ACOT13

Acyl-CoA thioesterase 13 is a protein that in humans is encoded by the ACOT13 gene.[5] This gene encodes a member of the thioesterase superfamily. In humans, the protein co-localizes with microtubules and is essential for sustained cell proliferation.[5]

ACOT13
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2F0X, 2H4U, 3F5O
Identifiers
Aliases	ACOT13, PNAS-27, THEM2, HT012, acyl-CoA thioesterase 13
External IDs	OMIM: 615652 MGI: 1914084 HomoloGene: 41273 GeneCards: ACOT13
Gene location (Human) Chr. Chromosome 6 (human)[1] Band 6p22.3 Start 24,667,035 bp[1] End 24,705,065 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13|13 A3.1 Start 24,817,948 bp[2] End 24,831,540 bp[2]
Gene ontology Molecular function • hydrolase activity • acyl-CoA hydrolase activity Cellular component • cytosol • spindle • extracellular exosome • cytoskeleton • mitochondrion • cell nucleus • cytoplasm Biological process • protein homotetramerization • acyl-CoA metabolic process • negative regulation of cold-induced thermogenesis Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	55856	66834
Ensembl	ENSG00000112304	ENSMUSG00000006717
UniProt	Q9NPJ3	Q9CQR4
RefSeq (mRNA)	NM_018473 NM_001160094	NM_025790
RefSeq (protein)	NP_001153566 NP_060943	NP_080066
Location (UCSC)	Chr 6: 24.67 – 24.71 Mb	Chr 13: 24.82 – 24.83 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[5]

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.[6] 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,[7] hexokinase IV,[8] 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.[9] 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.[10][11][12] Acyl-CoAs also mediate protein targeting to various membranes and regulation of G Protein α subunits, because they are substrates for protein acylation.[13] 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.[14] 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.[15]

References

1. GRCh38: Ensembl release 89: ENSG00000112304 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000006717 - 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 13".
6. 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.
7. 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 / FEBS. 89 (1): 33–41. doi:10.1111/j.1432-1033.1978.tb20893.x. PMID 29756.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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. PMID 8120000.
15. 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 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

• Pinel P, Fauchereau F, Moreno A, Barbot A, Lathrop M, Zelenika D, Le Bihan D, Poline JB, Bourgeron T, Dehaene S (Jan 2012). "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. doi:10.1523/JNEUROSCI.5996-10.2012. PMC 6621137. PMID 22262880.
• Venkatesh SK, Siddaiah A, Padakannaya P, Ramachandra NB (Oct 2013). "Lack of association between genetic polymorphisms in ROBO1, MRPL19/C2ORF3 and THEM2 with developmental dyslexia". Gene. 529 (2): 215–9. doi:10.1016/j.gene.2013.08.017. PMID 23954868.
• Cheng Z, Bao S, Shan X, Xu H, Gong W (Dec 2006). "Human thioesterase superfamily member 2 (hTHEM2) is co-localized with beta-tubulin onto the microtubule". Biochemical and Biophysical Research Communications. 350 (4): 850–3. doi:10.1016/j.bbrc.2006.09.105. PMID 17045243.
• Kanno K, Wu MK, Agate DS, Fanelli BJ, Wagle N, Scapa EF, Ukomadu C, Cohen DE (Oct 2007). "Interacting proteins dictate function of the minimal START domain phosphatidylcholine transfer protein/StarD2". The Journal of Biological Chemistry. 282 (42): 30728–36. doi:10.1074/jbc.M703745200. PMID 17704541.
• Walker LC, Waddell N, Ten Haaf A, Grimmond S, Spurdle AB (Nov 2008). "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. doi:10.1007/s10549-007-9848-5. PMID 18095154. S2CID 795870.
• Cao J, Xu H, Zhao H, Gong W, Dunaway-Mariano D (Feb 2009). "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. doi:10.1021/bi801879z. PMC 2929599. PMID 19170545.
• Wei J, Kang HW, Cohen DE (Jul 2009). "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. doi:10.1042/BJ20090039. PMC 3086008. PMID 19405909.
• Cheng Z, Song F, Shan X, Wei Z, Wang Y, Dunaway-Mariano D, Gong W (Oct 2006). "Crystal structure of human thioesterase superfamily member 2". Biochemical and Biophysical Research Communications. 349 (1): 172–7. 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.