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Database: UniProt
Entry: P35408
LinkDB: P35408
Original site: P35408 
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   29-SEP-2021, entry version 191.
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;
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   SMR; P35408; -.
DR   BioGRID; 111706; 47.
DR   DIP; DIP-61099N; -.
DR   IntAct; P35408; 43.
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; 373 antibodies.
DR   DNASU; 5734; -.
DR   Ensembl; ENST00000302472; ENSP00000302846; ENSG00000171522.
DR   GeneID; 5734; -.
DR   KEGG; hsa:5734; -.
DR   UCSC; uc003jlz.5; human.
DR   CTD; 5734; -.
DR   DisGeNET; 5734; -.
DR   GeneCards; PTGER4; -.
DR   HGNC; HGNC:9596; PTGER4.
DR   HPA; ENSG00000171522; Tissue enhanced (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; ENSGT01030000234559; -.
DR   HOGENOM; CLU_045991_0_2_1; -.
DR   InParanoid; P35408; -.
DR   OMA; LLYMPDL; -.
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   SIGNOR; P35408; -.
DR   BioGRID-ORCS; 5734; 5 hits in 1015 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 metanephric glomerulus and 223 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: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
//
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