AT1A1_RAT
ID AT1A1_RAT Reviewed; 1023 AA.
AC P06685; Q64609;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 03-AUG-2022, entry version 217.
DE RecName: Full=Sodium/potassium-transporting ATPase subunit alpha-1;
DE Short=Na(+)/K(+) ATPase alpha-1 subunit;
DE EC=7.2.2.13 {ECO:0000269|PubMed:17939993, ECO:0000269|PubMed:30388404};
DE AltName: Full=Sodium pump subunit alpha-1;
DE Flags: Precursor;
GN Name=Atp1a1;
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 TISSUE=Brain, and Kidney;
RX PubMed=3028470; DOI=10.1021/bi00373a001;
RA Shull G.E., Greeb J., Lingrel J.B.;
RT "Molecular cloning of three distinct forms of the Na+,K+-ATPase alpha-
RT subunit from rat brain.";
RL Biochemistry 25:8125-8132(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=2822682; DOI=10.1093/oxfordjournals.jbchem.a122039;
RA Hara Y., Urayama O., Kawakami K., Nojima H., Nagamune H., Kojima T.,
RA Ohta T., Nagano K., Nakao M.;
RT "Primary structures of two types of alpha-subunit of rat brain Na+,K+,-
RT ATPase deduced from cDNA sequences.";
RL J. Biochem. 102:43-58(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2822726; DOI=10.1083/jcb.105.4.1855;
RA Herrera V.L.M., Emanuel J.R., Ruiz-Opazo N., Levenson R., Nadal-Ginard B.;
RT "Three differentially expressed Na,K-ATPase alpha subunit isoforms:
RT structural and functional implications.";
RL J. Cell Biol. 105:1855-1865(1987).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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 PROTEIN SEQUENCE OF 157-162; 597-605; 630-647; 662-671 AND 744-773, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (JUL-2007) to UniProtKB.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 489-533.
RC TISSUE=Brain;
RX PubMed=2994074; DOI=10.1073/pnas.82.18.6357;
RA Schneider J.W., Mercer R.W., Caplan M., Emanuel J.R., Sweadner K.J.,
RA Benz E.J. Jr., Levenson R.;
RT "Molecular cloning of rat brain Na,K-ATPase alpha-subunit cDNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:6357-6361(1985).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-41.
RX PubMed=2166579; DOI=10.1016/0167-4781(90)90099-n;
RA Yagawa Y., Kawakami K., Nagano K.;
RT "Cloning and analysis of the 5'-flanking region of rat Na+/K(+)-ATPase
RT alpha 1 subunit gene.";
RL Biochim. Biophys. Acta 1049:286-292(1990).
RN [8]
RP PHOSPHORYLATION BY CAMP-DEPENDENT KINASE.
RX PubMed=7510709; DOI=10.1016/s0021-9258(17)37117-x;
RA Fisone G., Cheng S.X.-J., Nairn A.C., Czernik A.J., Hemmings H.C. Jr.,
RA Hoeoeg J.-O., Bertorello A.M., Kaiser R., Bergman T., Joernvall H.,
RA Aperia A., Greengard P.;
RT "Identification of the phosphorylation site for cAMP-dependent protein
RT kinase on Na+,K(+)-ATPase and effects of site-directed mutagenesis.";
RL J. Biol. Chem. 269:9368-9373(1994).
RN [9]
RP PHOSPHORYLATION AT SER-23 AND SER-943.
RX PubMed=9435504; DOI=10.1152/ajpcell.1997.273.6.c1981;
RA Cheng X.J., Hoeoeg J.O., Nairn A.C., Greengard P., Aperia A.;
RT "Regulation of rat Na(+)-K(+)-ATPase activity by PKC is modulated by state
RT of phosphorylation of Ser-943 by PKA.";
RL Am. J. Physiol. 273:C1981-C1986(1997).
RN [10]
RP PHOSPHORYLATION AT TYR-10.
RX PubMed=10473631; DOI=10.1091/mbc.10.9.2847;
RA Feraille E., Carranza M.L., Gonin S., Beguin P., Pedemonte C.,
RA Rousselot M., Caverzasio J., Geering K., Martin P.Y., Favre H.;
RT "Insulin-induced stimulation of Na+,K(+)-ATPase activity in kidney proximal
RT tubule cells depends on phosphorylation of the alpha-subunit at Tyr-10.";
RL Mol. Biol. Cell 10:2847-2859(1999).
