Genomes and Genes
Gene Symbol: Atp1a2
Description: ATPase Na+/K+ transporting subunit alpha 2
Alias: RATATPA2, sodium/potassium-transporting ATPase subunit alpha-2, ATPase, Na+/K+ transporting, alpha 2 polypeptide, ATPase, Na+K+ transporting, alpha 2, Na(+)/K(+) ATPase alpha(+) subunit, Na(+)/K(+) ATPase alpha-2 subunit, Na+/K+ -ATPase alpha 2 subunit, sodium pump subunit alpha-2
- TepavÄeviÄ‡ S, MilutinoviÄ‡ D, Macut D, StaniÅ¡iÄ‡ J, NikoliÄ‡ M, BoÅ¾iÄ‡ AntiÄ‡ I, et al. Cardiac Nitric Oxide Synthases and Naâº/Kâº-ATPase in the Rat Model of Polycystic Ovary Syndrome Induced by Dihydrotestosterone. Exp Clin Endocrinol Diabetes. 2015;123:303-7 pubmed publisher..Regarding the importance of NO production and sodium/potassium transport in the cardiac contraction and blood flow regulation, it implicates strong consequences of PCOS for heart functioning. ..
- Lee Y, Tokraks S, Pratley R, Bogardus C, Permana P. Identification of differentially expressed genes in skeletal muscle of non-diabetic insulin-resistant and insulin-sensitive Pima Indians by differential display PCR. Diabetologia. 2003;46:1567-75 pubmed..38, p=0.007), ATP1A2 (r=-0.27, p=0.05), MAP2K4 (r=-0.34, p=0.02), and PRPSAP1 (r=-0.37, p=0.008)...
- Despa S, Bers D. Functional analysis of Na+/K+-ATPase isoform distribution in rat ventricular myocytes. Am J Physiol Cell Physiol. 2007;293:C321-7 pubmed..The functional density of NKA-alpha2 is approximately 4.5 times higher in the T-tubules vs. ESL, whereas NKA-alpha1 is almost uniformly distributed between the TT and ESL...
- Moseley A, Lieske S, Wetzel R, James P, He S, Shelly D, et al. The Na,K-ATPase alpha 2 isoform is expressed in neurons, and its absence disrupts neuronal activity in newborn mice. J Biol Chem. 2003;278:5317-24 pubmed..These data demonstrate that the Na,K-ATPase alpha2 isoform could be important in the modulation of neuronal activity in the neonate. ..
- Vanmolkot K, Kors E, Hottenga J, Terwindt G, Haan J, Hoefnagels W, et al. Novel mutations in the Na+, K+-ATPase pump gene ATP1A2 associated with familial hemiplegic migraine and benign familial infantile convulsions. Ann Neurol. 2003;54:360-6 pubmed..Some CACNA1A mutations also may cause epilepsy. Here, we describe novel missense mutations in the ATP1A2 Na(+),K(+)-ATPase pump gene on chromosome 1q23 in two families with FHM...
- Swift F, Birkeland J, Tovsrud N, Enger U, Aronsen J, Louch W, et al. Altered Na+/Ca2+-exchanger activity due to downregulation of Na+/K+-ATPase alpha2-isoform in heart failure. Cardiovasc Res. 2008;78:71-8 pubmed publisher..Downregulation of the alpha2-isoform causes attenuated control of NCX activity in CHF, reducing its capability to extrude Ca2+ from cardiomyocytes. ..
- Kawakami K, Onaka T, Iwase M, Homma I, Ikeda K. Hyperphagia and obesity in Na,K-ATPase alpha2 subunit-defective mice. Obes Res. 2005;13:1661-71 pubmedThe Na,K-ATPase alpha2 subunit gene (Atp1a2) is expressed in the brain, skeletal muscles, heart, and adipocytes...
- Guo X, Wang J, Elimban V, Dhalla N. Both enalapril and losartan attenuate sarcolemmal Na+-K+-ATPase remodeling in failing rat heart due to myocardial infarction. Can J Physiol Pharmacol. 2008;86:139-47 pubmed publisher..These results provide further evidence that CHF due to MI is associated with remodeling of SL membrane and suggest that the blockade of RAS plays an important role in preventing these alterations in the failing heart. ..
- Adir Y, Welch L, Dumasius V, Factor P, Sznajder J, Ridge K. Overexpression of the Na-K-ATPase alpha2-subunit improves lung liquid clearance during ventilation-induced lung injury. Am J Physiol Lung Cell Mol Physiol. 2008;294:L1233-7 pubmed publisher..In summary, we provide evidence that augmentation of the Na-K-ATPase alpha(2)-subunit, via gene transfer, may accelerate LLC in the injured lung. ..
- Shelly D, He S, Moseley A, Weber C, Stegemeyer M, Lynch R, et al. Na(+) pump alpha 2-isoform specifically couples to contractility in vascular smooth muscle: evidence from gene-targeted neonatal mice. Am J Physiol Cell Physiol. 2004;286:C813-20 pubmed..Three-dimensional image-acquisition and deconvolution analyses suggest that the alpha(2)-isoform is distributed differently than the alpha(1)-isoform. Importantly, these isoforms do not localize to the same regions. ..
- Matsushita N, Kitazato K, Tada Y, Sumiyoshi M, Shimada K, Yagi K, et al. Increase in body Na+/water ratio is associated with cerebral aneurysm formation in oophorectomized rats. Hypertension. 2012;60:1309-15 pubmed publisher..We provide the new insight that the management of water-free Na(+) is important to prevent their development. ..
- Moseley A, Williams M, Schaefer T, Bohanan C, Neumann J, Behbehani M, et al. Deficiency in Na,K-ATPase alpha isoform genes alters spatial learning, motor activity, and anxiety in mice. J Neurosci. 2007;27:616-26 pubmed..The neurobehavioral changes seen in heterozygous mice suggest that these mouse models may be useful in future investigations of the associated human CNS disorders. ..
- Mohler P, Davis J, Bennett V. Ankyrin-B coordinates the Na/K ATPase, Na/Ca exchanger, and InsP3 receptor in a cardiac T-tubule/SR microdomain. PLoS Biol. 2005;3:e423 pubmed..Ankyrin-B also is not abundantly expressed in smooth muscle. We propose that the ankyrin-B-based complex is a specialized adaptation of cardiomyocytes with a role for cytosolic Ca2+ modulation. ..
- Segall L, Mezzetti A, Scanzano R, Gargus J, Purisima E, Blostein R. Alterations in the alpha2 isoform of Na,K-ATPase associated with familial hemiplegic migraine type 2. Proc Natl Acad Sci U S A. 2005;102:11106-11 pubmed
- Kravtsova V, Matchkov V, Bouzinova E, Vasiliev A, Razgovorova I, Heiny J, et al. Isoform-specific Na,K-ATPase alterations precede disuse-induced atrophy of rat soleus muscle. Biomed Res Int. 2015;2015:720172 pubmed publisher..Our findings suggest that skeletal muscle use is absolutely required for Î±2 Na,K-ATPase transport activity and provide the first evidence that Na,K-ATPase alterations precede HS-induced muscle atrophy. ..
- Pritchard T, Parvatiyar M, Bullard D, Lynch R, Lorenz J, Paul R. Transgenic mice expressing Na+-K+-ATPase in smooth muscle decreases blood pressure. Am J Physiol Heart Circ Physiol. 2007;293:H1172-82 pubmed..Our results show that smooth muscle displays unique coordinate expression of the alpha-isoforms. Increasing smooth muscle NKA decreases blood pressure and is dependent on the degree of increased alpha-isoform expression. ..
- Chibalin A, Heiny J, Benziane B, Prokofiev A, Vasiliev A, Kravtsova V, et al. Chronic nicotine modifies skeletal muscle Na,K-ATPase activity through its interaction with the nicotinic acetylcholine receptor and phospholemman. PLoS ONE. 2012;7:e33719 pubmed publisher..Cholinergic modulation of Na,K-ATPase activity is achieved, in part, through activation of PKC and phosphorylation of PLM. ..
- Yin J, Guo H, Yu D, Wang H, Li J, Wang Y. Mechanisms of isoform-specific Na/K pump regulation by short- and long-term adrenergic activation in rat ventricular myocytes. Cell Physiol Biochem. 2014;33:1681-97 pubmed publisher..Furthermore, long-term regulation involves transcription and translation of the respective ?-isoform, whereas short-term regulation involves the translocation of the available ?-isoform to the plasma membrane. ..
- Galuska D, Kotova O, Barres R, Chibalina D, Benziane B, Chibalin A. Altered expression and insulin-induced trafficking of Na+-K+-ATPase in rat skeletal muscle: effects of high-fat diet and exercise. Am J Physiol Endocrinol Metab. 2009;297:E38-49 pubmed publisher..Disturbances in skeletal muscle Na(+)-K(+)-ATPase regulation, particularly the alpha(2)-subunit, may contribute to impaired ion homeostasis in insulin-resistant states such as obesity and type 2 diabetes. ..
- Toustrup Jensen M, Einholm A, Schack V, Nielsen H, Holm R, Sobrido M, et al. Relationship between intracellular Na+ concentration and reduced Na+ affinity in Na+,K+-ATPase mutants causing neurological disease. J Biol Chem. 2014;289:3186-97 pubmed publisher..Moreover, two mutations that increase Na(+) affinity were found to reduce [Na(+)]i. It is concluded that the Na(+) affinity of the Na(+),K(+)-ATPase is an important determinant of [Na(+)]i. ..
- Dostanic I, Schultz J, Lorenz J, Lingrel J. The alpha 1 isoform of Na,K-ATPase regulates cardiac contractility and functionally interacts and co-localizes with the Na/Ca exchanger in heart. J Biol Chem. 2004;279:54053-61 pubmed..These results demonstrate that the alpha 1 isoform regulates cardiac contractility, and that both the alpha 1 and alpha 2 isoforms are functionally and physically coupled with the Na/Ca exchanger in heart. ..
- Efendiev R, Krmar R, Ogimoto G, Zwiller J, Tripodi G, Katz A, et al. Hypertension-linked mutation in the adducin alpha-subunit leads to higher AP2-mu2 phosphorylation and impaired Na+,K+-ATPase trafficking in response to GPCR signals and intracellular sodium. Circ Res. 2004;95:1100-8 pubmed
- Segall L, Javaid Z, Carl S, Lane L, Blostein R. Structural basis for alpha1 versus alpha2 isoform-distinct behavior of the Na,K-ATPase. J Biol Chem. 2003;278:9027-34 pubmed..In addition, we show that the E(1) shift of alpha2 results primarily from differences in the conformational transition of the dephosphoenzyme, (E(2)(K(+)) --> E(1) + K(+)), rather than phosphoenzyme (E(1)P --> E(2)P). ..
- Seidel B, Keilhoff G, Reinheckel T, Wolf G. Differentially expressed genes in hippocampal cell cultures in response to an excitotoxic insult by quinolinic acid. Brain Res Mol Brain Res. 1998;60:296-300 pubmed..The results provide emphasis to the participation of proteolysis and protease inhibition in neurodegenerative processes. ..
- Glenn B, Stewart W, Schwartz B, Bressler J. Relation of alleles of the sodium-potassium adenosine triphosphatase alpha 2 gene with blood pressure and lead exposure. Am J Epidemiol. 2001;153:537-45 pubmed..pressure, hypertension prevalence, and polymorphisms in the gene for the alpha 2 subunit of Na(+)-K(+)ATPase (ATP1A2) among 220 former organolead manufacturing workers from New Jersey...
- Maturana Teixeira S, Braga L, Carpi Santos R, Calaza K, Giestal de Araujo E, LeÃ£o Ferreira L. The (Na(+)/K (+))-ATPase activity in the developing rat retina: the role of insulin-like growth factor-I (IGF-I). Cell Mol Neurobiol. 2015;35:243-54 pubmed publisher..Together, these data demonstrate that the PI 3-kinase/PKB signaling pathway is involved in the IGF-I-sustained basal (Na(+)/K(+))-ATPase activity during the first 7 days of the postnatal development of rat retina. ..
- Xie J, Ye Q, Cui X, Madan N, Yi Q, Pierre S, et al. Expression of rat Na-K-ATPase Î±2 enables ion pumping but not ouabain-induced signaling in Î±1-deficient porcine renal epithelial cells. Am J Physiol Cell Physiol. 2015;309:C373-82 pubmed publisher..This further implies that the signaling mechanism of Na-K-ATPase is isoform specific, thereby supporting a model where Î±1 and Î±2 isoforms play distinct roles in mediating contraction and signaling in myocytes. ..
- He S, Shelly D, Moseley A, James P, James J, Paul R, et al. The alpha(1)- and alpha(2)-isoforms of Na-K-ATPase play different roles in skeletal muscle contractility. Am J Physiol Regul Integr Comp Physiol. 2001;281:R917-25 pubmed..These results demonstrate that the Na-K-ATPase alpha(1)- and alpha(2)-isoforms may play different roles in skeletal muscle contraction...
- Li J, Codina J, Petroske E, Werle M, Willingham M, Dubose T. The effect of beta-subunit assembly on function and localization of the colonic H+,K+-ATPase alpha-subunit. Kidney Int. 2004;66:1068-75 pubmed..Taken together, these and previous results from our laboratory indicate that beta(1)-Na(+),K(+)-ATPase is likely to represent the most physiologic and efficient subunit for HKalpha(2) assembly in distal colon. ..
- Crambert G, Schaer D, Roy S, Geering K. New molecular determinants controlling the accessibility of ouabain to its binding site in human Na,K-ATPase alpha isoforms. Mol Pharmacol. 2004;65:335-41 pubmed
- Baek M, Weiss M. Down-regulation of Na+ pump alpha 2 isoform in isoprenaline-induced cardiac hypertrophy in rat: evidence for increased receptor binding affinity but reduced inotropic potency of digoxin. J Pharmacol Exp Ther. 2005;313:731-9 pubmed..Coadministration of KB-R7943 significantly reduced cellular response generation at higher digoxin doses to the same limiting stimulus-response relationship in both the vehicle and isoprenaline group. ..
- Swarts H, Weigand K, Venselaar H, van den Maagdenberg A, Russel F, Koenderink J. Familial hemiplegic migraine mutations affect Na,K-ATPase domain interactions. Biochim Biophys Acta. 2013;1832:2173-9 pubmed publisher..One of the three known causative genes, ATP1A2, which encodes the ?2 isoform of Na,K-ATPase, causes FHM type 2 (FHM2)...
- Shen H, Liang P, Qiu S, Zhang B, Wang Y, Lv P. The role of Na(+), K(+)-ATPase in the hypoxic vasoconstriction in isolated rat basilar artery. Vascul Pharmacol. 2016;81:53-60 pubmed publisher..These results suggest that hypoxia may educe Na(+), K(+)-ATPase activity in SMCs through the Î±2 isoform contributing to vasoconstriction in the rat basilar artery. ..
- Song H, Lee M, Kinsey S, Weber D, Blaustein M. An N-terminal sequence targets and tethers Na+ pump alpha2 subunits to specialized plasma membrane microdomains. J Biol Chem. 2006;281:12929-40 pubmed..Amino acid substitutions in the 1-120 alpha1 and alpha2 constructs, and in full-length alpha1, revealed that Leu-27 and Ala-35 are essential for targeting/tethering the constructs to PM-S/ER junctions. ..
- Swift F, Tovsrud N, Enger U, Sjaastad I, Sejersted O. The Na+/K+-ATPase alpha2-isoform regulates cardiac contractility in rat cardiomyocytes. Cardiovasc Res. 2007;75:109-17 pubmed..The alpha2-isoform of the NKA is functionally coupled to the NCX and can regulate Ca2+ handling without changing global [Na+]i. ..
- Krenek P, Hamaide M, Morel N, Wibo M. A simple method for rapid separation of endothelial and smooth muscle mRNA reveals Na/K+ -ATPase alpha-subunit distribution in rat arteries. J Vasc Res. 2006;43:502-10 pubmed
- James P, Grupp I, Grupp G, Woo A, Askew G, Croyle M, et al. Identification of a specific role for the Na,K-ATPase alpha 2 isoform as a regulator of calcium in the heart. Mol Cell. 1999;3:555-63 pubmed..These results definitively illustrate a specific role for the alpha 2 Na,K-ATPase isoform in Ca2+ signaling during cardiac contraction. ..
- Ikeda K, Onaka T, Yamakado M, Nakai J, Ishikawa T, Taketo M, et al. Degeneration of the amygdala/piriform cortex and enhanced fear/anxiety behaviors in sodium pump alpha2 subunit (Atp1a2)-deficient mice. J Neurosci. 2003;23:4667-76 pubmed
- Tian G, Dang C, Lu Z. The change and significance of the Na+-K+-ATPase alpha-subunit in ouabain-hypertensive rats. Hypertens Res. 2001;24:729-34 pubmed..These results suggest that the high level of ouabain and the change of the Na+-K+-ATPase alpha-subunit isoforms may play a critical role in hypertension. ..
- Beguin P, Crambert G, Monnet Tschudi F, Uldry M, Horisberger J, Garty H, et al. FXYD7 is a brain-specific regulator of Na,K-ATPase alpha 1-beta isozymes. EMBO J. 2002;21:3264-73 pubmed..These data suggest that FXYD7 is a novel, tissue- and isoform-specific Na,K-ATPase regulator which could play an important role in neuronal excitability. ..
- Cholet N, Pellerin L, Magistretti P, Hamel E. Similar perisynaptic glial localization for the Na+,K+-ATPase alpha 2 subunit and the glutamate transporters GLAST and GLT-1 in the rat somatosensory cortex. Cereb Cortex. 2002;12:515-25 pubmed..Altogether these results demonstrate that alpha(2), GLAST and GLT-1 have comparable perisynaptic distribution within cortical astrocytes most likely associated with glutamatergic synapses. ..
- Ikeda K, Onimaru H, Yamada J, Inoue K, Ueno S, Onaka T, et al. Malfunction of respiratory-related neuronal activity in Na+, K+-ATPase alpha2 subunit-deficient mice is attributable to abnormal Cl- homeostasis in brainstem neurons. J Neurosci. 2004;24:10693-701 pubmedNa+, K+-ATPase 2 subunit gene (Atp1a2) knock-out homozygous mice (Atp1a2-/-) died immediately after birth resulting from lack of breathing...
- Shull G, Greeb J, Lingrel J. Molecular cloning of three distinct forms of the Na+,K+-ATPase alpha-subunit from rat brain. Biochemistry. 1986;25:8125-32 pubmed
- Yuan X, Luo S, Lin Z, Wu Y. Cyclic stretch translocates the alpha2-subunit of the Na pump to plasma membrane in skeletal muscle cells in vitro. Biochem Biophys Res Commun. 2006;348:750-7 pubmed
- Scherer E, Loureiro S, Vuaden F, Schmitz F, Kolling J, Siebert C, et al. Mild hyperhomocysteinemia reduces the activity and immunocontent, but does not alter the gene expression, of catalytic ? subunits of cerebral Na+,K+-ATPase. Mol Cell Biochem. 2013;378:91-7 pubmed publisher..The present findings support that the homocysteine modulates the Na(+),K(+)-ATPase and this could be associated, at least in part, with the risk to the development of cerebral diseases in individuals with mild hyperhomocysteinemia. ..
- De Fusco M, Marconi R, Silvestri L, Atorino L, Rampoldi L, Morgante L, et al. Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump alpha2 subunit associated with familial hemiplegic migraine type 2. Nat Genet. 2003;33:192-6 pubmed..Here we show that mutations in the gene ATP1A2 that encodes the alpha2 subunit of the Na+/K+ pump are associated with familial hemiplegic migraine type 2 (FHM2) ..
- Dostanic Larson I, Van Huysse J, Lorenz J, Lingrel J. The highly conserved cardiac glycoside binding site of Na,K-ATPase plays a role in blood pressure regulation. Proc Natl Acad Sci U S A. 2005;102:15845-50 pubmed..Taken together these results demonstrate that the cardiac glycoside binding site of the alpha isoforms of the Na,K-ATPase have a physiological function and supports the hypothesis for a role of the endogenous cardiac glycosides...
- Pierre S, Duran M, Carr D, Pressley T. Structure/function analysis of Na(+)-K(+)-ATPase central isoform-specific region: involvement in PKC regulation. Am J Physiol Renal Physiol. 2002;283:F1066-74 pubmed..Comparisons with rat full-length alpha(1)- and alpha(2)-isoforms expressed under the same conditions suggest an involvement of the central ISR in the response to PKC but not in K(+) deocclusion. ..
- Crambert G, Hasler U, Beggah A, Yu C, Modyanov N, Horisberger J, et al. Transport and pharmacological properties of nine different human Na, K-ATPase isozymes. J Biol Chem. 2000;275:1976-86 pubmed..In conclusion, our study reveals several new functional characteristics of human Na,K-ATPase isozymes which help to better understand their role in ion homeostasis in different tissues and in digitalis action and toxicity. ..