ID   P2RY4_HUMAN             Reviewed;         365 AA.
AC   P51582; Q4VBB7; Q4VBB8; Q502W2; Q5JT22;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   02-SEP-2026, entry version 196.
DE   RecName: Full=P2Y purinoceptor 4;
DE            Short=P2Y4;
DE   AltName: Full=P2P;
DE   AltName: Full=Uridine nucleotide receptor;
DE            Short=UNR;
GN   Name=P2RY4; Synonyms=NRU;
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].
RX   PubMed=8537336; DOI=10.1074/jbc.270.52.30849;
RA   Communi D., Pirotton S., Parmentier M., Boeynaems J.-M.;
RT   "Cloning and functional expression of a human uridine nucleotide
RT   receptor.";
RL   J. Biol. Chem. 270:30849-30852(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-178 AND ALA-234.
RX   PubMed=8537335; DOI=10.1074/jbc.270.52.30845;
RA   Nguyen T., Erb L., Weisman G.A., Marchese A., Heng H.H.Q., Garrad R.C.,
RA   George S.R., Turner J.T., O'Dowd B.F.;
RT   "Cloning, expression, and chromosomal localization of the human uridine
RT   nucleotide receptor gene.";
RL   J. Biol. Chem. 270:30845-30848(1995).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Pancreas;
RX   PubMed=8617367; DOI=10.1016/0014-5793(96)00321-3;
RA   Stam N.J., Klomp J., van der Heuvel M., Olijve W.;
RT   "Molecular cloning and characterization of a novel orphan receptor (P2P)
RT   expressed in human pancreas that shows high structural homology to the P2U
RT   purinoceptor.";
RL   FEBS Lett. 384:260-264(1996).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15772651; DOI=10.1038/nature03440;
RA   Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA   Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA   Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA   Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA   Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA   Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA   Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA   Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA   Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA   Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA   Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA   Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA   Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA   Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA   Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA   Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA   Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA   Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA   Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA   Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA   Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA   Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA   Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA   Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA   Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA   Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA   Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA   Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA   Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA   Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA   McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA   Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA   Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA   Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA   Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA   Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA   Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA   Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA   Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA   Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA   d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA   Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA   Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA   Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA   Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA   Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA   Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA   Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA   Rogers J., Bentley D.R.;
RT   "The DNA sequence of the human X chromosome.";
RL   Nature 434:325-337(2005).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-178.
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   [6]
RP   PHOSPHORYLATION AT SER-333 AND SER-334, AND MUTAGENESIS OF SER-243;
RP   SER-333; SER-334 AND SER-339.
RX   PubMed=11114308; DOI=10.1074/jbc.m009909200;
RA   Brinson A.E., Harden T.K.;
RT   "Differential regulation of the uridine nucleotide-activated P2Y4 and P2Y6
RT   receptors. Ser-333 and Ser-334 in the carboxyl terminus are involved in
RT   agonist-dependent phosphorylation desensitization and internalization of
RT   the P2Y4 receptor.";
RL   J. Biol. Chem. 276:11939-11948(2001).
CC   -!- FUNCTION: Receptor for UTP and UDP coupled to G proteins that activate
CC       a phosphatidylinositol-calcium second messenger system. Not activated
CC       by ATP or ADP.
CC   -!- INTERACTION:
CC       P51582; Q96CV9: OPTN; NbExp=3; IntAct=EBI-4392513, EBI-748974;
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC   -!- TISSUE SPECIFICITY: Pancreas.
CC   -!- PTM: Phosphorylation of Ser-333 and Ser-334 is a key step in agonist-
CC       dependent desensitization and loss of surface P2RY4. This
CC       phosphorylation does not involve PKC, nor other calcium activated
CC       kinases. {ECO:0000269|PubMed:11114308}.
CC   -!- SIMILARITY: Belongs to the G protein-coupled receptor 1 family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR   EMBL; X91852; CAA62963.1; -; Genomic_DNA.
DR   EMBL; U40223; AAC50347.1; -; Genomic_DNA.
DR   EMBL; X96597; CAA65415.1; -; Genomic_DNA.
