| Structural highlights
Function
S27A2_HUMAN Mediates the import of long-chain fatty acids (LCFA) into the cell by facilitating their transport across cell membranes, playing an important role in hepatic fatty acid uptake (PubMed:10198260, PubMed:10749848, PubMed:11980911, PubMed:20530735, PubMed:22022213, PubMed:24269233). Also functions as an acyl-CoA ligase catalyzing the ATP-dependent formation of fatty acyl-CoA using LCFA and very-long-chain fatty acids (VLCFA) as substrates, which prevents fatty acid efflux from cells and might drive more fatty acid uptake (PubMed:10198260, PubMed:10749848, PubMed:11980911, PubMed:20530735, PubMed:22022213, PubMed:24269233). Plays a pivotal role in regulating available LCFA substrates from exogenous sources in tissues undergoing high levels of beta-oxidation or triglyceride synthesis (PubMed:20530735). Can also activate branched-chain fatty acids such as phytanic acid and pristanic acid (PubMed:10198260). May contribute to the synthesis of sphingosine-1-phosphate (PubMed:24269233). Does not activate C24 bile acids, cholate and chenodeoxycholate (PubMed:11980911). In vitro, activates 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestanate (THCA), the C27 precursor of cholic acid deriving from the de novo synthesis from cholesterol (PubMed:11980911). However, it is not critical for THCA activation and bile synthesis in vivo (PubMed:20530735).[1] [2] [3] [4] [5] [6] Exhibits both long-chain fatty acids (LCFA) transport activity and acyl CoA synthetase towards very long-chain fatty acids (PubMed:10198260, PubMed:21768100). Shows a preference for generating CoA derivatives of n-3 fatty acids, which are preferentially trafficked into phosphatidylinositol (PubMed:21768100).[7] [8] Exhibits long-chain fatty acids (LCFA) transport activity but lacks acyl CoA synthetase towards very long-chain fatty acids.[9]
References
- ↑ Steinberg SJ, Wang SJ, Kim DG, Mihalik SJ, Watkins PA. Human very-long-chain acyl-CoA synthetase: cloning, topography, and relevance to branched-chain fatty acid metabolism. Biochem Biophys Res Commun. 1999 Apr 13;257(2):615-21. doi: , 10.1006/bbrc.1999.0510. PMID:10198260 doi:https://dx.doi.org/10.1006/bbrc.1999.0510
- ↑ Steinberg SJ, Mihalik SJ, Kim DG, Cuebas DA, Watkins PA. The human liver-specific homolog of very long-chain acyl-CoA synthetase is cholate:CoA ligase. J Biol Chem. 2000 May 26;275(21):15605-8. doi: 10.1074/jbc.C000015200. PMID:10749848 doi:https://dx.doi.org/10.1074/jbc.C000015200
- ↑ Mihalik SJ, Steinberg SJ, Pei Z, Park J, Kim DG, Heinzer AK, Dacremont G, Wanders RJ, Cuebas DA, Smith KD, Watkins PA. Participation of two members of the very long-chain acyl-CoA synthetase family in bile acid synthesis and recycling. J Biol Chem. 2002 Jul 5;277(27):24771-9. doi: 10.1074/jbc.M203295200. Epub 2002 , Apr 29. PMID:11980911 doi:https://dx.doi.org/10.1074/jbc.M203295200
- ↑ Falcon A, Doege H, Fluitt A, Tsang B, Watson N, Kay MA, Stahl A. FATP2 is a hepatic fatty acid transporter and peroxisomal very long-chain acyl-CoA synthetase. Am J Physiol Endocrinol Metab. 2010 Sep;299(3):E384-93. doi: , 10.1152/ajpendo.00226.2010. Epub 2010 Jun 8. PMID:20530735 doi:https://dx.doi.org/10.1152/ajpendo.00226.2010
- ↑ Krammer J, Digel M, Ehehalt F, Stremmel W, Fullekrug J, Ehehalt R. Overexpression of CD36 and acyl-CoA synthetases FATP2, FATP4 and ACSL1 increases fatty acid uptake in human hepatoma cells. Int J Med Sci. 2011;8(7):599-614. doi: 10.7150/ijms.8.599. Epub 2011 Oct 7. PMID:22022213 doi:https://dx.doi.org/10.7150/ijms.8.599
- ↑ Ohkuni A, Ohno Y, Kihara A. Identification of acyl-CoA synthetases involved in the mammalian sphingosine 1-phosphate metabolic pathway. Biochem Biophys Res Commun. 2013 Dec 13;442(3-4):195-201. doi: , 10.1016/j.bbrc.2013.11.036. Epub 2013 Nov 19. PMID:24269233 doi:https://dx.doi.org/10.1016/j.bbrc.2013.11.036
- ↑ Steinberg SJ, Wang SJ, Kim DG, Mihalik SJ, Watkins PA. Human very-long-chain acyl-CoA synthetase: cloning, topography, and relevance to branched-chain fatty acid metabolism. Biochem Biophys Res Commun. 1999 Apr 13;257(2):615-21. doi: , 10.1006/bbrc.1999.0510. PMID:10198260 doi:https://dx.doi.org/10.1006/bbrc.1999.0510
- ↑ Melton EM, Cerny RL, Watkins PA, DiRusso CC, Black PN. Human fatty acid transport protein 2a/very long chain acyl-CoA synthetase 1 (FATP2a/Acsvl1) has a preference in mediating the channeling of exogenous n-3 fatty acids into phosphatidylinositol. J Biol Chem. 2011 Sep 2;286(35):30670-30679. doi: 10.1074/jbc.M111.226316. Epub , 2011 Jul 15. PMID:21768100 doi:https://dx.doi.org/10.1074/jbc.M111.226316
- ↑ Melton EM, Cerny RL, Watkins PA, DiRusso CC, Black PN. Human fatty acid transport protein 2a/very long chain acyl-CoA synthetase 1 (FATP2a/Acsvl1) has a preference in mediating the channeling of exogenous n-3 fatty acids into phosphatidylinositol. J Biol Chem. 2011 Sep 2;286(35):30670-30679. doi: 10.1074/jbc.M111.226316. Epub , 2011 Jul 15. PMID:21768100 doi:https://dx.doi.org/10.1074/jbc.M111.226316
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