ID P2RX4_HUMAN Reviewed; 388 AA. AC Q99571; E7EPF7; F6RU17; O00450; O14722; Q5U089; Q5U090; Q8N4N1; Q9UBG9; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 2. DT 24-JAN-2024, entry version 204. DE RecName: Full=P2X purinoceptor 4; DE Short=P2X4; DE AltName: Full=ATP receptor; DE AltName: Full=Purinergic receptor; GN Name=P2RX4; 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 [MRNA] (ISOFORM 1), VARIANT SER-6, FUNCTION, RP TRANSPORTER ACTIVITY, AND ACTIVITY REGULATION. RC TISSUE=Brain; RX PubMed=9016352; DOI=10.1124/mol.51.1.109; RA Garcia-Guzman M., Soto F., Gomez-Hernandez J.M., Lund P.E., Stuhmer W.; RT "Characterization of recombinant human P2X4 receptor reveals RT pharmacological differences to the rat homologue."; RL Mol. Pharmacol. 51:109-118(1997). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1). RA Yamagata K., Oda N., Furuta H., Vaxillaire M., Southam L., Boriraj V., RA Chen X., Oda Y., Takeda J., Yamada S., Nishigori H., Lebeau M.M., RA Lathrop M., Cox R.D., Bell G.I.; RT "Transcription map of the 5cM region surrounding the hepatocyte nuclear RT factor-1a/MODY3 gene on chromosome 12."; RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANT SER-6. RA Korenaga R., Yamamoto K., Kamiya A., Ando J.; RT "Shear stress downregulates the expression of P2X4 receptor by human RT endothelial cells."; RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT RP SER-6. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLY-242. RC TISSUE=Blood; 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 NUCLEOTIDE SEQUENCE [MRNA] OF 35-388 (ISOFORM 1), AND VARIANT CYS-315. RA Takahashi K., Korenaga R., Kamiya A., Ando J.; RT "Human P2X purinoceptor."; RL Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 73-326 (ISOFORM 1). RC TISSUE=Kidney; RA Chang A.S., Chang S.M.; RT "Cloning of P2X4 cDNA from human embryonic kidney (HEK) 293 cells."; RL Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases. RN [9] RP ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), FUNCTION, AND SUBCELLULAR RP LOCATION. RX PubMed=10515189; DOI=10.1016/s0304-3940(99)00653-9; RA Carpenter D., Meadows H.J., Brough S., Chapman G., Clarke C., Coldwell M., RA Davis R., Harrison D., Meakin J., McHale M., Rice S.Q., Tomlinson W.J., RA Wood M., Sanger G.J.; RT "Site-specific splice variation of the human P2X4 receptor."; RL Neurosci. Lett. 273:183-186(1999). RN [10] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-184. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [11] RP SUBCELLULAR LOCATION. RX PubMed=24817123; DOI=10.1074/jbc.m114.552158; RA Huang P., Zou Y., Zhong X.Z., Cao Q., Zhao K., Zhu M.X., RA Murrell-Lagnado R., Dong X.P.; RT "P2X4 forms functional ATP-activated cation channels on lysosomal membranes RT regulated by luminal pH."; RL J. Biol. Chem. 289:17658-17667(2014). RN [12] RP INTERACTION WITH P2X7. RX PubMed=26456657; DOI=10.1016/j.bbrc.2015.10.025; RA Perez-Flores G., Levesque S.A., Pacheco J., Vaca L., Lacroix S., RA Perez-Cornejo P., Arreola J.; RT "The P2X7/P2X4 interaction shapes the purinergic response in murine RT macrophages."; RL Biochem. Biophys. Res. Commun. 