ID PE2R3_MOUSE Reviewed; 365 AA.
AC P30557;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 08-NOV-2023, entry version 158.
DE RecName: Full=Prostaglandin E2 receptor EP3 subtype;
DE Short=PGE receptor EP3 subtype;
DE Short=PGE2 receptor EP3 subtype;
DE AltName: Full=Prostanoid EP3 receptor;
GN Name=Ptger3; Synonyms=Ptgerep3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA), FUNCTION, SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RC STRAIN=BDF1;
RX PubMed=1372606; DOI=10.1016/s0021-9258(19)50448-3;
RA Sugimoto Y., Namba T., Honda A., Hayashi Y., Negishi M., Ichikawa A.,
RA Narumiya S.;
RT "Cloning and expression of a cDNA for mouse prostaglandin E receptor EP3
RT subtype.";
RL J. Biol. Chem. 267:6463-6466(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA), FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=8381413; DOI=10.1016/s0021-9258(18)53832-1;
RA Sugimoto Y., Negishi M., Hayashi Y., Namba T., Honda A., Watabe A.,
RA Hirata M., Narumiya S., Ichikawa A.;
RT "Two isoforms of the EP3 receptor with different carboxyl-terminal domains.
RT Identical ligand binding properties and different coupling properties with
RT Gi proteins.";
RL J. Biol. Chem. 268:2712-2718(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GAMMA), FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=8223569; DOI=10.1111/j.1432-1033.1993.tb18248.x;
RA Irie A., Sugimoto Y., Namba T., Harazono A., Honda A., Watabe A.,
RA Negishi M., Narumiya S., Ichikawa A.;
RT "Third isoform of the prostaglandin-E-receptor EP3 subtype with different
RT C-terminal tail coupling to both stimulation and inhibition of adenylate
RT cyclase.";
RL Eur. J. Biochem. 217:313-318(1993).
RN [4]
RP CHARACTERIZATION (ISOFORMS ALPHA AND BETA), AND FUNCTION.
RX PubMed=8567630; DOI=10.1074/jbc.271.4.1857;
RA Hasegawa H., Negishi M., Ichikawa A.;
RT "Two isoforms of the prostaglandin E receptor EP3 subtype different in
RT agonist-independent constitutive activity.";
RL J. Biol. Chem. 271:1857-1860(1996).
RN [5]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=9843913; DOI=10.1152/ajprenal.1998.275.6.f955;
RA Fleming E.F., Athirakul K., Oliverio M.I., Key M., Goulet J., Koller B.H.,
RA Coffman T.M.;
RT "Urinary concentrating function in mice lacking EP3 receptors for
RT prostaglandin E2.";
RL Am. J. Physiol. 275:F955-F961(1998).
RN [6]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=9751056; DOI=10.1038/26233;
RA Ushikubi F., Segi E., Sugimoto Y., Murata T., Matsuoka T., Kobayashi T.,
RA Hizaki H., Tuboi K., Katsuyama M., Ichikawa A., Tanaka T., Yoshida N.,
RA Narumiya S.;
RT "Impaired febrile response in mice lacking the prostaglandin E receptor
RT subtype EP3.";
RL Nature 395:281-284(1998).
RN [7]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=10535876; DOI=10.1016/s0016-5085(99)70398-7;
RA Takeuchi K., Ukawa H., Kato S., Furukawa O., Araki H., Sugimoto Y.,
RA Ichikawa A., Ushikubi F., Narumiya S.;
RT "Impaired duodenal bicarbonate secretion and mucosal integrity in mice
RT lacking prostaglandin E-receptor subtype EP(3).";
RL Gastroenterology 117:1128-1135(1999).
RN [8]
RP DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11535576; DOI=10.1161/hc3601.094003;
RA Ma H., Hara A., Xiao C.Y., Okada Y., Takahata O., Nakaya K., Sugimoto Y.,
RA Ichikawa A., Narumiya S., Ushikubi F.;
RT "Increased bleeding tendency and decreased susceptibility to
RT thromboembolism in mice lacking the prostaglandin E receptor subtype
RT EP(3).";
RL Circulation 104:1176-1180(2001).
