Prostaglandin D2 receptor 2 - Homo sapiens (Human)

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Q9Y5Y4 (PD2R2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 105. History...

Clusters with 100%, 90%, 50% identity |

Documents (7) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Prostaglandin D2 receptor 2

Alternative name(s):
Chemoattractant receptor-homologous molecule expressed on Th2 cells
G-protein coupled receptor 44
CD_antigen=CD294

Gene names

Name:	PTGDR2
Synonyms:	CRTH2, DL1R, GPR44

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	395 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for prostaglandin D2 (PGD2). Coupled to the G(i)-protein. Receptor activation may result in pertussis toxin-sensitive decreases in cAMP levels and Ca²⁺ mobilization. PI3K signaling is also implicated in mediating PTGDR2 effects. PGD2 induced receptor internalization. CRTH2 internalization can be regulated by diverse kinases such as, PKC, PKA, ADRBK1/GRK2, GPRK5/GRK5 and GRK6. Receptor activation is responsible, at least in part, in immune regulation and allergic/inflammation responses. Ref.7 Ref.9 Ref.11
Subcellular location	Cell membrane; Multi-pass membrane protein Potential. Note: Internalized receptors colocalized with RAB11A. Ref.12
Tissue specificity	Widespread expression. High expression in stomach, small intestine, heart and thymus. Intermediate expression in colon, spinal cord and peripheral blood and low expression in brain, skeletal muscle and spleen. Expressed also on Th2- and Tc2- type cells, eosinophils and basophils. Ref.2 Ref.8 Ref.9 Ref.10
Domain	The 330-DSEL-333 motif is involved in the recycling of PTGDR2 to the cell surface after agonist-induced internalization. This motif seems to be required for ADRBK1/GRK2 and GPRK5/GRK5 to promote agonist-induced internalization. Thr-347 is a major site for PKC-induced internalization of the receptor.
Post-translational modification	Phosphorylated. Ref.12
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.
Sequence caution	The sequence AAD21055.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence AAD21055.1 differs from that shown. Reason: Frameshift at position 375.

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
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway Inferred from electronic annotation. Source: Compara calcium-mediated signaling Inferred from direct assay Ref.9. Source: UniProtKB chemotaxis Inferred from direct assay Ref.9. Source: UniProtKB immune response Traceable author statement Ref.2. Source: ProtInc positive regulation of G-protein coupled receptor protein signaling pathway Inferred from electronic annotation. Source: Compara
Cellular_component	integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	N-formyl peptide receptor activity Inferred from electronic annotation. Source: InterPro prostaglandin D receptor activity Inferred from direct assay Ref.9. Source: UniProtKB prostaglandin F receptor activity Inferred from electronic annotation. Source: Compara prostaglandin J receptor activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 395

395

Prostaglandin D2 receptor 2

PRO_0000069572

Regions

Topological domain

1 – 33

Extracellular Potential

Transmembrane

34 – 56

Helical; Name=1; Potential

Topological domain

57 – 67

Cytoplasmic Potential

Transmembrane

68 – 89

Helical; Name=2; Potential

Topological domain

90 – 106

Extracellular Potential

Transmembrane

107 – 127

Helical; Name=3; Potential

Topological domain

128 – 146

Cytoplasmic Potential

Transmembrane

147 – 168

Helical; Name=4; Potential

Topological domain

169 – 210

Extracellular Potential

Transmembrane

211 – 231

Helical; Name=5; Potential

Topological domain

232 – 247

Cytoplasmic Potential

Transmembrane

248 – 269

Helical; Name=6; Potential

Topological domain

270 – 288

Extracellular Potential

Transmembrane

289 – 308

Helical; Name=7; Potential

Topological domain

309 – 395

Cytoplasmic Potential

Motif

330 – 333

Involved in the recycling of CRTH2

Amino acid modifications

Glycosylation

N-linked (GlcNAc...) Potential

Glycosylation

N-linked (GlcNAc...) Potential

Disulfide bond

104 ↔ 182

Potential

Natural variations

Natural variant

204

V → A. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6
Corresponds to variant rs2467642 [ dbSNP | Ensembl ].

