PE2R3_RAT
ID PE2R3_RAT Reviewed; 365 AA.
AC P34980; Q63194; Q64376;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 25-MAY-2022, entry version 160.
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;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Kidney;
RX PubMed=8393672; DOI=10.1006/bbrc.1993.1904;
RA Takeuchi K., Abe T., Takahashi N., Abe K.;
RT "Molecular cloning and intrarenal localization of rat prostaglandin E2
RT receptor EP3 subtype.";
RL Biochem. Biophys. Res. Commun. 194:885-891(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND GAMMA).
RC STRAIN=Sprague-Dawley; TISSUE=Kidney;
RX PubMed=8135830; DOI=10.1006/bbrc.1994.1304;
RA Takeuchi K., Takahashi N., Abe T., Abe K.;
RT "Two isoforms of the rat kidney EP3 receptor derived by alternative RNA
RT splicing: intrarenal expression co-localization.";
RL Biochem. Biophys. Res. Commun. 199:834-840(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA).
RC TISSUE=Hepatocyte;
RX PubMed=8076679; DOI=10.1016/0014-5793(94)00837-x;
RA Neuschaefer-Rube F., de Vries C., Haenecke K., Jungermann K.,
RA Pueschel G.P.;
RT "Molecular cloning and expression of a prostaglandin E2 receptor of the EP3
RT beta subtype from rat hepatocytes.";
RL FEBS Lett. 351:119-122(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA), AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain cortex;
RX PubMed=8919306; DOI=10.1016/0006-8993(95)01256-7;
RA Kitanaka J., Hashimoto H., Gotoh M., Kondo K., Sakata K., Hirasawa Y.,
RA Sawada M., Suzumura A., Marunouchi T., Matsuda T., Baba A.;
RT "Expression pattern of messenger RNAs for prostanoid receptors in glial
RT cell cultures.";
RL Brain Res. 707:282-287(1996).
RN [5]
RP FUNCTION, INTERACTION WITH MKLN1 (ISOFORM ALPHA), AND SUBCELLULAR LOCATION.
RX PubMed=11006128; DOI=10.1006/bbrc.2000.3467;
RA Hasegawa H., Katoh H., Fujita H., Mori K., Negishi M.;
RT "Receptor isoform-specific interaction of prostaglandin EP3 receptor with
RT muskelin.";
RL Biochem. Biophys. Res. Commun. 276:350-354(2000).
CC -!- FUNCTION: Receptor for prostaglandin E2 (PGE2) (PubMed:8393672,
CC PubMed:11006128). Required for normal development of fever in response
CC to pyrinogens, including IL1B, prostaglandin E2 and bacterial
CC lipopolysaccharide (LPS). Required for normal potentiation of platelet
CC aggregation by prostaglandin E2, and thus plays a role in the
CC regulation of blood coagulation. Required for increased HCO3(-)
CC secretion in the duodenum in response to mucosal acidification, and
CC thereby contributes to the protection of the mucosa against acid-
CC induced ulceration. Not required for normal kidney function, normal
CC urine volume and osmolality (By similarity).
CC {ECO:0000250|UniProtKB:P30557, ECO:0000269|PubMed:11006128,
CC ECO:0000269|PubMed:8393672}.
CC -!- FUNCTION: [Isoform Alpha]: Receptor for prostaglandin E2 (PGE2); ligand
CC binding activates a signaling cascade via G(i) proteins that leads to
CC the inhibition of adenylate cyclase. {ECO:0000269|PubMed:11006128}.
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:0000250|UniProtKB:P30557}.
CC -!- SUBUNIT: [Isoform Alpha]: Interacts (via C-terminus) with MKLN1
CC (PubMed:11006128). {ECO:0000269|PubMed:11006128}.
CC -!- SUBUNIT: [Isoform Beta]: Does not interact with MKLN1
CC (PubMed:11006128). {ECO:0000269|PubMed:11006128}.
