P2XA_DICDI
ID P2XA_DICDI Reviewed; 378 AA.
AC Q86JM7; Q55A88;
DT 15-DEC-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=P2X receptor A;
DE Short=DdP2X;
DE Short=P2XA;
GN Name=p2xA; ORFNames=DDB_G0272004;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, ACTIVITY
RP REGULATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF LYS-67; LYS-289 AND
RP ASP-330.
RX PubMed=17625565; DOI=10.1038/nature05926;
RA Fountain S.J., Parkinson K., Young M.T., Cao L., Thompson C.R.L.,
RA North R.A.;
RT "An intracellular P2X receptor required for osmoregulation in Dictyostelium
RT discoideum.";
RL Nature 448:200-203(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=12097910; DOI=10.1038/nature00847;
RA Gloeckner G., Eichinger L., Szafranski K., Pachebat J.A., Bankier A.T.,
RA Dear P.H., Lehmann R., Baumgart C., Parra G., Abril J.F., Guigo R.,
RA Kumpf K., Tunggal B., Cox E.C., Quail M.A., Platzer M., Rosenthal A.,
RA Noegel A.A.;
RT "Sequence and analysis of chromosome 2 of Dictyostelium discoideum.";
RL Nature 418:79-85(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18486207; DOI=10.1016/j.ceca.2008.04.001;
RA Ludlow M.J., Traynor D., Fisher P.R., Ennion S.J.;
RT "Purinergic-mediated Ca2+ influx in Dictyostelium discoideum.";
RL Cell Calcium 44:567-579(2008).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=19833731; DOI=10.1074/jbc.m109.045674;
RA Ludlow M.J., Durai L., Ennion S.J.;
RT "Functional characterization of intracellular Dictyostelium discoideum P2X
RT receptors.";
RL J. Biol. Chem. 284:35227-35239(2009).
CC -!- FUNCTION: P2X receptors are ATP-gated ion channels that play a role in
CC intracellular calcium signaling. Not required for the purinergic
CC response to extracellular nucleotides. Inward currents evoked by
CC intracellular ATP and ATP analogs. Exclusively selective for ATP over
CC other nucleotides. Insensitive to P2 receptor antagonists PPADS,
CC suramin and 2',3'-O-(2,4,6-trinitrophenyl)-ATP but inhibited by
CC nanomolar concentrations of copper and sodium ion. More permeable to
CC ammonium than either sodium or potassium ions and less permeable to
CC choline. It has been reported that p2xA is not essential for
CC osmoregulation (PubMed:19833731), however this information is in
CC contradiction with another source (PubMed:17625565) which indicates
CC that p2xA is required for osmoregulation. Found to be permeable to
CC chloride ions. Inhibited by copper and sodium ions.
CC {ECO:0000269|PubMed:17625565, ECO:0000269|PubMed:18486207,
CC ECO:0000269|PubMed:19833731}.
CC -!- SUBCELLULAR LOCATION: Contractile vacuole membrane
CC {ECO:0000269|PubMed:17625565, ECO:0000269|PubMed:19833731}. Note=Ligand
CC binding domain within the lumen of the vacuole.
CC -!- DISRUPTION PHENOTYPE: Response to extracellular ATP remains the same in
CC p2xA null strains. p2xA null cells have been reported to have
CC compromised contractile vacuoles and defective osmoregulation, and
CC exhibit cell swelling (PubMed:17625565). This is contradictory to other
CC reports (PubMed:19833731). Quintuple p2xA/p2xB/p2XC/p2xd/p2xE null
CC cells exhibit a slight delay in their osmoregulatory response, but are
CC ultimately still capable of regulating their cell volume in water.
CC Extracellular purinergic response to ATP persists in the quintuple null
CC cells with no alteration in the kinetics of the response, but the
CC magnitude of the response is lower. Responses to the calmodulin
CC antagonist calmidazolium are reduced and intracellular calcium
CC signaling is disrupted in quintuple null cells. The presence of copper
CC prevents both wild type and quintuple null cells from undergoing an
CC osmoregulatory decrease in cell volume. The quintuple null strains grow
CC slightly slower than wild type in shaking axenic cultures.
CC {ECO:0000269|PubMed:17625565, ECO:0000269|PubMed:18486207,
CC ECO:0000269|PubMed:19833731}.
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; EU047552; ABS88293.1; -; mRNA.
DR EMBL; AAFI02000007; EAL71436.1; -; Genomic_DNA.
DR RefSeq; XP_645378.1; XM_640286.1.
DR AlphaFoldDB; Q86JM7; -.
DR STRING; 44689.DDB0238349; -.
DR TCDB; 1.A.7.2.1; the atp-gated p2x receptor cation channel (p2x receptor) family.
DR PaxDb; Q86JM7; -.
DR EnsemblProtists; EAL71436; EAL71436; DDB_G0272004.
DR GeneID; 8618267; -.
DR KEGG; ddi:DDB_G0272004; -.
DR dictyBase; DDB_G0272004; p2xA.
DR eggNOG; ENOG502RE1D; Eukaryota.
DR HOGENOM; CLU_060033_0_0_1; -.
DR InParanoid; Q86JM7; -.
DR OMA; YWDENLV; -.
DR PhylomeDB; Q86JM7; -.
DR Reactome; R-DDI-139853; Elevation of cytosolic Ca2+ levels.
DR Reactome; R-DDI-418346; Platelet homeostasis.
DR Reactome; R-DDI-6798695; Neutrophil degranulation.
DR Reactome; R-DDI-844456; The NLRP3 inflammasome.
DR PRO; PR:Q86JM7; -.
DR Proteomes; UP000002195; Chromosome 2.
DR GO; GO:0031164; C:contractile vacuolar membrane; IDA:dictyBase.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005524; F:ATP binding; IDA:dictyBase.
DR GO; GO:0035381; F:ATP-gated ion channel activity; IBA:GO_Central.
DR GO; GO:0140417; F:ATP-sensitive calcium-release channel activity; IMP:dictyBase.
DR GO; GO:0015276; F:ligand-gated ion channel activity; IDA:dictyBase.
DR GO; GO:0031267; F:small GTPase binding; IPI:dictyBase.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IMP:dictyBase.
DR GO; GO:0071476; P:cellular hypotonic response; IGI:dictyBase.
DR GO; GO:0009992; P:cellular water homeostasis; IMP:dictyBase.
DR GO; GO:0070177; P:contractile vacuole discharge; IMP:dictyBase.
DR GO; GO:0140025; P:contractile vacuole tethering involved in discharge; IMP:dictyBase.
DR GO; GO:0006971; P:hypotonic response; IMP:dictyBase.
DR GO; GO:0006811; P:ion transport; IDA:dictyBase.
DR GO; GO:0034260; P:negative regulation of GTPase activity; IDA:dictyBase.
DR GO; GO:0031340; P:positive regulation of vesicle fusion; IDA:dictyBase.
DR GO; GO:0035590; P:purinergic nucleotide receptor signaling pathway; IMP:dictyBase.
DR GO; GO:0050848; P:regulation of calcium-mediated signaling; IGI:dictyBase.
PE 1: Evidence at protein level;
KW Ion channel; Ion transport; Ligand-gated ion channel; Membrane; Receptor;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport; Vacuole.
FT CHAIN 1..378
FT /note="P2X receptor A"
FT /id="PRO_0000390408"
FT TOPO_DOM 1..27
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 28..48
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 49..307
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 308..328
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 329..378
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 290..303
FT /note="Pore-forming motif"
FT /evidence="ECO:0000255"
FT MUTAGEN 67
FT /note="K->A: More than ten-fold decrease in ATP
FT sensitivity."
FT /evidence="ECO:0000269|PubMed:17625565"
FT MUTAGEN 289
FT /note="K->A: ATP elicits smaller currents."
FT /evidence="ECO:0000269|PubMed:17625565"
FT MUTAGEN 330
FT /note="D->A: Loss of function."
FT /evidence="ECO:0000269|PubMed:17625565"
SQ SEQUENCE 378 AA; 42186 MW; 1DCBD07B25093094 CRC64;
MGFSFDWDDI FQYSTVKIVR IRDRRLGILH LSFLVGIVAY IVVYSAIIKK GYLFTEVPIG
SVRTSLKGPN TFASNLTYCS NQQHNGSTYP FTPLECNYWD EQLALFPVGQ DSTFTCTTRV
RLSKQEANCN FTDPTCKFVD EPGSAKNIYI ADIESFTILI DHTMYASSSG SQFNAVDLHG
YILNQDGDEV QIDANGTSIG VSGKPDIMTI GQLLSFGGVS LDQASPVDSN VSIRYDGVVL
FVFITYSNTY TYSTSDFKYV YSVQQIANTI YDVPETIILE SIHSRLLYKR HGIRVIFIQT
GTIGSFHFQT LLLTLVSGLG LLAVATTVVD QLAIRLLPQR KSYSSLKFQV TESMSNPMKK
RITTDEGEDV LYTRIEGL
