title: Multiple erythroid isoforms of human long-chain acyl-CoA synthetases are produced by switch of the fatty acid gate domains.
abstract: BACKGROUND
  The formation of acyl-CoA by the action of acyl-CoA synthetases plays a crucial role in membrane lipid turnover, including the plasma membrane of erythrocytes. In human, five Acyl-CoA Synthetase Long-chain (ACSL) genes have been identified with as many as 3 different transcript variants for each.
  
  
  RESULTS
  Acyl-CoA Synthetase Long-chain member 6 (ACSL6) is responsible for activation of long-chain fatty acids in erythrocytes. Two additional transcript variants were also isolated from brain and testis. We report the expression in reticulocytes of two new variants and of the one isolated from brain. All three represented different spliced variants of a mutually exclusive exon pair. They encode a slightly different short motif which contains a conserved structural domain, the fatty acid Gate domain. The motifs differ in the presence of either the aromatic residue phenylalanine (Phe) or tyrosine (Tyr). Based on homology, two new isoforms for the closely related ACSL1 were predicted and characterized. One represented a switch of the Phe- to the Tyr-Gate domain motif, the other resulted from the exclusion of both. Swapping of this motif also appears to be common in all mammalian ACSL member 1 and 6 homologs.
  
  
  CONCLUSIONS
  We propose that a Phe to Tyr substitution or deletion of the Gate domain, is the structural reason for the conserved alternative splicing that affects these motifs. Our findings support our hypothesis that this region is structurally important to define the activity of these enzymes.
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, California 94609, USA. esoupene@chori.org
authors.forename: Eric
authors.initials: E
authors.lastname: Soupene
authors.forename: Frans A
authors.initials: FA
authors.lastname: Kuypers
mesh_terms: D017398:Alternative Splicing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002462:Cell Membrane; D003066:Coenzyme A Ligases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017124:Conserved Sequence; D005091:Exons; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012156:Reticulocytes / Q000201:enzymology*; D016415:Sequence Alignment; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
chemical_list: D005227:Fatty Acids; D007527:Isoenzymes; D003066:Coenzyme A Ligases; C403665:ACSL6 protein, human; D000098859:Long-Chain-Fatty-Acid-CoA Ligase