PD2R2_HUMAN
ID PD2R2_HUMAN Reviewed; 395 AA.
AC Q9Y5Y4; O94765; Q4QRI6;
DT 11-JUL-2001, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Prostaglandin D2 receptor 2;
DE AltName: Full=Chemoattractant receptor-homologous molecule expressed on Th2 cells;
DE AltName: Full=G-protein coupled receptor 44;
DE AltName: CD_antigen=CD294;
GN Name=PTGDR2; Synonyms=CRTH2, DL1R, GPR44;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-204.
RX PubMed=10036181; DOI=10.1006/geno.1998.5655;
RA Marchese A., Sawzdargo M., Nguyen T., Cheng R., Heng H.H.Q., Nowak T.,
RA Im D.-S., Lynch K.R., George S.R., O'Dowd B.F.;
RT "Discovery of three novel orphan G-protein-coupled receptors.";
RL Genomics 56:12-21(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANT ALA-204.
RC TISSUE=Blood;
RX PubMed=9973380;
RA Nagata K., Tanaka K., Ogawa K., Kemmotsu K., Imai T., Yoshie O., Abe H.,
RA Tada K., Nakamura M., Sugamura K., Takano S.;
RT "Selective expression of a novel surface molecule by human Th2 cells in
RT vivo.";
RL J. Immunol. 162:1278-1286(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ALA-204.
RC TISSUE=Placenta;
RA Methner A., Schroeder S.;
RT "Tissue expression and chromosomal organization of a novel G protein-
RT coupled receptor.";
RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-204.
RC TISSUE=Placenta;
RA King M.M., Aronstam R.S., Sharma S.V.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-204.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION AS RECEPTOR FOR PGD2.
RX PubMed=11535533; DOI=10.1182/blood.v98.6.1942;
RA Monneret G., Gravel S., Diamond M., Rokach J., Powell W.S.;
RT "Prostaglandin D2 is a potent chemoattractant for human eosinophils that
RT acts via a novel DP receptor.";
RL Blood 98:1942-1948(2001).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=11168006; DOI=10.1046/j.1365-2249.2001.01422.x;
RA Tsuda H., Michimata T., Sakai M., Nagata K., Nakamura M., Saito S.;
RT "A novel surface molecule of Th2- and Tc2-type cells, CRTH2 expression on
RT human peripheral and decidual CD4+ and CD8+ T cells during the early stage
RT of pregnancy.";
RL Clin. Exp. Immunol. 123:105-111(2001).
RN [9]
RP FUNCTION AS RECEPTOR FOR PGD2, AND TISSUE SPECIFICITY.
RX PubMed=11208866; DOI=10.1084/jem.193.2.255;
RA Hirai H., Tanaka K., Yoshie O., Ogawa K., Kenmotsu K., Takamori Y.,
RA Ichimasa M., Sugamura K., Nakamura M., Takano S., Nagata K.;
RT "Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells,
RT eosinophils, and basophils via seven-transmembrane receptor CRTH2.";
RL J. Exp. Med. 193:255-261(2001).
RN [10]
RP TISSUE SPECIFICITY, AND CHARACTERIZATION.
RX PubMed=12466225; DOI=10.1038/sj.bjp.0704973;
RA Sawyer N., Cauchon E., Chateauneuf A., Cruz R.P., Nicholson D.W.,
RA Metters K.M., O'Neill G.P., Gervais F.G.;
RT "Molecular pharmacology of the human prostaglandin D2 receptor, CRTH2.";
RL Br. J. Pharmacol. 137:1163-1172(2002).
RN [11]
RP FUNCTION AS PGD2 RECEPTOR, AND FUNCTION IN PI3K SIGNALING.
RX PubMed=17196174; DOI=10.1016/j.bcp.2006.11.021;
RA Xue L., Gyles S.L., Barrow A., Pettipher R.;
RT "Inhibition of PI3K and calcineurin suppresses chemoattractant receptor-
RT homologous molecule expressed on Th2 cells (CRTH2)-dependent responses of
RT Th2 lymphocytes to prostaglandin D(2).";
RL Biochem. Pharmacol. 73:843-853(2007).
