ID   AT1A3_RAT               Reviewed;        1013 AA.
AC   P06687; Q16732; Q9Z1G6;
DT   01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT   18-OCT-2001, sequence version 2.
DT   27-MAR-2024, entry version 210.
DE   RecName: Full=Sodium/potassium-transporting ATPase subunit alpha-3;
DE            Short=Na(+)/K(+) ATPase alpha-3 subunit;
DE            EC=7.2.2.13;
DE   AltName: Full=Na(+)/K(+) ATPase alpha(III) subunit;
DE   AltName: Full=Sodium pump subunit alpha-3;
GN   Name=Atp1a3;
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].
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] OF 1-930.
RC   TISSUE=Brain, and Liver;
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   PROTEIN SEQUENCE OF 58-64; 147-152; 246-254; 260-271; 425-434; 436-448;
RP   517-525; 587-595; 620-648; 734-763 AND 878-883, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RC   STRAIN=Sprague-Dawley; TISSUE=Brain;
RA   Lubec G., Kang S.U.;
RL   Submitted (JUL-2007) to UniProtKB.
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-37; SER-218 AND SER-442, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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   [6]
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).
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   -!- 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;
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       {ECO:0000269|PubMed:23532852}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane
CC       protein {ECO:0000250}.
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; M14513; AAA40777.1; -; mRNA.
DR   EMBL; X05883; CAA29307.1; -; mRNA.
DR   EMBL; M28648; AAA41672.1; -; mRNA.
DR   PIR; C24639; C24639.
DR   RefSeq; NP_036638.1; NM_012506.1.
DR   AlphaFoldDB; P06687; -.
DR   SMR; P06687; -.
DR   BioGRID; 246401; 10.
DR   IntAct; P06687; 4.
DR   MINT; P06687; -.
DR   STRING; 10116.ENSRNOP00000027497; -.
DR   BindingDB; P06687; -.
DR   ChEMBL; CHEMBL3885640; -.
DR   ChEMBL; CHEMBL4106149; -.
DR   CarbonylDB; P06687; -.
DR   iPTMnet; P06687; -.
DR   PhosphoSitePlus; P06687; -.
DR   jPOST; P06687; -.
DR   PaxDb; 10116-ENSRNOP00000027497; -.
DR   GeneID; 24213; -.
DR   KEGG; rno:24213; -.
DR   UCSC; RGD:2169; rat.
DR   AGR; RGD:2169; -.
DR   CTD; 478; -.
DR   RGD; 2169; Atp1a3.
DR   VEuPathDB; HostDB:ENSRNOG00000020263; -.
DR   eggNOG; KOG0203; Eukaryota.
DR   HOGENOM; CLU_002360_4_3_1; -.
DR   InParanoid; P06687; -.
DR   OrthoDB; 203629at2759; -.
DR   Reactome; R-RNO-5578775; Ion homeostasis.
DR   Reactome; R-RNO-936837; Ion transport by P-type ATPases.
DR   SABIO-RK; P06687; -.
DR   PRO; PR:P06687; -.
DR   Proteomes; UP000002494; Chromosome 1.
DR   Bgee; ENSRNOG00000020263; Expressed in cerebellum and 18 other cell types or tissues.
DR   GO; GO:0030424; C:axon; IDA:RGD.
DR   GO; GO:0044305; C:calyx of Held; IDA:SynGO.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:0044327; C:dendritic spine head; IDA:RGD.
DR   GO; GO:0044326; C:dendritic spine neck; IDA:RGD.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR   GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR   GO; GO:0016020; C:membrane; IDA:ARUK-UCL.
DR   GO; GO:0043209; C:myelin sheath; IDA:UniProtKB.
DR   GO; GO:0098984; C:neuron to neuron synapse; ISO:RGD.
DR   GO; GO:0043025; C:neuronal cell body; ISO:RGD.
DR   GO; GO:0005634; C:nucleus; ISO:RGD.