RN [11]
RP PROTEIN SEQUENCE OF N-TERMINUS, AND PHOSPHORYLATION AT SER-16 AND SER-23 BY
RP PROTEIN KINASE C.
RX PubMed=7775468; DOI=10.1074/jbc.270.23.14072;
RA Feschenko M.S., Sweadner K.J.;
RT "Structural basis for species-specific differences in the phosphorylation
RT of Na,K-ATPase by protein kinase C.";
RL J. Biol. Chem. 270:14072-14077(1995).
RN [12]
RP BINDING SITE FOR PHOSPHOINOSITIDE-3 KINASE, AND MUTAGENESIS OF SER-16 AND
RP PRO-83.
RX PubMed=10823893; DOI=10.1073/pnas.100128297;
RA Yudowski G.A., Efendiev R., Pedemonte C.H., Katz A.I., Berggren P.-O.,
RA Bertorello A.M.;
RT "Phosphoinositide-3 kinase binds to a proline-rich motif in the Na+, K+-
RT ATPase alpha subunit and regulates its trafficking.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:6556-6561(2000).
RN [13]
RP INTERACTION WITH FXYD3.
RX PubMed=15743908; DOI=10.1091/mbc.e04-10-0878;
RA Crambert G., Li C., Claeys D., Geering K.;
RT "FXYD3 (Mat-8), a new regulator of Na,K-ATPase.";
RL Mol. Biol. Cell 16:2363-2371(2005).
RN [14]
RP INTERACTION WITH FXYD1.
RX PubMed=17283221; DOI=10.1096/fj.06-7269com;
RA Pavlovic D., Fuller W., Shattock M.J.;
RT "The intracellular region of FXYD1 is sufficient to regulate cardiac Na/K
RT ATPase.";
RL FASEB J. 21:1539-1546(2007).
RN [15]
RP PHOSPHORYLATION, DEPHOSPHORYLATION, INTERACTION WITH SIK1, AND CATALYTIC
RP ACTIVITY.
RX PubMed=17939993; DOI=10.1073/pnas.0706838104;
RA Sjostrom M., Stenstrom K., Eneling K., Zwiller J., Katz A.I., Takemori H.,
RA Bertorello A.M.;
RT "SIK1 is part of a cell sodium-sensing network that regulates active sodium
RT transport through a calcium-dependent process.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:16922-16927(2007).
RN [16]
RP INTERACTION WITH FXYD1.
RX PubMed=19339511; DOI=10.1152/ajpcell.00523.2008;
RA Fuller W., Howie J., McLatchie L.M., Weber R.J., Hastie C.J., Burness K.,
RA Pavlovic D., Shattock M.J.;
RT "FXYD1 phosphorylation in vitro and in adult rat cardiac myocytes:
RT threonine 69 is a novel substrate for protein kinase C.";
RL Am. J. Physiol. 296:C1346-C1355(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-40; SER-47; SER-228; SER-452
RP AND SER-484, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [18]
RP INTERACTION WITH FXYD1.
RX PubMed=23532852; DOI=10.1074/jbc.m113.460956;
RA Wypijewski K.J., Howie J., Reilly L., Tulloch L.B., Aughton K.L.,
RA McLatchie L.M., Shattock M.J., Calaghan S.C., Fuller W.;
RT "A separate pool of cardiac phospholemman that does not regulate or
RT associate with the sodium pump: multimers of phospholemman in ventricular
RT muscle.";
RL J. Biol. Chem. 288:13808-13820(2013).
RN [19]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=29499166; DOI=10.1016/j.ajhg.2018.01.023;
RA Lassuthova P., Rebelo A.P., Ravenscroft G., Lamont P.J., Davis M.R.,
RA Manganelli F., Feely S.M., Bacon C., Brozkova D.S., Haberlova J.,
RA Mazanec R., Tao F., Saghira C., Abreu L., Courel S., Powell E., Buglo E.,
RA Bis D.M., Baxter M.F., Ong R.W., Marns L., Lee Y.C., Bai Y., Isom D.G.,
RA Barro-Soria R., Chung K.W., Scherer S.S., Larsson H.P., Laing N.G.,
RA Choi B.O., Seeman P., Shy M.E., Santoro L., Zuchner S.;
RT "Mutations in ATP1A1 Cause Dominant Charcot-Marie-Tooth Type 2.";
RL Am. J. Hum. Genet. 102:505-514(2018).
RN [20]
RP MUTAGENESIS OF LEU-302; GLY-303 AND MET-859, FUNCTION, AND CATALYTIC
RP ACTIVITY.
RX PubMed=30388404; DOI=10.1016/j.ajhg.2018.10.004;
RA Schlingmann K.P., Bandulik S., Mammen C., Tarailo-Graovac M., Holm R.,
RA Baumann M., Koenig J., Lee J.J.Y., Droegemoeller B., Imminger K.,
RA Beck B.B., Altmueller J., Thiele H., Waldegger S., Van't Hoff W., Kleta R.,
RA Warth R., van Karnebeek C.D.M., Vilsen B., Bockenhauer D., Konrad M.;
RT "Germline de novo mutations in ATP1A1 cause renal hypomagnesemia,
RT refractory seizures, and intellectual disability.";
RL Am. J. Hum. Genet. 103:808-816(2018).
RN [21]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLU-314.
RX PubMed=16914892; DOI=10.1159/000095169;
RA Lerner M., Lemke D., Bertram H., Schillers H., Oberleithner H.,
RA Caplan M.J., Reinhardt J.;
RT "An extracellular loop of the human non-gastric H,K-ATPase alpha-subunit is
RT involved in apical plasma membrane polarization.";
RL Cell. Physiol. Biochem. 18:75-84(2006).
RN [22]
RP STRUCTURE BY NMR OF 383-595 ALONE AND IN COMPLEX WITH ATP, AND ATP-BINDING
RP SITE.
RX PubMed=12730684; DOI=10.1038/nsb924;
RA Hilge M., Siegal G., Vuister G.W., Guntert P., Gloor S.M., Abrahams J.P.;
RT "ATP-induced conformational changes of the nucleotide-binding domain of
RT Na,K-ATPase.";
RL Nat. Struct. Biol. 10:468-474(2003).
CC -!- FUNCTION: This is the catalytic component of the active enzyme, which
CC catalyzes the hydrolysis of ATP coupled with the exchange of sodium and
CC potassium ions across the plasma membrane. This action creates the
CC electrochemical gradient of sodium and potassium ions, providing the
CC energy for active transport of various nutrients.
CC {ECO:0000269|PubMed:30388404}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + K(+)(out) + Na(+)(in) = ADP + H(+) + K(+)(in) +
CC Na(+)(out) + phosphate; Xref=Rhea:RHEA:18353, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29101, ChEBI:CHEBI:29103,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216;
CC EC=7.2.2.13; Evidence={ECO:0000269|PubMed:17939993,
CC ECO:0000269|PubMed:30388404};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:18354;
CC Evidence={ECO:0000269|PubMed:30388404};
CC -!- SUBUNIT: The sodium/potassium-transporting ATPase is composed of a
CC catalytic alpha subunit, an auxiliary non-catalytic beta subunit and an
CC additional regulatory subunit. Interacts with regulatory subunit FXYD1
CC (PubMed:17283221, PubMed:19339511, PubMed:23532852). Interacts with
CC regulatory subunit FXYD3 (PubMed:15743908). Interacts with SLC35G1 and
CC STIM1 (By similarity). Interacts with SIK1 (PubMed:17939993). Interacts
CC with CLN3; this interaction regulates the sodium/potassium-transporting
CC ATPase complex localization at the plasma membrane (By similarity).
CC {ECO:0000250|UniProtKB:P05023, ECO:0000269|PubMed:15743908,
CC ECO:0000269|PubMed:17283221, ECO:0000269|PubMed:17939993,
CC ECO:0000269|PubMed:19339511, ECO:0000269|PubMed:23532852}.
CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane
CC {ECO:0000269|PubMed:16914892}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane, sarcolemma
CC {ECO:0000250|UniProtKB:P05023}; Multi-pass membrane protein
CC {ECO:0000255}. Cell projection, axon {ECO:0000269|PubMed:29499166}.
CC Melanosome {ECO:0000250|UniProtKB:P05023}.