DR   EMBL; AL357752; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC095503; AAH95503.1; -; mRNA.
DR   EMBL; BC096067; AAH96067.1; -; mRNA.
DR   EMBL; BC096068; AAH96068.1; -; mRNA.
DR   EMBL; BC096069; AAH96069.1; -; mRNA.
DR   EMBL; BC096070; AAH96070.1; -; mRNA.
DR   CCDS; CCDS14398.1; -.
DR   PIR; S68679; S68679.
DR   RefSeq; NP_002556.1; NM_002565.4.
DR   PDB; 9K0K; EM; 3.14 A; I=1-365.
DR   AlphaFoldDB; P51582; -.
DR   EMDB; EMD-61947; -.
DR   SMR; P51582; -.
DR   BioGRID; 111069; 19.
DR   CORUM; P51582; -.
DR   FunCoup; P51582; 664.
DR   IntAct; P51582; 3.
DR   NDEx; IQUERY-CP-P2RY4; 4 NDEx IQuery Curated Pathways.
DR   STRING; 9606.ENSP00000363643; -.
DR   BindingDB; P51582; -.
DR   ChEMBL; CHEMBL2123; -.
DR   DrugBank; DB02431; Cytidine-5'-Triphosphate.
DR   DrugBank; DB05390; INS 316.
DR   DrugBank; DB01069; Promethazine.
DR   DrugBank; DB04005; Uridine 5'-triphosphate.
DR   DrugCentral; P51582; -.
DR   GuidetoPHARMACOLOGY; 325; -.
DR   iPTMnet; P51582; -.
DR   PhosphoSitePlus; P51582; -.
DR   BioMuta; P2RY4; -.
DR   DMDM; 1709524; -.
DR   MassIVE; P51582; -.
DR   PaxDb; 9606-ENSP00000363643; -.
DR   PeptideAtlas; P51582; -.
DR   Antibodypedia; 13260; 277 antibodies from 30 providers.
DR   DNASU; 5030; -.
DR   Ensembl; ENST00000374519.4; ENSP00000363643.2; ENSG00000186912.7.
DR   GeneID; 5030; -.
DR   KEGG; hsa:5030; -.
DR   MANE-Select; ENST00000374519.4; ENSP00000363643.2; NM_002565.4; NP_002556.1.
DR   UCSC; uc004dxz.2; human.
DR   AGR; HGNC:8542; -.
DR   ClinPGx; PA32871; -.
DR   CTD; 5030; -.
DR   DisGeNET; 5030; -.
DR   GeneCards; P2RY4; -.
DR   HGNC; HGNC:8542; P2RY4.
DR   HPA; ENSG00000186912; Tissue enhanced (intestine).
DR   MIM; 300038; gene.
DR   OpenTargets; ENSG00000186912; -.
DR   VEuPathDB; HostDB:ENSG00000186912; -.
DR   eggNOG; ENOG502QSTF; Eukaryota.
DR   GeneTree; ENSGT01030000234621; -.
DR   HOGENOM; CLU_009579_8_2_1; -.
DR   InParanoid; P51582; -.
DR   OMA; TRTIYYM; -.
DR   OrthoDB; 10018446at2759; -.
DR   PAN-GO; P51582; 3 GO annotations based on evolutionary models.
DR   PhylomeDB; P51582; -.
DR   PathwayCommons; P51582; -.
DR   Reactome; R-HSA-417957; P2Y receptors.
DR   Reactome; R-HSA-418594; G alpha (i) signalling events.
DR   SignaLink; P51582; -.
DR   SIGNOR; P51582; -.
DR   Agora; ENSG00000186912; -.
DR   BioGRID-ORCS; 5030; 14 hits in 764 CRISPR screens.
DR   GeneWiki; P2RY4; -.
DR   GenomeRNAi; 5030; -.
DR   Pharos; P51582; Tchem.
DR   PRO; PR:P51582; -.
