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P06685 (AT1A1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 149. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sodium/potassium-transporting ATPase subunit alpha-1

Short name=Na(+)/K(+) ATPase alpha-1 subunit
EC=3.6.3.9
Alternative name(s):
Sodium pump subunit alpha-1
Gene names
Name:Atp1a1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1023 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients.

Catalytic activity

ATP + H2O + Na+(In) + K+(Out) = ADP + phosphate + Na+(Out) + K+(In).

Subunit structure

Composed of three subunits: alpha (catalytic), beta and gamma. Interacts with SIK1. Ref.12

Subcellular location

Cell membrane; Multi-pass membrane protein. Melanosome By similarity.

Post-translational modification

Phosphorylation on Tyr-10 modulates pumping activity. Dephosphorylation by protein phosphatase 2A (PP2A) following increases in intracellular sodium, leading to increase catalytic activity.

Sequence similarities

Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIC subfamily. [View classification]

Ontologies

Keywords
   Biological processIon transport
Potassium transport
Sodium transport
Sodium/potassium transport
Transport
   Cellular componentCell membrane
Membrane
   DomainTransmembrane
Transmembrane helix
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
Potassium
Sodium
   Molecular functionHydrolase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processATP biosynthetic process

Inferred from electronic annotation. Source: InterPro

cellular response to mechanical stimulus

Inferred from direct assay PubMed 17458903. Source: RGD

energy coupled proton transmembrane transport, against electrochemical gradient

Traceable author statement PubMed 16269407. Source: RGD

membrane hyperpolarization

Inferred from mutant phenotype PubMed 17001300. Source: RGD

negative regulation of glucocorticoid biosynthetic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of heart contraction

Inferred from electronic annotation. Source: Ensembl

positive regulation of heart contraction

Inferred from electronic annotation. Source: Ensembl

positive regulation of striated muscle contraction

Inferred from electronic annotation. Source: Ensembl

potassium ion import

Inferred from direct assay PubMed 12531906. Source: RGD

regulation of blood pressure

Inferred from electronic annotation. Source: Ensembl

regulation of cardiac muscle cell contraction

Inferred from mutant phenotype PubMed 15629895. Source: RGD

regulation of sodium ion transport

Inferred from direct assay Ref.12. Source: UniProtKB

regulation of the force of heart contraction

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi apparatus

Inferred from direct assay PubMed 18768923. Source: BHF-UCL

T-tubule

Inferred from electronic annotation. Source: Ensembl

basolateral plasma membrane

Inferred from electronic annotation. Source: Ensembl

caveola

Inferred from direct assay PubMed 16624992. Source: RGD

endoplasmic reticulum

Inferred from direct assay PubMed 18768923. Source: BHF-UCL

endosome

Inferred from direct assay PubMed 16893515. Source: RGD

melanosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

sodium:potassium-exchanging ATPase complex

Inferred from direct assay PubMed 12093728PubMed 16624992PubMed 16893515. Source: RGD

   Molecular_functionADP binding

Inferred from direct assay Ref.13. Source: RGD

ATP binding

Inferred from direct assay Ref.13. Source: RGD

chaperone binding

Inferred from direct assay PubMed 18768923. Source: BHF-UCL

potassium ion binding

Inferred from direct assay PubMed 16269407. Source: RGD

sodium ion binding

Inferred from direct assay PubMed 16269407. Source: RGD

sodium:potassium-exchanging ATPase activity

Inferred from direct assay Ref.12. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Propeptide1 – 55
PRO_0000002489
Chain6 – 10231018Sodium/potassium-transporting ATPase subunit alpha-1
PRO_0000002490

Regions

Topological domain6 – 8782Cytoplasmic Potential
Transmembrane88 – 10821Helical; Potential
Topological domain109 – 13123Extracellular Potential
Transmembrane132 – 15221Helical; Potential
Topological domain153 – 288136Cytoplasmic Potential
Transmembrane289 – 30820Helical; Potential
Topological domain309 – 32012Extracellular Potential
Transmembrane321 – 33818Helical; Potential
Topological domain339 – 772434Cytoplasmic Potential
Transmembrane773 – 79220Helical; Potential
Topological domain793 – 80210Extracellular Potential
Transmembrane803 – 82321Helical; Potential
Topological domain824 – 84320Cytoplasmic Potential
Transmembrane844 – 86623Helical; Potential
Topological domain867 – 91852Extracellular Potential
Transmembrane919 – 93820Helical; Potential
Topological domain939 – 95113Cytoplasmic Potential
Transmembrane952 – 97019Helical; Potential
Topological domain971 – 98515Extracellular Potential
Transmembrane986 – 100621Helical; Potential
Topological domain1007 – 102317Cytoplasmic Potential
Region82 – 843Phosphoinositide-3 kinase binding

Sites

Active site37614-aspartylphosphate intermediate By similarity
Metal binding7171Magnesium By similarity
Metal binding7211Magnesium By similarity
Binding site4871ATP

Amino acid modifications

Modified residue91N6-acetyllysine By similarity
Modified residue101Phosphotyrosine Ref.9
Modified residue161Phosphoserine; by PKC
Modified residue211N6-acetyllysine By similarity
Modified residue231Phosphoserine; by PKC
Modified residue2601Phosphotyrosine By similarity
Modified residue5421Phosphotyrosine By similarity
Modified residue6611N6-succinyllysine By similarity
Modified residue9431Phosphoserine; by PKA

Experimental info

Mutagenesis161S → A: Dopamine fails to increase phosphoinositide-3 kinase activity and to promote its interaction with Na(+)/K(+) ATPase.
Mutagenesis831P → R: Dopamine fails to increase phosphoinositide-3 kinase activity and to promote its interaction with Na(+)/K(+) ATPase.
Sequence conflict68 – 692AA → PV in AAA41671. Ref.3
Sequence conflict1751G → E in AAA41671. Ref.3
Sequence conflict1881G → V in AAA41671. Ref.3
Sequence conflict3351G → V in AAA41671. Ref.3

Secondary structure

............................................. 1023
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P06685 [UniParc].

Last modified January 1, 1988. Version 1.
Checksum: 85E98233EE6C18E9

FASTA1,023113,054
        10         20         30         40         50         60 
MGKGVGRDKY EPAAVSEHGD KKSKKAKKER DMDELKKEVS MDDHKLSLDE LHRKYGTDLS 

        70         80         90        100        110        120 
RGLTPARAAE ILARDGPNAL TPPPTTPEWV KFCRQLFGGF SMLLWIGAIL CFLAYGIRSA 

       130        140        150        160        170        180 
TEEEPPNDDL YLGVVLSAVV IITGCFSYYQ EAKSSKIMES FKNMVPQQAL VIRNGEKMSI 

       190        200        210        220        230        240 
NAEDVVVGDL VEVKGGDRIP ADLRIISANG CKVDNSSLTG ESEPQTRSPD FTNENPLETR 

       250        260        270        280        290        300 
NIAFFSTNCV EGTARGIVVY TGDRTVMGRI ATLASGLEGG QTPIAEEIEH FIHLITGVAV 

       310        320        330        340        350        360 
FLGVSFFILS LILEYTWLEA VIFLIGIIVA NVPEGLLATV TVCLTLTAKR MARKNCLVKN 

       370        380        390        400        410        420 
LEAVETLGST STICSDKTGT LTQNRMTVAH MWFDNQIHEA DTTENQSGVS FDKTSATWFA 

       430        440        450        460        470        480 
LSRIAGLCNR AVFQANQENL PILKRAVAGD ASESALLKCI EVCCGSVMEM REKYTKIVEI 

       490        500        510        520        530        540 
PFNSTNKYQL SIHKNPNASE PKHLLVMKGA PERILDRCSS ILLHGKEQPL DEELKDAFQN 

       550        560        570        580        590        600 
AYLELGGLGE RVLGFCHLLL PDEQFPEGFQ FDTDEVNFPV DNLCFVGLIS MIDPPRAAVP 

       610        620        630        640        650        660 
DAVGKCRSAG IKVIMVTGDH PITAKAIAKG VGIISEGNET VEDIAARLNI PVNQVNPRDA 

       670        680        690        700        710        720 
KACVVHGSDL KDMTSEELDD ILRYHTEIVF ARTSPQQKLI IVEGCQRQGA IVAVTGDGVN 

       730        740        750        760        770        780 
DSPALKKADI GVAMGIVGSD VSKQAADMIL LDDNFASIVT GVEEGRLIFD NLKKSIAYTL 

       790        800        810        820        830        840 
TSNIPEITPF LIFIIANIPL PLGTVTILCI DLGTDMVPAI SLAYEQAESD IMKRQPRNPK 

       850        860        870        880        890        900 
TDKLVNERLI SMAYGQIGMI QALGGFFTYF VILAENGFLP FHLLGIRETW DDRWINDVED 

       910        920        930        940        950        960 
SYGQQWTYEQ RKIVEFTCHT AFFVSIVVVQ WADLVICKTR RNSVFQQGMK NKILIFGLFE 

       970        980        990       1000       1010       1020 
ETALAAFLSY CPGMGAALRM YPLKPTWWFC AFPYSLLIFV YDEVRKLIIR RRPGGWVEKE 


TYY 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning of three distinct forms of the Na+,K+-ATPase alpha-subunit from rat brain."
Shull G.E., Greeb J., Lingrel J.B.
Biochemistry 25:8125-8132(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain and Kidney.
[2]"Primary structures of two types of alpha-subunit of rat brain Na+,K+,-ATPase deduced from cDNA sequences."
Hara Y., Urayama O., Kawakami K., Nojima H., Nagamune H., Kojima T., Ohta T., Nagano K., Nakao M.
J. Biochem. 102:43-58(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[3]"Three differentially expressed Na,K-ATPase alpha subunit isoforms: structural and functional implications."
Herrera V.L.M., Emanuel J.R., Ruiz-Opazo N., Levenson R., Nadal-Ginard B.
J. Cell Biol. 105:1855-1865(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Prostate.
[5]Lubec G., Kang S.U.
Submitted (JUL-2007) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 157-162; 597-605; 630-647; 662-671 AND 744-773, MASS SPECTROMETRY.
Strain: Sprague-Dawley.
Tissue: Brain.
[6]"Molecular cloning of rat brain Na,K-ATPase alpha-subunit cDNA."
Schneider J.W., Mercer R.W., Caplan M., Emanuel J.R., Sweadner K.J., Benz E.J. Jr., Levenson R.
Proc. Natl. Acad. Sci. U.S.A. 82:6357-6361(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 489-533.
Tissue: Brain.
[7]"Cloning and analysis of the 5'-flanking region of rat Na+/K(+)-ATPase alpha 1 subunit gene."
Yagawa Y., Kawakami K., Nagano K.
Biochim. Biophys. Acta 1049:286-292(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-41.
[8]"Identification of the phosphorylation site for cAMP-dependent protein kinase on Na+,K(+)-ATPase and effects of site-directed mutagenesis."
Fisone G., Cheng S.X.-J., Nairn A.C., Czernik A.J., Hemmings H.C. Jr., Hoeoeg J.-O., Bertorello A.M., Kaiser R., Bergman T., Joernvall H., Aperia A., Greengard P.
J. Biol. Chem. 269:9368-9373(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY CAMP-DEPENDENT KINASE.
[9]"Insulin-induced stimulation of Na+,K(+)-ATPase activity in kidney proximal tubule cells depends on phosphorylation of the alpha-subunit at Tyr-10."
Feraille E., Carranza M.L., Gonin S., Beguin P., Pedemonte C., Rousselot M., Caverzasio J., Geering K., Martin P.Y., Favre H.
Mol. Biol. Cell 10:2847-2859(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-10.
[10]"Structural basis for species-specific differences in the phosphorylation of Na,K-ATPase by protein kinase C."
Feschenko M.S., Sweadner K.J.
J. Biol. Chem. 270:14072-14077(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF N-TERMINUS, PHOSPHORYLATION BY PROTEIN KINASE C.
[11]"Phosphoinositide-3 kinase binds to a proline-rich motif in the Na+, K+-ATPase alpha subunit and regulates its trafficking."
Yudowski G.A., Efendiev R., Pedemonte C.H., Katz A.I., Berggren P.-O., Bertorello A.M.
Proc. Natl. Acad. Sci. U.S.A. 97:6556-6561(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: BINDING SITE FOR PHOSPHOINOSITIDE-3 KINASE, MUTAGENESIS.
[12]"SIK1 is part of a cell sodium-sensing network that regulates active sodium transport through a calcium-dependent process."
Sjostrom M., Stenstrom K., Eneling K., Zwiller J., Katz A.I., Takemori H., Bertorello A.M.
Proc. Natl. Acad. Sci. U.S.A. 104:16922-16927(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, DEPHOSPHORYLATION, INTERACTION WITH SIK1.
[13]"ATP-induced conformational changes of the nucleotide-binding domain of Na,K-ATPase."
Hilge M., Siegal G., Vuister G.W., Guntert P., Gloor S.M., Abrahams J.P.
Nat. Struct. Biol. 10:468-474(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 383-595 ALONE AND IN COMPLEX WITH ATP, ATP-BINDING SITE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M14511 mRNA. Translation: AAA40775.1.
X05882 mRNA. Translation: CAA29306.1.
M28647 mRNA. Translation: AAA41671.1.
BC061968 mRNA. Translation: AAH61968.1.
M11733 mRNA. Translation: AAA40783.1.
X53233 Genomic DNA. Translation: CAA37325.1.
X53234 Genomic DNA. Translation: CAA37326.1.
PIRA24639.
RefSeqNP_036636.1. NM_012504.1.
UniGeneRn.217534.
Rn.2992.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1MO7NMR-A383-595[»]
1MO8NMR-A383-595[»]
ProteinModelPortalP06685.
SMRP06685. Positions 26-1023.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid246399. 10 interactions.
IntActP06685. 2 interactions.
MINTMINT-3089277.
STRING10116.ENSRNOP00000045650.

Chemistry

BindingDBP06685.

PTM databases

PhosphoSiteP06685.

Proteomic databases

PaxDbP06685.
PRIDEP06685.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000040430; ENSRNOP00000045650; ENSRNOG00000030019.
GeneID24211.
KEGGrno:24211.
UCSCRGD:2167. rat.

Organism-specific databases

CTD476.
RGD2167. Atp1a1.

Phylogenomic databases

eggNOGCOG0474.
GeneTreeENSGT00560000076866.
HOVERGENHBG004298.
KOK01539.
OMAQFPEGFQ.
OrthoDBEOG7327N0.

Enzyme and pathway databases

SABIO-RKP06685.

Gene expression databases

GenevestigatorP06685.

Family and domain databases

Gene3D1.20.1110.10. 2 hits.
2.70.150.10. 2 hits.
3.40.1110.10. 1 hit.
InterProIPR006068. ATPase_P-typ_cation-transptr_C.
IPR004014. ATPase_P-typ_cation-transptr_N.
IPR023299. ATPase_P-typ_cyto_domN.
IPR005775. ATPase_P-typ_Na/K_IIC.
IPR018303. ATPase_P-typ_P_site.
IPR023298. ATPase_P-typ_TM_dom.
IPR008250. ATPase_P-typ_transduc_dom_A.
IPR001757. Cation_transp_P_typ_ATPase.
IPR023214. HAD-like_dom.
[Graphical view]
PfamPF00689. Cation_ATPase_C. 1 hit.
PF00690. Cation_ATPase_N. 1 hit.
PF00122. E1-E2_ATPase. 1 hit.
PF00702. Hydrolase. 1 hit.
[Graphical view]
PRINTSPR00119. CATATPASE.
SMARTSM00831. Cation_ATPase_N. 1 hit.
[Graphical view]
SUPFAMSSF56784. SSF56784. 1 hit.
SSF81660. SSF81660. 1 hit.
TIGRFAMsTIGR01106. ATPase-IIC_X-K. 1 hit.
TIGR01494. ATPase_P-type. 2 hits.
PROSITEPS00154. ATPASE_E1_E2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP06685.
NextBio602617.

Entry information

Entry nameAT1A1_RAT
AccessionPrimary (citable) accession number: P06685
Secondary accession number(s): Q64609
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 1, 1988
Last modified: March 19, 2014
This is version 149 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references