ID P2RX4_RAT Reviewed; 388 AA. AC P51577; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 1. DT 10-JUN-2026, entry version 177. DE RecName: Full=P2X purinoceptor 4; DE Short=P2X4; DE AltName: Full=ATP receptor; DE AltName: Full=Purinergic receptor; GN Name=P2rx4; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=Sprague-Dawley; TISSUE=Forebrain; RX PubMed=8551329; DOI=10.1523/jneurosci.16-02-00448.1996; RA Seguela P., Haghighi A., Soghomonian J.J., Cooper E.; RT "A novel neuronal P2x ATP receptor ion channel with widespread distribution RT in the brain."; RL J. Neurosci. 16:448-455(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=7498461; DOI=10.1016/0014-5793(95)01203-q; RA Bo X., Zhang Y., Nassar M., Burnstock G., Schoepfer R.; RT "A P2X purinoceptor cDNA conferring a novel pharmacological profile."; RL FEBS Lett. 375:129-133(1995). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Pancreatic islet; RX PubMed=8602843; DOI=10.1006/bbrc.1996.0380; RA Wang C.-Z., Namba N., Gonoi T., Inagaki N., Seino S.; RT "Cloning and pharmacological characterization of a fourth P2X receptor RT subtype widely expressed in brain and peripheral tissues including various RT endocrine tissues."; RL Biochem. Biophys. Res. Commun. 220:196-202(1996). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF GLU-249, FUNCTION, AND TISSUE RP SPECIFICITY. RC TISSUE=Superior cervical ganglion; RX PubMed=8598206; DOI=10.1002/j.1460-2075.1996.tb00333.x; RA Buell G.N., Lewis C., Collo G., North R.A., Surprenant A.; RT "An antagonist-insensitive P2X receptor expressed in epithelia and brain."; RL EMBO J. 15:55-62(1996). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TRANSPORTER ACTIVITY. RC STRAIN=Sprague-Dawley; TISSUE=Brain; RX PubMed=8622997; DOI=10.1073/pnas.93.8.3684; RA Soto F., Garcia-Guzman M., Gomez-Hernandez J.M., Hollmann M., Karschin C., RA Stuemer W.; RT "P2X4: an ATP-activated ionotropic receptor cloned from rat brain."; RL Proc. Natl. Acad. Sci. U.S.A. 93:3684-3688(1996). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung; 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 SUBUNIT, AND INTERACTION WITH P2RX6. RX PubMed=12077178; DOI=10.1523/jneurosci.22-12-04814.2002; RA Bobanovic L.K., Royle S.J., Murrell-Lagnado R.D.; RT "P2X receptor trafficking in neurons is subunit specific."; RL J. Neurosci. 22:4814-4824(2002). RN [8] RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION BY NERVE INJURY. RX PubMed=12917686; DOI=10.1038/nature01786; RA Tsuda M., Shigemoto-Mogami Y., Koizumi S., Mizokoshi A., Kohsaka S., RA Salter M.W., Inoue K.; RT "P2X4 receptors induced in spinal microglia gate tactile allodynia after RT nerve injury."; RL Nature 424:778-783(2003). RN [9] RP FUNCTION, INTERACTION WITH AP1M2, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP TYR-372. RX PubMed=15985462; DOI=10.1242/jcs.02451; RA Royle S.J., Qureshi O.S., Bobanovic L.K., Evans P.R., Owen D.J., RA Murrell-Lagnado R.D.; RT "Non-canonical YXXGPhi endocytic motifs: recognition by AP2 and RT preferential utilization in P2X4 receptors."; RL J. Cell Sci. 118:3073-3080(2005). RN [10] RP FUNCTION, AND SUBUNIT. RX PubMed=15686495; DOI=10.1111/j.1471-4159.2004.02939.x; RA Nicke A., Kerschensteiner D., Soto F.; RT "Biochemical and functional evidence for heteromeric assembly of P2X1 and RT P2X4 subunits."; RL J. Neurochem. 