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 27-MAR-2024, entry version 226. 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 (PubMed:30388404). CC Could also be part of an osmosensory signaling pathway that senses CC body-fluid sodium levels and controls salt intake behavior as well as CC voluntary water intake to regulate sodium homeostasis (By similarity). CC {ECO:0000250|UniProtKB:Q8VDN2, 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 Interacts with SCN7A; activates ATP1A1 P-type sodium:potassium- CC exchanging transporter activity which indirectly signals to nearby CC neurons to regulate sodium homeostasis (By similarity). CC {ECO:0000250|UniProtKB:P05023, ECO:0000250|UniProtKB:Q8VDN2, CC ECO:0000269|PubMed:15743908, ECO:0000269|PubMed:17283221, CC ECO:0000269|PubMed:17939993, ECO:0000269|PubMed:19339511, CC ECO:0000269|PubMed:23532852}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8VDN2}; CC Multi-pass membrane protein {ECO:0000255}. 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}. 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; 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 GlyGen; P06685; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P06685; -. DR PhosphoSitePlus; P06685; -. DR jPOST; P06685; -. DR PaxDb; 10116-ENSRNOP00000045650; -. DR Ensembl; ENSRNOT00000040430.5; ENSRNOP00000045650.4; ENSRNOG00000030019.5. DR Ensembl; ENSRNOT00055033788; ENSRNOP00055027434; ENSRNOG00055019753. DR Ensembl; ENSRNOT00060049314; ENSRNOP00060041161; ENSRNOG00060028283. DR Ensembl; ENSRNOT00065051454; ENSRNOP00065042372; ENSRNOG00065029722. DR GeneID; 24211; -. DR KEGG; rno:24211; -. DR UCSC; RGD:2167; rat. DR AGR; RGD:2167; -. 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 OrthoDB; 203629at2759; -. 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 cell types or tissues. 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: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: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: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:0051087; F:protein-folding chaperone binding; IDA:BHF-UCL. 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: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: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:0060047; P:heart contraction; ISO:RGD. DR GO; GO:0030007; P:intracellular potassium ion homeostasis; ISO:RGD. DR GO; GO:0006883; P:intracellular sodium ion homeostasis; ISO:RGD. 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; Calcium-transporting ATPase, cytoplasmic domain N; 1. DR Gene3D; 2.70.150.10; Calcium-transporting ATPase, cytoplasmic transduction domain A; 1. DR Gene3D; 1.20.1110.10; Calcium-transporting ATPase, transmembrane domain; 1. DR Gene3D; 3.40.50.1000; HAD superfamily/HAD-like; 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 NCBIfam; TIGR01106; ATPase-IIC_X-K; 1. DR NCBIfam; TIGR01494; ATPase_P-type; 2. DR PANTHER; PTHR43294; SODIUM/POTASSIUM-TRANSPORTING ATPASE SUBUNIT ALPHA; 1. DR PANTHER; PTHR43294:SF9; SODIUM_POTASSIUM-TRANSPORTING ATPASE SUBUNIT ALPHA-1; 1. DR Pfam; PF13246; Cation_ATPase; 1. DR Pfam; PF00689; Cation_ATPase_C; 1. DR Pfam; PF00690; Cation_ATPase_N; 1. DR Pfam; PF00122; E1-E2_ATPase; 1. DR PRINTS; PR00119; CATATPASE. DR PRINTS; PR00121; NAKATPASE. DR SFLD; SFLDS00003; Haloacid_Dehalogenase; 1. DR SFLD; SFLDF00027; p-type_atpase; 1. DR SMART; SM00831; Cation_ATPase_N; 1. DR SUPFAM; SSF81653; Calcium ATPase, transduction domain A; 1. DR SUPFAM; SSF81665; Calcium ATPase, transmembrane domain M; 1. DR SUPFAM; SSF56784; HAD-like; 1. DR SUPFAM; SSF81660; Metal cation-transporting ATPase, ATP-binding domain N; 1. DR PROSITE; PS00154; ATPASE_E1_E2; 1. DR Genevisible; P06685; RN. 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 REGION 596..717 FT /note="Mediates interaction with SCN7A" FT /evidence="ECO:0000250|UniProtKB:Q8VDN2" 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 //