Map Key
Generic Enzyme
Generic kinase
Protein kinase
Lipid kinase
Generic phosphatase
Protein phosphatase
Lipid phosphatase
Generic phospholipase
Generic protease
RAS - superfamily
G beta/gamma
Regulators (GDI, GAP, GEF)
Generic channel
Ligand-gated channel
Voltage-gated channel
Normal process
Pathological process
Positive effect
Negative effect
Unspecified effect
Technical link
Disrupts in disease
Emerges in disease
Enhances in disease
Weakens in disease
Organsim specific interaction

Generic binding protein
Receptor ligand
Cell membrane glycoprotein
Transcription factor
Inorganic ion
Predicted metabolite or user's structure
Generic receptor
Receptors with enzyme activity

Normal process
Pathological process
Covalent modifications
Transcription regulation
MicroRNA binding
Influence on expression
Unspecified interactions
Pharmacological effect
Toxic effect
Group relation
Complex subunit
Similarity reaction
A complex or a group
Organism specific object

Sodium-coupled transporters and pumps

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Sodium-coupled transporters and pumps

Sodium-coupled transporters and pumps

Ionized calcium (Ca2+) is utilized by the cells as a ubiquitous signaling molecule.Changes in calcium concentration control a variety of diverse physiological events.Na+/Ca2+ exchange is among the pathways that mediate Ca2+ movement and the predominantmechanism for Ca2+ efflux across the plasma membrane [1], [2].

The Solute carrier family 24 (SLC24) and Solute carrier family 8 ( NCX1,NCX2, NCX3 ) gene families encode proteins responsible for Na+/Ca2+exchange. NCX1 is broadly expressed with particular abundance in heart, brain andkidney. NCX2 is expressed in brain. NCX3 is expressed in brain and skeletalmuscle. The NCX proteins perform variety of roles in different tissues and organs. Theseinclude cardiac excitation-contraction coupling, neuronal signalling and Ca2+reabsorptionin the kidney. SLC24 exchangers transport K+ and Ca2+ in exchange for Na+. SLC24A1is expressed in retinal rod photoreceptors, SLC24A2 is expressed in conephotoreceptors and in neurons throughout the brain, and SLC24A4 has a broadertissue distribution though it is especially abundant in brain. The SLC24 proteins arebelieved to play particularly prominent role in regulating Ca2+ flux in environmentswhich experience wide and frequent fluctuations in Na+ concentration [1],[2].

Solute carrier family 4 sodium bicarbonate cotransporter member 4 ( SLC4A4 )belongs to SLC4 family of HCO3- transporters. SLC4A4 provides Na+ - coupled HCO3-transport across the plasma membrane. SLC4 transporters play important roles inabsorption and secretion of H+ or HCO3- by several epithelia. In particular,SLC4A4 mediates the movement of HCO3- equivalents from the proximal-tubule cell tothe blood in the kidney. In the pancreas, SLC4A4 is involved in accumulation ofintracellular HCO3- [3].

Solute carrier family 7 member 6 ( SLC7A6 ) is a glycoprotein-associated aminoacid transporter. It heterodimerizes with Solute carrier family 3 member 2 (SLC3A2 ) and mediates obligatory amino acid exchange of neutral and cationic aminoacids at the 1:1 stoichiometry. The transport of neutral amino acids is coupled to Na+.Association of SLC7A6 with SLC3A2 glycoprotein is required for its surfaceexpression. The physiological role of this transporter is presently not clear [4].

The ATPase Na+/K+ transporting alpha 1- 4 polypeptides ( ATP1A1 - ATP1A4) form part of the Na-K-ATPase, or Na pump. This is membrane-bound protein complex thatestablishes and maintains high internal K+ and low internal Na+ concentrationscharacteristic of most animal cells. It is an oligomer comprised of equal numbers of twomajor polypeptides, the alpha- and beta-subunits. It hydrolyses one mole of ATP and usesthe released energy to export three moles of Na+ out in exchange to two moles ofimported K+. The electrochemical gradient that Na-K-ATPase generates is critical formaintaining the osmotic balance of the cell, as well as preserving the resting membranepotential of most tissues, and excitable properties of muscle and nerve cells. In thekidney, the Na-K-ATPase plays a primary role in driving the re-absorption of Na+ andwater [5].