ACOT2

Acyl-CoA thioesterase 2, also known as ACOT2, is an enzyme which in humans is encoded by the ACOT2 gene.^[5][6][7]

ACOT2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3HLK
Identifiers
Aliases	ACOT2, CTE-IA, CTE1A, MTE1, PTE2, PTE2A, ZAP128, acyl-CoA thioesterase 2
External IDs	OMIM: 609972; MGI: 2159605; HomoloGene: 25661; GeneCards: ACOT2; OMA:ACOT2 - orthologs
Gene location (Human) Chr. Chromosome 14 (human)[1] Band 14q24.3 Start 73,567,620 bp[1] End 73,575,658 bp[1]
Gene location (Mouse) Chr. Chromosome 12 (mouse)[2] Band 12|12 D1 Start 84,034,635 bp[2] End 84,040,647 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in apex of heart liver left ventricle right lobe of liver muscle of thigh skeletal muscle tissue gastrocnemius muscle right auricle of heart right adrenal gland right adrenal cortex Top expressed in interventricular septum aortic valve myocardium of ventricle ascending aorta muscle of thigh brown adipose tissue cumulus cell ciliary body decidua internal carotid artery More reference expression data BioGPS More reference expression data
Gene ontology Molecular function thiolester hydrolase activity palmitoyl-CoA hydrolase activity carboxylic ester hydrolase activity hydrolase activity signaling receptor binding acyl-CoA hydrolase activity myristoyl-CoA hydrolase activity protein binding Cellular component mitochondrial matrix mitochondrion peroxisomal matrix cytosol Biological process very long-chain fatty acid metabolic process long-chain fatty acid metabolic process acyl-CoA metabolic process protein targeting to peroxisome fatty acid metabolic process lipid metabolism Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 10965 171210 Ensembl ENSG00000119673 ENSMUSG00000021226 UniProt P49753 Q9QYR9 RefSeq (mRNA) NM_006821 NM_001364177 NM_001364178 NM_134188 RefSeq (protein) NP_006812 NP_001351106 NP_001351107 NP_598949 Location (UCSC) Chr 14: 73.57 – 73.58 Mb Chr 12: 84.03 – 84.04 Mb PubMed search [3] [4]
Wikidata
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Acyl-CoA thioesterases, such as ACOT2, are a group of enzymes that hydrolyze Coenzyme A (CoA) esters, such as acyl-CoAs, bile CoAs, and CoA esters of prostaglandins, to the corresponding free acid and CoA.^[8] ACOT2 shows high acyl-CoA thioesterase activity on medium- and long-chain acyl-CoAs, with an optimal pH of 8.5. It is most active on myristoyl-CoA but also shows high activity on palmitoyl-CoA, stearoyl-CoA, and arachidoyl-CoA.^[6]

Function

The protein encoded by the ACOT2 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.^[9] 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,^[10] hexokinase IV,^[11] 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.^[12] 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.^[13][14][15] Acyl-CoAs also mediate protein targeting to various membranes and regulation of G Protein α subunits, because they are substrates for protein acylation.^[16] 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.^[17] 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.^[18]