RN [12]
RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RX PubMed=17207480; DOI=10.1016/j.ejphar.2006.11.058;
RA Gallant M.A., Slipetz D., Hamelin E., Rochdi M.D., Talbot S.,
RA de Brum-Fernandes A.J., Parent J.L.;
RT "Differential regulation of the signaling and trafficking of the two
RT prostaglandin D2 receptors, prostanoid DP receptor and CRTH2.";
RL Eur. J. Pharmacol. 557:115-123(2007).
RN [13]
RP MUTAGENESIS OF ASP-330; SER-331; GLU-332; LEU-333 AND THR-347, AND
RP IDENTIFICATION OF A RECYCLING MOTIF.
RX PubMed=20035740; DOI=10.1016/j.ejphar.2009.12.022;
RA Roy S.J., Parent A., Gallant M.A., de Brum-Fernandes A.J., Stankova J.,
RA Parent J.L.;
RT "Characterization of C-terminal tail determinants involved in CRTH2
RT receptor trafficking: identification of a recycling motif.";
RL Eur. J. Pharmacol. 630:10-18(2010).
CC -!- FUNCTION: Receptor for prostaglandin D2 (PGD2). Coupled to the G(i)-
CC protein. Receptor activation may result in pertussis toxin-sensitive
CC decreases in cAMP levels and Ca(2+) mobilization. PI3K signaling is
CC also implicated in mediating PTGDR2 effects. PGD2 induced receptor
CC internalization. CRTH2 internalization can be regulated by diverse
CC kinases such as, PKC, PKA, GRK2, GPRK5/GRK5 and GRK6. Receptor
CC activation is responsible, at least in part, in immune regulation and
CC allergic/inflammation responses. {ECO:0000269|PubMed:11208866,
CC ECO:0000269|PubMed:11535533, ECO:0000269|PubMed:17196174}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}. Note=Internalized receptors colocalized with
CC RAB11A. {ECO:0000269|PubMed:17207480}.
CC -!- TISSUE SPECIFICITY: Widespread expression. High expression in stomach,
CC small intestine, heart and thymus. Intermediate expression in colon,
CC spinal cord and peripheral blood and low expression in brain, skeletal
CC muscle and spleen. Expressed also on Th2- and Tc2- type cells,
CC eosinophils and basophils. {ECO:0000269|PubMed:11168006,
CC ECO:0000269|PubMed:11208866, ECO:0000269|PubMed:12466225,
CC ECO:0000269|PubMed:9973380}.
CC -!- DOMAIN: The 330-DSEL-333 motif is involved in the recycling of PTGDR2
CC to the cell surface after agonist-induced internalization. This motif
CC seems to be required for GRK2 and GPRK5/GRK5 to promote agonist-induced
CC internalization. Thr-347 is a major site for PKC-induced
CC internalization of the receptor.
CC -!- PTM: Phosphorylated. {ECO:0000269|PubMed:17207480}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD21055.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAD21055.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF118265; AAD21055.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AB008535; BAA74518.1; -; mRNA.
DR EMBL; AF144308; AAD34539.1; -; mRNA.
DR EMBL; AY507142; AAR92484.1; -; mRNA.
DR EMBL; AP000777; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC096841; AAH96841.1; -; mRNA.
DR CCDS; CCDS7994.1; -.
DR RefSeq; NP_004769.2; NM_004778.2.
DR PDB; 6D26; X-ray; 2.80 A; A=1-339.
DR PDB; 6D27; X-ray; 2.74 A; A=1-339.
DR PDB; 7M8W; X-ray; 2.61 A; A=1-339.
DR PDBsum; 6D26; -.
DR PDBsum; 6D27; -.
DR PDBsum; 7M8W; -.
DR AlphaFoldDB; Q9Y5Y4; -.
DR SMR; Q9Y5Y4; -.
DR BioGRID; 116412; 5.
DR STRING; 9606.ENSP00000332812; -.
DR BindingDB; Q9Y5Y4; -.
DR ChEMBL; CHEMBL5071; -.
DR DrugBank; DB00770; Alprostadil.
DR DrugBank; DB12789; Dinoprost.
DR DrugBank; DB00917; Dinoprostone.
DR DrugBank; DB01088; Iloprost.
DR DrugBank; DB00328; Indomethacin.
