; Prostanoid ligand receptors. DR Reactome; R-HSA-418555; G alpha (s) signalling events. DR SABIO-RK; P35408; -. DR SignaLink; P35408; -. DR SIGNOR; P35408; -. DR Agora; ENSG00000171522; -. DR BioGRID-ORCS; 5734; 12 hits in 1164 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 194 other cell types or tissues. DR GO; GO:0016020; C:membrane; NAS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProt. 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; IDA:UniProt. DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IDA:UniProt. 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:0051492; P:regulation of stress fiber assembly; ISS:UniProtKB. DR GO; GO:0009612; P:response to mechanical stimulus; IEP:UniProtKB. DR GO; GO:0034695; P:response to prostaglandin E; IDA:UniProt. DR GO; GO:0042093; P:T-helper cell differentiation; ISS:UniProtKB. DR CDD; cd15142; 7tmA_PGE2_EP4; 1. DR FunFam; 1.20.1070.10:FF:000101; Prostaglandin E2 receptor EP4 subtype; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. 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; G-PROTEIN COUPLED RECEPTOR FAMILY 1 MEMBER; 1. DR PANTHER; PTHR11866:SF6; PROSTAGLANDIN E2 RECEPTOR EP4 SUBTYPE; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR00237; GPCRRHODOPSN. DR PRINTS; PR00428; PROSTAGLNDNR. DR PRINTS; PR01788; PROSTANOIDR. DR PRINTS; PR00586; PRSTNOIDEP4R. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1. DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1. DR PDBsum; 5YHL; -. DR PDBsum; 5YWY; -. DR PDBsum; 7D7M; -. DR PDBsum; 8GCM; -. DR PDBsum; 8GCP; -. DR PDBsum; 8GD9; -. DR PDBsum; 8GDA; -. DR PDBsum; 8GDB; -. DR PDBsum; 9JQY; -. DR PDBsum; 9JQZ; -. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Disulfide bond; G protein-coupled receptor; KW Glycoprotein; Membrane; Phosphoprotein; Proteomics identification; KW Receptor; Reference proteome; Transducer; Transmembrane; KW 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 COMPBIAS 361..376 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 437..449 FT /note="Polar residues" 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 23..44 FT /evidence="ECO:0007829|PDB:8GCP" FT HELIX 47..49 FT /evidence="ECO:0007829|PDB:8GDB" FT HELIX 53..81 FT /evidence="ECO:0007829|PDB:8GCP" FT STRAND 82..84 FT /evidence="ECO:0007829|PDB:8GCP" FT HELIX 92..112 FT /evidence="ECO:0007829|PDB:8GCP" FT TURN 113..115 FT /evidence="ECO:0007829|PDB:8GCP" FT HELIX 116..122 FT /evidence="ECO:0007829|PDB:8GCP" FT HELIX 124..130 FT /evidence="ECO:0007829|PDB:8GCP" FT STRAND 132..134 FT /evidence="ECO:0007829|PDB:8GCP" FT HELIX 135..151 FT /evidence="ECO:0007829|PDB:8GCP" FT HELIX 153..156 FT /evidence="ECO:0007829|PDB:8GCP" FT STRAND 161..164 FT /evidence="ECO:0007829|PDB:5YWY" FT TURN 165..168 FT /evidence="ECO:0007829|PDB:5YWY" FT STRAND 169..172 FT /evidence="ECO:0007829|PDB:5YWY" FT TURN 179..181 FT /evidence="ECO:0007829|PDB:8GCP" FT HELIX 182..217 FT /evidence="ECO:0007829|PDB:8GCP" FT TURN 267..269 FT /evidence="ECO:0007829|PDB:8GCP" FT HELIX 271..297 FT /evidence="ECO:0007829|PDB:8GCP" FT HELIX 299..301 FT /evidence="ECO:0007829|PDB:8GCP" FT TURN 306..308 FT /evidence="ECO:0007829|PDB:8GCP" FT HELIX 312..317 FT /evidence="ECO:0007829|PDB:8GCP" FT HELIX 320..323 FT /evidence="ECO:0007829|PDB:8GCP" FT TURN 326..330 FT /evidence="ECO:0007829|PDB:8GCP" FT TURN 335..337 FT /evidence="ECO:0007829|PDB:8GCP" 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 //