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Protein

Prostacyclin receptor

Gene

PTGIR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for prostacyclin (prostaglandin I2 or PGI2). The activity of this receptor is mediated by G(s) proteins which activate adenylate cyclase.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei309 – 3091Not S-palmitoylated

GO - Molecular functioni

  1. G-protein coupled receptor activity Source: UniProtKB-KW
  2. guanyl-nucleotide exchange factor activity Source: Reactome

GO - Biological processi

  1. adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: BHF-UCL
  2. blood coagulation Source: Reactome
  3. cell-cell signaling Source: ProtInc
  4. G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger Source: ProtInc
  5. negative regulation of platelet-derived growth factor receptor signaling pathway Source: BHF-UCL
  6. negative regulation of smooth muscle cell proliferation Source: BHF-UCL
  7. positive regulation of cAMP biosynthetic process Source: BHF-UCL
  8. positive regulation of cAMP-mediated signaling Source: BHF-UCL
  9. positive regulation of GTPase activity Source: GOC
  10. response to lipopolysaccharide Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiREACT_18425. Prostanoid ligand receptors.
REACT_19327. G alpha (s) signalling events.
REACT_23946. Prostacyclin signalling through prostacyclin receptor.

Names & Taxonomyi

Protein namesi
Recommended name:
Prostacyclin receptor
Alternative name(s):
Prostaglandin I2 receptor
Short name:
PGI receptor
Short name:
PGI2 receptor
Prostanoid IP receptor
Gene namesi
Name:PTGIR
Synonyms:PRIPR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 19

Organism-specific databases

HGNCiHGNC:9602. PTGIR.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1616ExtracellularSequence AnalysisAdd
BLAST
Transmembranei17 – 3822Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini39 – 5113CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei52 – 7625Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini77 – 9418ExtracellularSequence AnalysisAdd
BLAST
Transmembranei95 – 11521Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini116 – 13419CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei135 – 15824Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini159 – 18123ExtracellularSequence AnalysisAdd
BLAST
Transmembranei182 – 20827Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini209 – 23527CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei236 – 26025Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini261 – 27414ExtracellularSequence AnalysisAdd
BLAST
Transmembranei275 – 29521Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini296 – 38691CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. cytosol Source: BHF-UCL
  2. integral component of plasma membrane Source: ProtInc
  3. plasma membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi308 – 3081C → S: Reduced palmitoylation, coupling to G protein unaffected. Abolished palmitoylation and coupling to G protein; when associated with S-311. 1 Publication
Mutagenesisi309 – 3091C → S: No effect on palmitoylation level. 1 Publication
Mutagenesisi311 – 3111C → S: Reduced palmitoylation, coupling to G protein unaffected. Abolished palmitoylation and coupling to G protein; when associated with S-308. 1 Publication
Mutagenesisi383 – 3831C → S: Abolishes isoprenylation. 1 Publication

Organism-specific databases

PharmGKBiPA291.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 383383Prostacyclin receptorPRO_0000070075Add
BLAST
Propeptidei384 – 3863Removed in mature formSequence AnalysisPRO_0000240004

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi5 ↔ 1651 PublicationPROSITE-ProRule annotation
Glycosylationi7 – 71N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi92 ↔ 1701 PublicationPROSITE-ProRule annotation
Lipidationi308 – 3081S-palmitoyl cysteine1 Publication
Lipidationi311 – 3111S-palmitoyl cysteine1 Publication
Modified residuei383 – 3831Cysteine methyl esterCurated
Lipidationi383 – 3831S-farnesyl cysteine1 Publication

Post-translational modificationi

Palmitoylation of either Cys-308 or Cys-311 is sufficient to maintain functional coupling to G(s) and signaling.1 Publication
Isoprenylation does not influence ligand binding but is required for efficient coupling to the effectors adenylyl cyclase and phospholipase C.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Methylation, Palmitate, Prenylation

Proteomic databases

PaxDbiP43119.
PRIDEiP43119.

PTM databases

PhosphoSiteiP43119.

Expressioni

Gene expression databases

BgeeiP43119.
CleanExiHS_PTGIR.
ExpressionAtlasiP43119. baseline and differential.
GenevestigatoriP43119.

