Biology:ACOT13
 Generic protein structure example |
Acyl-CoA thioesterase 13 is a protein that in humans is encoded by the ACOT13 gene.[1] This gene encodes a member of the thioesterase superfamily. In humans, the protein co-localizes with microtubules and is essential for sustained cell proliferation.[1]
Structure
The orthologous mouse protein forms a homotetramer and is associated with mitochondria. The mouse protein functions as a medium- and long-chain acyl-CoA thioesterase. Multiple transcript variants encoding different isoforms have been found for this gene.[1]
Function
The protein encoded by the ACOT13 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.[2] 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,[3] hexokinase IV,[4] 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.[5] 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.[6][7][8] Acyl-CoAs also mediate protein targeting to various membranes and regulation of G Protein α subunits, because they are substrates for protein acylation.[9] 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.[10] 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.[11]
References
- ↑ 1.0 1.1 1.2 "Entrez Gene: Acyl-CoA thioesterase 13". https://www.ncbi.nlm.nih.gov/gene/55856.
- ↑ "Revised nomenclature for the mammalian long-chain acyl-CoA synthetase gene family". Journal of Lipid Research 45 (10): 1958–61. Oct 2004. doi:10.1194/jlr.E400002-JLR200. PMID 15292367.
- ↑ "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. Aug 1978. doi:10.1111/j.1432-1033.1978.tb20893.x. PMID 29756.
- ↑ "Palmityl-coenzyme A inhibition of the citrate-condensing enzyme". Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism 106 (3): 445–55. Dec 1965. doi:10.1016/0005-2760(65)90061-5. PMID 5881327.
- ↑ "Mechanism of cloned ATP-sensitive potassium channel activation by oleoyl-CoA". The Journal of Biological Chemistry 273 (41): 26383–7. Oct 1998. doi:10.1074/jbc.273.41.26383. PMID 9756869.
- ↑ "Protein kinase C and lipid signaling for sustained cellular responses". FASEB Journal 9 (7): 484–96. Apr 1995. doi:10.1096/fasebj.9.7.7737456. PMID 7737456.
- ↑ "Possible role for fatty acyl-coenzyme A in intracellular protein transport". Nature 326 (6110): 309–12. Mar 1987. doi:10.1038/326309a0. PMID 3821906. Bibcode: 1987Natur.326..309G.
- ↑ "Fatty acyl-CoAs inhibit retinoic acid-induced apoptosis in Hep3B cells". Cancer Letters 154 (1): 19–27. Jun 2000. doi:10.1016/s0304-3835(00)00341-4. PMID 10799735.
- ↑ "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. Jun 1998. doi:10.1074/jbc.273.25.15830. PMID 9624183.
- ↑ "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. Mar 1994. doi:10.1016/S0021-9258(17)37399-4. PMID 8120000.
- ↑ "The role Acyl-CoA thioesterases play in mediating intracellular lipid metabolism". Progress in Lipid Research 41 (2): 99–130. Mar 2002. doi:10.1016/s0163-7827(01)00017-0. PMID 11755680.
External links
- Human ACOT13 genome location and ACOT13 gene details page in the UCSC Genome Browser.
- Overview of all the structural information available in the PDB for UniProt: Q9NPJ3 (Acyl-coenzyme A thioesterase 13) at the PDBe-KB.
Further reading
- "Genetic variants of FOXP2 and KIAA0319/TTRAP/THEM2 locus are associated with altered brain activation in distinct language-related regions". The Journal of Neuroscience 32 (3): 817–25. Jan 2012. doi:10.1523/JNEUROSCI.5996-10.2012. PMID 22262880.
- "Lack of association between genetic polymorphisms in ROBO1, MRPL19/C2ORF3 and THEM2 with developmental dyslexia". Gene 529 (2): 215–9. Oct 2013. doi:10.1016/j.gene.2013.08.017. PMID 23954868.
- "Human thioesterase superfamily member 2 (hTHEM2) is co-localized with beta-tubulin onto the microtubule". Biochemical and Biophysical Research Communications 350 (4): 850–3. Dec 2006. doi:10.1016/j.bbrc.2006.09.105. PMID 17045243.
- "Interacting proteins dictate function of the minimal START domain phosphatidylcholine transfer protein/StarD2". The Journal of Biological Chemistry 282 (42): 30728–36. Oct 2007. doi:10.1074/jbc.M703745200. PMID 17704541.
- "Use of expression data and the CGEMS genome-wide breast cancer association study to identify genes that may modify risk in BRCA1/2 mutation carriers". Breast Cancer Research and Treatment 112 (2): 229–36. Nov 2008. doi:10.1007/s10549-007-9848-5. PMID 18095154.
- "The mechanisms of human hotdog-fold thioesterase 2 (hTHEM2) substrate recognition and catalysis illuminated by a structure and function based analysis". Biochemistry 48 (6): 1293–304. Feb 2009. doi:10.1021/bi801879z. PMID 19170545.
- "Thioesterase superfamily member 2 (Them2)/acyl-CoA thioesterase 13 (Acot13): a homotetrameric hotdog fold thioesterase with selectivity for long-chain fatty acyl-CoAs". The Biochemical Journal 421 (2): 311–22. Jul 2009. doi:10.1042/BJ20090039. PMID 19405909.
- "Crystal structure of human thioesterase superfamily member 2". Biochemical and Biophysical Research Communications 349 (1): 172–7. Oct 2006. doi:10.1016/j.bbrc.2006.08.025. PMID 16934754.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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