DR   GO; GO:0031090; C:organelle membrane; ISO:RGD.
DR   GO; GO:0001917; C:photoreceptor inner segment; ISO:RGD.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0098794; C:postsynapse; IDA:SynGO.
DR   GO; GO:0042734; C:presynaptic membrane; IDA:SynGO.
DR   GO; GO:0042383; C:sarcolemma; ISO:RGD.
DR   GO; GO:0005890; C:sodium:potassium-exchanging ATPase complex; IDA:RGD.
DR   GO; GO:0045202; C:synapse; IDA:UniProtKB.
DR   GO; GO:0001540; F:amyloid-beta binding; IDA:ARUK-UCL.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR   GO; GO:0031748; F:D1 dopamine receptor binding; IPI:RGD.
DR   GO; GO:0043395; F:heparan sulfate proteoglycan binding; ISO:RGD.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0005391; F:P-type sodium:potassium-exchanging transporter activity; ISS:UniProtKB.
DR   GO; GO:0086037; F:P-type sodium:potassium-exchanging transporter activity involved in regulation of cardiac muscle cell membrane potential; ISO:RGD.
DR   GO; GO:0051087; F:protein-folding chaperone binding; ISO:RGD.
DR   GO; GO:0008344; P:adult locomotory behavior; ISO:RGD.
DR   GO; GO:0060048; P:cardiac muscle contraction; ISO:RGD.
DR   GO; GO:1904646; P:cellular response to amyloid-beta; IDA:ARUK-UCL.
DR   GO; GO:0071300; P:cellular response to retinoic acid; IEP:RGD.
DR   GO; GO:0097067; P:cellular response to thyroid hormone stimulus; IEP:RGD.
DR   GO; GO:0021987; P:cerebral cortex development; IEP: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:0035235; P:ionotropic glutamate receptor signaling pathway; ISO:RGD.
DR   GO; GO:0007613; P:memory; ISO:RGD.
DR   GO; GO:1990535; P:neuron projection maintenance; ISO:RGD.
DR   GO; GO:1990573; P:potassium ion import across plasma membrane; ISO:RGD.
DR   GO; GO:0006813; P:potassium ion transport; IDA:RGD.
DR   GO; GO:1902600; P:proton transmembrane transport; IBA:GO_Central.
DR   GO; GO:0086036; P:regulation of cardiac muscle cell membrane potential; ISO:RGD.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; ISO:RGD.
DR   GO; GO:0036376; P:sodium ion export across plasma membrane; ISO:RGD.
DR   GO; GO:0006814; P:sodium ion transport; IDA:RGD.
DR   GO; GO:0008542; P:visual learning; ISO:RGD.
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:SF15; SODIUM_POTASSIUM-TRANSPORTING ATPASE SUBUNIT ALPHA-3; 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; SFLDG00002; C1.7:_P-type_atpase_like; 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; P06687; RN.
PE   1: Evidence at protein level;
KW   ATP-binding; Cell membrane; Direct protein sequencing; Ion transport;
KW   Magnesium; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW   Potassium; Potassium transport; Reference proteome; Sodium;
KW   Sodium transport; Sodium/potassium transport; Translocase; Transmembrane;
KW   Transmembrane helix; Transport.