Interactioni

Subunit structurei

Interacts (non-isoprenylated C-terminus) with PDZK1.By similarity

Protein-protein interaction databases

BioGridi111711. 14 interactions.
STRINGi9606.ENSP00000291294.

Structurei

3D structure databases

ProteinModelPortaliP43119.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG305292.
GeneTreeiENSGT00760000119188.
HOGENOMiHOG000115475.
HOVERGENiHBG003074.
InParanoidiP43119.
KOiK04263.
OMAiPLMIRIV.
OrthoDBiEOG72VH6G.
PhylomeDBiP43119.
TreeFamiTF324982.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR008365. Prostanoid_rcpt.
IPR000370. Prostglndn_IP_rcpt.
[Graphical view]
PANTHERiPTHR11866. PTHR11866. 1 hit.
PTHR11866:SF7. PTHR11866:SF7. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR01788. PROSTANOIDR.
PR00856. PRSTNOIDIPR.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P43119-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MADSCRNLTY VRGSVGPATS TLMFVAGVVG NGLALGILSA RRPARPSAFA
60 70 80 90 100
VLVTGLAATD LLGTSFLSPA VFVAYARNSS LLGLARGGPA LCDAFAFAMT
110 120 130 140 150
FFGLASMLIL FAMAVERCLA LSHPYLYAQL DGPRCARLAL PAIYAFCVLF
160 170 180 190 200
CALPLLGLGQ HQQYCPGSWC FLRMRWAQPG GAAFSLAYAG LVALLVAAIF
210 220 230 240 250
LCNGSVTLSL CRMYRQQKRH QGSLGPRPRT GEDEVDHLIL LALMTVVMAV
260 270 280 290 300
CSLPLTIRCF TQAVAPDSSS EMGDLLAFRF YAFNPILDPW VFILFRKAVF
310 320 330 340 350
QRLKLWVCCL CLGPAHGDSQ TPLSQLASGR RDPRAPSAPV GKEGSCVPLS
360 370 380
AWGEGQVEPL PPTQQSSGSA VGTSSKAEAS VACSLC
Length:386
Mass (Da):40,956
Last modified:November 1, 1995 - v1
Checksum:i2B6B0CDBACED1608
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti25 – 251V → M.
Corresponds to variant rs2229127 [ dbSNP | Ensembl ].
VAR_024260
Natural varianti319 – 3191S → W.
Corresponds to variant rs28590598 [ dbSNP | Ensembl ].
VAR_061226

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L29016 mRNA. Translation: AAA36448.1.
D25418 mRNA. Translation: BAA05008.1.
D29634 mRNA. Translation: BAA06110.1.
D38127 Genomic DNA. Translation: BAA07325.1.
AY242134 mRNA. Translation: AAO92301.1.
BC075814 mRNA. Translation: AAH75814.1.
CCDSiCCDS12686.1.
PIRiA57066.
RefSeqiNP_000951.1. NM_000960.3.
UniGeneiHs.458324.

Genome annotation databases

EnsembliENST00000291294; ENSP00000291294; ENSG00000160013.
GeneIDi5739.
KEGGihsa:5739.
UCSCiuc002pex.3. human.

Polymorphism databases

DMDMi1172500.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L29016 mRNA. Translation: AAA36448.1.
D25418 mRNA. Translation: BAA05008.1.
D29634 mRNA. Translation: BAA06110.1.
D38127 Genomic DNA. Translation: BAA07325.1.
AY242134 mRNA. Translation: AAO92301.1.
BC075814 mRNA. Translation: AAH75814.1.
CCDSiCCDS12686.1.
PIRiA57066.
RefSeqiNP_000951.1. NM_000960.3.
UniGeneiHs.458324.

3D structure databases

ProteinModelPortaliP43119.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111711. 14 interactions.
STRINGi9606.ENSP00000291294.

Chemistry

BindingDBiP43119.
ChEMBLiCHEMBL1995.
DrugBankiDB01160. Dinoprost Tromethamine.
DB01240. Epoprostenol.
DB01088. Iloprost.
DB00374. Treprostinil.
GuidetoPHARMACOLOGYi345.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiP43119.

Polymorphism databases

DMDMi1172500.