92:925-933(2005). RN [11] RP FUNCTION, AND MUTAGENESIS OF LEU-214. RX PubMed=24762105; DOI=10.1021/bi401711n; RA Zhang L., Xu H., Jie Y., Gao C., Chen W., Yin S., Samways D.S., Li Z.; RT "Involvement of ectodomain Leu 214 in ATP binding and channel RT desensitization of the P2X4 receptor."; RL Biochemistry 53:3012-3019(2014). RN [12] RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP LYS-67 AND SER-341. 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 [13] {ECO:0007744|PDB:2RUP} RP STRUCTURE BY NMR OF 111-167, AND DISULFIDE BONDS. RX PubMed=25662851; DOI=10.1016/j.febslet.2015.01.034; RA Igawa T., Abe Y., Tsuda M., Inoue K., Ueda T.; RT "Solution structure of the rat P2X4 receptor head domain involved in RT inhibitory metal binding."; RL FEBS Lett. 589:680-686(2015). RN [14] RP FUNCTION, AND MUTAGENESIS OF HIS-140 AND THR-186. RX PubMed=28332633; DOI=10.1038/srep45208; RA Kasuya G., Fujiwara Y., Tsukamoto H., Morinaga S., Ryu S., Touhara K., RA Ishitani R., Furutani Y., Hattori M., Nureki O.; RT "Structural insights into the nucleotide base specificity of P2X RT receptors."; RL Sci. Rep. 7:45208-45208(2017). CC -!- FUNCTION: ATP-gated nonselective transmembrane cation channel permeable CC to potassium, sodium and calcium. CTP, but not GTP or UTP, functions as CC a weak affinity agonist for P2RX4 (PubMed:28332633, PubMed:8622997). CC Activated by extracellularly released ATP, it plays multiple role in CC immunity and central nervous system physiology (PubMed:15985462, CC PubMed:24762105). Plays a key role in initial steps of T-cell CC activation and Ca(2+) microdomain formation (By similarity). Also CC participates in basal T-cell activity without TCR/CD3 stimulation (By CC similarity). Promotes the differentiation and activation of Th17 cells CC via expression of retinoic acid-related orphan receptor C/RORC (By CC similarity). Upon activation, drives microglia motility via the CC PI3K/Akt pathway (PubMed:12917686). Could also function as an ATP-gated CC cation channel of lysosomal membranes (PubMed:24817123). CC {ECO:0000250|UniProtKB:Q99571, ECO:0000250|UniProtKB:Q9JJX6, CC ECO:0000269|PubMed:12917686, ECO:0000269|PubMed:15985462, CC ECO:0000269|PubMed:24762105, ECO:0000269|PubMed:24817123, CC ECO:0000269|PubMed:28332633, ECO:0000269|PubMed:8598206, CC ECO:0000269|PubMed:8622997}. CC -!- CATALYTIC ACTIVITY: CC Reaction=K(+)(in) = K(+)(out); Xref=Rhea:RHEA:29463, ChEBI:CHEBI:29103; CC Evidence={ECO:0000250|UniProtKB:Q99571}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Na(+)(in) = Na(+)(out); Xref=Rhea:RHEA:34963, CC ChEBI:CHEBI:29101; Evidence={ECO:0000250|UniProtKB:Q99571}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Ca(2+)(in) = Ca(2+)(out); Xref=Rhea:RHEA:29671, CC ChEBI:CHEBI:29108; Evidence={ECO:0000269|PubMed:8622997}; CC -!