Human very long-chain acyl-CoA synthetase and two human homologs: initial characterization and relationship to fatty acid transport protein

Watkins, Paul A.; Pevsner, Jonathan; Steinberg, Steven J.

doi:10.1016/s0952-3278(99)80007-6

Cited by 58 publications

(35 citation statements)

References 25 publications

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“…by guest, on May 11, 2018 www.jlr.org Downloaded from the amino acid sequence encoded by rBAL displays significant sequence similarity to fatty acid CoA synthetase/ FATP proteins, indicating that rBAL is a member of this large gene family (23,24).…”

Section: Discussionmentioning

confidence: 99%

“…The first is the AMP-binding domain (residues 294-303) that is conserved among longand very-long chain acyl-CoA synthetases (23). The second is a domain highly conserved in the VLACS/fatty acid transport protein gene family located at amino acids 546-567 (24). These structural motifs increase the likelihood that rBAL is a member of the large fatty acid CoA synthetase/FATP gene family.…”

Section: Discussionmentioning

confidence: 99%

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Molecular cloning and expression of rat liver bile acid CoA ligase

Falany

Xie

Wheeler

et al. 2002

Journal of Lipid Research

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Molecular cloning and expression of rat liver bile acid CoA ligase

Falany

Xie

Wheeler

et al. 2002

Journal of Lipid Research

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“…Discussion FATP4 has been proposed to constitute the long-sought intestinal fatty acid transporter (Stahl et al, 1999), and is currently being classified as a member of the solute carrier family 27 (fatty acid transporter; HUGO Gene Nomenclature Committee). When it became evident that this protein and the other FATP family members have acyl-CoA synthetase activity, we and others began to express some doubt about the true function of this protein family (Coe et al, 1999;Watkins et al, 1999). Guided by our initial findings of an ER localization of FATP4-GFP, we chose the most straightforward strategy to determine whether FATP4 is a plasma membrane fatty acid transport protein: to analyze the subcellular localization.…”

Section: Analysis Of Fatty Acid Uptakementioning

confidence: 99%

Cellular uptake of fatty acids driven by the ER-localized acyl-CoA synthetase FATP4

Milger

Herrmann

Becker

et al. 2006

Journal of Cell Science

197

210

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Long-chain fatty acids are important metabolites for the generation of energy and the biosynthesis of lipids. The molecular mechanism of their cellular uptake has remained controversial. The fatty acid transport protein (FATP) family has been named according to its proposed function in mediating this process at the plasma membrane. Here, we show that FATP4 is in fact localized to the endoplasmic reticulum and not the plasma membrane as reported previously. Quantitative analysis confirms the positive correlation between expression of FATP4 and uptake of fatty acids. However, this is dependent on the enzymatic activity of FATP4, catalyzing the esterification of fatty acids with CoA. Monitoring fatty acid uptake at the single-cell level demonstrates that the ER localization of FATP4 is sufficient to drive transport of fatty acids. Expression of a mitochondrial acyl-CoA synthetase also enhances fatty acid uptake, suggesting a general relevance for this mechanism. Our results imply that cellular uptake of fatty acids can be regulated by intracellular acyl-CoA synthetases. We propose that the enzyme FATP4 drives fatty acid uptake indirectly by esterification. It is not a transporter protein involved in fatty acid translocation at the plasma membrane.

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“…Within mammalian systems, several members of this family (FATP1, FATP2, FATP4 and FATP6) have been shown to participate in the transport of exogenous fatty acids into the cell [2][3][4][5][6][7][8][9][10][11]. Additionally, some also condense either very long chain fatty acids (FATP1, FATP2, FATP3 and FATP4) or bile acids (FATP5) with CoA for downstream metabolism [8,[12][13][14][15][16][17][18]. The first FATP (now designated FATP1) was identified using expression cloning from a cDNA library prepared from murine 3T3-L1 adipocytes, directly demonstrating the physiological role of this protein in the net accumulation of fatty acids across a biological membrane [9].…”

Section: Introductionmentioning

confidence: 99%

Functional domains of the fatty acid transport proteins: Studies using protein chimeras

DiRusso

Darwis

Obermeyer

et al. 2008

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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SUMMARYFatty acid transport proteins (FATP) function in fatty acid trafficking pathways, several of which have been shown to participate in the transport of exogenous fatty acids into the cell. Members of this protein family also function as acyl CoA synthetases with specificity towards very long chain fatty acids or bile acids. These proteins have two identifying sequence motifs: The ATP/AMP motif, an approximately 100 amino acid segment required for ATP binding and common to members of the adenylate-forming super family of proteins, and the FATP/VLACS motif that consists of approximately 50 amino acid residues and is restricted to members of the FATP family. This latter motif has been implicated in fatty acid transport in the yeast FATP orthologue Fat1p. In the present studies using a yeast strain containing deletions in FAT1 (encoding Fat1p) and FAA1 (encoding the major acyl CoA synthetase (Acsl) Faa1p) as an experimental platform, the phenotypic and functional properties of specific murine FATP1-FATP4 and FATP6-FATP4 protein chimeras were evaluated in order to define elements within these proteins that further distinguish the fatty acid transport and activation functions. As expected from previous work FATP1 and FATP4 were functional in the fatty acid transport pathway, while and FATP6 was not. All three isoforms were able to activate the very long chain fatty acids arachidonate (C 20:4 ) and lignocerate (C 24:0 ), but with distinguishing activities between saturated and highly unsaturated ligands. A 73 amino acid segment common to FATP1 and FATP4 and between the ATP/AMP and FATP/VLACS motifs was identified by studying the chimeras, which is hypothesized to contribute to the transport function.

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Human very long-chain acyl-CoA synthetase and two human homologs: initial characterization and relationship to fatty acid transport protein

Cited by 58 publications

References 25 publications

Molecular cloning and expression of rat liver bile acid CoA ligase

Molecular cloning and expression of rat liver bile acid CoA ligase

Cellular uptake of fatty acids driven by the ER-localized acyl-CoA synthetase FATP4

Functional domains of the fatty acid transport proteins: Studies using protein chimeras

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