P2RY4_HUMAN
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 03-AUG-2022, entry version 177.
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_002565.3.
DR AlphaFoldDB; P51582; -.
DR SMR; P51582; -.
DR BioGRID; 111069; 19.
DR IntAct; P51582; 2.
DR STRING; 9606.ENSP00000363643; -.
DR BindingDB; P51582; -.
DR ChEMBL; CHEMBL2123; -.
DR DrugBank; DB01069; Promethazine.
DR DrugCentral; P51582; -.
DR GuidetoPHARMACOLOGY; 325; -.
DR iPTMnet; P51582; -.
DR PhosphoSitePlus; P51582; -.
DR BioMuta; P2RY4; -.
DR DMDM; 1709524; -.
DR PaxDb; P51582; -.
DR PeptideAtlas; P51582; -.
DR PRIDE; P51582; -.
DR Antibodypedia; 13260; 281 antibodies from 28 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 CTD; 5030; -.
DR DisGeNET; 5030; -.
DR GeneCards; P2RY4; -.
DR HGNC; HGNC:8542; P2RY4.
DR HPA; ENSG00000186912; Tissue enhanced (intestine).
DR MIM; 300038; gene.
DR neXtProt; NX_P51582; -.
DR OpenTargets; ENSG00000186912; -.
DR PharmGKB; PA32871; -.
DR VEuPathDB; HostDB:ENSG00000186912; -.
DR eggNOG; ENOG502QSTF; Eukaryota.
DR GeneTree; ENSGT01030000234621; -.
DR HOGENOM; CLU_009579_8_2_1; -.
DR InParanoid; P51582; -.
DR OMA; HWPFGTG; -.
DR OrthoDB; 1077455at2759; -.
DR PhylomeDB; P51582; -.
DR TreeFam; TF350009; -.
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 BioGRID-ORCS; 5030; 14 hits in 690 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 tissues.
DR Genevisible; P51582; HS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0099059; C:integral component of presynaptic active zone membrane; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:Ensembl.
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:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:0071318; P:cellular response to ATP; TAS:ARUK-UCL.
DR GO; GO:0071380; P:cellular response to prostaglandin E stimulus; IEA:Ensembl.
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:0099509; P:regulation of presynaptic cytosolic calcium ion concentration; IEA:Ensembl.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IEA:Ensembl.
DR GO; GO:0030321; P:transepithelial chloride transport; IEA:Ensembl.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR InterPro; IPR000018; P2Y4.
DR PANTHER; PTHR24231:SF21; PTHR24231:SF21; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PRINTS; PR01066; P2Y4PRNOCPTR.
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 Cell membrane; Disulfide bond; G-protein coupled receptor; Membrane;
KW Phosphoprotein; Receptor; Reference proteome; Transducer; Transmembrane;
KW 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"
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