Proteomic databases

PaxDbiP43119.
PRIDEiP43119.

Protocols and materials databases

DNASUi5739.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000291294; ENSP00000291294; ENSG00000160013.
GeneIDi5739.
KEGGihsa:5739.
UCSCiuc002pex.3. human.

Organism-specific databases

CTDi5739.
GeneCardsiGC19M047123.
HGNCiHGNC:9602. PTGIR.
MIMi600022. gene.
neXtProtiNX_P43119.
PharmGKBiPA291.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG305292.
GeneTreeiENSGT00760000119188.
HOGENOMiHOG000115475.
HOVERGENiHBG003074.
InParanoidiP43119.
KOiK04263.
OMAiPLMIRIV.
OrthoDBiEOG72VH6G.
PhylomeDBiP43119.
TreeFamiTF324982.

Enzyme and pathway databases

ReactomeiREACT_18425. Prostanoid ligand receptors.
REACT_19327. G alpha (s) signalling events.
REACT_23946. Prostacyclin signalling through prostacyclin receptor.

Miscellaneous databases

GeneWikiiProstacyclin_receptor.
GenomeRNAii5739.
NextBioi22340.
PROiP43119.
SOURCEiSearch...

Gene expression databases

BgeeiP43119.
CleanExiHS_PTGIR.
ExpressionAtlasiP43119. baseline and differential.
GenevestigatoriP43119.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR008365. Prostanoid_rcpt.
IPR000370. Prostglndn_IP_rcpt.
[Graphical view]
PANTHERiPTHR11866. PTHR11866. 1 hit.
PTHR11866:SF7. PTHR11866:SF7. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR01788. PROSTANOIDR.
PR00856. PRSTNOIDIPR.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and expression of a cDNA for the human prostanoid IP receptor."
    Boie Y., Rushmore T.H., Darmon-Goodwin A., Grygorczyk R., Slipetz D.M., Metters K.M., Abramovitz M.
    J. Biol. Chem. 269:12173-12178(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Lung.
  2. "Cloning and expression of a cDNA for the human prostacyclin receptor."
    Katsuyama M., Sugimoto Y., Namba T., Irie A., Negishi M., Narumiya S., Ichikawa A.
    FEBS Lett. 344:74-78(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "Molecular cloning of human prostacyclin receptor cDNA and its gene expression in the cardiovascular system."
    Nakagawa O., Tanaka I., Usui T., Harada M., Sasaki Y., Itoh H., Yoshimasa T., Namba T., Narumiya S., Nakao K.
    Circulation 90:1643-1647(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Lung.
  4. "Structural organization and chromosomal assignment of the human prostacyclin receptor gene."
    Ogawa Y., Tanaka I., Inoue M., Yoshitake Y., Isse N., Nakagawa O., Usui T., Itoh H., Yoshimasa T., Narumiya S.
    Genomics 27:142-148(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  5. "cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
    Warren C.N., Aronstam R.S., Sharma S.V.
    Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Placenta.
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Pancreas.
  7. "Investigation of a functional requirement for isoprenylation by the human prostacyclin receptor."
    Miggin S.M., Lawler O.A., Kinsella B.T.
    Eur. J. Biochem. 269:1714-1725(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: ISOPRENYLATION AT CYS-383, MUTAGENESIS OF CYS-383.
  8. "Palmitoylation of the human prostacyclin receptor. Functional implications of palmitoylation and isoprenylation."
    Miggin S.M., Lawler O.A., Kinsella B.T.
    J. Biol. Chem. 278:6947-6958(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: PALMITOYLATION AT CYS-308 AND CYS-311, LACK OF PALMITOYLATION AT CYS-309, MUTAGENESIS OF CYS-308; CYS-309 AND CYS-311.
  9. "Role of extracellular cysteine residues in dimerization/oligomerization of the human prostacyclin receptor."
    Giguere V., Gallant M.A., de Brum-Fernandes A.J., Parent J.-L.
    Eur. J. Pharmacol. 494:11-22(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISULFIDE BONDS.

Entry informationi

Entry nameiPI2R_HUMAN
AccessioniPrimary (citable) accession number: P43119
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: January 7, 2015
This is version 143 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.