467:484-490(2015). RN [13] RP FUNCTION. RX PubMed=35165166; DOI=10.4049/jimmunol.2100550; RA Hamoudi C., Zhao C., Abderrazak A., Salem M., Fortin P.R., Sevigny J., RA Aoudjit F.; RT "The Purinergic Receptor P2X4 Promotes Th17 Activation and the Development RT of Arthritis."; RL J. Immunol. 208:1115-1127(2022). RN [14] RP VARIANTS GLY-242 AND CYS-315, CHARACTERIZATION OF VARIANTS SER-6; GLY-242 RP AND CYS-315, MUTAGENESIS OF ILE-119, AND FUNCTION. RX PubMed=22068874; DOI=10.1161/hypertensionaha.111.176180; RA Stokes L., Scurrah K., Ellis J.A., Cromer B.A., Skarratt K.K., Gu B.J., RA Harrap S.B., Wiley J.S.; RT "A loss-of-function polymorphism in the human P2X4 receptor is associated RT with increased pulse pressure."; RL Hypertension 58:1086-1092(2011). RN [15] RP VARIANT CYS-315, CHARACTERIZATION OF VARIANT CYS-315, AND SUBCELLULAR RP LOCATION. RX PubMed=23303206; DOI=10.1096/fj.12-215368; RA Gu B.J., Baird P.N., Vessey K.A., Skarratt K.K., Fletcher E.L., RA Fuller S.J., Richardson A.J., Guymer R.H., Wiley J.S.; RT "A rare functional haplotype of the P2RX4 and P2RX7 genes leads to loss of RT innate phagocytosis and confers increased risk of age-related macular RT degeneration."; RL FASEB J. 27:1479-1487(2013). RN [16] RP VARIANTS CYS-3; SER-135; GLY-242 AND CYS-315, CHARACTERIZATION OF VARIANT RP SER-135, SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=28326637; DOI=10.1002/humu.23218; RA Sadovnick A.D., Gu B.J., Traboulsee A.L., Bernales C.Q., Encarnacion M., RA Yee I.M., Criscuoli M.G., Huang X., Ou A., Milligan C.J., Petrou S., RA Wiley J.S., Vilarino-Gueell C.; RT "Purinergic receptors P2RX4 and P2RX7 in familial multiple sclerosis."; RL Hum. Mutat. 38:736-744(2017). CC -!- FUNCTION: ATP-gated nonselective transmembrane cation channel permeable CC to potassium, sodium and calcium (PubMed:9016352). Activated by CC extracellularly released ATP, it plays multiple role in immunity and CC central nervous system physiology (PubMed:35165166). Plays a key role CC in initial steps of T-cell activation and Ca(2+) microdomain formation CC (By similarity). Participates also in basal T-cell activity without CC TCR/CD3 stimulation (By similarity). Promotes the differentiation and CC activation of Th17 cells via expression of retinoic acid-related orphan CC receptor C/RORC (PubMed:35165166). Upon activation, drives microglia CC motility via the PI3K/Akt pathway (By similarity). Could also function CC as an ATP-gated cation channel of lysosomal membranes (By similarity). CC {ECO:0000250|UniProtKB:P51577, ECO:0000250|UniProtKB:Q9JJX6, CC ECO:0000269|PubMed:35165166, ECO:0000269|PubMed:9016352}. CC -!- CATALYTIC ACTIVITY: CC Reaction=K(+)(in) = K(+)(out); Xref=Rhea:RHEA:29463, ChEBI:CHEBI:29103; CC Evidence={ECO:0000269|PubMed:9016352}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Na(+)(in) = Na(+)(out); Xref=Rhea:RHEA:34963, CC ChEBI:CHEBI:29101; Evidence={ECO:0000269|PubMed:9016352}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Ca(2+)(in) = Ca(2+)(out); Xref=Rhea:RHEA:29671, CC ChEBI:CHEBI:29108; Evidence={ECO:0000269|PubMed:9016352}; CC -!