DR DrugBank; DB02056; Prostaglandin D2.
DR DrugBank; DB13036; Ramatroban.
DR DrugBank; DB00605; Sulindac.
DR DrugBank; DB04828; Zomepirac.
DR DrugCentral; Q9Y5Y4; -.
DR GuidetoPHARMACOLOGY; 339; -.
DR SwissLipids; SLP:000001575; -.
DR GlyGen; Q9Y5Y4; 2 sites.
DR iPTMnet; Q9Y5Y4; -.
DR PhosphoSitePlus; Q9Y5Y4; -.
DR BioMuta; PTGDR2; -.
DR DMDM; 296439334; -.
DR MassIVE; Q9Y5Y4; -.
DR PaxDb; Q9Y5Y4; -.
DR PeptideAtlas; Q9Y5Y4; -.
DR PRIDE; Q9Y5Y4; -.
DR ProteomicsDB; 86540; -.
DR Antibodypedia; 2960; 623 antibodies from 39 providers.
DR DNASU; 11251; -.
DR Ensembl; ENST00000332539.5; ENSP00000332812.4; ENSG00000183134.5.
DR GeneID; 11251; -.
DR KEGG; hsa:11251; -.
DR MANE-Select; ENST00000332539.5; ENSP00000332812.4; NM_004778.3; NP_004769.2.
DR UCSC; uc001nqc.3; human.
DR CTD; 11251; -.
DR DisGeNET; 11251; -.
DR GeneCards; PTGDR2; -.
DR HGNC; HGNC:4502; PTGDR2.
DR HPA; ENSG00000183134; Tissue enhanced (brain, skeletal muscle, stomach).
DR MIM; 604837; gene.
DR neXtProt; NX_Q9Y5Y4; -.
DR OpenTargets; ENSG00000183134; -.
DR PharmGKB; PA28891; -.
DR VEuPathDB; HostDB:ENSG00000183134; -.
DR eggNOG; ENOG502QTYS; Eukaryota.
DR GeneTree; ENSGT00940000162009; -.
DR HOGENOM; CLU_009579_8_0_1; -.
DR InParanoid; Q9Y5Y4; -.
DR OMA; CPDLCRK; -.
DR OrthoDB; 1102944at2759; -.
DR PhylomeDB; Q9Y5Y4; -.
DR TreeFam; TF330976; -.
DR PathwayCommons; Q9Y5Y4; -.
DR Reactome; R-HSA-391908; Prostanoid ligand receptors.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR SignaLink; Q9Y5Y4; -.
DR BioGRID-ORCS; 11251; 11 hits in 1076 CRISPR screens.
DR GeneWiki; GPR44; -.
DR GenomeRNAi; 11251; -.
DR Pharos; Q9Y5Y4; Tchem.
DR PRO; PR:Q9Y5Y4; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9Y5Y4; protein.
DR Bgee; ENSG00000183134; Expressed in mucosa of transverse colon and 82 other tissues.
DR Genevisible; Q9Y5Y4; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IDA:UniProtKB.
DR GO; GO:0042923; F:neuropeptide binding; IBA:GO_Central.
DR GO; GO:0042277; F:peptide binding; IBA:GO_Central.
DR GO; GO:0004956; F:prostaglandin D receptor activity; IDA:UniProtKB.
DR GO; GO:0004958; F:prostaglandin F receptor activity; IEA:Ensembl.
DR GO; GO:0001785; F:prostaglandin J receptor activity; IEA:Ensembl.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0019722; P:calcium-mediated signaling; IDA:UniProtKB.
DR GO; GO:0006935; P:chemotaxis; IDA:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
DR GO; GO:2000255; P:negative regulation of male germ cell proliferation; IEA:Ensembl.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IBA:GO_Central.
DR GO; GO:0045745; P:positive regulation of G protein-coupled receptor signaling pathway; IEA:Ensembl.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Disulfide bond; G-protein coupled receptor;
KW Glycoprotein; Membrane; Phosphoprotein; Receptor; Reference proteome;
KW Transducer; Transmembrane; Transmembrane helix.
