| The 28aa Peptide sequence (~CT, cytoplasmic) corresponding to human Ca+-ATPases, autoinhibitory domain 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). The N-terminal signal peptide is cleaved off from the mature exchanger protein. NCX contains a highly basic region in the large hydrophilic, intracellular loop called XIP (Exchange inhibitory peptide, RRLLFYKYVYKRYRAGKQRG 20 aa), that inhibits Na-Ca+ exchange in cardiac sarcolemmal vesicles and in other cells. Little or no sequence identity is found between the NCX and the Ca-pump. However, XIP also inhibits the Ca pumps with more or less same efficiency as C28R2 peptide sequence (LRRGQILWFRGLNRIQTQIRVVKAFRSS, 28 aa) corresponding to the autoinhibitory domain of Ca-pump. Ca+-pump is a Mg+-dependent enzyme that catalyzes the hydrolysis of ATP with the transport of Ca+. Plasma membrane Ca+-ATPase (calcium pump) exists in several isoforms (human isofroms 1, 1084 aa, 1b, 1220 aa, from 2, 198/1243 aa, 3a/b 1173/1220 aa, 4, 1205 aa) and numerous sub-isoforms have been identified in various species. Ca+-pump displays 10 TM domains, with cytoplasmic N and C-termini. C28R2 is located in within the cytoplasmic, C-terminal domain of Ca+-ATPases. The C28R2 sequence is very conserved in various isoforms among various species. |
