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.
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
Wolfgang E
WE
Kaminski
Armin
A
Piehler
Jürgen J
JJ
Wenzel
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