CC -!- SUBUNIT: [Isoform Gamma]: Does not interact with MKLN1
CC (PubMed:11006128). {ECO:0000269|PubMed:11006128}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11006128,
CC ECO:0000269|PubMed:8393672}; Multi-pass membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist. Isoforms have identical
CC ligand binding properties but different coupling properties with G
CC proteins: isoform Alpha and isoform Beta couple to G(i) proteins,
CC whereas isoform Gamma couples to multiple G proteins, G(i) and G(s).;
CC Name=Alpha;
CC IsoId=P34980-1; Sequence=Displayed;
CC Name=Beta;
CC IsoId=P34980-2; Sequence=VSP_001949;
CC Name=Gamma;
CC IsoId=P34980-3; Sequence=VSP_001950;
CC -!- TISSUE SPECIFICITY: Principally expressed in the tubules of the renal
CC medulla. Specific expression is seen in medullary and cortical thick
CC ascending limbs; lower levels are detected in cortical and inner
CC medullary collecting ducts. Not detected significantly in the glomeruli
CC (PubMed:8393672). In the brain, expressed in all types of glial cells
CC (PubMed:8919306). {ECO:0000269|PubMed:8393672,
CC ECO:0000269|PubMed:8919306}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; D14869; BAA03585.1; -; mRNA.
DR EMBL; D16443; BAA03912.1; -; mRNA.
DR EMBL; X80133; CAA56432.1; -; mRNA.
DR EMBL; D29969; BAA06236.1; -; mRNA.
DR EMBL; X83855; CAA58735.1; -; mRNA.
DR PIR; JN0693; JN0693.
DR PIR; S48689; S48689.
DR PIR; S51280; S51280.
DR RefSeq; NP_036836.1; NM_012704.1.
DR AlphaFoldDB; P34980; -.
DR SMR; P34980; -.
DR STRING; 10116.ENSRNOP00000014034; -.
DR BindingDB; P34980; -.
DR ChEMBL; CHEMBL5674; -.
DR DrugCentral; P34980; -.
DR GuidetoPHARMACOLOGY; 342; -.
DR GlyGen; P34980; 2 sites.
DR PhosphoSitePlus; P34980; -.
DR PaxDb; P34980; -.
DR DNASU; 24929; -.
DR GeneID; 24929; -.
DR KEGG; rno:24929; -.
DR CTD; 5733; -.
DR RGD; 3435; Ptger3.
DR eggNOG; KOG3656; Eukaryota.
DR InParanoid; P34980; -.
DR PhylomeDB; P34980; -.
DR Reactome; R-RNO-391908; Prostanoid ligand receptors.
DR Reactome; R-RNO-418594; G alpha (i) signalling events.
DR PRO; PR:P34980; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0031526; C:brush border membrane; IDA:RGD.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0031965; C:nuclear membrane; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:1990769; C:proximal neuron projection; IDA:RGD.
DR GO; GO:0004957; F:prostaglandin E receptor activity; IDA:RGD.
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; ISO:RGD.
DR GO; GO:0015701; P:bicarbonate transport; ISO:RGD.
DR GO; GO:1904322; P:cellular response to forskolin; IMP:RGD.
DR GO; GO:0071347; P:cellular response to interleukin-1; IEP:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0002029; P:desensitization of G protein-coupled receptor signaling pathway; IMP:RGD.
DR GO; GO:0007565; P:female pregnancy; IEP:RGD.
DR GO; GO:0001660; P:fever generation; ISO:RGD.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0014827; P:intestine smooth muscle contraction; IMP:RGD.
DR GO; GO:0060137; P:maternal process involved in parturition; IEP:RGD.
DR GO; GO:0106072; P:negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway; IMP:RGD.
DR GO; GO:1903170; P:negative regulation of calcium ion transmembrane transport; IMP:RGD.
DR GO; GO:1904326; P:negative regulation of circadian sleep/wake cycle, wakefulness; IMP:RGD.
DR GO; GO:2000978; P:negative regulation of forebrain neuron differentiation; IMP:RGD.
DR GO; GO:0060455; P:negative regulation of gastric acid secretion; IMP:RGD.
DR GO; GO:1903640; P:negative regulation of gastrin-induced gastric acid secretion; IMP:RGD.
DR GO; GO:0046676; P:negative regulation of insulin secretion; IDA:RGD.
