Structures of P-type transporting ATPases and chromosomal locations of their genes

P-type ATPases (E1E2-ATPases) are primary active transporters which form ph ospho-intermediates during their catalytic cycle. They are classified into P1 to P4 based on the primary structure and potential transmembrane segment s. Although the classic P-type ATPases are cation transporters, two new mem bers have recently been found; one is a flippase catalyzing the flip-flop m ovement of aminophospholipids, but the substrate and function of the other one remain unknown. It would be interesting to determine whether the cation s and aminophospholipids are transported by similar or different mechanisms . P-type ATPases are believed to have been derived from a common ancestor, and their genes are found to be distributed in various chromosomal loci. Ho wever, gene duplication events can be traced from the tandem arrangement of genes and their linkage map. Na+/K+- and H+/K+-ATPases have not only close ly related alpha subunits but also similar beta subunits. Renal Na+/K+-ATPa se has an additional subunit gamma. Similar small polypeptides (phospholemm an, Mat-8 and CHIF), which induce Cl- and K+ currents, have been found. The idea of their functional and structural coupling with P-type ATPases, espe cially with H+/K+-ATPase, is intriguing. Each P-type ATPase must have speci fic domains or sequences for its intracellular trafficking (sorting, retent ion and recycling). Identification of such regions and studies on the molec ules playing role in their recognition may facilitate the unveiling of vari ous cellular processes regulated by P-type ATPases.