P2RX4_RAT
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 03-AUG-2022, entry version 161.
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].
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 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 [8]
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 [9]
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 [10] {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).
CC -!- FUNCTION: Receptor for extracellularly released ATP acting as a ligand-
CC gated ion channel that plays multiple role in immunity and central
CC nervous system physiology (PubMed:15985462, PubMed:24762105). Plays a
CC key role in initial steps of T-cell activation and Ca(2+) microdomain
CC formation (By similarity). Participates also in basal T-cell activity
CC without TCR/CD3 stimulation (By similarity). Promotes the
CC differentiation and activation of Th17 cells via expression of retinoic
CC acid-related orphan receptor C/RORC (By similarity). Upon activation,
CC drives microglia motility via the PI3K/Akt pathway (PubMed:12917686).
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:8598206}.
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 (By similarity). Interacts with
CC AP1M2 (PubMed:15985462). {ECO:0000250}.
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: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}.
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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_113782.1; NM_031594.1.
DR PDB; 2BP5; X-ray; 2.80 A; P=375-384.
DR PDB; 2RUP; NMR; -; A=111-167.
DR PDBsum; 2BP5; -.
DR PDBsum; 2RUP; -.
DR AlphaFoldDB; P51577; -.
DR BMRB; P51577; -.
DR SMR; P51577; -.
DR BioGRID; 248281; 2.
DR DIP; DIP-48411N; -.
DR IntAct; P51577; 2.
DR MINT; P51577; -.
DR STRING; 10116.ENSRNOP00000001752; -.
DR BindingDB; P51577; -.
DR ChEMBL; CHEMBL2818; -.
DR DrugCentral; P51577; -.
DR GuidetoPHARMACOLOGY; 481; -.
DR GlyGen; P51577; 6 sites.
DR PhosphoSitePlus; P51577; -.
DR PaxDb; P51577; -.
DR PRIDE; P51577; -.
DR Ensembl; ENSRNOT00000001752; ENSRNOP00000001752; ENSRNOG00000001300.
DR GeneID; 29659; -.
DR KEGG; rno:29659; -.
DR UCSC; RGD:62073; rat.
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; QGYCPEL; -.
DR OrthoDB; 1128763at2759; -.
DR PhylomeDB; P51577; -.
DR TreeFam; TF328633; -.
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 tissues.
DR Genevisible; P51577; RN.
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:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0043197; C:dendritic spine; IDA:RGD.
DR GO; GO:0005639; C:integral component of nuclear inner membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IMP:UniProtKB.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0014069; C:postsynaptic density; IDA:RGD.
DR GO; GO:0045202; C:synapse; IDA:RGD.
DR GO; GO:0043195; C:terminal bouton; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IDA:RGD.
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 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: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:0098662; P:inorganic cation transmembrane transport; IDA:RGD.
DR GO; GO:0034220; P:ion transmembrane transport; ISO:RGD.
DR GO; GO:0051899; P:membrane depolarization; 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 protein kinase B signaling; 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 Gene3D; 2.60.490.10; -; 1.
DR IDEAL; IID50123; -.
DR InterPro; IPR003047; P2X4_purnocptor.
DR InterPro; IPR027309; P2X_extracellular_dom_sf.
DR InterPro; IPR001429; P2X_purnocptor.
DR PIRSF; PIRSF005713; P2X_purinoceptor; 1.
DR PRINTS; PR01311; P2X4RECEPTOR.
DR PRINTS; PR01307; P2XRECEPTOR.
DR TIGRFAMs; TIGR00863; P2X; 1.
DR PROSITE; PS01212; P2X_RECEPTOR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Disulfide bond; Glycoprotein; Ion channel;
KW Ion transport; Ligand-gated ion channel; Membrane; Receptor;
KW Reference proteome; Transmembrane; 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: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: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"
FT DISULFID 261..270
FT /evidence="ECO:0000250"
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 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 TURN 129..131
FT /evidence="ECO:0007829|PDB:2RUP"
FT TURN 139..141
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
