P2RX4_MOUSE
ID P2RX4_MOUSE Reviewed; 388 AA.
AC Q9JJX6; Q9JJX3; Q9JJX4; Q9JJX5;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 25-MAY-2022, entry version 132.
DE RecName: Full=P2X purinoceptor 4;
DE Short=P2X4;
DE AltName: Full=ATP receptor;
DE AltName: Full=Purinergic receptor;
GN Name=P2rx4; Synonyms=P2x4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B; C AND D).
RA Simon J., Michel A.D., Chessell I.P., Kidd E.J., Jones C.A., Barnard E.A.,
RA Humphrey P.P.;
RT "Alternatively spliced variants of the mouse P2X4 receptor: cloning and
RT characterisation.";
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION.
RX PubMed=17299767; DOI=10.1002/glia.20489;
RA Ohsawa K., Irino Y., Nakamura Y., Akazawa C., Inoue K., Kohsaka S.;
RT "Involvement of P2X4 and P2Y12 receptors in ATP-induced microglial
RT chemotaxis.";
RL Glia 55:604-616(2007).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP INTERACTION WITH P2X7, FUNCTION, AND DISRUPTION PHENOTYPE.
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 [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION BY ATP.
RX PubMed=35119925; DOI=10.1126/sciadv.abl9770;
RA Brock V.J., Wolf I.M.A., Er-Lukowiak M., Lory N., Staehler T., Woelk L.M.,
RA Mittruecker H.W., Mueller C.E., Koch-Nolte F., Rissiek B., Werner R.,
RA Guse A.H., Diercks B.P.;
RT "P2X4 and P2X7 are essential players in basal T cell activity and Ca2+
RT signaling milliseconds after T cell activation.";
RL Sci. Adv. 8:eabl9770-eabl9770(2022).
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:26456657, PubMed:35119925). Plays a
CC key role in initial steps of T-cell activation and Ca(2+) microdomain
CC formation (PubMed:35119925). Participates also in basal T-cell activity
CC without TCR/CD3 stimulation (PubMed:35119925). 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:17299767).
CC {ECO:0000250|UniProtKB:Q99571, ECO:0000269|PubMed:17299767,
CC ECO:0000269|PubMed:26456657, ECO:0000269|PubMed:35119925}.
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 -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q99571}; Multi-
CC pass membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=a; Synonyms=P2X4a;
CC IsoId=Q9JJX6-1; Sequence=Displayed;
CC Name=b; Synonyms=P2X4b;
CC IsoId=Q9JJX6-2; Sequence=VSP_022023;
CC Name=c; Synonyms=P2X4c;
CC IsoId=Q9JJX6-3; Sequence=VSP_022024;
CC Name=d; Synonyms=P2X4d;
CC IsoId=Q9JJX6-4; Sequence=VSP_022023, VSP_022024;
CC -!- INDUCTION: By immediate ATP release following TCR stimulation
CC (PubMed:35119925). {ECO:0000269|PubMed:35119925}.
CC -!- DISRUPTION PHENOTYPE: Mutant T-cells show decreased Ca(2+) microdomains
CC directly in the initial period after TCR stimulation (PubMed:35119925).
CC In macrophages, an attenuation of P2X7-induced cell death is observed
CC correlated with altered cleavage of caspase-1/CASP1 and a decrease in
CC IL-1beta production (PubMed:26456657). {ECO:0000269|PubMed:26456657,
CC ECO:0000269|PubMed:35119925}.
CC -!- SIMILARITY: Belongs to the P2X receptor family. {ECO:0000305}.
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DR EMBL; AJ251459; CAB90749.1; -; mRNA.
DR EMBL; AJ251460; CAB90750.1; -; mRNA.
DR EMBL; AJ251461; CAB90751.1; -; mRNA.
DR EMBL; AJ251462; CAB90752.1; -; mRNA.
DR CCDS; CCDS19654.2; -. [Q9JJX6-1]
DR CCDS; CCDS80392.1; -. [Q9JJX6-3]
DR CCDS; CCDS80393.1; -. [Q9JJX6-2]
DR AlphaFoldDB; Q9JJX6; -.
DR SMR; Q9JJX6; -.
DR STRING; 10090.ENSMUSP00000031429; -.
DR BindingDB; Q9JJX6; -.
DR ChEMBL; CHEMBL2176849; -.
DR DrugCentral; Q9JJX6; -.
DR GuidetoPHARMACOLOGY; 481; -.
DR GlyConnect; 2572; 2 N-Linked glycans (2 sites).
DR GlyGen; Q9JJX6; 7 sites, 2 N-linked glycans (2 sites).
DR iPTMnet; Q9JJX6; -.
DR PhosphoSitePlus; Q9JJX6; -.
DR SwissPalm; Q9JJX6; -.
DR jPOST; Q9JJX6; -.
DR MaxQB; Q9JJX6; -.
DR PaxDb; Q9JJX6; -.
DR PeptideAtlas; Q9JJX6; -.
DR PRIDE; Q9JJX6; -.
DR ProteomicsDB; 294289; -. [Q9JJX6-1]
DR ProteomicsDB; 294290; -. [Q9JJX6-2]
DR ProteomicsDB; 294291; -. [Q9JJX6-3]
DR ProteomicsDB; 294292; -. [Q9JJX6-4]
DR MGI; MGI:1338859; P2rx4.
