ID   P2RX6_HUMAN             Reviewed;         441 AA.
AC   O15547; F6V3D7; Q32MB6; Q58F04; Q6IC33; Q9UL50;
DT   15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT   02-NOV-2010, sequence version 2.
DT   24-JAN-2024, entry version 194.
DE   RecName: Full=P2X purinoceptor 6;
DE            Short=P2X6;
DE   AltName: Full=ATP receptor;
DE   AltName: Full=P2XM;
DE   AltName: Full=Purinergic receptor;
DE   AltName: Full=Purinergic receptor P2X-like 1;
GN   Name=P2RX6; Synonyms=P2RXL1, P2X6;
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 [GENOMIC DNA / MRNA] (ISOFORM 1).
RX   PubMed=9242461;
RA   Urano T., Nishimori H., Han H., Furuhata T., Kimura Y., Nakamura Y.,
RA   Tokino T.;
RT   "Cloning of P2XM, a novel human P2X receptor gene regulated by p53.";
RL   Cancer Res. 57:3281-3287(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX   PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA   Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA   Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA   Beare D.M., Dunham I.;
RT   "A genome annotation-driven approach to cloning the human ORFeome.";
RL   Genome Biol. 5:R84.1-R84.11(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=10591208; DOI=10.1038/990031;
RA   Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA   Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA   Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA   Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA   Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA   Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA   Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA   Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA   Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA   Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA   Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA   Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA   Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA   Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA   Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA   Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA   Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA   Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA   Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA   Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA   Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA   Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA   Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA   Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA   Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA   Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA   Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA   Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA   Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA   Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA   Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA   Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA   Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA   McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA   Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA   Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA   Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA   Wright H.;
RT   "The DNA sequence of human chromosome 22.";
RL   Nature 402:489-495(1999).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE
RP   [LARGE SCALE MRNA] OF 6-441 (ISOFORM 1), AND VARIANT HIS-242.
RC   TISSUE=Brain;
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   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 5-441 (ISOFORM 1).
RC   TISSUE=Skeletal muscle;
RA   Cheng X., Jin H., Huang C.-C.;
RT   "Cloning and tissue distribution of a human cDNA encoding P2X6
RT   purinoceptor.";
RL   Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   PHOSPHORYLATION AT TYR-64.
RX   PubMed=12112843;
RX   DOI=10.1002/1615-9861(200206)2:6<642::aid-prot642>3.0.co;2-i;
RA   Maguire P.B., Wynne K.J., Harney D.F., O'Donoghue N.M., Stephens G.,
RA   Fitzgerald D.J.;
RT   "Identification of the phosphotyrosine proteome from thrombin activated
RT   platelets.";
RL   Proteomics 2:642-648(2002).
RN   [7]
RP   SUBUNIT, AND GLYCOSYLATION.
RX   PubMed=15657042; DOI=10.1074/jbc.m412265200;
RA   Barrera N.P., Ormond S.J., Henderson R.M., Murrell-Lagnado R.D.,
RA   Edwardson J.M.;
RT   "Atomic force microscopy imaging demonstrates that P2X2 receptors are
RT   trimers but that P2X6 receptor subunits do not oligomerize.";
RL   J. Biol. Chem. 280:10759-10765(2005).
CC   -!- FUNCTION: Receptor for ATP that acts as a ligand-gated ion channel.
CC       {ECO:0000250}.
CC   -!- SUBUNIT: Unlike most P2XRs, P2RX6 does not seem to form homotrimers or
CC       heterotrimers. {ECO:0000269|PubMed:15657042}.
CC   -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=O15547-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=O15547-2; Sequence=VSP_044799;
CC   -!- TISSUE SPECIFICITY: Expressed predominantly in skeletal muscle.
CC   -!- PTM: N-glycosylated. {ECO:0000269|PubMed:15657042}.
CC   -!- SIMILARITY: Belongs to the P2X receptor family. {ECO:0000305}.
CC   -!- CAUTION: It is uncertain whether Met-1 or Met-11 is the initiator.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAF13303.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=AAF13303.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};
CC       Sequence=AAH33488.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=AAI09210.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=BAA22046.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC       Sequence=BAA22047.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=P2X receptor entry;
CC       URL="https://en.wikipedia.org/wiki/P2X_receptor";
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DR   EMBL; AB002059; BAA22047.1; ALT_INIT; Genomic_DNA.