CC -!- TISSUE SPECIFICITY: Expressed in the central nervous system, in most
CC motor and sensory axons of the ventral and dorsal roots, as well as in
CC the large motor neurons of the ventral horn (at protein level).
CC {ECO:0000269|PubMed:29499166}.
CC -!- PTM: Phosphorylation on Tyr-10 modulates pumping activity.
CC Phosphorylation of Ser-943 by PKA modulates the response of ATP1A1 to
CC PKC. Dephosphorylation by protein phosphatase 2A (PP2A) following
CC increases in intracellular sodium, leading to increase catalytic
CC activity. {ECO:0000269|PubMed:10473631, ECO:0000269|PubMed:17939993,
CC ECO:0000269|PubMed:7510709, ECO:0000269|PubMed:7775468,
CC ECO:0000269|PubMed:9435504}.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3)
CC family. Type IIC subfamily. {ECO:0000305}.
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DR EMBL; M14511; AAA40775.1; -; mRNA.
DR EMBL; X05882; CAA29306.1; -; mRNA.
DR EMBL; M28647; AAA41671.1; -; mRNA.
DR EMBL; BC061968; AAH61968.1; -; mRNA.
DR EMBL; M11733; AAA40783.1; -; mRNA.
DR EMBL; X53233; CAA37325.1; -; Genomic_DNA.
DR EMBL; X53234; CAA37326.1; -; Genomic_DNA.
DR PIR; A24639; A24639.
DR RefSeq; NP_036636.1; NM_012504.1.
DR PDB; 1MO7; NMR; -; A=386-595.
DR PDB; 1MO8; NMR; -; A=386-595.
DR PDBsum; 1MO7; -.
DR PDBsum; 1MO8; -.
DR AlphaFoldDB; P06685; -.
DR BMRB; P06685; -.
DR SMR; P06685; -.
DR BioGRID; 246399; 19.
DR ELM; P06685; -.
DR IntAct; P06685; 7.
DR MINT; P06685; -.
DR STRING; 10116.ENSRNOP00000045650; -.
DR BindingDB; P06685; -.
DR ChEMBL; CHEMBL3010; -.
DR DrugCentral; P06685; -.
DR iPTMnet; P06685; -.
DR PhosphoSitePlus; P06685; -.
DR jPOST; P06685; -.
DR PaxDb; P06685; -.
DR PRIDE; P06685; -.
DR Ensembl; ENSRNOT00000040430; ENSRNOP00000045650; ENSRNOG00000030019.
DR GeneID; 24211; -.
DR KEGG; rno:24211; -.
DR UCSC; RGD:2167; rat.
DR CTD; 476; -.
DR RGD; 2167; Atp1a1.
DR eggNOG; KOG0203; Eukaryota.
DR GeneTree; ENSGT00940000154840; -.
DR HOGENOM; CLU_002360_3_0_1; -.
DR InParanoid; P06685; -.
DR OMA; CYIAYSV; -.
DR OrthoDB; 100699at2759; -.
DR PhylomeDB; P06685; -.
DR Reactome; R-RNO-5578775; Ion homeostasis.
DR Reactome; R-RNO-936837; Ion transport by P-type ATPases.
DR SABIO-RK; P06685; -.
DR EvolutionaryTrace; P06685; -.
DR PRO; PR:P06685; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000030019; Expressed in kidney and 20 other tissues.
DR Genevisible; P06685; RN.
DR GO; GO:0016324; C:apical plasma membrane; ISO:RGD.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0016323; C:basolateral plasma membrane; IMP:UniProtKB.
DR GO; GO:0005901; C:caveola; IDA:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:BHF-UCL.
DR GO; GO:0005768; C:endosome; IDA:RGD.
DR GO; GO:0005794; C:Golgi apparatus; IDA:BHF-UCL.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0014704; C:intercalated disc; IDA:BHF-UCL.
DR GO; GO:0016328; C:lateral plasma membrane; ISO:RGD.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IDA:ARUK-UCL.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0031090; C:organelle membrane; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0014069; C:postsynaptic density; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0042383; C:sarcolemma; IDA:BHF-UCL.
DR GO; GO:0005890; C:sodium:potassium-exchanging ATPase complex; IDA:ARUK-UCL.
DR GO; GO:0036126; C:sperm flagellum; ISO:RGD.
DR GO; GO:0030315; C:T-tubule; IDA:BHF-UCL.
DR GO; GO:0043531; F:ADP binding; IDA:RGD.
DR GO; GO:0030506; F:ankyrin binding; IPI:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IDA:BHF-UCL.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0019829; F:ATPase-coupled cation transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0051087; F:chaperone binding; IDA:BHF-UCL.
DR GO; GO:0005391; F:P-type sodium:potassium-exchanging transporter activity; IDA:UniProtKB.
DR GO; GO:0016791; F:phosphatase activity; ISO:RGD.
DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; IPI:RGD.
DR GO; GO:0030955; F:potassium ion binding; IDA:BHF-UCL.
DR GO; GO:0019904; F:protein domain specific binding; IPI:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:ARUK-UCL.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0031402; F:sodium ion binding; IDA:RGD.
DR GO; GO:1990239; F:steroid hormone binding; ISO:RGD.
DR GO; GO:0060048; P:cardiac muscle contraction; TAS:BHF-UCL.
DR GO; GO:0030007; P:cellular potassium ion homeostasis; ISO:RGD.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IDA:RGD.
DR GO; GO:0071383; P:cellular response to steroid hormone stimulus; ISO:RGD.
DR GO; GO:0006883; P:cellular sodium ion homeostasis; ISO:RGD.
DR GO; GO:0015988; P:energy coupled proton transmembrane transport, against electrochemical gradient; TAS:RGD.
DR GO; GO:0010248; P:establishment or maintenance of transmembrane electrochemical gradient; IC:BHF-UCL.
DR GO; GO:0060081; P:membrane hyperpolarization; IMP:RGD.
DR GO; GO:0086009; P:membrane repolarization; ISO:RGD.
DR GO; GO:0031947; P:negative regulation of glucocorticoid biosynthetic process; ISO:RGD.
DR GO; GO:0045822; P:negative regulation of heart contraction; ISO:RGD.
DR GO; GO:0045823; P:positive regulation of heart contraction; ISO:RGD.
DR GO; GO:0045989; P:positive regulation of striated muscle contraction; ISO:RGD.
DR GO; GO:1990573; P:potassium ion import across plasma membrane; IDA:BHF-UCL.
DR GO; GO:0006813; P:potassium ion transport; IDA:RGD.
DR GO; GO:1902600; P:proton transmembrane transport; IBA:GO_Central.
DR GO; GO:0008217; P:regulation of blood pressure; ISO:RGD.
DR GO; GO:0086004; P:regulation of cardiac muscle cell contraction; IMP:RGD.
DR GO; GO:0002028; P:regulation of sodium ion transport; IDA:UniProtKB.
DR GO; GO:0002026; P:regulation of the force of heart contraction; ISO:RGD.
DR GO; GO:0055119; P:relaxation of cardiac muscle; TAS:BHF-UCL.
DR GO; GO:1903416; P:response to glycoside; ISO:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:RGD.
DR GO; GO:0036376; P:sodium ion export across plasma membrane; IDA:BHF-UCL.
DR GO; GO:0006814; P:sodium ion transport; IDA:RGD.
DR GO; GO:0055085; P:transmembrane transport; IDA:BHF-UCL.
DR CDD; cd02608; P-type_ATPase_Na-K_like; 1.
DR Gene3D; 3.40.1110.10; -; 1.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR006068; ATPase_P-typ_cation-transptr_C.
DR InterPro; IPR004014; ATPase_P-typ_cation-transptr_N.
DR InterPro; IPR023299; ATPase_P-typ_cyto_dom_N.
DR InterPro; IPR018303; ATPase_P-typ_P_site.
DR InterPro; IPR023298; ATPase_P-typ_TM_dom_sf.
DR InterPro; IPR008250; ATPase_P-typ_transduc_dom_A_sf.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR005775; P-type_ATPase_IIC.
DR InterPro; IPR001757; P_typ_ATPase.
DR InterPro; IPR044492; P_typ_ATPase_HD_dom.
DR Pfam; PF00689; Cation_ATPase_C; 1.
DR Pfam; PF00690; Cation_ATPase_N; 1.
DR SFLD; SFLDF00027; p-type_atpase; 1.
