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P43119 (PI2R_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Prostacyclin receptor
Alternative name(s):
Prostaglandin I2 receptor
Short name=PGI receptor
Short name=PGI2 receptor
Prostanoid IP receptor
Gene names
Name:PTGIR
Synonyms:PRIPR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length386 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Subunit structure

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

Subcellular location

Cell membrane; Multi-pass membrane protein.

Post-translational modification

Palmitoylation of either Cys-308 or Cys-311 is sufficient to maintain functional coupling to G(s) and signaling. Ref.8

Isoprenylation does not influence ligand binding but is required for efficient coupling to the effectors adenylyl cyclase and phospholipase C.

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DomainTransmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Lipoprotein
Methylation
Palmitate
Prenylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger

Traceable author statement Ref.1. Source: ProtInc

adenylate cyclase-activating G-protein coupled receptor signaling pathway

Inferred from mutant phenotype PubMed 20622039. Source: BHF-UCL

blood coagulation

Traceable author statement. Source: Reactome

cell-cell signaling

Traceable author statement Ref.1. Source: ProtInc

negative regulation of platelet-derived growth factor receptor signaling pathway

Inferred from sequence or structural similarity PubMed 20622039. Source: BHF-UCL

negative regulation of smooth muscle cell proliferation

Inferred from direct assay PubMed 20622039. Source: BHF-UCL

positive regulation of cAMP biosynthetic process

Inferred from mutant phenotype PubMed 20622039. Source: BHF-UCL

positive regulation of cAMP-mediated signaling

Inferred from mutant phenotype PubMed 20622039. Source: BHF-UCL

regulation of GTPase activity

Traceable author statement. Source: GOC

response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytosol

Inferred from direct assay PubMed 20622039. Source: BHF-UCL

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

plasma membrane

Inferred from direct assay PubMed 20622039. Source: BHF-UCL

   Molecular_functionG-protein coupled receptor activity

Inferred from electronic annotation. Source: UniProtKB-KW

guanyl-nucleotide exchange factor activity

Traceable author statement. Source: Reactome

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 383383Prostacyclin receptor
PRO_0000070075
Propeptide384 – 3863Removed in mature form Potential
PRO_0000240004

Regions

Topological domain1 – 1616Extracellular Potential
Transmembrane17 – 3822Helical; Name=1; Potential
Topological domain39 – 5113Cytoplasmic Potential
Transmembrane52 – 7625Helical; Name=2; Potential
Topological domain77 – 9418Extracellular Potential
Transmembrane95 – 11521Helical; Name=3; Potential
Topological domain116 – 13419Cytoplasmic Potential
Transmembrane135 – 15824Helical; Name=4; Potential
Topological domain159 – 18123Extracellular Potential
Transmembrane182 – 20827Helical; Name=5; Potential
Topological domain209 – 23527Cytoplasmic Potential
Transmembrane236 – 26025Helical; Name=6; Potential
Topological domain261 – 27414Extracellular Potential
Transmembrane275 – 29521Helical; Name=7; Potential
Topological domain296 – 38691Cytoplasmic Potential

Sites

Site3091Not S-palmitoylated

Amino acid modifications

Modified residue3831Cysteine methyl ester Probable
Lipidation3081S-palmitoyl cysteine Ref.8
Lipidation3111S-palmitoyl cysteine Ref.8
Lipidation3831S-farnesyl cysteine Ref.7
Glycosylation71N-linked (GlcNAc...) Potential
Disulfide bond5 ↔ 165 Ref.9
Disulfide bond92 ↔ 170 Ref.9

Natural variations

Natural variant251V → M.
Corresponds to variant rs2229127 [ dbSNP | Ensembl ].
VAR_024260
Natural variant3191S → W.
Corresponds to variant rs28590598 [ dbSNP | Ensembl ].
VAR_061226

Experimental info

Mutagenesis3081C → S: Reduced palmitoylation, coupling to G protein unaffected. Abolished palmitoylation and coupling to G protein; when associated with S-311. Ref.8
Mutagenesis3091C → S: No effect on palmitoylation level. Ref.8
Mutagenesis3111C → S: Reduced palmitoylation, coupling to G protein unaffected. Abolished palmitoylation and coupling to G protein; when associated with S-308. Ref.8
Mutagenesis3831C → S: Abolishes isoprenylation. Ref.7

Sequences

Sequence LengthMass (Da)Tools
P43119 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: 2B6B0CDBACED1608

FASTA38640,956
        10         20         30         40         50         60 
MADSCRNLTY VRGSVGPATS TLMFVAGVVG NGLALGILSA RRPARPSAFA VLVTGLAATD 

        70         80         90        100        110        120 
LLGTSFLSPA VFVAYARNSS LLGLARGGPA LCDAFAFAMT FFGLASMLIL FAMAVERCLA 

       130        140        150        160        170        180 
LSHPYLYAQL DGPRCARLAL PAIYAFCVLF CALPLLGLGQ HQQYCPGSWC FLRMRWAQPG 

       190        200        210        220        230        240 
GAAFSLAYAG LVALLVAAIF LCNGSVTLSL CRMYRQQKRH QGSLGPRPRT GEDEVDHLIL 

       250        260        270        280        290        300 
LALMTVVMAV CSLPLTIRCF TQAVAPDSSS EMGDLLAFRF YAFNPILDPW VFILFRKAVF 

       310        320        330        340        350        360 
QRLKLWVCCL CLGPAHGDSQ TPLSQLASGR RDPRAPSAPV GKEGSCVPLS AWGEGQVEPL 

       370        380 
PPTQQSSGSA VGTSSKAEAS VACSLC 

« Hide

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS12686.1.
PIRA57066.
RefSeqNP_000951.1. NM_000960.3.
UniGeneHs.458324.

3D structure databases

ProteinModelPortalP43119.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111711. 14 interactions.
STRING9606.ENSP00000291294.

Chemistry

BindingDBP43119.
ChEMBLCHEMBL1995.
DrugBankDB01160. Dinoprost Tromethamine.
DB00917. Dinoprostone.
DB01240. Epoprostenol.
DB01088. Iloprost.
DB00929. Misoprostol.
GuidetoPHARMACOLOGY345.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP43119.

Polymorphism databases

DMDM1172500.

Proteomic databases

PaxDbP43119.
PRIDEP43119.

Protocols and materials databases

DNASU5739.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000291294; ENSP00000291294; ENSG00000160013.
GeneID5739.
KEGGhsa:5739.
UCSCuc002pex.3. human.

Organism-specific databases

CTD5739.
GeneCardsGC19M047123.
HGNCHGNC:9602. PTGIR.
MIM600022. gene.
neXtProtNX_P43119.
PharmGKBPA291.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG305292.
HOGENOMHOG000115475.
HOVERGENHBG003074.
InParanoidP43119.
KOK04263.
OMACFLSPAV.
OrthoDBEOG72VH6G.
PhylomeDBP43119.
TreeFamTF324982.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpressP43119.
BgeeP43119.
CleanExHS_PTGIR.
GenevestigatorP43119.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR008365. Prostanoid_rcpt.
IPR000370. Prostglndn_IP_rcpt.
[Graphical view]
PANTHERPTHR11866. PTHR11866. 1 hit.
PTHR11866:SF7. PTHR11866:SF7. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR01788. PROSTANOIDR.
PR00856. PRSTNOIDIPR.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiProstacyclin_receptor.
GenomeRNAi5739.
NextBio22340.
PROP43119.
SOURCESearch...

Entry information

Entry namePI2R_HUMAN
AccessionPrimary (citable) accession number: P43119
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: July 9, 2014
This is version 139 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries