Human very long-chain acyl-CoA synthetase and two human homologs: initial characterization and relationship to fatty acid transport protein.
Several human genes with a high degree of homology to rat very long-chain acyl-CoA synthetase (rVLCS) and mouse fatty acid transport protein (mFATP) were identified. Full-length cDNA clones were obtained for three genes, and predicted amino acid sequences were generated. Initial characterization indicated that one gene was most likely hVLCS, the human ortholog of rVLCS. The other two (hVLCS-H1 and hVLCS-H2) were more closely related to rVLCS than to mFATP. Phylogenetic analysis of amino acid sequences confirmed that hVLCS-H1 and hVLCS-H2 were evolutionarily closer to VLCSs than FATPs. Alignment of predicted amino acid sequences of human, rat and mouse VLCSs and FATPs revealed the existence of two highly conserved motifs. While one motif is also present in long-chain acyl-CoA synthetases, the other serves to distinguish the VLCS/FATP family from the long-chain synthetase family. Elucidation of the biochemical functions of all VLCS/FATP family members should provide new insights into cellular fatty acid metabolism.
Watkins
P A
PA
Kennedy Krieger Institute, Baltimore, MD 21205, USA. watkins@kennedykrieger.org
Pevsner
J
J
Steinberg
S J
SJ
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry*; D003001:Cloning, Molecular; D003066:Coenzyme A Ligases / Q000737:chemistry* / Q000378:metabolism; D017124:Conserved Sequence; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry*; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
D002352:Carrier Proteins; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; D007527:Isoenzymes; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D003066:Coenzyme A Ligases; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase