ID   AT1A1_RHIMB             Reviewed;        1023 AA.
AC   P30714;
DT   01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT   16-MAY-2003, sequence version 2.
DT   27-MAR-2024, entry version 141.
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   Rhinella marina (Cane toad) (Bufo marinus).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Neobatrachia; Hyloidea; Bufonidae; Rhinella.
OX   NCBI_TaxID=8386;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Urinary bladder urothelium;
RX   PubMed=1380956; DOI=10.1016/s0021-9258(18)41869-8;
RA   Jaisser F., Canessa C.M., Horisberger J.-D., Rossier B.C.;
RT   "Primary sequence and functional expression of a novel ouabain-resistant
RT   Na,K-ATPase. The beta subunit modulates potassium activation of the Na,K-
RT   pump.";
RL   J. Biol. Chem. 267:16895-16903(1992).
RN   [2]
RP   SEQUENCE REVISION TO 835-836.
RA   Jaisser F.;
RL   Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   PHOSPHORYLATION AT THR-15 AND SER-16 BY PROTEIN KINASE C, AND
RP   PHOSPHORYLATION AT SER-943 BY CAMP-DEPENDENT KINASE.
RX   PubMed=7929106; DOI=10.1016/s0021-9258(19)51103-6;
RA   Beguin P., Beggah A.T., Chibalin A.V., Burgener-Kairuz P., Jaisser F.,
RA   Mathews P.M., Rossier B.C., Cotecchia S., Geering K.;
RT   "Phosphorylation of the Na,K-ATPase alpha-subunit by protein kinase A and C
RT   in vitro and in intact cells. Identification of a novel motif for PKC-
RT   mediated phosphorylation.";
RL   J. Biol. Chem. 269:24437-24445(1994).
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:0000250|UniProtKB:P05023}.
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   -!- ACTIVITY REGULATION: This alpha subunit is resistant to ouabain.
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. {ECO:0000305}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane, sarcolemma
CC       {ECO:0000250|UniProtKB:P05023}; Multi-pass membrane protein
CC       {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Mainly expressed in kidney. Found in bladder,
CC       colon, eye, and testis. Found in low levels in brain, heart, spleen and
CC       liver.
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; Z11798; CAA77842.2; -; mRNA.
DR   PIR; A43451; S24650.
DR   AlphaFoldDB; P30714; -.
DR   SMR; P30714; -.
DR   iPTMnet; P30714; -.
DR   GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0042383; C:sarcolemma; IEA:UniProtKB-SubCell.
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; IEA:UniProtKB-EC.
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.
PE   1: Evidence at protein level;
KW   ATP-binding; Cell membrane; Ion transport; Magnesium; Membrane;
KW   Metal-binding; Nucleotide-binding; Phosphoprotein; Potassium;
KW   Potassium transport; Sodium; Sodium transport; Sodium/potassium transport;
KW   Translocase; Transmembrane; Transmembrane helix; Transport.
FT   PROPEP          1..5
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000002501"
FT   CHAIN           6..1023
FT                   /note="Sodium/potassium-transporting ATPase subunit alpha-
FT                   1"
FT                   /id="PRO_0000002502"
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..34
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          82..84
FT                   /note="Interaction with phosphoinositide-3 kinase"
FT                   /evidence="ECO:0000250"
FT   REGION          215..235
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        11..34
FT                   /note="Basic and acidic residues"
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:0000250"
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         15
FT                   /note="Phosphothreonine; by PKC"
FT                   /evidence="ECO:0000269|PubMed:7929106"
FT   MOD_RES         16
FT                   /note="Phosphoserine; by PKC"
FT                   /evidence="ECO:0000269|PubMed:7929106"
FT   MOD_RES         943
FT                   /note="Phosphoserine; by PKA"
FT                   /evidence="ECO:0000269|PubMed:7929106"
SQ   SEQUENCE   1023 AA;  112617 MW;  D66E8C4028F41BF1 CRC64;
     MGYGAGRDKY EPAATSEHGG KKGKGKGKDR DMEELKKEVT MEDHKMTLEE LHRKYGTDLT
     RGLTTARAAE ILARDGPNAL TPPPTTPEWV KFCRQLFGGF SMLLWIGAIL CFLAYGIRKA
     SDLEPDNDNL YLGVVLSAVV IITGCFSYYQ EAKSSRIMES FKNMVPQQAL VIRNGEKLSI
     NAENVVQGDL VEVKGGDRIP ADLRIISAHG CKVDNSSLTG ESEPQTRSPD FTNENPLETR
     NIAFFSTNCV EGTARGIVIN TGDRTVMGRI ATLASGLEGG QTPIAVEIGH FIHIITGVAV
     FLGVSFFILS LILHYTWLEA VIFLIGIIVA NVPEGLLATV TVCLTLTAKR MARKNCLVKN
     LEAVETLGST STICSDKTGT LTQNRMTVAH MWFDNQIHEA DTTENQSGAS FDKSSPTWTA
     LARIAGLCNR AVFPAGQENT PILKRDVVGD ASESALLKCI ELCCGSVKDM REKNQKVAEI
     PFNSTNKYQL SVHKNANPSE SRYLLVMKGA PERILDRCSS ILLQGKEQPL DEELKDAFQN
     AYLELGGLGE RVLGFCHLLL DDEQFPDGFS FDTEDVNFPT EGLCFVGLIS MIDPPRAAVP
     DRVGKCRSAG IKVIMVTGDH PITAKAIAKG VGIISEGNET VEDIAARLNI PVNQVNPRDA
     KACVIHGTDL KDMNADQIDD ILRHHTEIVF ARTSPQQKLI IVEGCQRQGA IVAVTGDGVN
     DSPALKKADI GIAMGIAGSD VSKQAADMIL LDDNFASIVT GVEEGRLIFD NLKKSIAYTL
     TSNIPEITPF LIFIIADIPL PLGTVTILCI DLGTDMVPAI SLAYEQAESD IMKRQPRNPK
     KDKLVNERLI SMAYGQIGMI QALGGFFAYF VILAENGFLP STLLGIRVAW EDRYVNDVED
     SYGQQWTYEQ RKIVEFTCHT AFFVSIVVVQ WADLIICKTR RNSVFQQGMK NKILIFGLFE
     ETALAAFLSY CPGMDVALRM YPLKPTWWFC AFPYSLLIFI YDEVRKLILR RSPGGWVEKE
     TYY
//