DR SMART; SM00831; Cation_ATPase_N; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR SUPFAM; SSF81653; SSF81653; 1.
DR SUPFAM; SSF81660; SSF81660; 1.
DR SUPFAM; SSF81665; SSF81665; 1.
DR TIGRFAMs; TIGR01106; ATPase-IIC_X-K; 1.
DR TIGRFAMs; TIGR01494; ATPase_P-type; 2.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Cell membrane; Cell projection;
KW Direct protein sequencing; Ion transport; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Potassium;
KW Potassium transport; Reference proteome; Sodium; Sodium transport;
KW Sodium/potassium transport; Translocase; Transmembrane;
KW Transmembrane helix; Transport.
FT PROPEP 1..5
FT /evidence="ECO:0000269|PubMed:7775468"
FT /id="PRO_0000002489"
FT CHAIN 6..1023
FT /note="Sodium/potassium-transporting ATPase subunit alpha-
FT 1"
FT /id="PRO_0000002490"
FT TOPO_DOM 6..87
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 88..108
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 109..131
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 132..152
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 153..288
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 289..308
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 309..320
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 321..338
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 339..772
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 773..792
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 793..802
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 803..823
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 824..843
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 844..866
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 867..918
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 919..938
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 939..951
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 952..970
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 971..985
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 986..1006
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1007..1023
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..38
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 82..84
FT /note="Phosphoinositide-3 kinase binding"
FT REGION 216..235
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 376
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250"
FT BINDING 487
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:12730684"
FT BINDING 717
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 721
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT MOD_RES 9
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8VDN2"
FT MOD_RES 10
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:10473631"
FT MOD_RES 16
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000269|PubMed:7775468"
FT MOD_RES 21
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8VDN2"
FT MOD_RES 23
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000269|PubMed:7775468,
FT ECO:0000269|PubMed:9435504"
FT MOD_RES 40
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 47
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 228
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 260
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q8VDN2"
FT MOD_RES 452
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 484
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 542
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P05023"
FT MOD_RES 661
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8VDN2"
FT MOD_RES 668
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VDN2"
FT MOD_RES 675
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VDN2"
FT MOD_RES 943
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:9435504"
FT MUTAGEN 16
FT /note="S->A: Dopamine fails to increase phosphoinositide-3
FT kinase activity and to promote its interaction with
FT Na(+)/K(+) ATPase."
FT /evidence="ECO:0000269|PubMed:10823893"
FT MUTAGEN 83
FT /note="P->R: Dopamine fails to increase phosphoinositide-3
FT kinase activity and to promote its interaction with
FT Na(+)/K(+) ATPase."
FT /evidence="ECO:0000269|PubMed:10823893"
FT MUTAGEN 302
FT /note="L->R: Results in altered sodium and potassium
FT transport."
FT /evidence="ECO:0000269|PubMed:30388404"
FT MUTAGEN 303
FT /note="G->R: Results in altered sodium and potassium
FT transport."
FT /evidence="ECO:0000269|PubMed:30388404"
FT MUTAGEN 314
FT /note="E->K: Abolishes targeting to the basolateral plasma
FT membrane."
FT /evidence="ECO:0000269|PubMed:16914892"
FT MUTAGEN 859
FT /note="M->R: Results in altered sodium and potassium
FT transport."