DR   Proteomes; UP000005640; Chromosome X.
DR   RNAct; P51582; protein.
DR   Bgee; ENSG00000186912; Expressed in tibialis anterior and 52 other cell types or tissues.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0045028; F:G protein-coupled purinergic nucleotide receptor activity; IEA:InterPro.
DR   GO; GO:0045030; F:G protein-coupled UTP receptor activity; IBA:GO_Central.
DR   GO; GO:0071318; P:cellular response to ATP; TAS:ARUK-UCL.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR   GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; TAS:ProtInc.
DR   GO; GO:0030321; P:transepithelial chloride transport; IEA:InterPro.
DR   CDD; cd15374; 7tmA_P2Y4; 1.
DR   FunFam; 1.20.1070.10:FF:000017; lysophosphatidic acid receptor 4; 1.
DR   Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1.
DR   InterPro; IPR000276; GPCR_Rhodpsn.
DR   InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR   InterPro; IPR000018; P2Y4.
DR   PANTHER; PTHR24231:SF21; P2Y PURINOCEPTOR 4; 1.
DR   PANTHER; PTHR24231; PURINOCEPTOR-RELATED G-PROTEIN COUPLED RECEPTOR; 1.
DR   Pfam; PF00001; 7tm_1; 1.
DR   PRINTS; PR00237; GPCRRHODOPSN.
DR   PRINTS; PR01066; P2Y4PRNOCPTR.
DR   PRINTS; PR01157; P2YPURNOCPTR.
DR   SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1.
DR   PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR   PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
DR   PDBsum; 9K0K; -.
PE   1: Evidence at protein level;
KW   3D-structure; Cell membrane; Disulfide bond; G protein-coupled receptor;
KW   Membrane; Phosphoprotein; Proteomics identification; Receptor;
KW   Reference proteome; Transducer; Transmembrane; Transmembrane helix.
FT   CHAIN           1..365
FT                   /note="P2Y purinoceptor 4"
FT                   /id="PRO_0000070020"
FT   TOPO_DOM        1..34
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        35..61
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        62..72
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        73..95
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        96..112
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        113..131
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        132..154
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        155..174
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        175..196
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        197..222
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        223..246
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        247..269
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        270..287
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        288..309
FT                   /note="Helical; Name=7"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        310..365
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         333
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000305|PubMed:11114308"
FT   MOD_RES         334
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000305|PubMed:11114308"
FT   DISULFID        108..185
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT   VARIANT         168
FT                   /note="V -> M (in dbSNP:rs1152186)"
FT                   /id="VAR_011854"
FT   VARIANT         178
FT                   /note="N -> T (in dbSNP:rs1152187)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:8537335"
FT                   /id="VAR_011855"
FT   VARIANT         191
FT                   /note="P -> L (in dbSNP:rs1152188)"
FT                   /id="VAR_011856"
FT   VARIANT         234
FT                   /note="S -> A (in dbSNP:rs3829709)"
FT                   /evidence="ECO:0000269|PubMed:8537335"
FT                   /id="VAR_049429"
FT   MUTAGEN         243
FT                   /note="S->A: No effect."
FT                   /evidence="ECO:0000269|PubMed:11114308"
FT   MUTAGEN         333..365
FT                   /note="Missing: Abolishes agonist-induced phosphorylation.
FT                   Prevents agonist-induced desensitization and loss of cell
FT                   surface receptors."
FT   MUTAGEN         333..359
FT                   /note="SSLALVSLPEDSSCRWAATPQDSSCST->AALALVALPEDAACRWAAAPQDA
FT                   ACAA: Greatly reduces agonist-induced desensitization and
FT                   loss of cell surface receptors."
FT   MUTAGEN         333
FT                   /note="S->A: Greatly reduces agonist-induced
FT                   desensitization and loss of cell surface receptors; when
FT                   associated with A-334 and A-339."
