Reactome | ATP1A:ATP1B:FXYD exchanges 3Na+ for 2K+

ATP1A:ATP1B:FXYD exchanges 3Na+ for 2K+

Stable Identifier

R-HSA-936897

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane

Synonyms

The Na+/K+-transporting ATPase trimer exchanges sodium for potassium

ReviewStatus

5/5

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The sodium/potassium-transporting ATPase (ATP1A:ATP1B:FXYD) is composed of three subunits - alpha (catalytic part), beta and gamma. The trimer catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane, creating the electrochemical gradient which provides energy for the active transport of various nutrients.
Four human genes encode the catalytic alpha subunits, ATP1A1-4 (Kawakami et al, 1986; Shull et al, 1989; Ovchinnikov et al, 1988; Keryanov and Gardner, 2002). Defects in ATP1A2 cause alternating hemiplegia of childhood (AHC) (Swoboda et al, 2004). Another defect in ATP1A2 causes familial hemiplegic migraine type 2 (FHM2) (Vanmolkot et al, 2003). Defects in ATP1A3 are the cause of dystonia type 12 (DYT12) (de Carvalho Aguiar et al, 2004).

Three human genes encode the non-catalytic beta subunits, ATP1B1-3. The beta subunits are thought to mediate the number of sodium pumps transported to the plasma membrane (Lane et al, 1989; Ruiz et al, 1996; Malik et al, 1996). FXYD proteins belong to a family of small membrane proteins that are auxiliary gamma subunits of Na-K-ATPase. At least six members of this family, FYD1-4, 6 and 7, have been shown to regulate Na-K-ATPase activity (Geering 2006, Choudhury et al. 2007). Defects in FXYD2 are the cause of hypomagnesemia type 2 (HOMG2) (Meij et al, 2000). ATP1A1-4 and ATP1B1-4 play a minor role during phase 2, since they begin to restore ion concentrations. The high concentration of intracellular calcium starts contraction of those cells, which is sustained in the plateau phase.

Literature References

PubMed ID	Title	Journal	Year
12953268	Novel mutations in the Na+, K+-ATPase pump gene ATP1A2 associated with familial hemiplegic migraine and benign familial infantile convulsions Vanmolkot, KR, Kors, EE, Hottenga, JJ, Terwindt, GM, Haan, J, Hoefnagels, WA, Black, DF, Sandkuijl, LA, Frants, RR, Ferrari, MD, van den Maagdenberg, AM	Ann Neurol	2003
15174025	Alternating hemiplegia of childhood or familial hemiplegic migraine? A novel ATP1A2 mutation Swoboda, KJ, Kanavakis, E, Xaidara, A, Johnson, JE, Leppert, MF, Schlesinger-Massart, MB, Ptácek, LJ, Silver, K, Youroukos, S	Ann Neurol	2004
17357072	A genetic association study of chromosome 11q22-24 in two different samples implicates the FXYD6 gene, encoding phosphohippolin, in susceptibility to schizophrenia Choudhury, K, McQuillin, A, Puri, V, Pimm, J, Datta, S, Thirumalai, S, Krasucki, R, Lawrence, J, Bass, NJ, Quested, D, Crombie, C, Fraser, G, Walker, N, Nadeem, H, Johnson, S, Curtis, D, St Clair, D, Gurling, HM	Am. J. Hum. Genet.	2007
2559024	Characterization of two genes for the human Na,K-ATPase beta subunit Lane, LK, Shull, MM, Whitmer, KR, Lingrel, JB	Genomics	1989
2430951	Primary structure of the alpha-subunit of human Na,K-ATPase deduced from cDNA sequence Kawakami, K, Ohta, T, Nojima, H, Nagano, K	J Biochem	1986
12119109	Physical mapping and characterization of the human Na,K-ATPase isoform, ATP1A4 Keryanov, S, Gardner, KL	Gene	2002
11062458	Dominant isolated renal magnesium loss is caused by misrouting of the Na(+),K(+)-ATPase gamma-subunit Meij, IC, Koenderink, JB, van Bokhoven, H, Assink, KF, Groenestege, WT, de Pont, JJ, Bindels, RJ, Monnens, LA, van den Heuvel, LP, Knoers, NV	Nat Genet	2000
2477373	Characterization of the human Na,K-ATPase alpha 2 gene and identification of intragenic restriction fragment length polymorphisms Shull, MM, Pugh, DG, Lingrel, JB	J Biol Chem	1989
2838329	Family of human Na+, K+-ATPase genes. Structure of the gene for the catalytic subunit (alpha III-form) and its relationship with structural features of the protein Ovchinnikov, YuA, Monastyrskaya, GS, Broude, NE, Ushkaryov, YuA, Melkov, AM, Smirnov, YuV, Malyshev, IV, Allikmets, RL, Kostina, MB, Dulubova, IE	FEBS Lett	1988
8918259	Expression and synthesis of the Na,K-ATPase beta 2 subunit in human retinal pigment epithelium Ruiz, A, Bhat, SP, Bok, D	Gene	1996
15260953	Mutations in the Na+/K+ -ATPase alpha3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism de Carvalho Aguiar, P, Sweadner, KJ, Penniston, JT, Zaremba, J, Liu, L, Caton, M, Linazasoro, G, Borg, M, Tijssen, MA, Bressman, SB, Dobyns, WB, Brashear, A, Ozelius, LJ	Neuron	2004
8798450	Identification of the mammalian Na,K-ATPase 3 subunit Malik, N, Canfield, VA, Beckers, MC, Gros, P, Levenson, R	J Biol Chem	1996