DR   EMBL; AB002058; BAA22046.1; ALT_INIT; mRNA.
DR   EMBL; CR456535; CAG30421.1; -; mRNA.
DR   EMBL; AC002472; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC033488; AAH33488.1; ALT_INIT; mRNA.
DR   EMBL; BC109209; AAI09210.1; ALT_INIT; mRNA.
DR   EMBL; AF065385; AAF13303.1; ALT_SEQ; mRNA.
DR   CCDS; CCDS13788.2; -. [O15547-1]
DR   CCDS; CCDS54504.1; -. [O15547-2]
DR   RefSeq; NP_001153026.1; NM_001159554.1. [O15547-2]
DR   RefSeq; NP_005437.2; NM_005446.3. [O15547-1]
DR   AlphaFoldDB; O15547; -.
DR   SMR; O15547; -.
DR   BioGRID; 114575; 63.
DR   IntAct; O15547; 4.
DR   STRING; 9606.ENSP00000416193; -.
DR   BindingDB; O15547; -.
DR   ChEMBL; CHEMBL2670; -.
DR   DrugBank; DB01069; Promethazine.
DR   GlyCosmos; O15547; 3 sites, No reported glycans.
DR   GlyGen; O15547; 4 sites, 1 O-linked glycan (1 site).
DR   iPTMnet; O15547; -.
DR   PhosphoSitePlus; O15547; -.
DR   BioMuta; P2RX6; -.
DR   jPOST; O15547; -.
DR   MassIVE; O15547; -.
DR   PaxDb; 9606-ENSP00000416193; -.
DR   PeptideAtlas; O15547; -.
DR   Antibodypedia; 8429; 177 antibodies from 25 providers.
DR   DNASU; 9127; -.
DR   Ensembl; ENST00000401443.5; ENSP00000385309.1; ENSG00000099957.17. [O15547-2]
DR   Ensembl; ENST00000413302.7; ENSP00000416193.2; ENSG00000099957.17. [O15547-1]
DR   GeneID; 9127; -.
DR   KEGG; hsa:9127; -.
DR   MANE-Select; ENST00000413302.7; ENSP00000416193.2; NM_005446.5; NP_005437.2.
DR   UCSC; uc002ztz.3; human. [O15547-1]
DR   AGR; HGNC:8538; -.
DR   CTD; 9127; -.
DR   DisGeNET; 9127; -.
DR   GeneCards; P2RX6; -.
DR   HGNC; HGNC:8538; P2RX6.
DR   HPA; ENSG00000099957; Group enriched (skeletal muscle, tongue).
DR   MIM; 608077; gene.
DR   neXtProt; NX_O15547; -.
DR   OpenTargets; ENSG00000099957; -.
DR   PharmGKB; PA162398523; -.
DR   VEuPathDB; HostDB:ENSG00000099957; -.
DR   eggNOG; ENOG502R480; Eukaryota.
DR   GeneTree; ENSGT01020000230351; -.
DR   HOGENOM; CLU_034469_1_0_1; -.
DR   InParanoid; O15547; -.
DR   OMA; ATMVCDL; -.
DR   OrthoDB; 5312692at2759; -.
DR   PhylomeDB; O15547; -.
DR   TreeFam; TF328633; -.
DR   PathwayCommons; O15547; -.
DR   Reactome; R-HSA-139853; Elevation of cytosolic Ca2+ levels.
DR   Reactome; R-HSA-418346; Platelet homeostasis.
DR   SignaLink; O15547; -.
DR   BioGRID-ORCS; 9127; 21 hits in 1146 CRISPR screens.
DR   GeneWiki; P2RX6; -.
DR   GenomeRNAi; 9127; -.
DR   Pharos; O15547; Tchem.
DR   PRO; PR:O15547; -.
DR   Proteomes; UP000005640; Chromosome 22.
DR   RNAct; O15547; Protein.
DR   Bgee; ENSG00000099957; Expressed in gastrocnemius and 92 other cell types or tissues.
DR   ExpressionAtlas; O15547; baseline and differential.
DR   GO; GO:0030054; C:cell junction; IDA:BHF-UCL.
DR   GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR   GO; GO:0043197; C:dendritic spine; IEA:Ensembl.
DR   GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR   GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR   GO; GO:0098688; C:parallel fiber to Purkinje cell synapse; IEA:Ensembl.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0099634; C:postsynaptic specialization membrane; IEA:Ensembl.
DR   GO; GO:0043235; C:receptor complex; IDA:ARUK-UCL.
DR   GO; GO:0005524; F:ATP binding; NAS:BHF-UCL.
DR   GO; GO:0015267; F:channel activity; TAS:ProtInc.
DR   GO; GO:0004931; F:extracellularly ATP-gated monoatomic cation channel activity; IBA:GO_Central.
DR   GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR   GO; GO:0001614; F:purinergic nucleotide receptor activity; NAS:BHF-UCL.
DR   GO; GO:0004888; F:transmembrane signaling receptor activity; TAS:ProtInc.
DR   GO; GO:0070588; P:calcium ion transmembrane transport; IBA:GO_Central.
DR   GO; GO:0006936; P:muscle contraction; TAS:ProtInc.
DR   GO; GO:0033198; P:response to ATP; IEA:InterPro.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
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; IPR003049; P2X6_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:SF21; P2X PURINOCEPTOR 6; 1.
DR   Pfam; PF00864; P2X_receptor; 1.
DR   PIRSF; PIRSF005713; P2X_purinoceptor; 1.
DR   PRINTS; PR01313; P2X6RECEPTOR.
DR   PRINTS; PR01307; P2XRECEPTOR.
DR   PROSITE; PS01212; P2X_RECEPTOR; 1.
DR   Genevisible; O15547; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Disulfide bond; Glycoprotein; Ion channel;
KW   Ion transport; Ligand-gated ion channel; Membrane; Phosphoprotein;
KW   Receptor; Reference proteome; Transmembrane; Transmembrane helix;
KW   Transport.
FT   CHAIN           1..441
FT                   /note="P2X purinoceptor 6"
FT                   /id="PRO_0000161557"
FT   TOPO_DOM        11..39
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        40..60
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        61..333
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        334..354
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        355..441
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          410..441
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        411..441
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         64
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000269|PubMed:12112843"
FT   CARBOHYD        165
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        195
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        210
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        127..177
FT                   /evidence="ECO:0000250"
FT   DISULFID        138..161
FT                   /evidence="ECO:0000250"
FT   DISULFID        144..171
FT                   /evidence="ECO:0000250"
FT   DISULFID        228..238
FT                   /evidence="ECO:0000250"
FT   DISULFID        272..281
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         30..55
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_044799"
FT   VARIANT         38
FT                   /note="V -> G (in dbSNP:rs2006846)"
FT                   /id="VAR_057664"
FT   VARIANT         242
FT                   /note="R -> H (in dbSNP:rs2277838)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_020338"
FT   CONFLICT        393
FT                   /note="L -> F (in Ref. 5; AAF13303)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   441 AA;  48829 MW;  EFD45BDC81234A64 CRC64;
     MCPQLAGAGS MGSPGATTGW GLLDYKTEKY VMTRNWRVGA LQRLLQFGIV VYVVGWALLA
     KKGYQERDLE PQFSIITKLK GVSVTQIKEL GNRLWDVADF VKPPQGENVF FLVTNFLVTP
     AQVQGRCPEH PSVPLANCWV DEDCPEGEGG THSHGVKTGQ CVVFNGTHRT CEIWSWCPVE
     SGVVPSRPLL AQAQNFTLFI KNTVTFSKFN FSKSNALETW DPTYFKHCRY EPQFSPYCPV
     FRIGDLVAKA GGTFEDLALL GGSVGIRVHW DCDLDTGDSG CWPHYSFQLQ EKSYNFRTAT
     HWWEQPGVEA RTLLKLYGIR FDILVTGQAG KFGLIPTAVT LGTGAAWLGV VTFFCDLLLL
     YVDREAHFYW RTKYEEAKAP KATANSVWRE LALASQARLA ECLRRSSAPA PTATAAGSQT
     QTPGWPCPSS DTHLPTHSGS L
//