P2RX6_HUMAN
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 03-AUG-2022, entry version 186.
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; 62.
DR IntAct; O15547; 4.
DR STRING; 9606.ENSP00000416193; -.
DR BindingDB; O15547; -.
DR ChEMBL; CHEMBL2670; -.
DR DrugBank; DB01069; Promethazine.
DR GlyGen; O15547; 4 sites, 1 O-linked glycan (1 site).
DR iPTMnet; O15547; -.
DR PhosphoSitePlus; O15547; -.
DR BioMuta; P2RX6; -.
DR jPOST; O15547; -.
DR PaxDb; O15547; -.
DR PeptideAtlas; O15547; -.
DR PRIDE; O15547; -.
DR Antibodypedia; 8429; 159 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 CTD; 9127; -.
DR DisGeNET; 9127; -.
DR GeneCards; P2RX6; -.
DR HGNC; HGNC:8538; P2RX6.
DR HPA; ENSG00000099957; Group enriched (brain, 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; WPPQGEN; -.
DR OrthoDB; 1128763at2759; -.
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 1067 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 tissues.
DR ExpressionAtlas; O15547; baseline and differential.
DR Genevisible; O15547; HS.
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:0005639; C:integral component of nuclear inner membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0099060; C:integral component of postsynaptic specialization membrane; 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; TAS:Reactome.
DR GO; GO:0014069; C:postsynaptic density; 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 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: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; 2.60.490.10; -; 1.
DR InterPro; IPR003049; P2X6_purnocptor.
DR InterPro; IPR027309; P2X_extracellular_dom_sf.
DR InterPro; IPR001429; P2X_purnocptor.
DR PANTHER; PTHR10125:SF21; PTHR10125:SF21; 1.
DR PIRSF; PIRSF005713; P2X_purinoceptor; 1.
DR PRINTS; PR01313; P2X6RECEPTOR.
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; 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