CC -!- FUNCTION: Receptor for prostaglandin E2 (PGE2) (PubMed:1372606,
CC PubMed:8381413, PubMed:8223569). Required for normal development of
CC fever in response to pyrinogens, including IL1B, prostaglandin E2 and
CC bacterial lipopolysaccharide (LPS) (PubMed:9751056). Required for
CC normal potentiation of platelet aggregation by prostaglandin E2, and
CC thus plays a role in the regulation of blood coagulation
CC (PubMed:11535576). Required for increased HCO3(-) secretion in the
CC duodenum in response to mucosal acidification, and thereby contributes
CC to the protection of the mucosa against acid-induced ulceration
CC (PubMed:10535876). Not required for normal kidney function, normal
CC urine volume and osmolality (PubMed:9843913).
CC {ECO:0000269|PubMed:10535876, ECO:0000269|PubMed:11535576,
CC ECO:0000269|PubMed:1372606, ECO:0000269|PubMed:8223569,
CC ECO:0000269|PubMed:8381413, ECO:0000269|PubMed:9751056,
CC ECO:0000269|PubMed:9843913}.
CC -!- FUNCTION: [Isoform Alpha]: Receptor for prostaglandin E2 (PGE2); ligand
CC binding activates a signaling cascade via G(i) proteins that leads to
CC inhibition of adenylate cyclase (PubMed:1372606, PubMed:8381413). Shows
CC high agonist-independent constitutive inhibition of adenylate cyclase
CC (PubMed:8223569). {ECO:0000269|PubMed:1372606,
CC ECO:0000269|PubMed:8223569, ECO:0000269|PubMed:8381413}.
CC -!- FUNCTION: [Isoform Beta]: Receptor for prostaglandin E2 (PGE2); ligand
CC binding activates a signaling cascade via G(i) proteins that leads to
CC inhibition of adenylate cyclase. Requires much higher ligand
CC concentrations than isoform Alpha for activation (PubMed:8381413). Does
CC not display agonist-independent constitutive inhibition of adenylate
CC cyclase (PubMed:8223569). {ECO:0000269|PubMed:8223569,
CC ECO:0000269|PubMed:8381413}.
CC -!- FUNCTION: [Isoform Gamma]: Receptor for prostaglandin E2 (PGE2); ligand
CC binding can activate several distinct signaling cascades, resulting in
CC activation or inhibition of adenylate cyclase.
CC {ECO:0000269|PubMed:8223569}.
CC -!- SUBUNIT: Interacts (via C-terminus) with MKLN1.
CC {ECO:0000250|UniProtKB:P34980}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:1372606,
CC ECO:0000269|PubMed:8223569, ECO:0000269|PubMed:8381413}; Multi-pass
CC membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist (Probable). Isoforms have
CC identical ligand binding properties but different coupling properties
CC with G proteins: isoform Alpha and isoform Beta couple to G(i)
CC proteins, whereas isoform Gamma couples to multiple G proteins, G(i)
CC and G(s) (PubMed:1372606, PubMed:8381413, PubMed:8223569).
CC {ECO:0000269|PubMed:1372606, ECO:0000269|PubMed:8223569,
CC ECO:0000269|PubMed:8381413, ECO:0000305};
CC Name=Alpha;
CC IsoId=P30557-1; Sequence=Displayed;
CC Name=Beta;
CC IsoId=P30557-2; Sequence=VSP_001940;
CC Name=Gamma;
CC IsoId=P30557-3; Sequence=VSP_001941;
CC -!- TISSUE SPECIFICITY: Detected in platelets (PubMed:11535576). Kidney,
CC uterus, and mastocytoma cells, and in a lesser amount in brain, thymus,
CC lung, heart, stomach and spleen (PubMed:1372606).
CC {ECO:0000269|PubMed:11535576, ECO:0000269|PubMed:1372606}.
