Target Information

Target General Infomation
Target ID
T40800
Former ID
TTDS00045
Target Name
Sodium/potassium-transporting ATPase alpha-1 chain
Gene Name
ATP1A1
Synonyms
Na+/K+ ATPase 1; Sodium pump 1; Sodium/potassium-transporting ATPase alpha1; ATP1A1
Target Type
Successful
Disease Anesthesia [ICD9: 338; ICD10: R20.0]
Atrial fibrillation; Heart failure [ICD9: 427.31, 428.0; ICD10: I48, I50]
Chronic obstructive pulmonary disease [ICD9: 490-492, 494-496; ICD10: J40-J44, J47]
Cancer [ICD9: 140-229; ICD10: C00-C96]
Congestive heart failure [ICD9: 428; ICD10: I50]
Congestive cardiac insufficiency; Arrhythmias; Heart failure [ICD9: 427, 428; ICD10: I47-I49, I50]
Hyperhidrosis [ICD9: 780.8; ICD10: R61]
Malaria [ICD10: B54]
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.
BioChemical Class
Acid anhydrides hydrolase
Target Validation
T40800
UniProt ID
P05023
EC Number
EC 3.6.3.9
Sequence
MGKGVGRDKYEPAAVSEQGDKKGKKGKKDRDMDELKKEVSMDDHKLSLDELHRKYGTDLS
RGLTSARAAEILARDGPNALTPPPTTPEWIKFCRQLFGGFSMLLWIGAILCFLAYSIQAA
TEEEPQNDNLYLGVVLSAVVIITGCFSYYQEAKSSKIMESFKNMVPQQALVIRNGEKMSI
NAEEVVVGDLVEVKGGDRIPADLRIISANGCKVDNSSLTGESEPQTRSPDFTNENPLETR
NIAFFSTNCVEGTARGIVVYTGDRTVMGRIATLASGLEGGQTPIAAEIEHFIHIITGVAV
FLGVSFFILSLILEYTWLEAVIFLIGIIVANVPEGLLATVTVCLTLTAKRMARKNCLVKN
LEAVETLGSTSTICSDKTGTLTQNRMTVAHMWFDNQIHEADTTENQSGVSFDKTSATWLA
LSRIAGLCNRAVFQANQENLPILKRAVAGDASESALLKCIELCCGSVKEMRERYAKIVEI
PFNSTNKYQLSIHKNPNTSEPQHLLVMKGAPERILDRCSSILLHGKEQPLDEELKDAFQN
AYLELGGLGERVLGFCHLFLPDEQFPEGFQFDTDDVNFPIDNLCFVGLISMIDPPRAAVP
DAVGKCRSAGIKVIMVTGDHPITAKAIAKGVGIISEGNETVEDIAARLNIPVSQVNPRDA
KACVVHGSDLKDMTSEQLDDILKYHTEIVFARTSPQQKLIIVEGCQRQGAIVAVTGDGVN
DSPALKKADIGVAMGIAGSDVSKQAADMILLDDNFASIVTGVEEGRLIFDNLKKSIAYTL
TSNIPEITPFLIFIIANIPLPLGTVTILCIDLGTDMVPAISLAYEQAESDIMKRQPRNPK
TDKLVNERLISMAYGQIGMIQALGGFFTYFVILAENGFLPIHLLGLRVDWDDRWINDVED
SYGQQWTYEQRKIVEFTCHTAFFVSIVVVQWADLVICKTRRNSVFQQGMKNKILIFGLFE
ETALAAFLSYCPGMGVALRMYPLKPTWWFCAFPYSLLIFVYDEVRKLIIRRRPGGWVEKE
TYY
Drugs and Mode of Action
Drug(s) Acetyldigitoxin Drug Info Approved Congestive heart failure [538419], [541875]
Almitrine Drug Info Approved Chronic obstructive pulmonary disease [534891]
Aluminium Drug Info Approved Hyperhidrosis [550682]
Artemether Drug Info Approved Malaria [536602]
Chloroprocaine Drug Info Approved Anesthesia [538175], [542152]
Deslanoside Drug Info Approved Congestive cardiac insufficiency; Arrhythmias; Heart failure [538415], [541888], [551871]
Lumefantrine Drug Info Approved Malaria [551871]
Ouabain Drug Info Approved Atrial fibrillation; Heart failure [468058], [550772]
Artemether Drug Info Phase 3 Malaria [531808], [551871]
UNBS-1450 Drug Info Phase 1 Cancer [548863]
Modulator Acetyldigitoxin Drug Info [556264]
Binder Almitrine Drug Info [537663], [537686]
Aluminium Drug Info [535839], [536035]
Artemether Drug Info [536602]
Deslanoside Drug Info [536316]
Lumefantrine Drug Info [536602]
Ouabain Drug Info [536316]
Blocker Chloroprocaine Drug Info [535175]
Inhibitor DIGITOXIGENIN Drug Info [525814]
UNBS-1450 Drug Info [533266]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway cGMP-PKG signaling pathway
cAMP signaling pathway
Cardiac muscle contraction
Adrenergic signaling in cardiomyocytes
Insulin secretion
Thyroid hormone synthesis
Thyroid hormone signaling pathway
Aldosterone-regulated sodium reabsorption
Endocrine and other factor-regulated calcium reabsorption
Proximal tubule bicarbonate reclamation
Salivary secretion
Gastric acid secretion
Pancreatic secretion
Carbohydrate digestion and absorption
Protein digestion and absorption
Bile secretion
Mineral absorption
PathWhiz Pathway Kidney Function
Lactose Degradation
Trehalose Degradation
Muscle/Heart Contraction
Reactome Ion transport by P-type ATPases
WikiPathways Iron uptake and transport
References
Ref 468058(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4826).
Ref 531808Lack of association of the S769N mutation in Plasmodium falciparum SERCA (PfATP6) with resistance to artemisinins. Antimicrob Agents Chemother. 2012 May;56(5):2546-52.
Ref 534891Improving oxygenation during bronchopulmonary lavage using nitric oxide inhalation and almitrine infusion. Anesth Analg. 1999 Aug;89(2):302-4.
Ref 536602The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
Ref 538175FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (ANDA) 040273.
Ref 538415FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 009282.
Ref 538419FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 009436.
Ref 541875(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6794).
Ref 541888(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6806).
Ref 542152(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7145).
Ref 548863Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800029692)
Ref 550682Drug information of Cocculin, 2008. eduDrugs.
Ref 550772Drug information of Ouabain, 2008. eduDrugs.
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 525814J Med Chem. 2000 Jun 15;43(12):2332-49.17beta-O-Aminoalkyloximes of 5beta-androstane-3beta,14beta-diol with digitalis-like activity: synthesis, cardiotonic activity, structure-activity relationships,and molecular modeling of the Na(+),K(+)-ATPase receptor.
Ref 533266Early downregulation of Mcl-1 regulates apoptosis triggered by cardiac glycoside UNBS1450. Cell Death Dis. 2015 Jun 11;6:e1782.
Ref 535175Inhibition of the Na,K-ATPase of canine renal medulla by several local anesthetics. Pharmacol Res. 2001 Apr;43(4):399-403.
Ref 535839The inhibitory effect of aluminium on the (Na+/K+)ATPase activity of rat brain cortex synaptosomes. J Inorg Biochem. 2003 Sep 15;97(1):143-50.
Ref 536035Effects of aluminium and lead on ATPase activity of knockout +/- mouse cerebral synaptosomes in vitro. Altern Lab Anim. 2004 Oct;32(4):361-7.
Ref 536316How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
Ref 536602The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr Med Chem. 2008;15(2):161-71.
Ref 537663Flux-dependent increase in the stoichiometry of charge translocation by mitochondrial ATPase/ATP synthase induced by almitrine. Biochim Biophys Acta. 1990 Jul 17;1018(1):91-7.
Ref 537686Almitrine, a new kind of energy-transduction inhibitor acting on mitochondrial ATP synthase. Biochim Biophys Acta. 1989 Aug 3;975(3):325-9.
Ref 556264Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.

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