- ACTIVITY REGULATION: Activated by ATP (PubMed:9016352). pH-dependent CC and inhibited by acidic pH (By similarity). CC {ECO:0000250|UniProtKB:P51577, ECO:0000269|PubMed:9016352}. CC -!- SUBUNIT: Functional P2XRs are organized as homomeric and heteromeric CC trimers. Interacts with P2X7 (via C-terminus); this interaction is CC functional only in the presence of ATP (PubMed:26456657). Interacts CC with AP1M2 (By similarity). {ECO:0000250|UniProtKB:P51577, CC ECO:0000269|PubMed:26456657}. CC -!- INTERACTION: CC Q99571; Q9NQM4: DNAAF6; NbExp=3; IntAct=EBI-2828248, EBI-10239299; CC Q99571; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-2828248, EBI-11959885; CC Q99571; P60328: KRTAP12-3; NbExp=3; IntAct=EBI-2828248, EBI-11953334; CC Q99571; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-2828248, EBI-3958099; CC Q99571; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-2828248, EBI-945833; CC Q99571; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-2828248, EBI-22310682; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10515189, CC ECO:0000269|PubMed:23303206, ECO:0000269|PubMed:28326637}; Multi-pass CC membrane protein {ECO:0000255}. Lysosome membrane CC {ECO:0000269|PubMed:24817123}; Multi-pass membrane protein CC {ECO:0000255}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q99571-1; Sequence=Displayed; CC Name=2; CC IsoId=Q99571-2; Sequence=VSP_053812; CC Name=3; CC IsoId=Q99571-3; Sequence=VSP_053813; CC -!- SIMILARITY: Belongs to the P2X receptor family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=P2X receptor entry; CC URL="https://en.wikipedia.org/wiki/P2X_receptor"; 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; Y07684; CAA68948.1; -; mRNA. DR EMBL; U87270; AAD00556.1; -; Genomic_DNA. DR EMBL; U85971; AAD00556.1; JOINED; Genomic_DNA. DR EMBL; U85972; AAD00556.1; JOINED; Genomic_DNA. DR EMBL; U85973; AAD00556.1; JOINED; Genomic_DNA. DR EMBL; U85974; AAD00556.1; JOINED; Genomic_DNA. DR EMBL; U85975; AAD00556.1; JOINED; Genomic_DNA. DR EMBL; U83993; AAD00553.1; -; mRNA. DR EMBL; AF191093; AAF06661.1; -; Genomic_DNA. DR EMBL; BT019738; AAV38543.1; -; mRNA. DR EMBL; BT019739; AAV38544.1; -; mRNA. DR EMBL; AC069209; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC033826; AAH33826.1; -; mRNA. DR EMBL; AF000234; AAB58405.1; -; mRNA. DR EMBL; AF012903; AAB66834.1; -; mRNA. DR CCDS; CCDS58282.1; -. [Q99571-2] DR CCDS; CCDS9214.1; -. [Q99571-1] DR RefSeq; NP_001243725.1; NM_001256796.1. [Q99571-2] DR RefSeq; NP_001248326.1; NM_001261397.1. [Q99571-3] DR RefSeq; NP_002551.2; NM_002560.2. [Q99571-1] DR AlphaFoldDB; Q99571; -. DR SMR; Q99571; -. DR BioGRID; 111064; 47. DR IntAct; Q99571; 26. DR STRING; 9606.ENSP00000353032; -. DR BindingDB; Q99571; -. DR ChEMBL; CHEMBL2104; -. DR DrugBank; DB14575; Eslicarbazepine. DR DrugBank; DB09119; Eslicarbazepine acetate. DR DrugBank; DB01069; Promethazine. DR DrugCentral; Q99571; -. DR GuidetoPHARMACOLOGY; 481; -. DR TCDB; 1.A.7.1.5; the atp-gated p2x receptor cation channel (p2x receptor) family. DR GlyConnect; 1590; 12 N-Linked glycans (4 sites). DR GlyCosmos; Q99571; 6 sites, 11 glycans. DR GlyGen; Q99571; 7 sites, 11 N-linked glycans (4 sites), 1 O-linked glycan (1 site). DR iPTMnet; Q99571; -. DR PhosphoSitePlus; Q99571; -. DR SwissPalm; Q99571; -. DR BioMuta; P2RX4; -. DR DMDM; 116242696; -. DR EPD; Q99571; -. DR jPOST; Q99571; -. DR MassIVE; Q99571; -. DR MaxQB; Q99571; -. DR PaxDb; 9606-ENSP00000353032; -. DR PeptideAtlas; Q99571; -. DR ProteomicsDB; 17348; -. DR ProteomicsDB; 27898; -. DR ProteomicsDB; 78331; -. [Q99571-1] DR Antibodypedia; 31537; 315 antibodies from 35 providers. DR DNASU; 5025; -. DR Ensembl; ENST00000337233.9; ENSP00000336607.4; ENSG00000135124.16. [Q99571-1] DR Ensembl; ENST00000359949.11; ENSP00000353032.7; ENSG00000135124.16. [Q99571-2] DR Ensembl; ENST00000542067.5; ENSP00000438329.1; ENSG00000135124.16. [Q99571-3] DR GeneID; 5025; -. DR KEGG; hsa:5025; -. DR MANE-Select; ENST00000337233.9; ENSP00000336607.4; NM_002560.3; NP_002551.2. DR UCSC; uc001tzr.4; human. [Q99571-1] DR AGR; HGNC:8535; -. DR CTD; 5025; -. DR DisGeNET; 5025; -. DR GeneCards; P2RX4; -. DR HGNC; HGNC:8535; P2RX4. DR HPA; ENSG00000135124; Low tissue specificity. DR MIM; 600846; gene. DR neXtProt; NX_Q99571; -. DR OpenTargets; ENSG00000135124; -. DR PharmGKB; PA32864; -. DR VEuPathDB; HostDB:ENSG00000135124; -. DR eggNOG; ENOG502QSUI; Eukaryota. DR GeneTree; ENSGT01020000230351; -. DR InParanoid; Q99571; -. DR OMA; NNCVPGY; -. DR OrthoDB; 5312692at2759; -. DR PhylomeDB; Q99571; -. DR TreeFam; TF328633; -. DR PathwayCommons; Q99571; -. DR Reactome; R-HSA-139853; Elevation of cytosolic Ca2+ levels. DR Reactome; R-HSA-418346; Platelet homeostasis. DR Reactome; R-HSA-9660826; Purinergic signaling in leishmaniasis infection. DR SignaLink; Q99571; -. DR BioGRID-ORCS; 5025; 12 hits in 1166 CRISPR screens. DR ChiTaRS; P2RX4; human. DR GeneWiki; P2RX4; -. DR GenomeRNAi; 5025; -. DR Pharos; Q99571; Tchem. DR PRO; PR:Q99571; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q99571; Protein. DR Bgee; ENSG00000135124; Expressed in mucosa of transverse colon and 160 other cell types or tissues. DR ExpressionAtlas; Q99571; baseline and differential. DR GO; GO:0044297; C:cell body; ISS:ARUK-UCL. DR GO; GO:0030054; C:cell junction; IDA:BHF-UCL. DR GO; GO:0043197; C:dendritic spine; IEA:Ensembl. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:BHF-UCL. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0043195; C:terminal bouton; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IC:BHF-UCL. DR GO; GO:0045296; F:cadherin binding; IPI:BHF-UCL. DR GO; GO:0005507; F:copper ion binding; ISS:BHF-UCL. DR GO; GO:0004931; F:extracellularly ATP-gated monoatomic cation channel activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:BHF-UCL. DR GO; GO:0099604; F:ligand-gated calcium channel activity; IDA:BHF-UCL. DR GO; GO:0001614; F:purinergic nucleotide receptor activity; IDA:BHF-UCL. DR GO; GO:0005102; F:signaling receptor binding; ISS:BHF-UCL. DR GO; GO:0008270; F:zinc ion binding; ISS:BHF-UCL. DR GO; GO:0097190; P:apoptotic signaling pathway; IDA:BHF-UCL. DR GO; GO:0048266; P:behavioral response to pain; ISS:ARUK-UCL. DR GO; GO:0070588; P:calcium ion transmembrane transport; IDA:BHF-UCL. DR GO; GO:0019722; P:calcium-mediated signaling; TAS:ARUK-UCL. DR GO; GO:0071318; P:cellular