CC -!- PTM: Ligand binding is affected by cAMP-dependent phosphorylation in
CC brain membranes.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Mice are born at the
CC expected Mendelian rate. Females have normal fertility. Mutant mice
CC have normal renal function, urine volume and urine osmolality
CC (PubMed:9843913). Mutant mice fail to develop fever in response to
CC pyrinogens, including IL1B, prostaglandin E2 and bacterial
CC lipopolysaccharide (LPS) (PubMed:9751056). Mutant mice lack the normal
CC potentiation of platelet aggregation by prostaglandin E2 and display
CC prolonged bleeding times and decreased susceptibility to
CC thromboembolism (PubMed:11535576). Mutant mice have normal basal levels
CC of HCO3(-) secretion in the duodenum, but fail to respond to mucosal
CC acidification by increased HCO3(-) secretion. Unlike wild-type, they
CC have a high incidence of ulcers in response to mucosal acidification
CC (PubMed:10535876). {ECO:0000269|PubMed:10535876,
CC ECO:0000269|PubMed:11535576, ECO:0000269|PubMed:9751056,
CC ECO:0000269|PubMed:9843913}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; D10204; BAA01051.1; -; mRNA.
DR EMBL; D13321; BAA02578.1; -; mRNA.
DR EMBL; D17406; BAA04229.1; -; mRNA.
DR PIR; A42414; A42414.
DR PIR; A45211; A45211.
DR PIR; S65009; S65009.
DR AlphaFoldDB; P30557; -.
DR SMR; P30557; -.
DR STRING; 10090.ENSMUSP00000043302; -.
DR BindingDB; P30557; -.
DR ChEMBL; CHEMBL4336; -.
DR DrugCentral; P30557; -.
DR GuidetoPHARMACOLOGY; 342; -.
DR GlyCosmos; P30557; 2 sites, No reported glycans.
DR GlyGen; P30557; 2 sites.
DR iPTMnet; P30557; -.
DR PhosphoSitePlus; P30557; -.
DR PaxDb; 10090-ENSMUSP00000043302; -.
DR ProteomicsDB; 287908; -. [P30557-1]
DR ProteomicsDB; 287909; -. [P30557-2]
DR ProteomicsDB; 287910; -. [P30557-3]
DR AGR; MGI:97795; -.
DR MGI; MGI:97795; Ptger3.
DR eggNOG; KOG3656; Eukaryota.
DR InParanoid; P30557; -.
DR PhylomeDB; P30557; -.
DR Reactome; R-MMU-391908; Prostanoid ligand receptors.
DR Reactome; R-MMU-418594; G alpha (i) signalling events.
DR ChiTaRS; Ptger3; mouse.
DR PRO; PR:P30557; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P30557; Protein.
DR GO; GO:0031526; C:brush border membrane; ISO:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:1990769; C:proximal neuron projection; ISO:MGI.
DR GO; GO:0004957; F:prostaglandin E receptor activity; IDA:MGI.
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:MGI.
DR GO; GO:0015701; P:bicarbonate transport; IMP:MGI.
DR GO; GO:1904322; P:cellular response to forskolin; ISO:MGI.
DR GO; GO:0002029; P:desensitization of G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:0001660; P:fever generation; IDA:MGI.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0014827; P:intestine smooth muscle contraction; ISO:MGI.
DR GO; GO:0106072; P:negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway; ISO:MGI.
DR GO; GO:1903170; P:negative regulation of calcium ion transmembrane transport; ISO:MGI.
DR GO; GO:1904326; P:negative regulation of circadian sleep/wake cycle, wakefulness; ISO:MGI.
DR GO; GO:2000978; P:negative regulation of forebrain neuron differentiation; ISO:MGI.
DR GO; GO:0060455; P:negative regulation of gastric acid secretion; IBA:GO_Central.
DR GO; GO:1903640; P:negative regulation of gastrin-induced gastric acid secretion; ISO:MGI.
DR GO; GO:0046676; P:negative regulation of insulin secretion; ISO:MGI.
DR GO; GO:0010700; P:negative regulation of norepinephrine secretion; ISO:MGI.
DR GO; GO:1901380; P:negative regulation of potassium ion transmembrane transport; ISO:MGI.
DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; IDA:MGI.
DR GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; ISO:MGI.
DR GO; GO:0046010; P:positive regulation of circadian sleep/wake cycle, non-REM sleep; ISO:MGI.
DR GO; GO:1904343; P:positive regulation of colon smooth muscle contraction; ISO:MGI.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:MGI.