VAR_063131

Experimental info

Mutagenesis

330

D → A: 45% increases internalization of PTGDR2. Ref.13

Mutagenesis

331

S → A: 45% increases internalization of PTGDR2. Ref.13

Mutagenesis

332

E → A: 45% increases internalization of PTGDR2. Ref.13

Mutagenesis

333

L → A: 45% increase in internalization of PTGDR2. Ref.13

Mutagenesis

347

T → A: Decreases in PKC-induced internalization of PTGDR2. Ref.13

Sequences

Sequence

Length

Mass (Da)

Tools

Q9Y5Y4 [UniParc].

Last modified May 18, 2010. Version 3.
Checksum: 99A63CBDA418DEC9
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FASTA

395

43,268

        10         20         30         40         50         60 
MSANATLKPL CPILEQMSRL QSHSNTSIRY IDHAAVLLHG LASLLGLVEN GVILFVVGCR 

        70         80         90        100        110        120 
MRQTVVTTWV LHLALSDLLA SASLPFFTYF LAVGHSWELG TTFCKLHSSI FFLNMFASGF 

       130        140        150        160        170        180 
LLSAISLDRC LQVVRPVWAQ NHRTVAAAHK VCLVLWALAV LNTVPYFVFR DTISRLDGRI 

       190        200        210        220        230        240 
MCYYNVLLLN PGPDRDATCN SRQVALAVSK FLLAFLVPLA IIASSHAAVS LRLQHRGRRR 

       250        260        270        280        290        300 
PGRFVRLVAA VVAAFALCWG PYHVFSLLEA RAHANPGLRP LVWRGLPFVT SLAFFNSVAN 

       310        320        330        340        350        360 
PVLYVLTCPD MLRKLRRSLR TVLESVLVDD SELGGAGSSR RRRTSSTARS ASPLALCSRP 