- ACTIVITY REGULATION: Activated by ATP (PubMed:28332633, CC PubMed:8622997). pH-dependent and inhibited by acidic pH CC (PubMed:24817123). {ECO:0000250|UniProtKB:Q99571, CC ECO:0000269|PubMed:24817123, ECO:0000269|PubMed:28332633, CC ECO:0000269|PubMed:8622997}. CC -!- SUBUNIT: Functional P2RXs are organized as homomeric and heteromeric CC trimers. Forms heterotrimer with P2RX1 (PubMed:15686495). Interacts CC with P2RX7 (via C-terminus); this interaction is functional only in the CC presence of ATP (By similarity). Forms heterotrimer with P2RX4; CC functional differences between homomeric P2RX4 and P2RX4/6 heterotrimer CC are minor (PubMed:12077178). Interacts with AP1M2 (PubMed:15985462). CC {ECO:0000250, ECO:0000269|PubMed:12077178, CC ECO:0000269|PubMed:15686495}. CC -!- INTERACTION: CC P51577; P49653: P2rx2; NbExp=4; IntAct=EBI-9511617, EBI-9511543; CC P51577; P51577: P2rx4; NbExp=2; IntAct=EBI-9511617, EBI-9511617; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15985462}; CC Multi-pass membrane protein {ECO:0000250|UniProtKB:F8W463}. Lysosome CC membrane {ECO:0000269|PubMed:24817123}; Multi-pass membrane protein CC {ECO:0000255}. CC -!- TISSUE SPECIFICITY: Widespread distribution in the brain. Strongly CC expressed in microglial cells (PubMed:12917686). Also expressed in CC epithelial cells (PubMed:8598206). {ECO:0000269|PubMed:12917686, CC ECO:0000269|PubMed:8598206}. CC -!- INDUCTION: By nerve injury. {ECO:0000269|PubMed:12917686}. CC -!- SIMILARITY: Belongs to the P2X receptor family. {ECO:0000305}. 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; U32497; AAC52380.1; -; mRNA. DR EMBL; X91200; CAA62607.1; -; mRNA. DR EMBL; U47031; AAA99777.1; -; mRNA. DR EMBL; X87763; CAA61037.1; -; mRNA. DR EMBL; X93565; CAA63778.1; -; mRNA. DR EMBL; BC078792; AAH78792.1; -; mRNA. DR PIR; JC6137; JC6137. DR RefSeq; NP_113782.2; NM_031594.2. DR PDB; 2BP5; X-ray; 2.80 A; P=375-384. DR PDB; 2RUP; NMR; -; A=111-167. DR AlphaFoldDB; P51577; -. DR BMRB; P51577; -. DR SMR; P51577; -. DR BioGRID; 248281; 2. DR DIP; DIP-48411N; -. DR FunCoup; P51577; 26. DR IntAct; P51577; 2. DR MINT; P51577; -. DR STRING; 10116.ENSRNOP00000001752; -. DR BindingDB; P51577; -. DR ChEMBL; CHEMBL2818; -. DR DrugCentral; P51577; -. DR GuidetoPHARMACOLOGY; 481; -. DR GlyCosmos; P51577; 6 sites, No reported glycans. DR GlyGen; P51577; 7 sites. DR PhosphoSitePlus; P51577; -. DR SwissPalm; P51577; -. DR PaxDb; 10116-ENSRNOP00000001752; -. DR Ensembl; ENSRNOT00000001752.7; ENSRNOP00000001752.4; ENSRNOG00000001300.9. DR Ensembl; ENSRNOT00055025035; ENSRNOP00055020465; ENSRNOG00055014564. DR Ensembl; ENSRNOT00060002980; ENSRNOP00060001967; ENSRNOG00060001911. DR Ensembl; ENSRNOT00065010473; ENSRNOP00065007698; ENSRNOG00065006722. DR GeneID; 29659; -. DR KEGG; rno:29659; -. DR UCSC; RGD:62073; rat. DR AGR; RGD:62073; -. DR CTD; 5025; -. DR RGD; 62073; P2rx4. DR eggNOG; ENOG502QSUI; Eukaryota. DR GeneTree; ENSGT01020000230351; -. DR HOGENOM; CLU_034469_2_0_1; -. DR InParanoid; P51577; -. DR OMA; NNCVPGY; -. DR