DR GO; GO:0031622; P:positive regulation of fever generation; IMP:BHF-UCL.
DR GO; GO:1904346; P:positive regulation of gastric mucosal blood circulation; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:1904325; P:positive regulation of inhibitory G protein-coupled receptor phosphorylation; ISO:MGI.
DR GO; GO:1904330; P:positive regulation of myofibroblast contraction; ISO:MGI.
DR GO; GO:2000391; P:positive regulation of neutrophil extravasation; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:1904320; P:positive regulation of smooth muscle contraction involved in micturition; ISO:MGI.
DR GO; GO:0035810; P:positive regulation of urine volume; IMP:MGI.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; ISO:MGI.
DR GO; GO:1990767; P:prostaglandin receptor internalization; ISO:MGI.
DR GO; GO:0031623; P:receptor internalization; ISO:MGI.
DR GO; GO:0010840; P:regulation of circadian sleep/wake cycle, wakefulness; ISO:MGI.
DR GO; GO:0014061; P:regulation of norepinephrine secretion; ISO:MGI.
DR GO; GO:0032496; P:response to lipopolysaccharide; IMP:MGI.
DR GO; GO:0014832; P:urinary bladder smooth muscle contraction; ISO:MGI.
DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR InterPro; IPR000154; EP3_rcpt_3.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR008365; Prostanoid_rcpt.
DR InterPro; IPR001244; Prostglndn_DP_rcpt.
DR InterPro; IPR000265; Prostglndn_EP3_rcpt.
DR PANTHER; PTHR11866; G-PROTEIN COUPLED RECEPTOR FAMILY 1 MEMBER; 1.
DR PANTHER; PTHR11866:SF10; PROSTAGLANDIN E2 RECEPTOR EP3 SUBTYPE; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR00428; PROSTAGLNDNR.
DR PRINTS; PR01788; PROSTANOIDR.
DR PRINTS; PR00585; PRSTNOIDE33R.
DR PRINTS; PR00582; PRSTNOIDEP3R.
DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Lipoprotein; Membrane; Palmitate;
KW Phosphoprotein; Receptor; Reference proteome; Transducer; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..365
FT /note="Prostaglandin E2 receptor EP3 subtype"
FT /id="PRO_0000070059"
FT TOPO_DOM 1..30
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 31..55
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 56..68
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 69..89
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 90..108
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 109..130
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 131..151
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 152..173
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 174..203
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 204..229
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 230..259
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 260..283
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 284..303
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 304..325
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 326..365
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 16
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 193
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 107..184
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VAR_SEQ 336..365
FT /note="IRDHTNYASSSTSLPCPGSSALMWSDQLER -> MMNNLKWTFIAVPVSLGL
FT RISSPREG (in isoform Beta)"
FT /evidence="ECO:0000303|PubMed:8381413"
FT /id="VSP_001940"
FT VAR_SEQ 336..365
FT /note="IRDHTNYASSSTSLPCPGSSALMWSDQLER -> VANAVSSCSSDGQKGQAI
FT SLSNEVVQPGP (in isoform Gamma)"
FT /evidence="ECO:0000303|PubMed:8223569"
FT /id="VSP_001941"
SQ SEQUENCE 365 AA; 40077 MW; 1FEBEBB30C5EA67E CRC64;
MASMWAPEHS AEAHSNLSST TDDCGSVSVA FPITMMVTGF VGNALAMLLV SRSYRRRESK
RKKSFLLCIG WLALTDLVGQ LLTSPVVILV YLSQRRWEQL DPSGRLCTFF GLTMTVFGLS
SLLVASAMAV ERALAIRAPH WYASHMKTRA TPVLLGVWLS VLAFALLPVL GVGRYSVQWP
GTWCFISTGP AGNETDPARE PGSVAFASAF ACLGLLALVV TFACNLATIK ALVSRCRAKA
AVSQSSAQWG RITTETAIQL MGIMCVLSVC WSPLLIMMLK MIFNQMSVEQ CKTQMGKEKE
CNSFLIAVRL ASLNQILDPW VYLLLRKILL RKFCQIRDHT NYASSSTSLP CPGSSALMWS
DQLER
//
