The ACSL4 gene is located on the 4th chromosome, with its specific location being 4q35.1. The gene contains 28 exons.[3]
The protein encoded by this gene is an isozyme of the long-chain fatty-acid-coenzyme A ligase family. Although differing in substrate specificity, subcellular localization, and tissue distribution, all isozymes of this family convert free long-chain fatty acids into fatty acyl-CoA esters, and thereby play a key role in lipid biosynthesis and fatty acid degradation.[3]
In melanocytic cells ACSL1 gene expression may be regulated by MITF.[4]
Function
The protein encoded by this gene is an isozyme of the long-chain fatty-acid-coenzyme A ligase family. Although differing in substrate specificity, subcellular localization, and tissue distribution, all isozymes of this family convert free long-chain fatty acids into fatty acyl-CoA esters, and thereby play a key role in lipid biosynthesis and fatty acid degradation.[3] Several transcript variants encoding different isoforms have been found for this gene. This specific protein is most commonly found in mitochondria and peroxisomes.[5]
Clinical significance
ACSL1 was shown to be involved in nonspecific mental retardation and fatty-acid metabolism.[6] Since the ACSL4 gene is highly expressed in brain, where it encodes a brain specific isoform, an ASCL1 mutation may be an efficient diagnostic tool in mentally retarded males.[7]
↑Suzuki H, Kawarabayasi Y, Kondo J, Abe T, Nishikawa K, Kimura S, Hashimoto T, Yamamoto T (May 1990). "Structure and regulation of rat long-chain acyl-CoA synthetase". The Journal of Biological Chemistry. 265 (15): 8681–5. PMID2341402.
↑Stanczak H, Stanczak JJ, Singh I (Feb 1992). "Chromosomal localization of the human gene for palmitoyl-CoA ligase (FACL1)". Cytogenetics and Cell Genetics. 59 (1): 17–9. doi:10.1159/000133189. PMID1531127.
↑Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (Dec 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID19067971.
↑Singh I, Lazo O, Kremser K (Sep 1993). "Purification of peroxisomes and subcellular distribution of enzyme activities for activation and oxidation of very-long-chain fatty acids in rat brain". Biochimica et Biophysica Acta. 1170 (1): 44–52. doi:10.1016/0005-2760(93)90174-8. PMID8399326.
↑Meloni I, Muscettola M, Raynaud M, Longo I, Bruttini M, Moizard MP, Gomot M, Chelly J, des Portes V, Fryns JP, Ropers HH, Magi B, Bellan C, Volpi N, Yntema HG, Lewis SE, Schaffer JE, Renieri A (Apr 2002). "FACL4, encoding fatty acid-CoA ligase 4, is mutated in nonspecific X-linked mental retardation". Nature Genetics. 30 (4): 436–40. doi:10.1038/ng857. PMID11889465.
Abe T, Fujino T, Fukuyama R, Minoshima S, Shimizu N, Toh H, Suzuki H, Yamamoto T (Jan 1992). "Human long-chain acyl-CoA synthetase: structure and chromosomal location". Journal of Biochemistry. 111 (1): 123–8. PMID1607358.
Lageweg W, Wanders RJ, Tager JM (Mar 1991). "Long-chain-acyl-CoA synthetase and very-long-chain-acyl-CoA synthetase activities in peroxisomes and microsomes from rat liver. An enzymological study". European Journal of Biochemistry / FEBS. 196 (2): 519–23. doi:10.1111/j.1432-1033.1991.tb15844.x. PMID2007410.
Singh I, Bhushan A, Relan NK, Hashimoto T (Dec 1988). "Acyl-CoA ligases from rat brain microsomes: an immunochemical study". Biochimica et Biophysica Acta. 963 (3): 509–14. doi:10.1016/0005-2760(88)90319-0. PMID2973813.
Cantú ES, Sprinkle TJ, Ghosh B, Singh I (Aug 1995). "The human palmitoyl-CoA ligase (FACL2) gene maps to the chromosome 4q34-q35 region by fluorescence in situ hybridization (FISH) and somatic cell hybrid panels". Genomics. 28 (3): 600–2. doi:10.1006/geno.1995.1199. PMID7490105.
Wu P, Bremer J (Nov 1994). "Activation of alkylthioacrylic acids in subcellular fractions of rat tissues: a new spectrophotometric method for assay of acyl-CoA synthetase". Biochimica et Biophysica Acta. 1215 (1–2): 87–92. doi:10.1016/0005-2760(94)90095-7. PMID7948012.
Singh I, Lazo O, Kremser K (Sep 1993). "Purification of peroxisomes and subcellular distribution of enzyme activities for activation and oxidation of very-long-chain fatty acids in rat brain". Biochimica et Biophysica Acta. 1170 (1): 44–52. doi:10.1016/0005-2760(93)90174-8. PMID8399326.
Ghosh B, Barbosa E, Singh I (Oct 1995). "Molecular cloning and sequencing of human palmitoyl-CoA ligase and its tissue specific expression". Molecular and Cellular Biochemistry. 151 (1): 77–81. doi:10.1007/BF01076899. PMID8584017.
Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID8889548.
