P43119 (PI2R_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	386 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.
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 component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Lipoprotein Methylation Palmitate Prenylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	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 response to lipopolysaccharide Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Inferred from direct assay PubMed 20622039. Source: BHF-UCL integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	G-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 383	383	Prostacyclin receptor		PRO_0000070075
	Propeptide	384 – 386	3	Removed in mature form Potential		PRO_0000240004
Regions
	Topological domain	1 – 16	16	Extracellular Potential
	Transmembrane	17 – 38	22	Helical; Name=1; Potential
	Topological domain	39 – 51	13	Cytoplasmic Potential
	Transmembrane	52 – 76	25	Helical; Name=2; Potential
	Topological domain	77 – 94	18	Extracellular Potential
	Transmembrane	95 – 115	21	Helical; Name=3; Potential
	Topological domain	116 – 134	19	Cytoplasmic Potential
	Transmembrane	135 – 158	24	Helical; Name=4; Potential
	Topological domain	159 – 181	23	Extracellular Potential
	Transmembrane	182 – 208	27	Helical; Name=5; Potential
	Topological domain	209 – 235	27	Cytoplasmic Potential
	Transmembrane	236 – 260	25	Helical; Name=6; Potential
	Topological domain	261 – 274	14	Extracellular Potential
	Transmembrane	275 – 295	21	Helical; Name=7; Potential
	Topological domain	296 – 386	91	Cytoplasmic Potential
Sites
	Site	309	1	Not S-palmitoylated
Amino acid modifications
	Modified residue	383	1	Cysteine methyl ester
	Lipidation	308	1	S-palmitoyl cysteine Ref.8
	Lipidation	311	1	S-palmitoyl cysteine Ref.8
	Lipidation	383	1	S-farnesyl cysteine Ref.7
	Glycosylation	7	1	N-linked (GlcNAc...) Potential
	Disulfide bond	5 ↔ 165		Ref.9
	Disulfide bond	92 ↔ 170		Ref.9
Natural variations
	Natural variant	25	1	V → M. Corresponds to variant rs2229127 [ dbSNP | Ensembl ].		VAR_024260
	Natural variant	319	1	S → W. Corresponds to variant rs28590598 [ dbSNP | Ensembl ].		VAR_061226
Experimental info
	Mutagenesis	308	1	C → S: Reduced palmitoylation, coupling to G protein unaffected. Abolished palmitoylation and coupling to G protein; when associated with S-311. Ref.8
	Mutagenesis	309	1	C → S: No effect on palmitoylation level. Ref.8
	Mutagenesis	311	1	C → S: Reduced palmitoylation, coupling to G protein unaffected. Abolished palmitoylation and coupling to G protein; when associated with S-308. Ref.8
	Mutagenesis	383	1	C → S: Abolishes isoprenylation. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	P43119 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 2B6B0CDBACED1608	FASTA	386	40,956
	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

References

	« Hide 'large scale' referencesShow '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.
IPI	IPI00016317.
PIR	A57066.
RefSeq	NP_000951.1. NM_000960.3.
UniGene	Hs.458324.
3D structure databases
ProteinModelPortal	P43119.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000291294.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	P43119.
Polymorphism databases
DMDM	1172500.
Proteomic databases
PaxDb	P43119.
PRIDE	P43119.
Protocols and materials databases
DNASU	5739.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000291294; ENSP00000291294; ENSG00000160013.
GeneID	5739.
KEGG	hsa:5739.
UCSC	uc002pex.3. human.
Organism-specific databases
CTD	5739.
GeneCards	GC19M047123.
HGNC	HGNC:9602. PTGIR.
MIM	600022. gene.
neXtProt	NX_P43119.
PharmGKB	PA291.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG305292.
HOGENOM	HOG000115475.
HOVERGEN	HBG003074.
InParanoid	P43119.
KO	K04263.
OMA	ATSTLMF.
OrthoDB	EOG4T7843.
PhylomeDB	P43119.
Enzyme and pathway databases
Pathway_Interaction_DB	txa2pathway. Thromboxane A2 receptor signaling.
Reactome	REACT_111102. Signal Transduction. REACT_604. Hemostasis.
Gene expression databases
Bgee	P43119.
CleanEx	HS_PTGIR.
Genevestigator	P43119.
GermOnline	ENSG00000160013. Homo sapiens.
Family and domain databases
InterPro	IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. IPR008365. Prostanoid_rcpt. IPR000370. Prostglndn_IP_rcpt. [Graphical view]
PANTHER	PTHR11866. PTHR11866. 1 hit. PTHR11866:SF7. PTHR11866:SF7. 1 hit.
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR01788. PROSTANOIDR. PR00856. PRSTNOIDIPR.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P43119.
ChEMBL	CHEMBL1995.
DrugBank	DB01160. Dinoprost Tromethamine. DB00917. Dinoprostone. DB01240. Epoprostenol. DB01088. Iloprost. DB00929. Misoprostol.
GenomeRNAi	5739.
NextBio	22340.
SOURCE	Search...

Entry information

Entry name

PI2R_HUMAN

Accession

Primary (citable) accession number: P43119

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	May 1, 2013
This is version 128 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.