Mouse fatty acid transport protein 4 (FATP4): Characterization of the gene and functional assessment as a very long chain acyl-CoA synthetase

Thomas Herrmann, Florian Buchkremer, Isabella Gosch, Angela M. Hall, David A. Bernlohr, Wolfgang Stremmel

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Abstract

FATP4 (SLC27A4) is a member of the fatty acid transport protein (FATP) family, a group of evolutionarily conserved proteins that are involved in cellular uptake and metabolism of long and very long chain fatty acids. We cloned and characterized the murine FATP4 gene and its cDNA. From database analysis we identified the human FATP4 genomic sequence. The FATP4 gene was assigned to mouse chromosome 2 band B, syntenic to the region 9q34 encompassing the human gene. The open reading frame was determined to be 1929 bp in length, encoding a polypeptide of 643 amino acids. Within the coding region, the exon-intron structures of the murine FATP4 gene and its human counterpart are identical, revealing a high similarity to the FATP1 gene. The overall amino acid identity between the deduced murine and human FATP4 polypeptides is 92.2%, and between the murine FATP1 and FATP4 polypeptides is 60.3%. Northern analysis showed that FATP4 mRNA was expressed most abundantly in small intestine, brain, kidney, liver, skin and heart. Transfection of FATP4 cDNA into COS1 cells resulted in a 2-fold increase in palmitoyl-CoA synthetase (C16:0) and a 5-fold increase in lignoceroyl-CoA synthetase (C24:0) activity from membrane extracts, indicating that the FATP4 gene encodes an acyl-CoA synthetase with substrate specificity biased towards very long chain fatty acids.

Original languageEnglish (US)
Pages (from-to)31-40
Number of pages10
JournalGene
Volume270
Issue number1-2
DOIs
StatePublished - May 30 2001

Bibliographical note

Funding Information:
The genomic mouse lambda phage library, kindly provided by Dr A.F. Stewart, EMBL Heidelberg, was constructed by Dr K. Kaestner, German Cancer Research Institute Heidelberg. The primers for the RT-PCR synthesis of the partial mmFATP1 cDNA clone were a gift from Dr B. Fitscher, University of Heidelberg. We thank R. Krauss and I. Kaiser for dedicated technical help, and D. Ha-Hao, Dr S. Stewart, and Dr A.F. Stewart for critical reading of the manuscript. This work was supported by a grant from the Faculty of Medicine, University of Heidelberg (T.H.), the Deutsche Forschungsgemeinschaft (SFB 601) and the Dietmar-Hopp-Foundation (W.S.) and NIH DK 49807, NSF MCB 9816575 and NSF 9816575 (D.A.B.).

Keywords

  • Fluorescence in situ hybridization (FISH)
  • Gene structure
  • Mouse chromosome 2
  • SLC27A4

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