OrthoDB; 494673at2759; -. DR PhylomeDB; P51577; -. DR Reactome; R-RNO-139853; Elevation of cytosolic Ca2+ levels. DR Reactome; R-RNO-418346; Platelet homeostasis. DR EvolutionaryTrace; P51577; -. DR PRO; PR:P51577; -. DR Proteomes; UP000002494; Chromosome 12. DR Bgee; ENSRNOG00000001300; Expressed in pancreas and 20 other cell types or tissues. DR ExpressionAtlas; P51577; baseline and differential. DR GO; GO:0045177; C:apical part of cell; ISO:RGD. DR GO; GO:0030424; C:axon; IDA:RGD. DR GO; GO:0044297; C:cell body; IDA:ARUK-UCL. DR GO; GO:0030054; C:cell junction; ISO:RGD. DR GO; GO:0009986; C:cell surface; IDA:RGD. DR GO; GO:0030425; C:dendrite; IDA:RGD. DR GO; GO:0043197; C:dendritic spine; IDA:RGD. DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO. DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; ISO:RGD. DR GO; GO:0043025; C:neuronal cell body; IDA:RGD. DR GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; IDA:SynGO. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD. DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL. DR GO; GO:0098839; C:postsynaptic density membrane; IDA:SynGO. DR GO; GO:0043195; C:terminal bouton; IDA:RGD. DR GO; GO:0005524; F:ATP binding; IDA:RGD. DR GO; GO:0035381; F:ATP-gated ion channel activity; IDA:UniProtKB. DR GO; GO:0045296; F:cadherin binding; ISO:RGD. DR GO; GO:0005507; F:copper ion binding; IDA: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:IntAct. DR GO; GO:0099604; F:ligand-gated calcium channel activity; IMP:ARUK-UCL. DR GO; GO:0099094; F:ligand-gated monoatomic cation channel activity; ISO:RGD. DR GO; GO:0001614; F:purinergic nucleotide receptor activity; IDA:BHF-UCL. DR GO; GO:0005102; F:signaling receptor binding; IPI:BHF-UCL. DR GO; GO:0008270; F:zinc ion binding; IDA:BHF-UCL. DR GO; GO:0097190; P:apoptotic signaling pathway; ISO:RGD. DR GO; GO:0048266; P:behavioral response to pain; IMP:ARUK-UCL. DR GO; GO:0070588; P:calcium ion transmembrane transport; IDA:UniProtKB. DR GO; GO:0006816; P:calcium ion transport; ISO:RGD. DR GO; GO:0071318; P:cellular response to ATP; IDA:UniProtKB. DR GO; GO:0071294; P:cellular response to zinc ion; IDA:UniProtKB. DR GO; GO:0060079; P:excitatory postsynaptic potential; ISO:RGD. DR GO; GO:0051899; P:membrane depolarization; ISO:RGD. DR GO; GO:0006812; P:monoatomic cation transport; IDA:RGD. DR GO; GO:0034220; P:monoatomic ion transmembrane transport; ISO:RGD. DR GO; GO:0010614; P:negative regulation of cardiac muscle hypertrophy; ISO:RGD. DR GO; GO:0019228; P:neuronal action potential; IDA:RGD. DR GO; GO:0006809; P:nitric oxide biosynthetic process; ISO:RGD. DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:RGD. DR GO; GO:0010524; P:positive regulation of calcium ion transport into cytosol; ISO:RGD. DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; ISO:RGD. DR GO; GO:2001028; P:positive regulation of endothelial cell chemotaxis; ISO:RGD. DR GO; GO:1904141; P:positive regulation of microglial cell migration; IMP:ARUK-UCL. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:ARUK-UCL. DR GO; GO:0035590; P:purinergic nucleotide receptor signaling pathway; ISO:RGD. DR GO; GO:0008217; P:regulation of blood pressure; ISO:RGD. DR GO; GO:0055117; P:regulation of cardiac muscle contraction; ISO:RGD. DR GO; GO:0050920; P:regulation of chemotaxis; IMP:ARUK-UCL. DR GO; GO:0002028; P:regulation of sodium ion transport; IDA:BHF-UCL. DR GO; GO:0055119; P:relaxation of cardiac muscle; ISO:RGD. DR GO; GO:0033198; P:response to ATP; ISO:RGD. DR GO; GO:0048678; P:response to axon injury; IMP:ARUK-UCL. DR GO; GO:0034405; P:response to fluid shear stress; ISO:RGD. DR GO; GO:0002931; P:response to ischemia; IMP:ARUK-UCL. DR GO; GO:0019233; P:sensory perception of pain; IMP:ARUK-UCL. DR GO; GO:0050975; P:sensory perception of touch; IMP:ARUK-UCL. DR GO; GO:0007165; P:signal transduction; ISO:RGD. DR GO; GO:0042311; P:vasodilation; ISO:RGD. DR FunFam; 1.10.287.940:FF:000001; P2X purinoceptor; 1. DR FunFam; 2.60.490.10:FF:000001; P2X purinoceptor; 1. DR FunFam; 1.10.287.940:FF:000010; P2X receptor E; 1. 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 IDEAL; IID50123; -. DR InterPro; IPR003047; P2X4_purnocptor. DR InterPro; IPR027309; P2X_extracellular_dom_sf. DR InterPro; IPR001429; P2X_purnocptor. DR InterPro; IPR059116; P2X_receptor. DR InterPro; IPR053792; P2X_RECEPTOR_CS. 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 PDBsum; 2BP5; -. DR PDBsum; 2RUP; -. PE 1: Evidence at protein level; KW 3D-structure; ATP-binding; Cell membrane; Disulfide bond; Glycoprotein; KW Ion channel; Ion transport; Ligand-gated ion channel; Lysosome; Membrane; KW Nucleotide-binding; Receptor; Reference proteome; Transmembrane; KW Transmembrane helix; Transport. FT CHAIN 1..388 FT /note="P2X purinoceptor 4" FT /id="PRO_0000161554" FT TOPO_DOM 1..33 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:F8W463" FT TRANSMEM 34..54 FT /note="Helical; Name=1" FT /evidence="ECO:0000250|UniProtKB:F8W463" FT TOPO_DOM 55..338 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:F8W463" FT TRANSMEM 339..359 FT /note="Helical; Name=2" FT /evidence="ECO:0000250|UniProtKB:F8W463" FT TOPO_DOM 360..388 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:F8W463" FT BINDING 67 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:F8W463" FT BINDING 67 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /evidence="ECO:0000250|UniProtKB:F8W463" FT BINDING 69 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:F8W463" FT BINDING 69 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /evidence="ECO:0000250|UniProtKB:F8W463" FT BINDING 186 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:F8W463" FT BINDING 186 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /evidence="ECO:0000250|UniProtKB:F8W463" FT BINDING 188 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:F8W463" FT BINDING 293 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:F8W463" FT BINDING 293 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /evidence="ECO:0000250|UniProtKB:F8W463" FT BINDING 295 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:F8W463" FT BINDING 