ABC A-subfamily transporters: structure, function and disease.
ABC transporters constitute a family of evolutionarily highly conserved multispan proteins that mediate the translocation of defined substrates across membrane barriers. Evidence has accumulated during the past years to suggest that a subgroup of 12 structurally related "full-size" transporters, referred to as ABC A-subfamily transporters, mediates the transport of a variety of physiologic lipid compounds. The emerging importance of ABC A-transporters in human disease is reflected by the fact that as yet four members of this protein family (ABCA1, ABCA3, ABCR/ABCA4, ABCA12) have been causatively linked to completely unrelated groups of monogenetic disorders including familial high-density lipoprotein (HDL) deficiency, neonatal surfactant deficiency, degenerative retinopathies and congenital keratinization disorders. Although the biological function of the remaining 8 ABC A-transporters currently awaits clarification, they represent promising candidate genes for a presumably equally heterogenous group of Mendelian diseases associated with perturbed cellular lipid transport. This review summarizes our current knowledge on the role of ABC A-subfamily transporters in physiology and disease and explores clinical entities which may be potentially associated with dysfunctional members of this gene subfamily.
Kaminski
Wolfgang E
WE
Institute for Clinical Chemistry, Faculty for Clinical Medicine Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. wolfgang.kaminski@ikc.ma.uni-heidelberg.de
Piehler
Armin
A
Wenzel
Jürgen J
JJ
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004194:Disease; D004198:Disease Susceptibility; D019143:Evolution, Molecular; D006801:Humans; D013631:Tangier Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology
D018528:ATP-Binding Cassette Transporters