PI2R_HUMAN
ID PI2R_HUMAN Reviewed; 386 AA.
AC P43119;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Prostacyclin receptor;
DE AltName: Full=Prostaglandin I2 receptor;
DE Short=PGI receptor;
DE Short=PGI2 receptor;
DE AltName: Full=Prostanoid IP receptor;
DE Flags: Precursor;
GN Name=PTGIR; Synonyms=PRIPR;
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=7512962; DOI=10.1016/s0021-9258(17)32697-2;
RA Boie Y., Rushmore T.H., Darmon-Goodwin A., Grygorczyk R., Slipetz D.M.,
RA Metters K.M., Abramovitz M.;
RT "Cloning and expression of a cDNA for the human prostanoid IP receptor.";
RL J. Biol. Chem. 269:12173-12178(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7514139; DOI=10.1016/0014-5793(94)00355-6;
RA Katsuyama M., Sugimoto Y., Namba T., Irie A., Negishi M., Narumiya S.,
RA Ichikawa A.;
RT "Cloning and expression of a cDNA for the human prostacyclin receptor.";
RL FEBS Lett. 344:74-78(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lung;
RX PubMed=7923647; DOI=10.1161/01.cir.90.4.1643;
RA Nakagawa O., Tanaka I., Usui T., Harada M., Sasaki Y., Itoh H.,
RA Yoshimasa T., Namba T., Narumiya S., Nakao K.;
RT "Molecular cloning of human prostacyclin receptor cDNA and its gene
RT expression in the cardiovascular system.";
RL Circulation 90:1643-1647(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7665161; DOI=10.1006/geno.1995.1016;
RA Ogawa Y., Tanaka I., Inoue M., Yoshitake Y., Isse N., Nakagawa O., Usui T.,
RA Itoh H., Yoshimasa T., Narumiya S.;
RT "Structural organization and chromosomal assignment of the human
RT prostacyclin receptor gene.";
RL Genomics 27:142-148(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RA Warren C.N., 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 (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
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 [7]
RP ISOPRENYLATION AT CYS-383, AND MUTAGENESIS OF CYS-383.
RX PubMed=11895442; DOI=10.1046/j.1432-1327.2002.02817.x;
RA Miggin S.M., Lawler O.A., Kinsella B.T.;
RT "Investigation of a functional requirement for isoprenylation by the human
RT prostacyclin receptor.";
RL Eur. J. Biochem. 269:1714-1725(2002).
RN [8]
RP RETRACTED PAPER.
RX PubMed=12488443; DOI=10.1074/jbc.m210637200;
RA Miggin S.M., Lawler O.A., Kinsella B.T.;
RT "Palmitoylation of the human prostacyclin receptor. Functional implications
RT of palmitoylation and isoprenylation.";
RL J. Biol. Chem. 278:6947-6958(2003).
RN [9]
RP RETRACTION NOTICE OF PUBMED:12488443.
RX PubMed=27613955; DOI=10.1074/jbc.a116.210637;
RA Miggin S.M., Lawler O.A., Kinsella B.T.;
RL J. Biol. Chem. 291:19259-19259(2016).
RN [10]
RP DISULFIDE BONDS.
RX PubMed=15194446; DOI=10.1016/j.ejphar.2004.04.041;
RA Giguere V., Gallant M.A., de Brum-Fernandes A.J., Parent J.-L.;
RT "Role of extracellular cysteine residues in dimerization/oligomerization of
RT the human prostacyclin receptor.";
RL Eur. J. Pharmacol. 494:11-22(2004).
CC -!- FUNCTION: Receptor for prostacyclin (prostaglandin I2 or PGI2). The
CC activity of this receptor is mediated by G(s) proteins which activate
CC adenylate cyclase.
CC -!- SUBUNIT: Interacts (non-isoprenylated C-terminus) with PDZK1.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- PTM: Isoprenylation does not influence ligand binding but is required
CC for efficient coupling to the effectors adenylyl cyclase and
CC phospholipase C. {ECO:0000269|PubMed:11895442}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- CAUTION: Palmitoylation of either Cys-308 or Cys-311 was reported to be
CC sufficient to maintain functional coupling to G(s) proteins and
CC signaling (PubMed:12488443). However, this publication was retracted
CC due to figure duplication. {ECO:0000269|PubMed:12488443,
CC ECO:0000305|PubMed:27613955}.
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DR EMBL; L29016; AAA36448.1; -; mRNA.
DR EMBL; D25418; BAA05008.1; -; mRNA.
DR EMBL; D29634; BAA06110.1; -; mRNA.
DR EMBL; D38127; BAA07325.1; -; Genomic_DNA.
DR EMBL; AY242134; AAO92301.1; -; mRNA.
DR EMBL; BC075814; AAH75814.1; -; mRNA.
DR CCDS; CCDS12686.1; -.
DR PIR; A57066; A57066.
DR RefSeq; NP_000951.1; NM_000960.3.
DR AlphaFoldDB; P43119; -.
DR SMR; P43119; -.
DR BioGRID; 111711; 221.
DR IntAct; P43119; 54.
DR STRING; 9606.ENSP00000291294; -.
DR BindingDB; P43119; -.
DR ChEMBL; CHEMBL1995; -.
DR DrugBank; DB05229; Beraprost.
DR DrugBank; DB01160; Dinoprost tromethamine.
DR DrugBank; DB01240; Epoprostenol.
DR DrugBank; DB01088; Iloprost.
DR DrugBank; DB11362; Selexipag.
DR DrugBank; DB00374; Treprostinil.
DR DrugCentral; P43119; -.
DR GuidetoPHARMACOLOGY; 345; -.
