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Q9Y5Y4

- PD2R2_HUMAN

UniProt

Q9Y5Y4 - PD2R2_HUMAN

Protein

Prostaglandin D2 receptor 2

Gene

PTGDR2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 117 (01 Oct 2014)
      Sequence version 3 (18 May 2010)
      Previous versions | rss
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    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. prostaglandin D receptor activity Source: UniProtKB
    3. prostaglandin F receptor activity Source: Ensembl
    4. 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. immune response Source: ProtInc
    6. positive regulation of G-protein coupled receptor protein signaling pathway Source: Ensembl

    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

    GO - Cellular componenti

    1. integral component of plasma membrane Source: ProtInc
    2. plasma membrane Source: Reactome

    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...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 3333ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini57 – 6711CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini90 – 10617ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini128 – 14619CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini169 – 21042ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini232 – 24716CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini270 – 28819ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini309 – 39587CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei34 – 5623Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei68 – 8922Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei107 – 12721Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei147 – 16822Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei211 – 23121Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei248 – 26922Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei289 – 30820Helical; Name=7Sequence AnalysisAdd
    BLAST

    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.
    HOGENOMiHOG000234122.
    HOVERGENiHBG099857.
    InParanoidiQ9Y5Y4.
    KOiK06715.
    OMAiAFALCWG.
    OrthoDBiEOG71RXKP.
    PhylomeDBiQ9Y5Y4.
    TreeFamiTF330976.

    Family and domain databases

    Gene3Di1.20.1070.10. 1 hit.
    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

    MSANATLKPL CPILEQMSRL QSHSNTSIRY IDHAAVLLHG LASLLGLVEN    50
    GVILFVVGCR MRQTVVTTWV LHLALSDLLA SASLPFFTYF LAVGHSWELG 100
    TTFCKLHSSI FFLNMFASGF LLSAISLDRC LQVVRPVWAQ NHRTVAAAHK 150
    VCLVLWALAV LNTVPYFVFR DTISRLDGRI MCYYNVLLLN PGPDRDATCN 200
    SRQVALAVSK FLLAFLVPLA IIASSHAAVS LRLQHRGRRR PGRFVRLVAA 250
    VVAAFALCWG PYHVFSLLEA RAHANPGLRP LVWRGLPFVT SLAFFNSVAN 300
    PVLYVLTCPD MLRKLRRSLR TVLESVLVDD SELGGAGSSR RRRTSSTARS 350
    ASPLALCSRP EEPRGPARLL GWLLGSCAAS PQTGPLNRAL SSTSS 395
    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.
    The sequence AAD21055.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS7994.1.
    RefSeqi NP_004769.2. NM_004778.2.
    UniGenei Hs.299567.

    3D structure databases

    ProteinModelPortali Q9Y5Y4.
    SMRi Q9Y5Y4. Positions 34-320.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 116412. 3 interactions.
    STRINGi 9606.ENSP00000332812.

    Chemistry

    ChEMBLi CHEMBL5071.
    GuidetoPHARMACOLOGYi 339.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei Q9Y5Y4.

    Polymorphism databases

    DMDMi 296439334.

    Proteomic databases

    PaxDbi Q9Y5Y4.
    PRIDEi Q9Y5Y4.

    Protocols and materials databases

    DNASUi 11251.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000332539 ; ENSP00000332812 ; ENSG00000183134 .
    GeneIDi 11251.
    KEGGi hsa:11251.
    UCSCi uc001nqc.2. human.

    Organism-specific databases

    CTDi 11251.
    GeneCardsi GC11M060619.
    HGNCi HGNC:4502. PTGDR2.
    HPAi HPA014259.
    MIMi 604837. gene.
    neXtProti NX_Q9Y5Y4.
    PharmGKBi PA28891.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG147342.
    HOGENOMi HOG000234122.
    HOVERGENi HBG099857.
    InParanoidi Q9Y5Y4.
    KOi K06715.
    OMAi AFALCWG.
    OrthoDBi EOG71RXKP.
    PhylomeDBi Q9Y5Y4.
    TreeFami TF330976.

    Enzyme and pathway databases

    Reactomei REACT_18425. Prostanoid ligand receptors.
    REACT_19231. G alpha (i) signalling events.

    Miscellaneous databases

    GeneWikii GPR44.
    GenomeRNAii 11251.
    NextBioi 42814.
    PROi Q9Y5Y4.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q9Y5Y4.
    CleanExi HS_GPR44.
    Genevestigatori Q9Y5Y4.

    Family and domain databases

    Gene3Di 1.20.1070.10. 1 hit.
    InterProi IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    [Graphical view ]
    Pfami PF00001. 7tm_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00237. GPCRRHODOPSN.
    PROSITEi PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
    PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 117 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