title: P4 ATPases: flippases in health and disease.
abstract: P4 ATPases catalyze the translocation of phospholipids from the exoplasmic to the cytosolic leaflet of biological membranes, a process termed "lipid flipping". Accumulating evidence obtained in lower eukaryotes points to an important role for P4 ATPases in vesicular protein trafficking. The human genome encodes fourteen P4 ATPases (fifteen in mouse) of which the cellular and physiological functions are slowly emerging. Thus far, deficiencies of at least two P4 ATPases, ATP8B1 and ATP8A2, are the cause of severe human disease. However, various mouse models and in vitro studies are contributing to our understanding of the cellular and physiological functions of P4-ATPases. This review summarizes current knowledge on the basic function of these phospholipid translocating proteins, their proposed action in intracellular vesicle transport and their physiological role.
authors.affiliation: Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Meibergdreef 69-71, 1105 BK Amsterdam, The Netherlands. v.a.vandermark@amc.uva.nl.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: van der Mark
authors.forename: Ronald P J Oude
authors.initials: RP
authors.lastname: Elferink
authors.forename: Coen C
authors.initials: CC
authors.lastname: Paulusma
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000235:genetics; D004195:Disease Models, Animal; D015894:Genome, Human; D006801:Humans; D008659:Metabolic Diseases / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D051379:Mice; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism*; D010743:Phospholipids / Q000235:genetics / Q000378:metabolism
chemical_list: D049294:Phospholipid Transfer Proteins; D010743:Phospholipids; C545446:ATP8a2 protein, mouse; D000251:Adenosine Triphosphatases; C111067:ATP8B1 protein, human; C491742:Atp8b1 protein, mouse; C545445:ATP8A2 protein, human