DR eggNOG; ENOG502QSUI; Eukaryota.
DR InParanoid; Q9JJX6; -.
DR PhylomeDB; Q9JJX6; -.
DR Reactome; R-MMU-139853; Elevation of cytosolic Ca2+ levels.
DR Reactome; R-MMU-418346; Platelet homeostasis.
DR PRO; PR:Q9JJX6; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9JJX6; protein.
DR GO; GO:0045177; C:apical part of cell; IDA:MGI.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0044297; C:cell body; ISO:MGI.
DR GO; GO:0030054; C:cell junction; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0043197; C:dendritic spine; ISO:MGI.
DR GO; GO:0005639; C:integral component of nuclear inner membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; ISO:MGI.
DR GO; GO:0045202; C:synapse; ISO:MGI.
DR GO; GO:0043195; C:terminal bouton; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0045296; F:cadherin binding; ISO:MGI.
DR GO; GO:0005507; F:copper ion binding; ISO:MGI.
DR GO; GO:0004931; F:extracellularly ATP-gated cation channel activity; IMP:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0099604; F:ligand-gated calcium channel activity; ISO:MGI.
DR GO; GO:0001614; F:purinergic nucleotide receptor activity; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; ISO:MGI.
DR GO; GO:0097190; P:apoptotic signaling pathway; ISO:MGI.
DR GO; GO:0048266; P:behavioral response to pain; ISO:MGI.
DR GO; GO:0070588; P:calcium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:0006816; P:calcium ion transport; IMP:MGI.
DR GO; GO:0071318; P:cellular response to ATP; ISS:UniProtKB.
DR GO; GO:0071294; P:cellular response to zinc ion; ISS:UniProtKB.
DR GO; GO:0060079; P:excitatory postsynaptic potential; IMP:MGI.
DR GO; GO:0098662; P:inorganic cation transmembrane transport; ISO:MGI.
DR GO; GO:0034220; P:ion transmembrane transport; ISO:MGI.
DR GO; GO:0051899; P:membrane depolarization; ISO:MGI.
DR GO; GO:0010614; P:negative regulation of cardiac muscle hypertrophy; ISO:MGI.
DR GO; GO:0019228; P:neuronal action potential; ISO:MGI.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; IDA:MGI.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:MGI.
DR GO; GO:0010524; P:positive regulation of calcium ion transport into cytosol; ISO:MGI.
DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; ISO:MGI.
DR GO; GO:2001028; P:positive regulation of endothelial cell chemotaxis; ISO:MGI.
DR GO; GO:1904141; P:positive regulation of microglial cell migration; ISO:MGI.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:MGI.
DR GO; GO:0035590; P:purinergic nucleotide receptor signaling pathway; ISO:MGI.
DR GO; GO:0008217; P:regulation of blood pressure; ISO:MGI.
DR GO; GO:0055117; P:regulation of cardiac muscle contraction; ISO:MGI.
DR GO; GO:0050920; P:regulation of chemotaxis; ISO:MGI.
DR GO; GO:0002028; P:regulation of sodium ion transport; ISO:MGI.
DR GO; GO:0055119; P:relaxation of cardiac muscle; ISO:MGI.
DR GO; GO:0033198; P:response to ATP; ISO:MGI.
DR GO; GO:0048678; P:response to axon injury; ISO:MGI.
DR GO; GO:0034405; P:response to fluid shear stress; ISO:MGI.
DR GO; GO:0002931; P:response to ischemia; ISO:MGI.
DR GO; GO:0019233; P:sensory perception of pain; ISO:MGI.
DR GO; GO:0050975; P:sensory perception of touch; ISO:MGI.
DR GO; GO:0007165; P:signal transduction; ISO:MGI.
DR GO; GO:0042311; P:vasodilation; IMP:MGI.
DR Gene3D; 2.60.490.10; -; 1.
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 Alternative splicing; 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_0000269194"
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 131
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: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 176..202
FT /note="Missing (in isoform b and isoform d)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_022023"
FT VAR_SEQ 328..349
FT /note="Missing (in isoform c and isoform d)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_022024"
SQ SEQUENCE 388 AA; 43438 MW; 4F388F006DB6DF45 CRC64;
MAGCCSVLGS FLFEYDTPRI VLIRSRKVGL MNRVVQLLIL AYVIGWVFVW EKGYQETDSV
VSSVTTKAKG VAVTNTSQLG FRIWDVADYV VPAQEENSLF IMTNMIVTVN QTQGTCPEIP
DKTSICDSDA NCTLGSSDTH SSGIGTGRCV PFNASVKTCE VAAWCPVEND AGVPTPAFLK
AAENFTLLVK NNIWYPKFNF SKRNILPNIT TSYLKSCIYN ARTDPFCPIF RLGQIVADAG
HSFQEMAVEG GIMGIQIKWD CNLDRAASHC LPRYSFRRLD TRDLEHNVSP GYNFRFAKYY
RDLAGNEQRT LTKAYGIRFD IIVFGKAGKF DIIPTMINVG SGLALLGVAT VLCDVIVLYC
MKKRYYYRDK KYKYVEDYEQ GLSGEMNQ