FT   CHAIN           1..1013
FT                   /note="Sodium/potassium-transporting ATPase subunit alpha-
FT                   3"
FT                   /id="PRO_0000046300"
FT   TOPO_DOM        1..77
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        78..98
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        99..121
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        122..142
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        143..278
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        279..298
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        299..310
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        311..328
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        329..762
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        763..782
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        783..792
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        793..813
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        814..833
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        834..856
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        857..908
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        909..928
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        929..941
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        942..960
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        961..975
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        976..996
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        997..1013
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          1..24
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          72..74
FT                   /note="Interaction with phosphoinositide-3 kinase"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        366
FT                   /note="4-aspartylphosphate intermediate"
FT                   /evidence="ECO:0000250"
FT   BINDING         707
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   BINDING         711
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         37
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         56
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q6PIC6"
FT   MOD_RES         218
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         265
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q6PIC6"
FT   MOD_RES         442
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MOD_RES         548
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:Q6PIC6"
FT   MOD_RES         933
FT                   /note="Phosphoserine; by PKA"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        1..3
FT                   /note="MGD -> MNL (in Ref. 3; AAA41672)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        104
FT                   /note="A -> R (in Ref. 3; AAA41672)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        114
FT                   /note="D -> E (in Ref. 3; AAA41672)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        128
FT                   /note="A -> G (in Ref. 3; AAA41672)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        149
FT                   /note="E -> Q (in Ref. 3; AAA41672)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        152
FT                   /note="K -> T (in Ref. 3; AAA41672)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        166
FT                   /note="E -> D (in Ref. 3; AAA41672)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        192..194
FT                   /note="DLR -> ELG (in Ref. 3; AAA41672)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        200
FT                   /note="G -> R (in Ref. 3; AAA41672)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        339
FT                   /note="Missing (in Ref. 3; AAA41672)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        621
FT                   /note="V -> K (in Ref. 3; AAA41672)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        807..809
FT                   /note="VPA -> DPT (in Ref. 3; AAA41672)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        908
FT                   /note="C -> F (in Ref. 1; AAA40777)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1013 AA;  111692 MW;  72F051406284EA8A CRC64;
     MGDKKDDKSS PKKSKAKERR DLDDLKKEVA MTEHKMSVEE VCRKYNTDCV QGLTHSKAQE
     ILARDGPNAL TPPPTTPEWV KFCRQLFGGF SILLWIGAIL CFLAYGIQAG TEDDPSGDNL
     YLGIVLAAVV IITGCFSYYQ EAKSSKIMES FKNMVPQQAL VIREGEKMQV NAEEVVVGDL
     VEIKGGDRVP ADLRIISAHG CKVDNSSLTG ESEPQTRSPD CTHDNPLETR NITFFSTNCV
     EGTARGVVVA TGDRTVMGRI ATLASGLEVG KTPIAIEIEH FIQLITGVAV FLGVSFFILS
     LILGYTWLEA VIFLIGIIVA NVPEGLLATV TVCLTLTAKR MARKNCLVKN LEAVETLGST
     STICSDKTGT LTQNRMTVAH MWFDNQIHEA DTTEDQSGTS FDKSSHTWVA LSHIAGLCNR
     AVFKGGQDNI PVLKRDVAGD ASESALLKCI ELSSGSVKLM RERNKKVAEI PFNSTNKYQL
     SIHETEDPND NRYLLVMKGA PERILDRCAT ILLQGKEQPL DEEMKEAFQN AYLELGGLGE
     RVLGFCHYYL PEEQFPKGFA FDCDDVNFTT DNLCFVGLMS MIDPPRAAVP DAVGKCRSAG
     IKVIMVTGDH PITAKAIAKG VGIISEGNET VEDIAARLNI PVSQVNPRDA KACVIHGTDL
     KDFTSEQIDE ILQNHTEIVF ARTSPQQKLI IVEGCQRQGA IVAVTGDGVN DSPALKKADI
     GVAMGIAGSD VSKQAADMIL LDDNFASIVT GVEEGRLIFD NLKKSIAYTL TSNIPEITPF
     LLFIMANIPL PLGTITILCI DLGTDMVPAI SLAYEAAESD IMKRQPRNPR TDKLVNERLI
     SMAYGQIGMI QALGGFFSYF VILAENGFLP GNLVGIRLNW DDRTVNDLED SYGQQWTYEQ
     RKVVEFTCHT AFFVSIVVVQ WADLIICKTR RNSVFQQGMK NKILIFGLFE ETALAAFLSY
     CPGMDVALRM YPLKPSWWFC AFPYSFLIFV YDEIRKLILR RNPGGWVEKE TYY
//