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 11-NOV-2015, entry version 133. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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., RA Garrad R.C., George S.R., Turner J.T., O'Dowd B.F.; RT "Cloning, expression, and chromosomal localization of the human RT uridine 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 RT (P2P) expressed in human pancreas that shows high structural homology RT to the P2U 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., RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S., RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., RA 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., RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., RA 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., RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., RA 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., RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., RA Williams G., Williams L., Williamson A., Williamson H., Wilming L., RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., RA 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., RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., RA Gibbs R.A., Beck S., 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 RT project: 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 RT P2Y6 receptors. Ser-333 and Ser-334 in the carboxyl terminus are RT involved in agonist-dependent phosphorylation desensitization and RT internalization of the P2Y4 receptor."; RL J. Biol. Chem. 276:11939-11948(2001). CC -!- FUNCTION: Receptor for UTP and UDP coupled to G-proteins that CC activate a phosphatidylinositol-calcium second messenger system. CC Not activated by ATP or ADP. 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 CC agonist-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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X91852; CAA62963.1; -; Genomic_DNA. DR EMBL; U40223; AAC50347.1; -; Genomic_DNA. DR EMBL; X96597; CAA65415.1; -; Genomic_DNA. DR EMBL; AL357752; CAI41492.1; -; 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 UniGene; Hs.673854; -. DR PDB; 2B6Q; Model; -; A=1-365. DR PDBsum; 2B6Q; -. DR ProteinModelPortal; P51582; -. DR SMR; P51582; 33-316. DR IntAct; P51582; 1. DR STRING; 9606.ENSP00000363643; -. DR BindingDB; P51582; -. DR ChEMBL; CHEMBL2123; -. DR GuidetoPHARMACOLOGY; 325; -. DR PhosphoSite; P51582; -. DR BioMuta; P2RY4; -. DR DMDM; 1709524; -. DR PaxDb; P51582; -. DR PRIDE; P51582; -. DR Ensembl; ENST00000374519; ENSP00000363643; ENSG00000186912. DR GeneID; 5030; -. DR KEGG; hsa:5030; -. DR UCSC; uc004dxz.1; human. DR CTD; 5030; -. DR GeneCards; P2RY4; -. DR HGNC; HGNC:8542; P2RY4. DR HPA; CAB022644; -. DR MIM; 300038; gene. DR neXtProt; NX_P51582; -. DR PharmGKB; PA32871; -. DR eggNOG; ENOG410IIAQ; Eukaryota. DR eggNOG; ENOG410XQNZ; LUCA. DR GeneTree; ENSGT00760000118784; -. DR HOGENOM; HOG000231307; -. DR HOVERGEN; HBG101120; -. DR InParanoid; P51582; -. DR KO; K04271; -. DR OMA; DATATYM; -. DR OrthoDB; EOG7QNVM4; -. DR PhylomeDB; P51582; -. DR TreeFam; TF350009; -. DR Reactome; R-HSA-417957; P2Y receptors. DR Reactome; R-HSA-418594; G alpha (i) signalling events. DR GeneWiki; P2RY4; -. DR GenomeRNAi; 5030; -. DR NextBio; 19374; -. DR PRO; PR:P51582; -. DR Proteomes; UP000005640; Chromosome X. DR Bgee; P51582; -. DR CleanEx; HS_P2RY4; -. 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:0005829; C:cytosol; TAS:GOC. DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. 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:0015065; F:uridine nucleotide receptor activity; TAS:ProtInc. DR GO; GO:0045030; F:UTP-activated nucleotide receptor activity; IEA:Ensembl. DR GO; GO:0071380; P:cellular response to prostaglandin E stimulus; IEA:Ensembl. 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: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 3D-structure; Cell membrane; Complete proteome; Disulfide bond; KW G-protein coupled receptor; Membrane; Phosphoprotein; Polymorphism; KW Receptor; Reference proteome; Transducer; Transmembrane; KW Transmembrane helix. FT CHAIN 1 365 P2Y purinoceptor 4. FT /FTId=PRO_0000070020. FT TOPO_DOM 1 34 Extracellular. {ECO:0000255}. FT TRANSMEM 35 61 Helical; Name=1. {ECO:0000255}. FT TOPO_DOM 62 72 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 73 95 Helical; Name=2. {ECO:0000255}. FT TOPO_DOM 96 112 Extracellular. {ECO:0000255}. FT TRANSMEM 113 131 Helical; Name=3. {ECO:0000255}. FT TOPO_DOM 132 154 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 155 174 Helical; Name=4. {ECO:0000255}. FT TOPO_DOM 175 196 Extracellular. {ECO:0000255}. FT TRANSMEM 197 222 Helical; Name=5. {ECO:0000255}. FT TOPO_DOM 223 246 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 247 269 Helical; Name=6. {ECO:0000255}. FT TOPO_DOM 270 287 Extracellular. {ECO:0000255}. FT TRANSMEM 288 309 Helical; Name=7. {ECO:0000255}. FT TOPO_DOM 310 365 Cytoplasmic. {ECO:0000255}. FT MOD_RES 333 333 Phosphoserine. FT {ECO:0000305|PubMed:11114308}. FT MOD_RES 334 334 Phosphoserine. FT {ECO:0000305|PubMed:11114308}. FT DISULFID 108 185 {ECO:0000255|PROSITE-ProRule:PRU00521}. FT VARIANT 168 168 V -> M (in dbSNP:rs1152186). FT /FTId=VAR_011854. FT VARIANT 178 178 N -> T (in dbSNP:rs1152187). FT {ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:8537335}. FT /FTId=VAR_011855. FT VARIANT 191 191 P -> L (in dbSNP:rs1152188). FT /FTId=VAR_011856. FT VARIANT 234 234 S -> A (in dbSNP:rs3829709). FT {ECO:0000269|PubMed:8537335}. FT /FTId=VAR_049429. FT MUTAGEN 243 243 S->A: No effect. FT {ECO:0000269|PubMed:11114308}. FT MUTAGEN 333 365 Missing: Abolishes agonist-induced FT phosphorylation. Prevents agonist-induced FT desensitization and loss of cell surface FT receptors. FT MUTAGEN 333 359 SSLALVSLPEDSSCRWAATPQDSSCST->AALALVALPEDA FT ACRWAAAPQDAACAA: Greatly reduces agonist- FT induced desensitization and loss of cell FT surface receptors. FT MUTAGEN 333 333 S->A: Greatly reduces agonist-induced FT desensitization and loss of cell surface FT receptors; when associated with A-334 and FT A-339. {ECO:0000269|PubMed:11114308}. FT MUTAGEN 334 334 S->A: Greatly reduces agonist-induced FT desensitization and loss of cell surface FT receptors; when associated with A-333 and FT A-339. {ECO:0000269|PubMed:11114308}. FT MUTAGEN 339 339 S->A: Greatly reduces agonist-induced FT desensitization and loss of cell surface FT receptors; when associated with A-333 and FT A-334. {ECO:0000269|PubMed:11114308}. FT MUTAGEN 344 365 Missing: No effect on agonist-induced FT phosphorylation, no functional effect. FT MUTAGEN 356 365 Missing: No functional effect. FT CONFLICT 86 86 L -> V (in Ref. 2; AAC50347). FT {ECO:0000305}. FT CONFLICT 121 121 C -> S (in Ref. 5; AAH96068). FT {ECO:0000305}. FT CONFLICT 247 247 I -> V (in Ref. 5; AAH96069). FT {ECO:0000305}. FT CONFLICT 352 352 P -> T (in Ref. 5; AAH96069). FT {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 //