ID   AT1A1_BOVIN             Reviewed;        1021 AA.
AC   Q08DA1;
DT   02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT   31-OCT-2006, sequence version 1.
DT   27-MAR-2024, entry version 116.
DE   RecName: Full=Sodium/potassium-transporting ATPase subunit alpha-1;
DE            Short=Na(+)/K(+) ATPase alpha-1 subunit;
DE            EC=7.2.2.13;
DE   AltName: Full=Sodium pump subunit alpha-1;
DE   Flags: Precursor;
GN   Name=ATP1A1;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Basal ganglia;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   SUBCELLULAR LOCATION.
RX   PubMed=12169672; DOI=10.1073/pnas.182267299;
RA   Crambert G., Fuzesi M., Garty H., Karlish S., Geering K.;
RT   "Phospholemman (FXYD1) associates with Na,K-ATPase and regulates its
RT   transport properties.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:11476-11481(2002).
RN   [3]
RP   INTERACTION WITH FXYD1.
RX   PubMed=12657675; DOI=10.1523/jneurosci.23-06-02161.2003;
RA   Feschenko M.S., Donnet C., Wetzel R.K., Asinovski N.K., Jones L.R.,
RA   Sweadner K.J.;
RT   "Phospholemman, a single-span membrane protein, is an accessory protein of
RT   Na,K-ATPase in cerebellum and choroid plexus.";
RL   J. Neurosci. 23:2161-2169(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 (By similarity). Could
CC       also be part of an osmosensory signaling pathway that senses body-fluid
CC       sodium levels and controls salt intake behavior as well as voluntary
CC       water intake to regulate sodium homeostasis (By similarity).
CC       {ECO:0000250|UniProtKB:P05023, ECO:0000250|UniProtKB:Q8VDN2}.
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       (PubMed:12657675). Interacts with regulatory subunit FXYD3 (By
CC       similarity). Interacts with SIK1 (By similarity). Interacts with
CC       SLC35G1 and STIM1 (By similarity). Interacts with CLN3; this
CC       interaction regulates the sodium/potassium-transporting ATPase complex
CC       localization at the plasma membrane (By similarity). Interacts with
CC       SCN7A; activates ATP1A1 P-type sodium:potassium-exchanging transporter
CC       activity which indirectly signals to nearby neurons to regulate sodium
CC       homeostasis (By similarity). {ECO:0000250|UniProtKB:P05023,
CC       ECO:0000250|UniProtKB:P06685, ECO:0000250|UniProtKB:Q8VDN2,
CC       ECO:0000269|PubMed:12657675}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8VDN2};
CC       Multi-pass membrane protein {ECO:0000255}. Basolateral cell membrane
CC       {ECO:0000250|UniProtKB:P06685}; Multi-pass membrane protein
CC       {ECO:0000255}. Cell membrane, sarcolemma {ECO:0000269|PubMed:12169672};
CC       Multi-pass membrane protein {ECO:0000255}. Cell projection, axon
CC       {ECO:0000250|UniProtKB:P06685}. Melanosome
CC       {ECO:0000250|UniProtKB:P05023}.
CC   -!- PTM: Phosphorylation on Tyr-10 modulates pumping activity.
CC       Phosphorylation of Ser-941 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 (By similarity). {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; BC123864; AAI23865.1; -; mRNA.
DR   RefSeq; NP_001070266.1; NM_001076798.1.
DR   PDB; 4XE5; X-ray; 3.90 A; A=1-1021.
DR   PDBsum; 4XE5; -.
DR   AlphaFoldDB; Q08DA1; -.
DR   SMR; Q08DA1; -.
DR   STRING; 9913.ENSBTAP00000060814; -.
DR   SwissPalm; Q08DA1; -.
DR   PaxDb; 9913-ENSBTAP00000001646; -.
DR   PeptideAtlas; Q08DA1; -.
DR   Ensembl; ENSBTAT00000085581.1; ENSBTAP00000074408.1; ENSBTAG00000001246.6.
DR   GeneID; 282144; -.
DR   KEGG; bta:282144; -.
DR   CTD; 476; -.
DR   VEuPathDB; HostDB:ENSBTAG00000001246; -.
DR   VGNC; VGNC:26282; ATP1A1.
DR   eggNOG; KOG0203; Eukaryota.
DR   GeneTree; ENSGT00940000154840; -.
DR   InParanoid; Q08DA1; -.
DR   OMA; QQPPIFN; -.
DR   OrthoDB; 203629at2759; -.
DR   BRENDA; 7.2.2.13; 908.
DR   Reactome; R-BTA-5578775; Ion homeostasis.
DR   Reactome; R-BTA-936837; Ion transport by P-type ATPases.
DR   Proteomes; UP000009136; Chromosome 3.
DR   Bgee; ENSBTAG00000001246; Expressed in metanephros cortex and 103 other cell types or tissues.
DR   ExpressionAtlas; Q08DA1; baseline.
DR   GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR   GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB.
DR   GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0045121; C:membrane raft; IDA:ARUK-UCL.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0042383; C:sarcolemma; IBA:GO_Central.
DR   GO; GO:0005890; C:sodium:potassium-exchanging ATPase complex; IBA:GO_Central.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
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:0030007; P:intracellular potassium ion homeostasis; IBA:GO_Central.
