AT1A2_RAT
ID AT1A2_RAT Reviewed; 1020 AA.
AC P06686;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=Sodium/potassium-transporting ATPase subunit alpha-2;
DE Short=Na(+)/K(+) ATPase alpha-2 subunit;
DE EC=7.2.2.13;
DE AltName: Full=Na(+)/K(+) ATPase alpha(+) subunit;
DE AltName: Full=Sodium pump subunit alpha-2;
DE Flags: Precursor;
GN Name=Atp1a2;
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 [LARGE SCALE MRNA].
RC TISSUE=Heart;
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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-39.
RX PubMed=2170235; DOI=10.1016/0378-1119(90)90098-c;
RA Kawakami K., Yagawa Y., Nagano K.;
RT "Regulation of Na+,K(+)-ATPases. I. Cloning and analysis of the 5'-flanking
RT region of the rat NKAA2 gene encoding the alpha 2 subunit.";
RL Gene 91:267-270(1990).
RN [4]
RP PROTEIN SEQUENCE OF 594-602; 645-655; 659-668 AND 741-770, 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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-439; SER-450; SER-496 AND
RP SER-672, AND 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: Membrane {ECO:0000250}; Multi-pass membrane
CC protein {ECO:0000250}. 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; M14512; AAA40776.1; -; mRNA.
DR EMBL; BC085764; AAH85764.1; -; mRNA.
DR EMBL; D90049; BAA14102.1; -; Genomic_DNA.
DR PIR; B24639; B24639.
DR PIR; I54059; I54059.
DR RefSeq; NP_036637.1; NM_012505.2.
DR AlphaFoldDB; P06686; -.
DR SMR; P06686; -.
DR BioGRID; 246400; 11.
DR IntAct; P06686; 3.
DR MINT; P06686; -.
DR STRING; 10116.ENSRNOP00000054947; -.
DR BindingDB; P06686; -.
DR ChEMBL; CHEMBL3885640; -.
DR ChEMBL; CHEMBL4106148; -.
DR CarbonylDB; P06686; -.
DR iPTMnet; P06686; -.
DR PhosphoSitePlus; P06686; -.
DR jPOST; P06686; -.
DR PaxDb; P06686; -.
DR PRIDE; P06686; -.
DR Ensembl; ENSRNOT00000058143; ENSRNOP00000054947; ENSRNOG00000007290.
DR GeneID; 24212; -.
DR KEGG; rno:24212; -.
DR UCSC; RGD:2168; rat.
DR CTD; 477; -.
DR RGD; 2168; Atp1a2.
DR eggNOG; KOG0203; Eukaryota.
DR GeneTree; ENSGT00940000159936; -.
DR HOGENOM; CLU_002360_4_1_1; -.
DR InParanoid; P06686; -.
DR OMA; RYCAMTG; -.
DR OrthoDB; 388324at2759; -.
DR PhylomeDB; P06686; -.
DR TreeFam; TF312838; -.
DR BRENDA; 7.2.2.3; 5301.
DR Reactome; R-RNO-5578775; Ion homeostasis.
DR Reactome; R-RNO-936837; Ion transport by P-type ATPases.
DR SABIO-RK; P06686; -.
DR PRO; PR:P06686; -.
DR Proteomes; UP000002494; Chromosome 13.
DR Bgee; ENSRNOG00000007290; Expressed in Ammon's horn and 20 other tissues.
DR Genevisible; P06686; RN.
DR GO; GO:0005901; C:caveola; IDA:RGD.
DR GO; GO:0042995; C:cell projection; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0043197; C:dendritic spine; IDA:RGD.
DR GO; GO:0005768; C:endosome; IDA:RGD.
DR GO; GO:0014704; C:intercalated disc; IDA:BHF-UCL.
DR GO; GO:0016020; C:membrane; IDA:ARUK-UCL.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; ISO:RGD.
DR GO; GO:0031090; C:organelle membrane; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0042383; C:sarcolemma; IDA:RGD.
DR GO; GO:0005890; C:sodium:potassium-exchanging ATPase complex; IDA:ARUK-UCL.
DR GO; GO:0045202; C:synapse; IDA:RGD.
DR GO; GO:0030315; C:T-tubule; IDA:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IMP:RGD.
DR GO; GO:0016887; F:ATP hydrolysis activity; ISO:RGD.
DR GO; GO:0019829; F:ATPase-coupled cation transmembrane transporter activity; IMP:RGD.
DR GO; GO:0051087; F:chaperone binding; ISO:RGD.
DR GO; GO:0005391; F:P-type sodium:potassium-exchanging transporter activity; IDA:RGD.
DR GO; GO:0030955; F:potassium ion binding; ISO:RGD.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:ARUK-UCL.
DR GO; GO:0031402; F:sodium ion binding; ISO:RGD.
DR GO; GO:0005496; F:steroid binding; ISO:RGD.
DR GO; GO:1990239; F:steroid hormone binding; IDA:BHF-UCL.
DR GO; GO:0008344; P:adult locomotory behavior; ISO:RGD.
DR GO; GO:0021764; P:amygdala development; ISO:RGD.
DR GO; GO:0046034; P:ATP metabolic process; ISO:RGD.
DR GO; GO:0001662; P:behavioral fear response; ISO:RGD.
DR GO; GO:0060048; P:cardiac muscle contraction; IC:BHF-UCL.
DR GO; GO:0098655; P:cation transmembrane transport; ISO:RGD.
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; IMP:BHF-UCL.
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:0040011; P:locomotion; ISO:RGD.
DR GO; GO:0035641; P:locomotory exploration behavior; ISO:RGD.