295 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /evidence="ECO:0000250|UniProtKB:F8W463" FT BINDING 313 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:F8W463" FT BINDING 313 FT /ligand="CTP" FT /ligand_id="ChEBI:CHEBI:37563" FT /evidence="ECO:0000250|UniProtKB:F8W463" 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:0000255" 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:0000269|PubMed:25662851, FT ECO:0007744|PDB:2RUP" FT DISULFID 126..149 FT /evidence="ECO:0000269|PubMed:25662851, FT ECO:0007744|PDB:2RUP" FT DISULFID 132..159 FT /evidence="ECO:0000269|PubMed:25662851, FT ECO:0007744|PDB:2RUP" FT DISULFID 217..227 FT /evidence="ECO:0000250|UniProtKB:F8W463" FT DISULFID 261..270 FT /evidence="ECO:0000250|UniProtKB:F8W463" FT MUTAGEN 67 FT /note="K->A: Decreased cation transport." FT /evidence="ECO:0000269|PubMed:24817123" FT MUTAGEN 140 FT /note="H->A: Exhibits about 2.5-fold reduced ATP affinity FT and 14-fold reduced CTP affinity." FT /evidence="ECO:0000269|PubMed:28332633" FT MUTAGEN 140 FT /note="H->R: Exhibits about 2-fold reduced both ATP FT affinity and CTP affinity." FT /evidence="ECO:0000269|PubMed:28332633" FT MUTAGEN 186 FT /note="T->A,V: Abolishes ATP- and CTP-evoked current." FT /evidence="ECO:0000269|PubMed:28332633" FT MUTAGEN 186 FT /note="T->S: Does not affect ATP- and CTP-evoked current. FT Reduced ATP affinity. Does not affect CTP affinity." FT /evidence="ECO:0000269|PubMed:28332633" FT MUTAGEN 214 FT /note="L->A: Markedly reduced sensitivity to ATP." FT /evidence="ECO:0000269|PubMed:24762105" FT MUTAGEN 249 FT /note="E->K: Restores antagonism by PPADS." FT /evidence="ECO:0000269|PubMed:8598206" FT MUTAGEN 341 FT /note="S->W: Decreased cation transport." FT /evidence="ECO:0000269|PubMed:24817123" FT MUTAGEN 372 FT /note="Y->A: Complete loss of receptor functionality." FT /evidence="ECO:0000269|PubMed:15985462" FT CONFLICT 136..137 FT /note="SV -> LR (in Ref. 1; AAC52380)" FT /evidence="ECO:0000305" FT CONFLICT 237 FT /note="E -> G (in Ref. 4; CAA61037)" FT /evidence="ECO:0000305" FT CONFLICT 305 FT /note="G -> A (in Ref. 2; CAA62607)" FT /evidence="ECO:0000305" FT STRAND 114..117 FT /evidence="ECO:0007829|PDB:2RUP" FT HELIX 118..120 FT /evidence="ECO:0007829|PDB:2RUP" FT TURN 129..131 FT /evidence="ECO:0007829|PDB:2RUP" FT TURN 139..142 FT /evidence="ECO:0007829|PDB:2RUP" FT STRAND 143..150 FT /evidence="ECO:0007829|PDB:2RUP" FT STRAND 153..155 FT /evidence="ECO:0007829|PDB:2RUP" FT STRAND 158..163 FT /evidence="ECO:0007829|PDB:2RUP" FT STRAND 379..381 FT /evidence="ECO:0007829|PDB:2BP5" SQ SEQUENCE 388 AA; 43501 MW; C7B0FC9A94EF8D9A CRC64; MAGCCSVLGS FLFEYDTPRI VLIRSRKVGL MNRAVQLLIL AYVIGWVFVW EKGYQETDSV VSSVTTKAKG VAVTNTSQLG FRIWDVADYV IPAQEENSLF IMTNMIVTVN QTQSTCPEIP DKTSICNSDA DCTPGSVDTH SSGVATGRCV PFNESVKTCE VAAWCPVEND VGVPTPAFLK AAENFTLLVK NNIWYPKFNF SKRNILPNIT TSYLKSCIYN AQTDPFCPIF RLGTIVEDAG HSFQEMAVEG GIMGIQIKWD CNLDRAASLC LPRYSFRRLD TRDLEHNVSP GYNFRFAKYY RDLAGKEQRT LTKAYGIRFD IIVFGKAGKF DIIPTMINVG SGLALLGVAT VLCDVIVLYC MKKKYYYRDK KYKYVEDYEQ GLSGEMNQ //