response to ATP; IDA:UniProtKB. DR GO; GO:0071294; P:cellular response to zinc ion; ISS:UniProtKB. DR GO; GO:0042118; P:endothelial cell activation; TAS:BHF-UCL. DR GO; GO:0051899; P:membrane depolarization; IDA:BHF-UCL. DR GO; GO:0034220; P:monoatomic ion transmembrane transport; IDA:UniProtKB. DR GO; GO:0010614; P:negative regulation of cardiac muscle hypertrophy; IMP:BHF-UCL. DR GO; GO:0019228; P:neuronal action potential; IEA:Ensembl. DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IMP:CAFA. DR GO; GO:0051928; P:positive regulation of calcium ion transport; NAS:BHF-UCL. DR GO; GO:0010524; P:positive regulation of calcium ion transport into cytosol; IDA:BHF-UCL. DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; IDA:BHF-UCL. DR GO; GO:2001028; P:positive regulation of endothelial cell chemotaxis; IMP:CAFA. DR GO; GO:1904141; P:positive regulation of microglial cell migration; ISS:ARUK-UCL. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; NAS:BHF-UCL. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISS:ARUK-UCL. DR GO; GO:0032308; P:positive regulation of prostaglandin secretion; NAS:BHF-UCL. DR GO; GO:0035590; P:purinergic nucleotide receptor signaling pathway; IMP:BHF-UCL. DR GO; GO:0008217; P:regulation of blood pressure; IMP:BHF-UCL. DR GO; GO:0055117; P:regulation of cardiac muscle contraction; IMP:BHF-UCL. DR GO; GO:0050920; P:regulation of chemotaxis; ISS:ARUK-UCL. DR GO; GO:0002028; P:regulation of sodium ion transport; ISS:BHF-UCL. DR GO; GO:0055119; P:relaxation of cardiac muscle; IMP:BHF-UCL. DR GO; GO:0033198; P:response to ATP; IDA:BHF-UCL. DR GO; GO:0048678; P:response to axon injury; ISS:ARUK-UCL. DR GO; GO:0034405; P:response to fluid shear stress; IDA:BHF-UCL. DR GO; GO:0002931; P:response to ischemia; ISS:ARUK-UCL. DR GO; GO:0019233; P:sensory perception of pain; ISS:ARUK-UCL. DR GO; GO:0050975; P:sensory perception of touch; ISS:ARUK-UCL. DR GO; GO:0007165; P:signal transduction; IDA:BHF-UCL. DR GO; GO:0001894; P:tissue homeostasis; NAS:BHF-UCL. DR Gene3D; 1.10.287.940; atp-gated p2x4 ion channel; 1. DR Gene3D; 2.60.490.10; atp-gated p2x4 ion channel domain; 1. DR InterPro; IPR003047; P2X4_purnocptor. DR InterPro; IPR027309; P2X_extracellular_dom_sf. DR InterPro; IPR001429; P2X_purnocptor. DR NCBIfam; TIGR00863; P2X; 1. DR PANTHER; PTHR10125; P2X PURINOCEPTOR; 1. DR PANTHER; PTHR10125:SF18; P2X PURINOCEPTOR 4; 1. DR Pfam; PF00864; P2X_receptor; 1. DR PIRSF; PIRSF005713; P2X_purinoceptor; 1. DR PRINTS; PR01311; P2X4RECEPTOR. DR PRINTS; PR01307; P2XRECEPTOR. DR PROSITE; PS01212; P2X_RECEPTOR; 1. DR Genevisible; Q99571; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein; KW Ion channel; Ion transport; Ligand-gated ion channel; Lysosome; Membrane; KW Receptor; Reference proteome; Transmembrane; Transmembrane helix; KW Transport. FT CHAIN 1..388 FT /note="P2X purinoceptor 4" FT /id="PRO_0000161553" FT TOPO_DOM 1..33 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 34..54 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 55..338 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 339..359 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 