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Protein

Prostaglandin D2 receptor 2

Gene

PTGDR2

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

Functioni

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.3 Publications

GO - Molecular functioni

  1. G-protein coupled receptor activity Source: UniProtKB
  2. neuropeptide binding Source: GO_Central
  3. prostaglandin D receptor activity Source: UniProtKB
  4. prostaglandin F receptor activity Source: Ensembl
  5. prostaglandin J receptor activity Source: Ensembl

GO - Biological processi

  1. adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway Source: Ensembl
  2. calcium-mediated signaling Source: UniProtKB
  3. chemotaxis Source: UniProtKB
  4. G-protein coupled receptor signaling pathway Source: UniProtKB
  5. G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger Source: GO_Central
  6. immune response Source: ProtInc
  7. neuropeptide signaling pathway Source: GO_Central
  8. positive regulation of G-protein coupled receptor protein signaling pathway Source: Ensembl
  9. synaptic transmission Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiREACT_18425. Prostanoid ligand receptors.
REACT_19231. G alpha (i) signalling events.

Names & Taxonomyi

Protein namesi
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 namesi
Name:PTGDR2
Synonyms:CRTH2, DL1R, GPR44
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 11

Organism-specific databases

HGNCiHGNC:4502. PTGDR2.

Subcellular locationi

Cell membrane Curated; Multi-pass membrane protein Curated
Note: Internalized receptors colocalized with RAB11A.1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3333ExtracellularSequence AnalysisAdd
BLAST
Transmembranei34 – 5623Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini57 – 6711CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei68 – 8922Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini90 – 10617ExtracellularSequence AnalysisAdd
BLAST
Transmembranei107 – 12721Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini128 – 14619CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei147 – 16822Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini169 – 21042ExtracellularSequence AnalysisAdd
BLAST
Transmembranei211 – 23121Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini232 – 24716CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei248 – 26922Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini270 – 28819ExtracellularSequence AnalysisAdd
BLAST
Transmembranei289 – 30820Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini309 – 39587CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. integral component of plasma membrane Source: ProtInc
  2. neuron projection Source: GO_Central
  3. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi330 – 3301D → A: 45% increases internalization of PTGDR2. 1 Publication
Mutagenesisi331 – 3311S → A: 45% increases internalization of PTGDR2. 1 Publication
Mutagenesisi332 – 3321E → A: 45% increases internalization of PTGDR2. 1 Publication
Mutagenesisi333 – 3331L → A: 45% increase in internalization of PTGDR2. 1 Publication
Mutagenesisi347 – 3471T → A: Decreases in PKC-induced internalization of PTGDR2. 1 Publication

Organism-specific databases

PharmGKBiPA28891.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 395395Prostaglandin D2 receptor 2PRO_0000069572Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi4 – 41N-linked (GlcNAc...)Sequence Analysis
Glycosylationi25 – 251N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi104 ↔ 182PROSITE-ProRule annotation

Post-translational modificationi

Phosphorylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9Y5Y4.
PRIDEiQ9Y5Y4.

PTM databases

PhosphoSiteiQ9Y5Y4.

Expressioni

Tissue specificityi

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.4 Publications

Gene expression databases

BgeeiQ9Y5Y4.
CleanExiHS_GPR44.
GenevestigatoriQ9Y5Y4.

Organism-specific databases

HPAiHPA014259.

Interactioni

Protein-protein interaction databases

BioGridi116412. 3 interactions.
STRINGi9606.ENSP00000332812.

Structurei

3D structure databases

ProteinModelPortaliQ9Y5Y4.
SMRiQ9Y5Y4. Positions 34-320.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi330 – 3334Involved in the recycling of CRTH2

Domaini

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.