FT                   /evidence="ECO:0000269|PubMed:11114308"
FT   MUTAGEN         334
FT                   /note="S->A: Greatly reduces agonist-induced
FT                   desensitization and loss of cell surface receptors; when
FT                   associated with A-333 and A-339."
FT                   /evidence="ECO:0000269|PubMed:11114308"
FT   MUTAGEN         339
FT                   /note="S->A: Greatly reduces agonist-induced
FT                   desensitization and loss of cell surface receptors; when
FT                   associated with A-333 and A-334."
FT                   /evidence="ECO:0000269|PubMed:11114308"
FT   MUTAGEN         344..365
FT                   /note="Missing: No effect on agonist-induced
FT                   phosphorylation, no functional effect."
FT   MUTAGEN         356..365
FT                   /note="Missing: No functional effect."
FT   CONFLICT        86
FT                   /note="L -> V (in Ref. 2; AAC50347)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        121
FT                   /note="C -> S (in Ref. 5; AAH96068)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        247
FT                   /note="I -> V (in Ref. 5; AAH96069)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        352
FT                   /note="P -> T (in Ref. 5; AAH96069)"
FT                   /evidence="ECO:0000305"
FT   HELIX           32..35
FT                   /evidence="ECO:0007829|PDB:9K0K"
FT   HELIX           38..52
FT                   /evidence="ECO:0007829|PDB:9K0K"
FT   HELIX           54..62
FT                   /evidence="ECO:0007829|PDB:9K0K"
FT   HELIX           69..86
FT                   /evidence="ECO:0007829|PDB:9K0K"
FT   HELIX           89..96
FT                   /evidence="ECO:0007829|PDB:9K0K"
FT   HELIX           105..138
FT                   /evidence="ECO:0007829|PDB:9K0K"
FT   HELIX           140..145
FT                   /evidence="ECO:0007829|PDB:9K0K"
FT   HELIX           149..166
FT                   /evidence="ECO:0007829|PDB:9K0K"
FT   HELIX           168..173
FT                   /evidence="ECO:0007829|PDB:9K0K"
FT   STRAND          179..182
FT                   /evidence="ECO:0007829|PDB:9K0K"
FT   HELIX           191..193
FT                   /evidence="ECO:0007829|PDB:9K0K"
FT   HELIX           194..205
FT                   /evidence="ECO:0007829|PDB:9K0K"
FT   HELIX           206..210
FT                   /evidence="ECO:0007829|PDB:9K0K"
FT   HELIX           211..228
FT                   /evidence="ECO:0007829|PDB:9K0K"
FT   STRAND          232..234
FT                   /evidence="ECO:0007829|PDB:9K0K"
FT   HELIX           239..274
FT                   /evidence="ECO:0007829|PDB:9K0K"
FT   HELIX           278..296
FT                   /evidence="ECO:0007829|PDB:9K0K"
FT   HELIX           298..306
FT                   /evidence="ECO:0007829|PDB:9K0K"
FT   HELIX           311..319
FT                   /evidence="ECO:0007829|PDB:9K0K"
SQ   SEQUENCE   365 AA;  40963 MW;  23E0AFED3B7BDEED CRC64;
     MASTESSLLR SLGLSPGPGS SEVELDCWFD EDFKFILLPV SYAVVFVLGL GLNAPTLWLF
     IFRLRPWDAT ATYMFHLALS DTLYVLSLPT LIYYYAAHNH WPFGTEICKF VRFLFYWNLY
     CSVLFLTCIS VHRYLGICHP LRALRWGRPR LAGLLCLAVW LVVAGCLVPN LFFVTTSNKG
     TTVLCHDTTR PEEFDHYVHF SSAVMGLLFG VPCLVTLVCY GLMARRLYQP LPGSAQSSSR
     LRSLRTIAVV LTVFAVCFVP FHITRTIYYL ARLLEADCRV LNIVNVVYKV TRPLASANSC
     LDPVLYLLTG DKYRRQLRQL CGGGKPQPRT AASSLALVSL PEDSSCRWAA TPQDSSCSTP
     RADRL
//