360..388 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT CARBOHYD 75 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 110 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 153 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 184 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT CARBOHYD 199 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 208 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 116..165 FT /evidence="ECO:0000250" FT DISULFID 126..149 FT /evidence="ECO:0000250" FT DISULFID 132..159 FT /evidence="ECO:0000250" FT DISULFID 217..227 FT /evidence="ECO:0000250" FT DISULFID 261..270 FT /evidence="ECO:0000250" FT VAR_SEQ 45 FT /note="G -> GCYHPHLAEVEMESPRR (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_053812" FT VAR_SEQ 149..175 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|Ref.4" FT /id="VSP_053813" FT VARIANT 3 FT /note="G -> C (in dbSNP:rs200492184)" FT /evidence="ECO:0000269|PubMed:28326637" FT /id="VAR_079856" FT VARIANT 6 FT /note="A -> S (does not change ATP-induced inward current; FT does not change affinity for ATP; dbSNP:rs1044249)" FT /evidence="ECO:0000269|PubMed:22068874, FT ECO:0000269|PubMed:9016352, ECO:0000269|Ref.3, FT ECO:0000269|Ref.4" FT /id="VAR_028307" FT VARIANT 135 FT /note="G -> S (does not change protein expression; does not FT affect membrane subcellular location; increases ATP-induced FT inward current; dbSNP:rs765866317)" FT /evidence="ECO:0000269|PubMed:28326637" FT /id="VAR_079857" FT VARIANT 242 FT /note="S -> G (does not change ATP-induced inward current; FT does not change affinity for ATP; dbSNP:rs25644)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:22068874, ECO:0000269|PubMed:28326637" FT /id="VAR_014942" FT VARIANT 315 FT /note="Y -> C (may influence susceptibility to multiple FT sclerosis in the presence of variants M-205 and S-361 in FT P2RX7; does not affect membrane subcellular location; FT reduces ATP-induced inward current; decreases affinity for FT ATP; dbSNP:rs28360472)" FT /evidence="ECO:0000269|PubMed:22068874, FT ECO:0000269|PubMed:23303206, ECO:0000269|PubMed:28326637, FT ECO:0000269|Ref.7" FT /id="VAR_079858" FT MUTAGEN 119 FT /note="I->V: Does not change ATP-induced inward current. FT Does not change affinity for ATP." FT /evidence="ECO:0000269|PubMed:22068874" FT CONFLICT 121 FT /note="D -> S (in Ref. 8; AAB66834)" FT /evidence="ECO:0000305" FT CONFLICT 148 FT /note="R -> W (in Ref. 8; AAB66834)" FT /evidence="ECO:0000305" FT CONFLICT 179 FT /note="L -> F (in Ref. 8; AAB66834)" FT /evidence="ECO:0000305" FT CONFLICT 238 FT /note="N -> I (in Ref. 8; AAB66834)" FT /evidence="ECO:0000305" SQ SEQUENCE 388 AA; 43369 MW; BA3BE7F30114C2A5 CRC64; MAGCCAALAA FLFEYDTPRI VLIRSRKVGL MNRAVQLLIL AYVIGWVFVW EKGYQETDSV VSSVTTKVKG VAVTNTSKLG FRIWDVADYV IPAQEENSLF VMTNVILTMN QTQGLCPEIP DATTVCKSDA SCTAGSAGTH SNGVSTGRCV AFNGSVKTCE VAAWCPVEDD THVPQPAFLK AAENFTLLVK NNIWYPKFNF SKRNILPNIT TTYLKSCIYD AKTDPFCPIF RLGKIVENAG HSFQDMAVEG GIMGIQVNWD CNLDRAASLC LPRYSFRRLD TRDVEHNVSP GYNFRFAKYY RDLAGNEQRT LIKAYGIRFD IIVFGKAGKF DIIPTMINIG SGLALLGMAT VLCDIIVLYC MKKRLYYREK KYKYVEDYEQ GLASELDQ //