DR GO; GO:1903170; P:negative regulation of calcium ion transmembrane transport; IMP:BHF-UCL.
DR GO; GO:1903280; P:negative regulation of calcium:sodium antiporter activity; IMP:BHF-UCL.
DR GO; GO:0051481; P:negative regulation of cytosolic calcium ion concentration; ISO:RGD.
DR GO; GO:0045822; P:negative regulation of heart contraction; ISO:RGD.
DR GO; GO:0045988; P:negative regulation of striated muscle contraction; ISO:RGD.
DR GO; GO:0001504; P:neurotransmitter uptake; ISO:RGD.
DR GO; GO:0021989; P:olfactory cortex development; ISO:RGD.
DR GO; GO:1990573; P:potassium ion import across plasma membrane; ISO:RGD.
DR GO; GO:0071805; P:potassium ion transmembrane transport; ISO:RGD.
DR GO; GO:0006813; P:potassium ion transport; IDA:RGD.
DR GO; GO:1902600; P:proton transmembrane transport; IMP:RGD.
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:0010882; P:regulation of cardiac muscle contraction by calcium ion signaling; IC:BHF-UCL.
DR GO; GO:0006937; P:regulation of muscle contraction; ISO:RGD.
DR GO; GO:0002087; P:regulation of respiratory gaseous exchange by nervous system process; ISO:RGD.
DR GO; GO:0006940; P:regulation of smooth muscle contraction; ISO:RGD.
DR GO; GO:0006942; P:regulation of striated muscle contraction; ISO:RGD.
DR GO; GO:0002026; P:regulation of the force of heart contraction; ISO:RGD.
DR GO; GO:0019229; P:regulation of vasoconstriction; ISO:RGD.
DR GO; GO:0055119; P:relaxation of cardiac muscle; IC:BHF-UCL.
DR GO; GO:0010996; P:response to auditory stimulus; ISO:RGD.
DR GO; GO:1903416; P:response to glycoside; IMP:BHF-UCL.
DR GO; GO:0035094; P:response to nicotine; IDA:RGD.
DR GO; GO:0036376; P:sodium ion export across plasma membrane; ISO:RGD.
DR GO; GO:0035725; P:sodium ion transmembrane transport; 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; -; 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 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 PROPEP 1..5
FT /id="PRO_0000002507"
FT CHAIN 6..1020
FT /note="Sodium/potassium-transporting ATPase subunit alpha-
FT 2"
FT /id="PRO_0000002508"
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..769
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 770..789
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 790..799
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 800..820
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 821..840
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 841..863
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 864..915
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 916..935
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 936..948
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 949..967
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 968..982
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 983..1003
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1004..1020
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..31
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 80..82
FT /note="Interaction with phosphoinositide-3 kinase"
FT /evidence="ECO:0000250"
FT REGION 212..231
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 212..230
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 374
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250"
FT BINDING 714
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 718
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PIE5"
FT MOD_RES 439
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 450
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 496
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 559
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6PIE5"
FT MOD_RES 570
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P50993"
FT MOD_RES 587
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P50993"
FT MOD_RES 672
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 826
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P09626"
FT MOD_RES 940
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250"
SQ SEQUENCE 1020 AA; 112217 MW; 5436E795BD5B4CFA CRC64;
MGRGAGREYS PAATTAENGG GKKKQKEKEL DELKKEVAMD DHKLSLDELG RKYQVDLSKG
LTNQRAQDIL ARDGPNALTP PPTTPEWVKF CRQLFGGFSI LLWIGALLCF LAYGILAAME
DEPSNDNLYL GIVLAAVVIV TGCFSYYQEA KSSKIMDSFK NMVPQQALVI REGEKMQINA
EEVVVGDLVE VKGGDRVPAD LRIISSHGCK VDNSSLTGES EPQTRSPEFT HENPLETRNI
CFFSTNCVEG TARGIVIATG DRTVMGRIAT LASGLEVGQT PIAMEIEHFI QLITGVAVFL
GVSFFVLSLI LGYSWLEAVI FLIGIIVANV PEGLLATVTV CLTLTAKRMA RKNCLVKNLE
AVETLGSTST ICSDKTGTLT QNRMTVAHMW FDNQIHEADT TEDQSGATFD KRSPTWTALS
RIAGLCNRAV FKAGQENISV SKRDTAGDAS ESALLKCIEL SCGSVRKMRD RNPKVAEIPF
NSTNKYQLSI HEREDSPQSH VLVMKGAPER ILDRCSTILV QGKEIPLDKE MQDAFQNAYM
ELGGLGERVL GFCQLNLPSG KFPRGFKFDT DELNFPTEKL CFVGLMSMID PPRAAVPDAV
GKCRSAGIKV IMVTGDHPIT AKAIAKGVGI ISEGNETVED IAARLNIPVS QVNPREAKAC
VVHGSDLKDM TSEQLDEILR DHTEIVFART SPQQKLIIVE GCQRQGAIVA VTGDGVNDSP
ALKKADIGIA MGISGSDVSK QAADMILLDD NFASIVTGVE EGRLIFDNLK KSIAYTLTSN
IPEITPFLLF IIANIPLPLG TVTILCIDLG TDMVPAISLA YEAAESDIMK RQPRNSQTDK
LVNERLISMA YGQIGMIQAL GGFFTYFVIL AENGFLPSRL LGIRLDWDDR TTNDLEDSYG
QEWTYEQRKV VEFTCHTAFF ASIVVVQWAD LIICKTRRNS VFQQGMKNKI LIFGLLEETA
LAAFLSYCPG MGVALRMYPL KVTWWFCAFP YSLLIFIYDE VRKLILRRYP GGWVEKETYY