DR GlyGen; P43119; 1 site.
DR iPTMnet; P43119; -.
DR PhosphoSitePlus; P43119; -.
DR SwissPalm; P43119; -.
DR BioMuta; PTGIR; -.
DR DMDM; 1172500; -.
DR MassIVE; P43119; -.
DR PaxDb; P43119; -.
DR PeptideAtlas; P43119; -.
DR PRIDE; P43119; -.
DR ProteomicsDB; 55588; -.
DR Antibodypedia; 18117; 256 antibodies from 29 providers.
DR DNASU; 5739; -.
DR Ensembl; ENST00000291294.7; ENSP00000291294.1; ENSG00000160013.9.
DR GeneID; 5739; -.
DR KEGG; hsa:5739; -.
DR MANE-Select; ENST00000291294.7; ENSP00000291294.1; NM_000960.4; NP_000951.1.
DR UCSC; uc002pex.4; human.
DR CTD; 5739; -.
DR DisGeNET; 5739; -.
DR GeneCards; PTGIR; -.
DR HGNC; HGNC:9602; PTGIR.
DR HPA; ENSG00000160013; Tissue enhanced (lung).
DR MIM; 600022; gene.
DR neXtProt; NX_P43119; -.
DR OpenTargets; ENSG00000160013; -.
DR PharmGKB; PA291; -.
DR VEuPathDB; HostDB:ENSG00000160013; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01050000244902; -.
DR HOGENOM; CLU_045991_0_1_1; -.
DR InParanoid; P43119; -.
DR OMA; IHPFCGD; -.
DR OrthoDB; 972015at2759; -.
DR PhylomeDB; P43119; -.
DR TreeFam; TF324982; -.
DR PathwayCommons; P43119; -.
DR Reactome; R-HSA-391908; Prostanoid ligand receptors.
DR Reactome; R-HSA-392851; Prostacyclin signalling through prostacyclin receptor.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SABIO-RK; P43119; -.
DR SignaLink; P43119; -.
DR SIGNOR; P43119; -.
DR BioGRID-ORCS; 5739; 15 hits in 1076 CRISPR screens.
DR ChiTaRS; PTGIR; human.
DR GeneWiki; Prostacyclin_receptor; -.
DR GenomeRNAi; 5739; -.
DR Pharos; P43119; Tclin.
DR PRO; PR:P43119; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P43119; protein.
DR Bgee; ENSG00000160013; Expressed in ascending aorta and 117 other tissues.
DR ExpressionAtlas; P43119; baseline and differential.
DR Genevisible; P43119; HS.
DR GO; GO:0005829; C:cytosol; IDA:BHF-UCL.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; TAS:Reactome.
DR GO; GO:0016501; F:prostacyclin receptor activity; IBA:GO_Central.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0007187; P:G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; TAS:ProtInc.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0010642; P:negative regulation of platelet-derived growth factor receptor signaling pathway; ISS:BHF-UCL.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IDA:BHF-UCL.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IBA:GO_Central.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR008365; Prostanoid_rcpt.
DR InterPro; IPR000370; Prostglndn_IP_rcpt.
DR PANTHER; PTHR11866; PTHR11866; 1.
DR PANTHER; PTHR11866:SF7; PTHR11866:SF7; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR01788; PROSTANOIDR.
DR PRINTS; PR00856; PRSTNOIDIPR.
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 Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein;
KW Lipoprotein; Membrane; Methylation; Prenylation; Receptor;
KW Reference proteome; Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..383
FT /note="Prostacyclin receptor"
FT /id="PRO_0000070075"
FT PROPEP 384..386
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000240004"
FT TOPO_DOM 1..16
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 17..38
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 39..51
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 52..76
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 77..94
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 95..115
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 116..134
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 135..158
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 159..181
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 182..208
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 209..235
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 236..260
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 261..274
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 275..295
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 296..386
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 322..376
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 359..376
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 383
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000305"
FT LIPID 383
FT /note="S-farnesyl cysteine"
FT /evidence="ECO:0000269|PubMed:11895442"
FT CARBOHYD 7
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 5..165
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521,
FT ECO:0000269|PubMed:15194446"
FT DISULFID 92..170
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521,
FT ECO:0000269|PubMed:15194446"
FT VARIANT 25
FT /note="V -> M (in dbSNP:rs2229127)"
FT /id="VAR_024260"
FT VARIANT 319
FT /note="S -> W (in dbSNP:rs28590598)"
FT /id="VAR_061226"
FT MUTAGEN 383
FT /note="C->S: Abolishes isoprenylation."
FT /evidence="ECO:0000269|PubMed:11895442"
SQ SEQUENCE 386 AA; 40956 MW; 2B6B0CDBACED1608 CRC64;
MADSCRNLTY VRGSVGPATS TLMFVAGVVG NGLALGILSA RRPARPSAFA VLVTGLAATD
LLGTSFLSPA VFVAYARNSS LLGLARGGPA LCDAFAFAMT FFGLASMLIL FAMAVERCLA
LSHPYLYAQL DGPRCARLAL PAIYAFCVLF CALPLLGLGQ HQQYCPGSWC FLRMRWAQPG
GAAFSLAYAG LVALLVAAIF LCNGSVTLSL CRMYRQQKRH QGSLGPRPRT GEDEVDHLIL
LALMTVVMAV CSLPLTIRCF TQAVAPDSSS EMGDLLAFRF YAFNPILDPW VFILFRKAVF
QRLKLWVCCL CLGPAHGDSQ TPLSQLASGR RDPRAPSAPV GKEGSCVPLS AWGEGQVEPL
PPTQQSSGSA VGTSSKAEAS VACSLC