FT CHAIN 1..395
FT /note="Prostaglandin D2 receptor 2"
FT /id="PRO_0000069572"
FT TOPO_DOM 1..33
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 34..56
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 57..67
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 68..89
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 90..106
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 107..127
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 128..146
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 147..168
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 169..210
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 211..231
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 232..247
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 248..269
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 270..288
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 289..308
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 309..395
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 333..363
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 330..333
FT /note="Involved in the recycling of CRTH2"
FT COMPBIAS 338..353
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 331
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6XKD3"
FT MOD_RES 345
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2J6"
FT CARBOHYD 4
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 25
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 104..182
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VARIANT 204
FT /note="V -> A (in dbSNP:rs2467642)"
FT /evidence="ECO:0000269|PubMed:10036181,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9973380,
FT ECO:0000269|Ref.3, ECO:0000269|Ref.4"
FT /id="VAR_063131"
FT MUTAGEN 330
FT /note="D->A: 45% increases internalization of PTGDR2."
FT /evidence="ECO:0000269|PubMed:20035740"
FT MUTAGEN 331
FT /note="S->A: 45% increases internalization of PTGDR2."
FT /evidence="ECO:0000269|PubMed:20035740"
FT MUTAGEN 332
FT /note="E->A: 45% increases internalization of PTGDR2."
FT /evidence="ECO:0000269|PubMed:20035740"
FT MUTAGEN 333
FT /note="L->A: 45% increase in internalization of PTGDR2."
FT /evidence="ECO:0000269|PubMed:20035740"
FT MUTAGEN 347
FT /note="T->A: Decreases in PKC-induced internalization of
FT PTGDR2."
FT /evidence="ECO:0000269|PubMed:20035740"
FT HELIX 12..19
FT /evidence="ECO:0007829|PDB:7M8W"
FT STRAND 22..26
FT /evidence="ECO:0007829|PDB:7M8W"
FT HELIX 33..59
FT /evidence="ECO:0007829|PDB:7M8W"
FT HELIX 65..92
FT /evidence="ECO:0007829|PDB:7M8W"
FT HELIX 102..134
FT /evidence="ECO:0007829|PDB:7M8W"
FT HELIX 136..142
FT /evidence="ECO:0007829|PDB:7M8W"
FT HELIX 145..162
FT /evidence="ECO:0007829|PDB:7M8W"
FT HELIX 164..168
FT /evidence="ECO:0007829|PDB:7M8W"
FT STRAND 169..174
FT /evidence="ECO:0007829|PDB:7M8W"
FT STRAND 176..178
FT /evidence="ECO:0007829|PDB:6D27"
FT STRAND 180..184
FT /evidence="ECO:0007829|PDB:7M8W"
FT HELIX 186..188
FT /evidence="ECO:0007829|PDB:7M8W"
FT HELIX 195..213
FT /evidence="ECO:0007829|PDB:7M8W"
FT HELIX 216..236
FT /evidence="ECO:0007829|PDB:7M8W"
FT HELIX 245..272
FT /evidence="ECO:0007829|PDB:7M8W"
FT HELIX 278..306
FT /evidence="ECO:0007829|PDB:7M8W"
FT HELIX 309..324
FT /evidence="ECO:0007829|PDB:7M8W"
FT TURN 325..327
FT /evidence="ECO:0007829|PDB:7M8W"
SQ SEQUENCE 395 AA; 43268 MW; 99A63CBDA418DEC9 CRC64;
MSANATLKPL CPILEQMSRL QSHSNTSIRY IDHAAVLLHG LASLLGLVEN GVILFVVGCR
MRQTVVTTWV LHLALSDLLA SASLPFFTYF LAVGHSWELG TTFCKLHSSI FFLNMFASGF
LLSAISLDRC LQVVRPVWAQ NHRTVAAAHK VCLVLWALAV LNTVPYFVFR DTISRLDGRI
MCYYNVLLLN PGPDRDATCN SRQVALAVSK FLLAFLVPLA IIASSHAAVS LRLQHRGRRR
PGRFVRLVAA VVAAFALCWG PYHVFSLLEA RAHANPGLRP LVWRGLPFVT SLAFFNSVAN
PVLYVLTCPD MLRKLRRSLR TVLESVLVDD SELGGAGSSR RRRTSSTARS ASPLALCSRP
EEPRGPARLL GWLLGSCAAS PQTGPLNRAL SSTSS
