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Q9Y5Y4 (PD2R2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | 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:
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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length395 AA.
Sequence statusComplete.
Protein existenceEvidence 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 componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DomainTransmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Inferred from direct assay Ref.9. Source: UniProtKB

adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

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: Ensembl

   Cellular_componentintegral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionG-protein coupled receptor activity

Inferred from direct assay Ref.9. Source: UniProtKB

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: Ensembl

prostaglandin J receptor activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 395395Prostaglandin D2 receptor 2
PRO_0000069572

Regions

Topological domain1 – 3333Extracellular Potential
Transmembrane34 – 5623Helical; Name=1; Potential
Topological domain57 – 6711Cytoplasmic Potential
Transmembrane68 – 8922Helical; Name=2; Potential
Topological domain90 – 10617Extracellular Potential
Transmembrane107 – 12721Helical; Name=3; Potential
Topological domain128 – 14619Cytoplasmic Potential
Transmembrane147 – 16822Helical; Name=4; Potential
Topological domain169 – 21042Extracellular Potential
Transmembrane211 – 23121Helical; Name=5; Potential
Topological domain232 – 24716Cytoplasmic Potential
Transmembrane248 – 26922Helical; Name=6; Potential
Topological domain270 – 28819Extracellular Potential
Transmembrane289 – 30820Helical; Name=7; Potential
Topological domain309 – 39587Cytoplasmic Potential
Motif330 – 3334Involved in the recycling of CRTH2

Amino acid modifications

Glycosylation41N-linked (GlcNAc...) Potential
Glycosylation251N-linked (GlcNAc...) Potential
Disulfide bond104 ↔ 182 Potential

Natural variations

Natural variant2041V → A. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6
Corresponds to variant rs2467642 [ dbSNP | Ensembl ].
VAR_063131

Experimental info

Mutagenesis3301D → A: 45% increases internalization of PTGDR2. Ref.13
Mutagenesis3311S → A: 45% increases internalization of PTGDR2. Ref.13
Mutagenesis3321E → A: 45% increases internalization of PTGDR2. Ref.13
Mutagenesis3331L → A: 45% increase in internalization of PTGDR2. Ref.13
Mutagenesis3471T → A: Decreases in PKC-induced internalization of PTGDR2. Ref.13

Sequences

Sequence LengthMass (Da)Tools
Q9Y5Y4 [UniParc].

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

FASTA39543,268
        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' 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. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., 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.
CCDSCCDS7994.1.
RefSeqNP_004769.2. NM_004778.2.
UniGeneHs.299567.

3D structure databases

ProteinModelPortalQ9Y5Y4.
SMRQ9Y5Y4. Positions 34-320.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116412. 3 interactions.
STRING9606.ENSP00000332812.

Chemistry

ChEMBLCHEMBL5071.
GuidetoPHARMACOLOGY339.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteQ9Y5Y4.

Polymorphism databases

DMDM296439334.

Proteomic databases

PaxDbQ9Y5Y4.
PRIDEQ9Y5Y4.

Protocols and materials databases

DNASU11251.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000332539; ENSP00000332812; ENSG00000183134.
GeneID11251.
KEGGhsa:11251.
UCSCuc001nqc.2. human.

Organism-specific databases

CTD11251.
GeneCardsGC11M060619.
HGNCHGNC:4502. PTGDR2.
HPAHPA014259.
MIM604837. gene.
neXtProtNX_Q9Y5Y4.
PharmGKBPA28891.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG147342.
HOGENOMHOG000234122.
HOVERGENHBG099857.
InParanoidQ9Y5Y4.
KOK06715.
OMAAFALCWG.
OrthoDBEOG71RXKP.
PhylomeDBQ9Y5Y4.
TreeFamTF330976.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

BgeeQ9Y5Y4.
CleanExHS_GPR44.
GenevestigatorQ9Y5Y4.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00237. GPCRRHODOPSN.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiGPR44.
GenomeRNAi11251.
NextBio42814.
PROQ9Y5Y4.
SOURCESearch...

Entry information

Entry namePD2R2_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 115 of the entry and version 3 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 11

Human chromosome 11: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries