Ca2+ plays a critical role in intracellular signaling. Intracellular Ca2+ levels are tightly controlled by continuos removal of Ca2+ via ATP-driven Ca2+ pump in the endoplasmic reticulum and plasma membrane, and Ca2+ transport system, the Na+/Ca2+ exchangers (NCX), in the plasma membrane. NCX can move Ca2+ either into or out of cells, depending on the net Na+, Ca2+, and K+ gradient across the membrane. In most cells, 3 Na+ are exchanged for 1 Ca2+. In mammals, at least 5 distinct genes code for the exchangers: Three NCX (NCX1, NCX2, and NCX3), and two in the NCKX family (NCKX1 and NCKX2). NCX share significant sequence homology (~70%), display 11 TM domains, a large central, intracellular hydrophilic regulatory loop between TM5 and 6, extracellular N-terminus and cytoplasmic C-terminus. The N-terminal signal peptide is cleaved off from the mature exchanger protein. NCX1 (rat 971 aa, human 970aa, mouse 970aa) is most prominently expressed in the heart where it plays a major role in excitation-contraction coupling, but is also present in most other tissues. Alternative spicing of NCX1/NACA1 produces numerous tissue specific isoforms (heart NACA1; Kidney NACA2, -3, and -7; brain NACA4-6). NCX2 (rat 921aa) is restricted to brain and skeletal muscle. NCX3 (rat 927aa) shares 73-75% with NCX1 and NCX2. NCX3 is also restricted to brain and muscle.
Intended for research use only. Not for use in human, therapeutic, or diagnostic applications.