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ACOT1
Identifiers
Aliases	ACOT1, ACH2, CTE-1, LACH2, acyl-CoA thioesterase 1
External IDs	OMIM: 614313; MGI: 2159619; HomoloGene: 134585; GeneCards: ACOT1; OMA:ACOT1 - orthologs
Gene location (Human) Chr. Chromosome 14 (human) Band 14q24.3 Start 73,537,143 bp End 73,543,796 bp
Gene location (Mouse) Chr. Chromosome 12 (mouse) Band 12|12 D1 Start 84,098,918 bp End 84,107,176 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gonad testicle right lobe of liver smooth muscle tissue left ventricle gastrocnemius muscle apex of heart gastric mucosa human kidney right adrenal gland Top expressed in zygote secondary oocyte primary oocyte renal cortex proximal tubule human kidney right kidney salivary gland hair hepatobiliary system More reference expression data BioGPS n/a
Gene ontology Molecular function palmitoyl-CoA hydrolase activity carboxylic ester hydrolase activity hydrolase activity thiolester hydrolase activity acyl-CoA hydrolase activity myristoyl-CoA hydrolase activity Cellular component cytoplasm cytosol Biological process very long-chain fatty acid metabolic process long-chain fatty acid metabolic process acyl-CoA metabolic process fatty acid metabolic process lipid metabolism Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 641371 171281 Ensembl ENSG00000184227 ENSMUSG00000021228 UniProt Q86TX2 Q9QYR7 RefSeq (mRNA) NM_001037161 NM_134246 NM_001346701 RefSeq (protein) NP_001032238 NP_001333630 NP_599007 Location (UCSC) Chr 14: 73.54 – 73.54 Mb Chr 12: 84.1 – 84.11 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Acyl-CoA thioesterase 1 is a protein that in humans is encoded by the ACOT1 gene.

Structure

The ACOT1 gene is located on the 14th chromosome, with its specific localization being 14q24.3. It contains 7 exons.

The protein encoded by this gene contains 410 amino acids, and forms a homodimer with another chain. The protein contains a StAR-related transfer domain, which is a domain responsible for binding to lipids. There are 4 known ligands that bind to this homodimer: polyethylene glycol, chlorine, glycerol, and a form of TCEP.

Function

The protein encoded by the ACOT1 gene is part of a family of Acyl-CoA thioesterases, which catalyze the hydrolysis of various Coenzyme A esters of various molecules to the free acid plus CoA. These enzymes have also been referred to in the literature as acyl-CoA hydrolases, acyl-CoA thioester hydrolases, and palmitoyl-CoA hydrolases. The reaction carried out by these enzymes is as follows:

CoA ester + H₂O → free acid + coenzyme A

These enzymes use the same substrates as long-chain acyl-CoA synthetases, but have a unique purpose in that they generate the free acid and CoA, as opposed to long-chain acyl-CoA synthetases, which ligate fatty acids to CoA, to produce the CoA ester. The role of the ACOT- family of enzymes is not well understood; however, it has been suggested that they play a crucial role in regulating the intracellular levels of CoA esters, Coenzyme A, and free fatty acids. Recent studies have shown that Acyl-CoA esters have many more functions than simply an energy source. These functions include allosteric regulation of enzymes such as acetyl-CoA carboxylase, hexokinase IV, and the citrate condensing enzyme. Long-chain acyl-CoAs also regulate opening of ATP-sensitive potassium channels and activation of Calcium ATPases, thereby regulating insulin secretion. A number of other cellular events are also mediated via acyl-CoAs, for example signal transduction through protein kinase C, inhibition of retinoic acid-induced apoptosis, and involvement in budding and fusion of the endomembrane system. Acyl-CoAs also mediate protein targeting to various membranes and regulation of G protein α subunits, because they are substrates for protein acylation. In the mitochondria, acyl-CoA esters are involved in the acylation of mitochondrial NAD+ dependent dehydrogenases; because these enzymes are responsible for amino acid catabolism, this acylation renders the whole process inactive. This mechanism may provide metabolic crosstalk and act to regulate the NADH/NAD+ ratio in order to maintain optimal mitochondrial beta oxidation of fatty acids. The role of CoA esters in lipid metabolism and numerous other intracellular processes are well defined, and thus it is hypothesized that ACOT- enzymes play a role in modulating the processes these metabolites are involved in.

References

1. ^ GRCh38: Ensembl release 89: ENSG00000184227 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000021228 – 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.
5. ^ "Entrez Gene: Acyl-CoA thioesterase 1".
6. "Model Results". SwissProt. Retrieved 21 May 2015.
7. Thorsell AG, Lee WH, Persson C, Siponen MI, Nilsson M, Busam RD, Kotenyova T, Schüler H, Lehtiö L (2011). "Comparative structural analysis of lipid binding START domains". PLOS ONE. 6 (6): e19521. Bibcode:2011PLoSO...619521T. doi:10.1371/journal.pone.0019521. PMC 3127847. PMID 21738568.
8. Mashek DG, Bornfeldt KE, Coleman RA, Berger J, Bernlohr DA, Black P, DiRusso CC, Farber SA, Guo W, Hashimoto N, Khodiyar V, Kuypers FA, Maltais LJ, Nebert DW, Renieri A, Schaffer JE, Stahl A, Watkins PA, Vasiliou V, Yamamoto TT (Oct 2004). "Revised nomenclature for the mammalian long-chain acyl-CoA synthetase gene family". Journal of Lipid Research. 45 (10): 1958–61. doi:10.1194/jlr.E400002-JLR200. PMID 15292367.
9. Ogiwara H, Tanabe T, Nikawa J, Numa S (Aug 1978). "Inhibition of rat-liver acetyl-coenzyme-A carboxylase by palmitoyl-coenzyme A. Formation of equimolar enzyme-inhibitor complex". European Journal of Biochemistry. 89 (1): 33–41. doi:10.1111/j.1432-1033.1978.tb20893.x. PMID 29756.
10. Srere PA (Dec 1965). "Palmityl-coenzyme A inhibition of the citrate-condensing enzyme". Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism. 106 (3): 445–55. doi:10.1016/0005-2760(65)90061-5. PMID 5881327.
11. Gribble FM, Proks P, Corkey BE, Ashcroft FM (Oct 1998). "Mechanism of cloned ATP-sensitive potassium channel activation by oleoyl-CoA". The Journal of Biological Chemistry. 273 (41): 26383–7. doi:10.1074/jbc.273.41.26383. PMID 9756869.
12. Nishizuka Y (Apr 1995). "Protein kinase C and lipid signaling for sustained cellular responses". FASEB Journal. 9 (7): 484–96. doi:10.1096/fasebj.9.7.7737456. PMID 7737456. S2CID 31065063.
13. Glick BS, Rothman JE (Mar 1987). "Possible role for fatty acyl-coenzyme A in intracellular protein transport". Nature. 326 (6110): 309–12. Bibcode:1987Natur.326..309G. doi:10.1038/326309a0. PMID 3821906. S2CID 4306469.
14. Wan YJ, Cai Y, Cowan C, Magee TR (Jun 2000). "Fatty acyl-CoAs inhibit retinoic acid-induced apoptosis in Hep3B cells". Cancer Letters. 154 (1): 19–27. doi:10.1016/s0304-3835(00)00341-4. PMID 10799735.
15. Duncan JA, Gilman AG (Jun 1998). "A cytoplasmic acyl-protein thioesterase that removes palmitate from G protein alpha subunits and p21(RAS)". The Journal of Biological Chemistry. 273 (25): 15830–7. doi:10.1074/jbc.273.25.15830. PMID 9624183.
16. Berthiaume L, Deichaite I, Peseckis S, Resh MD (Mar 1994). "Regulation of enzymatic activity by active site fatty acylation. A new role for long chain fatty acid acylation of proteins". The Journal of Biological Chemistry. 269 (9): 6498–505. doi:10.1016/S0021-9258(17)37399-4. PMID 8120000.
17. Hunt MC, Alexson SE (Mar 2002). "The role Acyl-CoA thioesterases play in mediating intracellular lipid metabolism". Progress in Lipid Research. 41 (2): 99–130. doi:10.1016/s0163-7827(01)00017-0. PMID 11755680.

External links

• Human ACOT1 genome location and ACOT1 gene details page in the UCSC Genome Browser.
• Overview of all the structural information available in the PDB for UniProt: Q86TX2 (Acyl-coenzyme A thioesterase 1) at the PDBe-KB.

Further reading

• Hunt MC, Yamada J, Maltais LJ, Wright MW, Podesta EJ, Alexson SE (Sep 2005). "A revised nomenclature for mammalian acyl-CoA thioesterases/hydrolases". Journal of Lipid Research. 46 (9): 2029–32. doi:10.1194/jlr.E500003-JLR200. PMID 16103133.
• Hunt MC, Rautanen A, Westin MA, Svensson LT, Alexson SE (Sep 2006). "Analysis of the mouse and human acyl-CoA thioesterase (ACOT) gene clusters shows that convergent, functional evolution results in a reduced number of human peroxisomal ACOTs". FASEB Journal. 20 (11): 1855–64. doi:10.1096/fj.06-6042com. PMID 16940157. S2CID 501610.
• Li J, Liu F, Wang H, Liu X, Liu J, Li N, Wan F, Wang W, Zhang C, Jin S, Liu J, Zhu P, Liu Y (Nov 2010). "Systematic mapping and functional analysis of a family of human epididymal secretory sperm-located proteins". Molecular & Cellular Proteomics. 9 (11): 2517–28. doi:10.1074/mcp.M110.001719. PMC 2984238. PMID 20736409.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

• Genes on human chromosome 14