DR GO; GO:0010700; P:negative regulation of norepinephrine secretion; IMP:RGD.
DR GO; GO:0090331; P:negative regulation of platelet aggregation; IMP:RGD.
DR GO; GO:1901380; P:negative regulation of potassium ion transmembrane transport; IMP:RGD.
DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; ISO:RGD.
DR GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; IMP:RGD.
DR GO; GO:0046010; P:positive regulation of circadian sleep/wake cycle, non-REM sleep; IMP:RGD.
DR GO; GO:1904343; P:positive regulation of colon smooth muscle contraction; IMP:RGD.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IMP:RGD.
DR GO; GO:0031622; P:positive regulation of fever generation; ISO:RGD.
DR GO; GO:1904346; P:positive regulation of gastric mucosal blood circulation; IMP:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:RGD.
DR GO; GO:1904325; P:positive regulation of inhibitory G protein-coupled receptor phosphorylation; IMP:RGD.
DR GO; GO:1904330; P:positive regulation of myofibroblast contraction; IMP:RGD.
DR GO; GO:2000391; P:positive regulation of neutrophil extravasation; IMP:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:RGD.
DR GO; GO:1904320; P:positive regulation of smooth muscle contraction involved in micturition; IMP:RGD.
DR GO; GO:0035810; P:positive regulation of urine volume; ISO:RGD.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; IMP:RGD.
DR GO; GO:1990767; P:prostaglandin receptor internalization; IMP:RGD.
DR GO; GO:0031623; P:receptor internalization; IMP:RGD.
DR GO; GO:0010840; P:regulation of circadian sleep/wake cycle, wakefulness; IMP:RGD.
DR GO; GO:0014061; P:regulation of norepinephrine secretion; IMP:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISO:RGD.
DR GO; GO:0032570; P:response to progesterone; IEP:RGD.
DR GO; GO:1902074; P:response to salt; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0014832; P:urinary bladder smooth muscle contraction; IMP:RGD.
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; PTHR11866; 1.
DR PANTHER; PTHR11866:SF10; PTHR11866:SF10; 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 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 Receptor; Reference proteome; Transducer; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..365
FT /note="Prostaglandin E2 receptor EP3 subtype"
FT /id="PRO_0000070062"
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 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="IRDHTNYASSSTSLPCPGSSVLMWSDQLER -> MMNNLKRSFIAIPASLSM
FT RISSPREG (in isoform Beta)"
FT /evidence="ECO:0000303|PubMed:8076679,
FT ECO:0000303|PubMed:8919306"
FT /id="VSP_001949"
FT VAR_SEQ 336..365
FT /note="IRDHTNYASSSTSLPCPGSSVLMWSDQLER -> VANAVSSCSSDQQKGQAI
FT SLSNEVVHPGP (in isoform Gamma)"
FT /evidence="ECO:0000303|PubMed:8135830"
FT /id="VSP_001950"
FT VARIANT 152
FT /note="P -> RA"
FT CONFLICT 51
FT /note="V -> S (in Ref. 3 and 4)"
FT /evidence="ECO:0000305"
FT CONFLICT 354
FT /note="S -> F (in Ref. 3; CAA58735)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 365 AA; 39942 MW; 3247190CF95FD825 CRC64;
MAGVWAPEHS VEAHSNQSSA ADGCGSVSVA FPITMMVTGF VGNALAMLLV VRSYRRRESK
RKKSFLLCIG WLALTDLVGQ LLTSPVVILV YLSQRRWEQL DPSGRLCTFF GLTMTVFGLS
SLLVASAMAV ERALAIRAPH WYASHMKTRA TPVLLGVWLS VLAFALLPVL GVGRYSVQWP
GTWCFISTGP AGNETDSARE PGSVAFASAF ACLGLLALVV TFACNLATIK ALVSRCRAKA
AASQSSAQWG RITTETAIQL MGIMCVLSVC WSPLLIMMLK MIFNQMSVEQ CKTQMGKEKE
CNSFLIAVRL ASLNQILDPW VYLLLRKILL RKFCQIRDHT NYASSSTSLP CPGSSVLMWS
DQLER