Sequence similaritiesi

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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG147342.
GeneTreeiENSGT00760000118990.
HOGENOMiHOG000234122.
HOVERGENiHBG099857.
InParanoidiQ9Y5Y4.
KOiK06715.
OMAiGCRMRQT.
OrthoDBiEOG71RXKP.
PhylomeDBiQ9Y5Y4.
TreeFamiTF330976.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9Y5Y4-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MSANATLKPL CPILEQMSRL QSHSNTSIRY IDHAAVLLHG LASLLGLVEN
60 70 80 90 100
GVILFVVGCR MRQTVVTTWV LHLALSDLLA SASLPFFTYF LAVGHSWELG
110 120 130 140 150
TTFCKLHSSI FFLNMFASGF LLSAISLDRC LQVVRPVWAQ NHRTVAAAHK
160 170 180 190 200
VCLVLWALAV LNTVPYFVFR DTISRLDGRI MCYYNVLLLN PGPDRDATCN
210 220 230 240 250
SRQVALAVSK FLLAFLVPLA IIASSHAAVS LRLQHRGRRR PGRFVRLVAA
260 270 280 290 300
VVAAFALCWG PYHVFSLLEA RAHANPGLRP LVWRGLPFVT SLAFFNSVAN
310 320 330 340 350
PVLYVLTCPD MLRKLRRSLR TVLESVLVDD SELGGAGSSR RRRTSSTARS
360 370 380 390
ASPLALCSRP EEPRGPARLL GWLLGSCAAS PQTGPLNRAL SSTSS
Length:395
Mass (Da):43,268
Last modified:May 18, 2010 - v3
Checksum:i99A63CBDA418DEC9
GO

Sequence cautioni

The sequence AAD21055.1 differs from that shown. Reason: Frameshift at position 375. Curated
The sequence AAD21055.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti204 – 2041V → A.5 Publications
Corresponds to variant rs2467642 [ dbSNP | Ensembl ].
VAR_063131

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS7994.1.
RefSeqiNP_004769.2. NM_004778.2.
UniGeneiHs.299567.

Genome annotation databases

EnsembliENST00000332539; ENSP00000332812; ENSG00000183134.
GeneIDi11251.
KEGGihsa:11251.
UCSCiuc001nqc.2. human.

Polymorphism databases

DMDMi296439334.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS7994.1.
RefSeqiNP_004769.2. NM_004778.2.
UniGeneiHs.299567.

3D structure databases

ProteinModelPortaliQ9Y5Y4.
SMRiQ9Y5Y4. Positions 34-320.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116412. 3 interactions.
STRINGi9606.ENSP00000332812.

Chemistry

BindingDBiQ9Y5Y4.
ChEMBLiCHEMBL5071.
DrugBankiDB00328. Indomethacin.
DB00605. Sulindac.
GuidetoPHARMACOLOGYi339.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiQ9Y5Y4.

Polymorphism databases

DMDMi296439334.

Proteomic databases

PaxDbiQ9Y5Y4.
PRIDEiQ9Y5Y4.

Protocols and materials databases

DNASUi11251.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000332539; ENSP00000332812; ENSG00000183134.
GeneIDi11251.
KEGGihsa:11251.
UCSCiuc001nqc.2. human.

Organism-specific databases

CTDi11251.
GeneCardsiGC11M060619.
HGNCiHGNC:4502. PTGDR2.
HPAiHPA014259.
MIMi604837. gene.
neXtProtiNX_Q9Y5Y4.
PharmGKBiPA28891.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG147342.
GeneTreeiENSGT00760000118990.
HOGENOMiHOG000234122.
HOVERGENiHBG099857.
InParanoidiQ9Y5Y4.
KOiK06715.
OMAiGCRMRQT.
OrthoDBiEOG71RXKP.
PhylomeDBiQ9Y5Y4.
TreeFamiTF330976.

Enzyme and pathway databases

ReactomeiREACT_18425. Prostanoid ligand receptors.
REACT_19231. G alpha (i) signalling events.

Miscellaneous databases

GeneWikiiGPR44.
GenomeRNAii11251.
NextBioi42814.
PROiQ9Y5Y4.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Y5Y4.
CleanExiHS_GPR44.
GenevestigatoriQ9Y5Y4.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
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. 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. 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. 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.

Entry informationi

Entry nameiPD2R2_HUMAN
AccessioniPrimary (citable) accession number: Q9Y5Y4
Secondary accession number(s): O94765, Q4QRI6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 11, 2001
Last sequence update: May 18, 2010
Last modified: February 4, 2015
This is version 121 of the entry and version 3 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 cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  3. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  4. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  7. 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.