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Protein

Sodium/potassium-transporting ATPase subunit alpha-2

Gene

ATP1A2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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, providing the energy for active transport of various nutrients.

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei3744-aspartylphosphate intermediateBy similarity1
Metal bindingi714MagnesiumBy similarity1
Metal bindingi718MagnesiumBy similarity1

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • chaperone binding Source: BHF-UCL
  • metal ion binding Source: UniProtKB-KW
  • sodium:potassium-exchanging ATPase activity Source: BHF-UCL
  • steroid hormone binding Source: BHF-UCL

GO - Biological processi

  • adult locomotory behavior Source: Ensembl
  • ATP hydrolysis coupled proton transport Source: Ensembl
  • ATP metabolic process Source: BHF-UCL
  • cardiac muscle contraction Source: BHF-UCL
  • cell communication by electrical coupling involved in cardiac conduction Source: BHF-UCL
  • cellular potassium ion homeostasis Source: BHF-UCL
  • cellular response to mechanical stimulus Source: Ensembl
  • cellular response to steroid hormone stimulus Source: BHF-UCL
  • cellular sodium ion homeostasis Source: BHF-UCL
  • locomotion Source: Ensembl
  • membrane depolarization during cardiac muscle cell action potential Source: BHF-UCL
  • membrane repolarization Source: BHF-UCL
  • negative regulation of calcium:sodium antiporter activity Source: BHF-UCL
  • negative regulation of calcium ion transmembrane transport Source: BHF-UCL
  • negative regulation of cytosolic calcium ion concentration Source: Ensembl
  • negative regulation of heart contraction Source: Ensembl
  • negative regulation of striated muscle contraction Source: Ensembl
  • neurotransmitter uptake Source: Ensembl
  • potassium ion import Source: BHF-UCL
  • potassium ion import across plasma membrane Source: BHF-UCL
  • potassium ion transport Source: UniProtKB
  • regulation of blood pressure Source: Ensembl
  • regulation of cardiac muscle cell contraction Source: Ensembl
  • regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion Source: BHF-UCL
  • regulation of glutamate uptake involved in transmission of nerve impulse Source: BHF-UCL
  • regulation of respiratory gaseous exchange by neurological system process Source: Ensembl
  • regulation of smooth muscle contraction Source: Ensembl
  • regulation of striated muscle contraction Source: UniProtKB
  • regulation of synaptic transmission, glutamatergic Source: BHF-UCL
  • regulation of the force of heart contraction Source: Ensembl
  • regulation of vasoconstriction Source: Ensembl
  • relaxation of cardiac muscle Source: BHF-UCL
  • response to glycoside Source: BHF-UCL
  • response to nicotine Source: Ensembl
  • sodium ion export across plasma membrane Source: BHF-UCL
  • sodium ion transport Source: UniProtKB
  • visual learning Source: Ensembl

Keywordsi

Molecular functionHydrolase
Biological processIon transport, Potassium transport, Sodium transport, Sodium/potassium transport, Transport
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding, Potassium, Sodium

Enzyme and pathway databases

ReactomeiR-HSA-5578775 Ion homeostasis
R-HSA-936837 Ion transport by P-type ATPases

Protein family/group databases

TCDBi3.A.3.1.1 the p-type atpase (p-atpase) superfamily

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium/potassium-transporting ATPase subunit alpha-2 (EC:3.6.3.9)
Short name:
Na(+)/K(+) ATPase alpha-2 subunit
Alternative name(s):
Sodium pump subunit alpha-2
Gene namesi
Name:ATP1A2
Synonyms:KIAA0778
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000018625.14
HGNCiHGNC:800 ATP1A2
MIMi182340 gene
neXtProtiNX_P50993

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini6 – 85CytoplasmicSequence analysisAdd BLAST80
Transmembranei86 – 106HelicalSequence analysisAdd BLAST21
Topological domaini107 – 129ExtracellularSequence analysisAdd BLAST23
Transmembranei130 – 150HelicalSequence analysisAdd BLAST21
Topological domaini151 – 286CytoplasmicSequence analysisAdd BLAST136
Transmembranei287 – 306HelicalSequence analysisAdd BLAST20
Topological domaini307 – 318ExtracellularSequence analysisAdd BLAST12
Transmembranei319 – 336HelicalSequence analysisAdd BLAST18
Topological domaini337 – 769CytoplasmicSequence analysisAdd BLAST433
Transmembranei770 – 789HelicalSequence analysisAdd BLAST20
Topological domaini790 – 799ExtracellularSequence analysis10
Transmembranei800 – 820HelicalSequence analysisAdd BLAST21
Topological domaini821 – 840CytoplasmicSequence analysisAdd BLAST20
Transmembranei841 – 863HelicalSequence analysisAdd BLAST23
Topological domaini864 – 915ExtracellularSequence analysisAdd BLAST52
Transmembranei916 – 935HelicalSequence analysisAdd BLAST20
Topological domaini936 – 948CytoplasmicSequence analysisAdd BLAST13
Transmembranei949 – 967HelicalSequence analysisAdd BLAST19
Topological domaini968 – 982ExtracellularSequence analysisAdd BLAST15
Transmembranei983 – 1003HelicalSequence analysisAdd BLAST21
Topological domaini1004 – 1020CytoplasmicSequence analysisAdd BLAST17

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Migraine, familial hemiplegic, 2 (FHM2)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA subtype of migraine with aura associated with hemiparesis in some families. Migraine is a disabling symptom complex of periodic headaches, usually temporal and unilateral. Headaches are often accompanied by irritability, nausea, vomiting and photophobia, preceded by constriction of the cranial arteries. Migraine with aura is characterized by recurrent attacks of reversible neurological symptoms (aura) that precede or accompany the headache. Aura may include a combination of sensory disturbances, such as blurred vision, hallucinations, vertigo, numbness and difficulty in concentrating and speaking.
See also OMIM:602481
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_019935689R → Q in FHM2. 1 PublicationCorresponds to variant dbSNP:rs28933401EnsemblClinVar.1
Natural variantiVAR_065685715G → R in FHM2; de novo mutation in a sporadic case. 1 Publication1
Natural variantiVAR_019936731M → T in FHM2. 1 PublicationCorresponds to variant dbSNP:rs28933400EnsemblClinVar.1
Natural variantiVAR_019937764L → P in FHM2; loss of function. 1 PublicationCorresponds to variant dbSNP:rs28933398EnsemblClinVar.1
Natural variantiVAR_069991874G → S in FHM2; some patients exhibit a clinical overlap between migraine and epilepsy. 1 Publication1
Natural variantiVAR_019938887W → R in FHM2; loss of function. 1 PublicationCorresponds to variant dbSNP:rs28933399EnsemblClinVar.1
Natural variantiVAR_0699921007R → W in FHM2; some patients exhibit a clinical overlap between migraine and epilepsy. 1 Publication1
Alternating hemiplegia of childhood 1 (AHC1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare syndrome of episodic hemi- or quadriplegia lasting minutes to days. Most cases are accompanied by dystonic posturing, choreoathetoid movements, nystagmus, other ocular motor abnormalities, autonomic disturbances, and progressive cognitive impairment. It is typically distinguished from familial hemiplegic migraine by infantile onset and high prevalence of associated neurological deficits that become increasingly obvious with age.
See also OMIM:104290
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_019934378T → N in AHC1. 1 PublicationCorresponds to variant dbSNP:rs28934002EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi477
GeneReviewsiATP1A2
MalaCardsiATP1A2
MIMi104290 phenotype
602481 phenotype
OpenTargetsiENSG00000018625
Orphaneti2131 Alternating hemiplegia of childhood
569 Familial or sporadic hemiplegic migraine
PharmGKBiPA30796

Chemistry databases

ChEMBLiCHEMBL2095186
DrugBankiDB09479 Rubidium chloride Rb-82

Polymorphism and mutation databases

BioMutaiATP1A2
DMDMi1703467

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_00000025031 – 5By similarity5
ChainiPRO_00000025046 – 1020Sodium/potassium-transporting ATPase subunit alpha-2Add BLAST1015

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei10PhosphoserineBy similarity1
Modified residuei439PhosphoserineBy similarity1
Modified residuei450PhosphoserineBy similarity1
Modified residuei496PhosphoserineBy similarity1
Modified residuei559PhosphoserineBy similarity1
Modified residuei570PhosphothreonineCombined sources1
Modified residuei587PhosphoserineCombined sources1
Modified residuei672PhosphoserineBy similarity1
Modified residuei826PhosphoserineBy similarity1
Modified residuei940Phosphoserine; by PKABy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP50993
MaxQBiP50993
PaxDbiP50993
PeptideAtlasiP50993
PRIDEiP50993
ProteomicsDBi56274

PTM databases

iPTMnetiP50993
PhosphoSitePlusiP50993
SwissPalmiP50993

Expressioni

Gene expression databases

BgeeiENSG00000018625
CleanExiHS_ATP1A2
ExpressionAtlasiP50993 baseline and differential
GenevisibleiP50993 HS

Organism-specific databases

HPAiCAB022230

Interactioni

Subunit structurei

The sodium/potassium-transporting ATPase is composed of a catalytic alpha subunit, an auxiliary non-catalytic beta subunit and an additional regulatory subunit. Interacts with regulatory subunit FXYD1.By similarity

GO - Molecular functioni

  • chaperone binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi106967, 20 interactors
IntActiP50993, 2 interactors
STRINGi9606.ENSP00000354490

Chemistry databases

BindingDBiP50993

Structurei

3D structure databases

ProteinModelPortaliP50993
SMRiP50993
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni80 – 82Interaction with phosphoinositide-3 kinaseBy similarity3

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0203 Eukaryota
COG0474 LUCA
GeneTreeiENSGT00890000139334
HOGENOMiHOG000265622
HOVERGENiHBG004298
InParanoidiP50993
KOiK01539
OMAiYVFGGFC
OrthoDBiEOG091G01BB
PhylomeDBiP50993
TreeFamiTF312838

Family and domain databases

CDDicd02608 P-type_ATPase_Na-K_like, 1 hit
Gene3Di3.40.1110.10, 1 hit
3.40.50.1000, 2 hits
InterProiView protein in InterPro
IPR006068 ATPase_P-typ_cation-transptr_C
IPR004014 ATPase_P-typ_cation-transptr_N
IPR023299 ATPase_P-typ_cyto_dom_N
IPR018303 ATPase_P-typ_P_site
IPR023298 ATPase_P-typ_TM_dom_sf
IPR008250 ATPase_P-typ_transduc_dom_A_sf
IPR036412 HAD-like_sf
IPR023214 HAD_sf
IPR005775 P-type_ATPase_IIC
IPR001757 P_typ_ATPase
PfamiView protein in Pfam
PF00689 Cation_ATPase_C, 1 hit
PF00690 Cation_ATPase_N, 1 hit
SMARTiView protein in SMART
SM00831 Cation_ATPase_N, 1 hit
SUPFAMiSSF56784 SSF56784, 2 hits
SSF81653 SSF81653, 1 hit
SSF81660 SSF81660, 1 hit
SSF81665 SSF81665, 3 hits
TIGRFAMsiTIGR01106 ATPase-IIC_X-K, 1 hit
TIGR01494 ATPase_P-type, 2 hits
PROSITEiView protein in PROSITE
PS00154 ATPASE_E1_E2, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P50993-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGRGAGREYS PAATTAENGG GKKKQKEKEL DELKKEVAMD DHKLSLDELG
60 70 80 90 100
RKYQVDLSKG LTNQRAQDVL ARDGPNALTP PPTTPEWVKF CRQLFGGFSI
110 120 130 140 150
LLWIGAILCF LAYGIQAAME DEPSNDNLYL GVVLAAVVIV TGCFSYYQEA
160 170 180 190 200
KSSKIMDSFK NMVPQQALVI REGEKMQINA EEVVVGDLVE VKGGDRVPAD
210 220 230 240 250
LRIISSHGCK VDNSSLTGES EPQTRSPEFT HENPLETRNI CFFSTNCVEG
260 270 280 290 300
TARGIVIATG DRTVMGRIAT LASGLEVGRT PIAMEIEHFI QLITGVAVFL
310 320 330 340 350
GVSFFVLSLI LGYSWLEAVI FLIGIIVANV PEGLLATVTV CLTLTAKRMA
360 370 380 390 400
RKNCLVKNLE AVETLGSTST ICSDKTGTLT QNRMTVAHMW FDNQIHEADT
410 420 430 440 450
TEDQSGATFD KRSPTWTALS RIAGLCNRAV FKAGQENISV SKRDTAGDAS
460 470 480 490 500
ESALLKCIEL SCGSVRKMRD RNPKVAEIPF NSTNKYQLSI HEREDSPQSH
510 520 530 540 550
VLVMKGAPER ILDRCSTILV QGKEIPLDKE MQDAFQNAYM ELGGLGERVL
560 570 580 590 600
GFCQLNLPSG KFPRGFKFDT DELNFPTEKL CFVGLMSMID PPRAAVPDAV
610 620 630 640 650
GKCRSAGIKV IMVTGDHPIT AKAIAKGVGI ISEGNETVED IAARLNIPMS
660 670 680 690 700
QVNPREAKAC VVHGSDLKDM TSEQLDEILK NHTEIVFART SPQQKLIIVE
710 720 730 740 750
GCQRQGAIVA VTGDGVNDSP ALKKADIGIA MGISGSDVSK QAADMILLDD
760 770 780 790 800
NFASIVTGVE EGRLIFDNLK KSIAYTLTSN IPEITPFLLF IIANIPLPLG
810 820 830 840 850
TVTILCIDLG TDMVPAISLA YEAAESDIMK RQPRNSQTDK LVNERLISMA
860 870 880 890 900
YGQIGMIQAL GGFFTYFVIL AENGFLPSRL LGIRLDWDDR TMNDLEDSYG
910 920 930 940 950
QEWTYEQRKV VEFTCHTAFF ASIVVVQWAD LIICKTRRNS VFQQGMKNKI
960 970 980 990 1000
LIFGLLEETA LAAFLSYCPG MGVALRMYPL KVTWWFCAFP YSLLIFIYDE
1010 1020
VRKLILRRYP GGWVEKETYY
Length:1,020
Mass (Da):112,265
Last modified:October 1, 1996 - v1
Checksum:iAFBD8EA94FFB4FC3
GO

Sequence cautioni

The sequence BAA34498 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_078231366G → A Probable disease-associated mutation found in a patient with early infantile epileptic encephalopathy. 1 PublicationCorresponds to variant dbSNP:rs1057518514Ensembl.1
Natural variantiVAR_019934378T → N in AHC1. 1 PublicationCorresponds to variant dbSNP:rs28934002EnsemblClinVar.1
Natural variantiVAR_078232593R → W Found in a patient with early infantile epileptic encephalopathy; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs886039530EnsemblClinVar.1
Natural variantiVAR_019935689R → Q in FHM2. 1 PublicationCorresponds to variant dbSNP:rs28933401EnsemblClinVar.1
Natural variantiVAR_065685715G → R in FHM2; de novo mutation in a sporadic case. 1 Publication1
Natural variantiVAR_019936731M → T in FHM2. 1 PublicationCorresponds to variant dbSNP:rs28933400EnsemblClinVar.1
Natural variantiVAR_019937764L → P in FHM2; loss of function. 1 PublicationCorresponds to variant dbSNP:rs28933398EnsemblClinVar.1
Natural variantiVAR_069991874G → S in FHM2; some patients exhibit a clinical overlap between migraine and epilepsy. 1 Publication1
Natural variantiVAR_019938887W → R in FHM2; loss of function. 1 PublicationCorresponds to variant dbSNP:rs28933399EnsemblClinVar.1
Natural variantiVAR_0699921007R → W in FHM2; some patients exhibit a clinical overlap between migraine and epilepsy. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J05096 Genomic DNA Translation: AAA51797.1
AB018321 mRNA Translation: BAA34498.2 Different initiation.
AL121987 Genomic DNA No translation available.
CH471121 Genomic DNA Translation: EAW52740.1
CH471121 Genomic DNA Translation: EAW52741.1
BC052271 mRNA Translation: AAH52271.2
M16795 mRNA Translation: AAA51799.1
M27578, M27571, M27576 Genomic DNA Translation: AAA35575.1
Y07494 mRNA Translation: CAA68793.1 Sequence problems.
CCDSiCCDS1196.1
PIRiA34474
RefSeqiNP_000693.1, NM_000702.3
UniGeneiHs.34114

Genome annotation databases

EnsembliENST00000361216; ENSP00000354490; ENSG00000018625
GeneIDi477
KEGGihsa:477
UCSCiuc001fvc.4 human

Similar proteinsi

Entry informationi

Entry nameiAT1A2_HUMAN
AccessioniPrimary (citable) accession number: P50993
Secondary accession number(s): D3DVE4
, Q07059, Q5JW74, Q86UZ5, Q9UQ25
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: June 20, 2018
This is version 189 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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