       370        380        390 
EEPRGPARLL GWLLGSCAAS PQTGPLNRAL SSTSS

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Discovery of three novel orphan G-protein-coupled receptors." Marchese A., Sawzdargo M., Nguyen T., Cheng R., Heng H.H.Q., Nowak T., Im D.-S., Lynch K.R., George S.R., O'Dowd B.F. Genomics 56:12-21(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ALA-204.
[2]	"Selective expression of a novel surface molecule by human Th2 cells in vivo." Nagata K., Tanaka K., Ogawa K., Kemmotsu K., Imai T., Yoshie O., Abe H., Tada K., Nakamura M., Sugamura K., Takano S. J. Immunol. 162:1278-1286(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANT ALA-204. Tissue: Blood.
[3]	"Tissue expression and chromosomal organization of a novel G protein-coupled receptor." Methner A., Schroeder S. Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ALA-204. Tissue: Placenta.
[4]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." King M.M., Aronstam R.S., Sharma S.V. Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-204. Tissue: Placenta.
[5]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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], VARIANT ALA-204.
[7]	"Prostaglandin D2 is a potent chemoattractant for human eosinophils that acts via a novel DP receptor." Monneret G., Gravel S., Diamond M., Rokach J., Powell W.S. Blood 98:1942-1948(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS RECEPTOR FOR PGD2.
[8]	"A novel surface molecule of Th2- and Tc2-type cells, CRTH2 expression on human peripheral and decidual CD4+ and CD8+ T cells during the early stage of pregnancy." Tsuda H., Michimata T., Sakai M., Nagata K., Nakamura M., Saito S. Clin. Exp. Immunol. 123:105-111(2001) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[9]	"Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2." Hirai H., Tanaka K., Yoshie O., Ogawa K., Kenmotsu K., Takamori Y., Ichimasa M., Sugamura K., Nakamura M., Takano S., Nagata K. J. Exp. Med. 193:255-261(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS RECEPTOR FOR PGD2, TISSUE SPECIFICITY.
[10]	"Molecular pharmacology of the human prostaglandin D2 receptor, CRTH2." Sawyer N., Cauchon E., Chateauneuf A., Cruz R.P., Nicholson D.W., Metters K.M., O'Neill G.P., Gervais F.G. Br. J. Pharmacol. 137:1163-1172(2002) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, CHARACTERIZATION.
[11]	"Inhibition of PI3K and calcineurin suppresses chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2)-dependent responses of Th2 lymphocytes to prostaglandin D(2)." Xue L., Gyles S.L., Barrow A., Pettipher R. Biochem. Pharmacol. 73:843-853(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS PGD2 RECEPTOR, FUNCTION IN PI3K SIGNALING.
[12]	"Differential regulation of the signaling and trafficking of the two prostaglandin D2 receptors, prostanoid DP receptor and CRTH2." Gallant M.A., Slipetz D., Hamelin E., Rochdi M.D., Talbot S., de Brum-Fernandes A.J., Parent J.L. Eur. J. Pharmacol. 557:115-123(2007) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION.
[13]	"Characterization of C-terminal tail determinants involved in CRTH2 receptor trafficking: identification of a recycling motif." Roy S.J., Parent A., Gallant M.A., de Brum-Fernandes A.J., Stankova J., Parent J.L. Eur. J. Pharmacol. 630:10-18(2010) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ASP-330; SER-331; GLU-332; LEU-333 AND THR-347, IDENTIFICATION OF A RECYCLING MOTIF.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF118265 Genomic DNA. Translation: AAD21055.1. Sequence problems. AB008535 mRNA. Translation: BAA74518.1. AF144308 mRNA. Translation: AAD34539.1. AY507142 mRNA. Translation: AAR92484.1. AP000777 Genomic DNA. No translation available. BC096841 mRNA. Translation: AAH96841.1.
IPI	IPI00001921.
RefSeq	NP_004769.2. NM_004778.2.
UniGene	Hs.299567.
3D structure databases
ProteinModelPortal	Q9Y5Y4.
SMR	Q9Y5Y4. Positions 38-306.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000332812.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	Q9Y5Y4.
Polymorphism databases
DMDM	296439334.
Proteomic databases
PaxDb	Q9Y5Y4.
PRIDE	Q9Y5Y4.
Protocols and materials databases
DNASU	11251.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000332539; ENSP00000332812; ENSG00000183134.
GeneID	11251.
KEGG	hsa:11251.
UCSC	uc001nqc.2. human.
Organism-specific databases
CTD	11251.
GeneCards	GC11M060619.
HGNC	HGNC:4502. PTGDR2.
HPA	HPA014259.
MIM	604837. gene.
neXtProt	NX_Q9Y5Y4.
PharmGKB	PA28891.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG147342.
HOGENOM	HOG000234122.
HOVERGEN	HBG099857.
InParanoid	Q9Y5Y4.
KO	K06715.
OMA	AFALCWG.
OrthoDB	EOG473PS0.
PhylomeDB	Q9Y5Y4.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
Bgee	Q9Y5Y4.
CleanEx	HS_GPR44.
Genevestigator	Q9Y5Y4.
GermOnline	ENSG00000183134. Homo sapiens.
Family and domain databases
InterPro	IPR000826. Formyl_pep_rcpt. IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00526. FMETLEUPHER. PR00237. GPCRRHODOPSN.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL5071.
GenomeRNAi	11251.
NextBio	42814.
SOURCE	Search...

Entry information

Entry name

PD2R2_HUMAN

Accession

Primary (citable) accession number: Q9Y5Y4
Secondary accession number(s): O94765, Q4QRI6

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 11, 2001
Last sequence update:	May 18, 2010
Last modified:	May 1, 2013
This is version 105 of the entry and version 3 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.