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Beschreibung

Long-chain fatty acid transport protein 4 (UniProt: Q91VE0, also known as FATP-4, Fatty acid transport protein 4, Arachidonate--CoA ligase, Long-chain-fatty-acid-CoA ligase, Solute carrier family 27 member 4, Very long-chain acyl-CoA synthetase 4, ACSVL4) is encoded by the Slc27a4 (also known as AcsvI4, Fatp4) gene (Gene ID: 26569) in murine species. FATP4 is a multi-pass transmembrane protein with an endoplasmic reticulum (ER) localization domain and two transmembrane domains (aa 20-42 and 139-156). It is involved in translocation of long-chain fatty acids (LFCA) across the plasma membrane and has acyl-CoA synthetase activity towards long-chain and very-long-chain fatty acids (VLCFAs). It is abundantly expressed in small intestine, brain kidney, liver, skin, and heart. It is considered as the principal fatty acid transporter in small intestinal enterocytes and is present on the apical side of mature enterocytes. Its expression is also observed in the retinal pigment epithelium and in the retina. It is identified as a negative regulator of the ER-associated retinal pigment epithelium (RPE) 65 isomerase necessary for recycling 11-cis-retinal, the light-sensitive chromophore of both rod and cone opsin visual pigments. FATP4 is reported to indirectly inhibits RPE65 via substrate competition and via production of VLCFA derivatives like lignoceroyl-CoA. Deficiency of FATP4 in RPE is shown to cause a significant increase in the level of 11-cis and 9-cis-retinals that improves dark adaptation and survival function of rods in murine model of Leber congenital amaurosis (LCA). (Ref.: Li, S., et al. (2020). Proc. Natl. Acad. Sci. USA. 117(50), 32114-32123, Newberry, EP., et al. (2003). J. Biol. Chem. 278(51), 51664- 51672, Stahl, A., et al. (1999). Mol. Cell. 4(3), 299-308).