FT /evidence="ECO:0000269|PubMed:30388404"
FT CONFLICT 68..69
FT /note="AA -> PV (in Ref. 3; AAA41671)"
FT /evidence="ECO:0000305"
FT CONFLICT 175
FT /note="G -> E (in Ref. 3; AAA41671)"
FT /evidence="ECO:0000305"
FT CONFLICT 188
FT /note="G -> V (in Ref. 3; AAA41671)"
FT /evidence="ECO:0000305"
FT CONFLICT 335
FT /note="G -> V (in Ref. 3; AAA41671)"
FT /evidence="ECO:0000305"
FT STRAND 394..396
FT /evidence="ECO:0007829|PDB:1MO7"
FT STRAND 403..405
FT /evidence="ECO:0007829|PDB:1MO7"
FT HELIX 416..427
FT /evidence="ECO:0007829|PDB:1MO7"
FT STRAND 431..435
FT /evidence="ECO:0007829|PDB:1MO7"
FT STRAND 438..440
FT /evidence="ECO:0007829|PDB:1MO7"
FT HELIX 442..444
FT /evidence="ECO:0007829|PDB:1MO8"
FT STRAND 447..449
FT /evidence="ECO:0007829|PDB:1MO7"
FT TURN 451..453
FT /evidence="ECO:0007829|PDB:1MO7"
FT HELIX 454..461
FT /evidence="ECO:0007829|PDB:1MO7"
FT TURN 462..464
FT /evidence="ECO:0007829|PDB:1MO7"
FT HELIX 467..473
FT /evidence="ECO:0007829|PDB:1MO7"
FT STRAND 478..480
FT /evidence="ECO:0007829|PDB:1MO7"
FT TURN 483..485
FT /evidence="ECO:0007829|PDB:1MO8"
FT STRAND 489..494
FT /evidence="ECO:0007829|PDB:1MO7"
FT STRAND 496..500
FT /evidence="ECO:0007829|PDB:1MO7"
FT STRAND 502..509
FT /evidence="ECO:0007829|PDB:1MO7"
FT HELIX 511..515
FT /evidence="ECO:0007829|PDB:1MO7"
FT STRAND 518..521
FT /evidence="ECO:0007829|PDB:1MO7"
FT STRAND 526..529
FT /evidence="ECO:0007829|PDB:1MO8"
FT HELIX 532..546
FT /evidence="ECO:0007829|PDB:1MO7"
FT STRAND 556..558
FT /evidence="ECO:0007829|PDB:1MO8"
FT TURN 562..564
FT /evidence="ECO:0007829|PDB:1MO7"
FT TURN 572..574
FT /evidence="ECO:0007829|PDB:1MO7"
SQ SEQUENCE 1023 AA; 113054 MW; 85E98233EE6C18E9 CRC64;
MGKGVGRDKY EPAAVSEHGD KKSKKAKKER DMDELKKEVS MDDHKLSLDE LHRKYGTDLS
RGLTPARAAE ILARDGPNAL TPPPTTPEWV KFCRQLFGGF SMLLWIGAIL CFLAYGIRSA
TEEEPPNDDL YLGVVLSAVV IITGCFSYYQ EAKSSKIMES FKNMVPQQAL VIRNGEKMSI
NAEDVVVGDL VEVKGGDRIP ADLRIISANG CKVDNSSLTG ESEPQTRSPD FTNENPLETR
NIAFFSTNCV EGTARGIVVY TGDRTVMGRI ATLASGLEGG QTPIAEEIEH FIHLITGVAV
FLGVSFFILS LILEYTWLEA VIFLIGIIVA NVPEGLLATV TVCLTLTAKR MARKNCLVKN
LEAVETLGST STICSDKTGT LTQNRMTVAH MWFDNQIHEA DTTENQSGVS FDKTSATWFA
LSRIAGLCNR AVFQANQENL PILKRAVAGD ASESALLKCI EVCCGSVMEM REKYTKIVEI
PFNSTNKYQL SIHKNPNASE PKHLLVMKGA PERILDRCSS ILLHGKEQPL DEELKDAFQN
AYLELGGLGE RVLGFCHLLL PDEQFPEGFQ FDTDEVNFPV DNLCFVGLIS MIDPPRAAVP
DAVGKCRSAG IKVIMVTGDH PITAKAIAKG VGIISEGNET VEDIAARLNI PVNQVNPRDA
KACVVHGSDL KDMTSEELDD ILRYHTEIVF ARTSPQQKLI IVEGCQRQGA IVAVTGDGVN
DSPALKKADI GVAMGIVGSD VSKQAADMIL LDDNFASIVT GVEEGRLIFD NLKKSIAYTL
TSNIPEITPF LIFIIANIPL PLGTVTILCI DLGTDMVPAI SLAYEQAESD IMKRQPRNPK
TDKLVNERLI SMAYGQIGMI QALGGFFTYF VILAENGFLP FHLLGIRETW DDRWINDVED
SYGQQWTYEQ RKIVEFTCHT AFFVSIVVVQ WADLVICKTR RNSVFQQGMK NKILIFGLFE
ETALAAFLSY CPGMGAALRM YPLKPTWWFC AFPYSLLIFV YDEVRKLIIR RRPGGWVEKE
TYY