DR   GO; GO:0006883; P:intracellular sodium ion homeostasis; IBA:GO_Central.
DR   GO; GO:1990573; P:potassium ion import across plasma membrane; IBA:GO_Central.
DR   GO; GO:1902600; P:proton transmembrane transport; IBA:GO_Central.
DR   GO; GO:0002028; P:regulation of sodium ion transport; ISS:UniProtKB.
DR   GO; GO:0036376; P:sodium ion export across plasma membrane; IBA:GO_Central.
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; 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.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; ATP-binding; Cell membrane; Cell projection;
KW   Ion transport; Magnesium; Membrane; Metal-binding; Nucleotide-binding;
KW   Phosphoprotein; Potassium; Potassium transport; Reference proteome; Sodium;
KW   Sodium transport; Sodium/potassium transport; Translocase; Transmembrane;
KW   Transmembrane helix; Transport.
FT   PROPEP          1..5
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000305975"
FT   CHAIN           6..1021
FT                   /note="Sodium/potassium-transporting ATPase subunit alpha-
FT                   1"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000305976"
FT   TOPO_DOM        6..85
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        86..106
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        107..129
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        130..150
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        151..286
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        287..306
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        307..318
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        319..336
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        337..770
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        771..790
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        791..800
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        801..821
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        822..841
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        842..864
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        865..916
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        917..936
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        937..949
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        950..968
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        969..983
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        984..1004
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        1005..1021
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          1..36
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          80..82
FT                   /note="Phosphoinositide-3 kinase binding"
FT                   /evidence="ECO:0000250"
FT   REGION          594..715
FT                   /note="Mediates interaction with SCN7A"
FT                   /evidence="ECO:0000250|UniProtKB:Q8VDN2"
FT   ACT_SITE        374
FT                   /note="4-aspartylphosphate intermediate"
FT                   /evidence="ECO:0000250"
FT   BINDING         485
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   BINDING         715
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   BINDING         719
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:0000250|UniProtKB:P06685"
FT   MOD_RES         16
FT                   /note="Phosphoserine; by PKC"
FT                   /evidence="ECO:0000250|UniProtKB:P06685"
FT   MOD_RES         21
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8VDN2"
FT   MOD_RES         38
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P06685"
FT   MOD_RES         45
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P06685"
FT   MOD_RES         226
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8VDN2"
FT   MOD_RES         258
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8VDN2"
FT   MOD_RES         450
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P06685"
FT   MOD_RES         482
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P06685"
FT   MOD_RES         540
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:P05023"
FT   MOD_RES         666
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8VDN2"
FT   MOD_RES         941
FT                   /note="Phosphoserine; by PKA"
FT                   /evidence="ECO:0000250|UniProtKB:P06685"
SQ   SEQUENCE   1021 AA;  112643 MW;  E01CAF82B6F1A6FC CRC64;
     MGKGVGRDKY EPAAVSEHGD KKKAKKERDM DELKKEVSMD DHKLSLDELH RKYGTDLSRG
     LTTARAAEIL ARDGPNALTP PPTTPEWVKF CRQLFGGFSM LLWIGAVLCF LAYGIQAATE
     EEPQNDNLYL GVVLSAVVII TGCFSYYQEA KSSKIMESFK NMVPQQALVI RNGEKMSINA
     EEVVVGDLVE VKGGDRIPAD LRIISANGCK VDNSSLTGES EPQTRSPDFT NENPLETRNI
     AFFSTNCVEG TARGIVVYTG DRTVMGRIAT LASGLEGGQT PIAAEIEHFI HIITGVAVFL
     GVSFFILSLI LEYTWLEAVI FLIGIIVANV PEGLLATVTV CLTLTAKRMA RKNCLVKNLE
     AVETLGSTST ICSDKTGTLT QNRMTVAHMW FDNQIHEADT TENQSGVSFD KTSATWLALS
     RIAGLCNRAV FQANQDNLPI LKRAVAGDAS ESALLKCIEV CCGSVKEMRE RYTKIVEIPF
     NSTNKYQLSI HKNANAGEPR HLLVMKGAPE RILDRCSSIL IHGKEQPLDE ELKDAFQNAY
     LELGGLGERV LGFCHLLLPD EQFPEGFQFD TDDVNFPVDN LCFVGLISMI DPPRAAVPDA
     VGKCRSAGIK VIMVTGDHPI TAKAIAKGVG IISEGNETVE DIAARLNIPV SQVNPRDARA
     CVVHGSDLKD MTPEQLDDIL KYHTEIVFAR TSPQQKLIIV EGCQRQGAIV AVTGDGVNDS
     PALKKADIGV AMGIAGSDVS KQAADMILLD DNFASIVTGV EEGRLIFDNL KKSIAYTLTS
     NIPEITPFLI FIIANIPLPL GTVTILCIDL GTDMVPAISL AYEQAESDIM KRQPRNPQTD
     KLVNERLISM AYGQIGMIQA LGGFFTYFVI MAENGFLPNH LLGIRVTWDD RWINDVEDSY
     GQQWTYEQRK IVEFTCHTAF FVSIVVVQWA DLVICKTRRN SVFQQGMKNK ILIFGLFEET
     ALAAFLSYCP GMGVALRMYP LKPTWWFCAF PYSLLIFVYD EVRKLIIRRR PGGWVEKETY
     Y
//