Na+/K+-ATPase (sodium-potassium adenosine triphosphatase) is an enzyme (EC 188.8.131.52) located in the plasma membrane. This enzyme consists of different isozymes, each resulting from the association of distinct molecular forms of the alpha (alpha 1, alpha 2, alpha 3 and alpha 4) and beta (beta 1, beta 2 and beta 3) subunits that constitute the enzyme. While the alpha subunit is responsible for the catalytic and transport functions of the Na,K-ATPase, the beta polypeptide participates in the correct folding and targeting of the holoenzyme to the plasma membrane. Besides the alpha and beta isoforms, a third subunit, the gamma subunit forms part of the Na,K-ATPase. This polypeptide appears to be involved in the modulation of the enzymatic properties of the enzyme.
CHEMICAL STRUCTURE AND IMAGES
When relevant for the function
- Primary structure
- Secondary structure
- Tertiary structure
- Quaternary structure
Protein Aminoacids Percentage
The Protein Aminoacids Percentage gives useful information on the local environment and the metabolic status of the cell (starvation, lack of essential AA, hypoxia)
Protein Aminoacids Percentage (Width 700 px)
SYNTHESIS AND TURNOVER
[Effect of aldosterone on aquaporin and ionophorous protein expressions in guinea pig cochlea].
[Article in Chinese] 2007
Early after aldosterone injection, the expression level of Na-K ATPase beta(1) and beta(3) subunit mRNAs remained unchanged and level of ENaC alpha subunit mRNA was up-regulated in the cochlear lateral wall (P<0.05), and 1 month after the injection, the expression of AQP1 protein was down-regulated (P<0.05).
The Na,K-ATPase or Na pump is an enzyme of the plasma membrane, that uses the free energy from the hydrolysis of ATP to transport cytoplasmic Na+ out of the cell in exchange for extracellular K+. The Na,K-ATPase is critical in maintaining cell volume and pH, the membrane excitability of muscle and nervous tissue, and plays a major role in the reabsorption of Na+ and water in the kidney.
NaK and HETE
NaK and Hearth
Glucose intestinal absorption
- Cell signaling and Ligand transport
- Structural proteins
Phosphorylation of PLM by PKA modifies the interaction between PLM and the Na/K-ATPase α1 subunit and increases the Vmax of the Na/K-ATPase enzyme complex.
Agrin Regulation of α3 Sodium-Potassium ATPase Activity Modulates Cardiac Myocyte Contraction, 2009
J Biol Chem. 2010 Apr 13. [Epub ahead of print]
Selectivity of digitalis glycosides for isoforms of human Na,K-ATPase.
There are four isoforms of the alpha subunit (alpha1-4) and three isoforms of the beta subunit (beta1-3) of Na,K-ATPase, with distinct tissue-specific distribution and physiological functions. alpha2 is thought to play a key role in cardiac and smooth muscle contraction and be an important target of cardiac glycosides. An alpha2-selective cardiac glycoside could provide important insights into physiological and pharmacological properties of alpha2. The isoform selectivity of a large number of cardiac glycosides has been assessed utilizing alpha1beta1, alpha2beta1 and alpha3beta1 isoforms of human Na,K-ATPase expressed in P. pastoris and the purified detergent-soluble isoform proteins. Binding affinities of the digitalis glycosides, digoxin, beta-methyl digoxin and digitoxin show moderate but highly significant selectivity (up to 4-fold) for alpha2/alpha3 over alpha1 (KDalpha1>alpha2=alpha3). By contrast, ouabain shows moderate selectivity ( approximately 2.5-fold) for alpha1 over alpha2 (KDalpha1</=alpha3<alpha2). Binding affinities for the three isoforms of digoxigenin, digitoxigenin, and all other aglycones tested, are indistinguishable (KDalpha1=alpha3=alpha2), showing that the sugar determines isoform selectivity. Selectivity patterns for inhibition of Na,K-ATPase activity of the purified isoform proteins are consistent with binding selectivities, modified somewhat by different affinities of K ions for antagonizing cardiac glycoside binding on the three isoforms. The mechanistic insight on the role of the sugars is strongly supported by a recent structure of Na,K-ATPase with bound ouabain, which implies that aglycones of cardiac glycosides cannot discriminate between isoforms. In conclusion, several digitalis glycosides, but not ouabain, are moderately alpha2-selective. This supports a major role of alpha2 in cardiac contraction and cardiotonic effects of digitalis glycosides.
Agrin and synuclein
Agrin binds alpha-synuclein and modulates alpha-synuclein fibrillation. 2005
Particularly, it has been shown that agrin is associated with the pathological lesions of Alzheimer's disease (AD) and may contribute to the formation of beta-amyloid (Abeta) plaques in AD.
We also show that agrin accelerates the formation of protofibrils by alpha-synuclein and decreases the half-time of fibril formation. The association of agrin with Parkinson's Disease lesions was also explored in PD human brain, and these studies shown that agrin colocalizes with alpha-synuclein in neuronal Lewy bodies in the substantia nigra of PD brain.