ACSL1

ACSL1
Identifiers
Aliases	ACSL1, ACS1, FACL1, FACL2, LACS, LACS1, LACS2, acyl-CoA synthetase long-chain family member 1, acyl-CoA synthetase long chain family member 1
External IDs	OMIM: 152425 MGI: 102797 HomoloGene: 37561 GeneCards: ACSL1
Gene location (Human)
Chr.	Chromosome 4 (human)[1]
End	184,826,818 bp[1]
Gene location (Mouse)
Chr.	Chromosome 8 (mouse)[2]
End	46,536,051 bp[2]
RNA expression pattern
	; ;
	More reference expression data
Gene ontology
Molecular function	• long-chain fatty acid-CoA ligase activity; • nucleotide binding; • ligase activity; • catalytic activity; • ATP binding; • decanoate--CoA ligase activity; • acyl-CoA ligase activity;
Cellular component	• organelle membrane; • integral component of membrane; • endoplasmic reticulum membrane; • membrane; • intracellular membrane-bounded organelle; • cell membrane; • peroxisomal membrane; • peroxisome; • mitochondrial outer membrane; • mitochondrion; • endoplasmic reticulum;
Biological process	• linoleic acid metabolic process; • lipid biosynthetic process; • xenobiotic catabolic process; • response to organic cyclic compound; • response to nutrient; • lipid metabolism; • alpha-linolenic acid metabolic process; • fatty acid transport; • response to organic substance; • adiponectin-activated signaling pathway; • fatty acid metabolic process; • positive regulation of protein serine/threonine kinase activity; • long-chain fatty-acyl-CoA biosynthetic process; • long-chain fatty acid import; • metabolism; • long-chain fatty acid metabolic process; • triglyceride metabolic process; • response to drug; • response to oleic acid; • regulation of lipid metabolic process; • triglyceride biosynthetic process; • positive regulation of cold-induced thermogenesis;
	Sources:Amigo / QuickGO
Orthologs
	2180
	14081
	ENSG00000151726
	ENSMUSG00000018796
	P33121
	P41216
	NM_001286708; NM_001286710; NM_001286711; NM_001286712; NM_001995
	NM_007981; NM_001302163
NP_001273637; NP_001273639; NP_001273640; NP_001986; NP_001368806;
	NP_001368807; NP_001368808; NP_001368809; NP_001368810; NP_001368811; NP_001368812; NP_001368813; NP_001368814; NP_001368815; NP_001368816; NP_001368817; NP_001368818; NP_001368819
	NP_001289092; NP_032007
	Wikidata
View/Edit Human	View/Edit Mouse

Long-chain-fatty-acid—CoA ligase 1 is an enzyme that in humans is encoded by the ACSL1 gene.[5][6][7]

Structure

Gene

The ACSL1 gene is located on the 4th chromosome, with its specific location being 4q35.1. The gene contains 28 exons.[7]

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.[7]

In melanocytic cells ACSL1 gene expression may be regulated by MITF.[8]

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.[7] Several transcript variants encoding different isoforms have been found for this gene. This specific protein is most commonly found in mitochondria and peroxisomes.[9]

Clinical significance

ACSL1 is known to be involved in fatty-acid metabolism critical for heart function [10] and nonspecific mental retardation.[11] 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.[12]

Interactions

ACSL1 expression is regulated by SHP2 activity.[13] Additionally, ACSL4 interacts with ACSL3, APP, DSE, ELAVL1, HECW2, MINOS1, PARK2, SPG20, SUMO2, TP53, TUBGCP3, UBC, UBD, and YWHAQ.[7]

References

GRCh38: Ensembl release 89: ENSG00000151726 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000018796 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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. PMID 2341402.
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. PMID 1531127.
"Entrez Gene: ACSL1 acyl-CoA synthetase long-chain family member 1".
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. PMID 19067971. S2CID 24698373.
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 (BBA) - Lipids and Lipid Metabolism. 1170 (1): 44–52. doi:10.1016/0005-2760(93)90174-8. PMID 8399326.
Lewandowski, Doug (2019), Scientists find metabolic target to prevent, treat heart failure at earliest stage (published March 2019)
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. PMID 11889465. S2CID 23901437.
Longo I, Frints SG, Fryns JP, Meloni I, Pescucci C, Ariani F, Borghgraef M, Raynaud M, Marynen P, Schwartz C, Renieri A, Froyen G (Jan 2003). "A third MRX family (MRX68) is the result of mutation in the long chain fatty acid-CoA ligase 4 (FACL4) gene: proposal of a rapid enzymatic assay for screening mentally retarded patients". Journal of Medical Genetics. 40 (1): 11–7. doi:10.1136/jmg.40.1.11. PMC 1735250. PMID 12525535.
Cooke M, Orlando U, Maloberti P, Podestá EJ, Cornejo Maciel F (Nov 2011). "Tyrosine phosphatase SHP2 regulates the expression of acyl-CoA synthetase ACSL4". Journal of Lipid Research. 52 (11): 1936–48. doi:10.1194/jlr.m015552. PMC 3196225. PMID 21903867.

External links

Human ACSL1 genome location and ACSL1 gene details page in the UCSC Genome Browser.

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000151726 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000018796 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid2341402-5] 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. PMID 2341402.

[pmid1531127-6] 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. PMID 1531127.

[entrez-7] "Entrez Gene: ACSL1 acyl-CoA synthetase long-chain family member 1".

[pmid19067971-8] 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. PMID 19067971. S2CID 24698373.

[9] 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 (BBA) - Lipids and Lipid Metabolism. 1170 (1): 44–52. doi:10.1016/0005-2760(93)90174-8. PMID 8399326.

[10] Lewandowski, Doug (2019), Scientists find metabolic target to prevent, treat heart failure at earliest stage (published March 2019)

[11] 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. PMID 11889465. S2CID 23901437.

[12] Longo I, Frints SG, Fryns JP, Meloni I, Pescucci C, Ariani F, Borghgraef M, Raynaud M, Marynen P, Schwartz C, Renieri A, Froyen G (Jan 2003). "A third MRX family (MRX68) is the result of mutation in the long chain fatty acid-CoA ligase 4 (FACL4) gene: proposal of a rapid enzymatic assay for screening mentally retarded patients". Journal of Medical Genetics. 40 (1): 11–7. doi:10.1136/jmg.40.1.11. PMC 1735250. PMID 12525535.

[13] Cooke M, Orlando U, Maloberti P, Podestá EJ, Cornejo Maciel F (Nov 2011). "Tyrosine phosphatase SHP2 regulates the expression of acyl-CoA synthetase ACSL4". Journal of Lipid Research. 52 (11): 1936–48. doi:10.1194/jlr.m015552. PMC 3196225. PMID 21903867.