Misplaced Pages

ACOT4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3K2I
Identifiers
Aliases	ACOT4, PTE-Ib, PTE1B, PTE2B, acyl-CoA thioesterase 4
External IDs	OMIM: 614314; MGI: 2159621; HomoloGene: 44237; GeneCards: ACOT4; OMA:ACOT4 - orthologs
Gene location (Human) Chr. Chromosome 14 (human) Band 14q24.3 Start 73,591,873 bp End 73,595,766 bp
Gene location (Mouse) Chr. Chromosome 12 (mouse) Band 12|12 D1 Start 84,085,153 bp End 84,095,375 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in mucosa of ileum right lobe of liver gonad oocyte testicle human kidney buccal mucosa cell secondary oocyte prefrontal cortex jejunal mucosa Top expressed in right kidney proximal tubule zygote lumbar subsegment of spinal cord human kidney hepatobiliary system liver epithelium of small intestine yolk sac duodenum More reference expression data BioGPS n/a
Gene ontology Molecular function palmitoyl-CoA hydrolase activity carboxylic ester hydrolase activity succinyl-CoA hydrolase activity signaling receptor binding hydrolase activity thiolester hydrolase activity acyl-CoA hydrolase activity myristoyl-CoA hydrolase activity Cellular component peroxisome peroxisomal matrix cytosol Biological process dicarboxylic acid metabolic process butyrate metabolic process succinyl-CoA metabolic process unsaturated monocarboxylic acid metabolic process very long-chain fatty acid metabolic process short-chain fatty acid metabolic process dicarboxylic acid catabolic process saturated monocarboxylic acid metabolic process long-chain fatty acid metabolic process acyl-CoA metabolic process protein targeting to peroxisome fatty acid metabolic process lipid metabolism fatty acid biosynthetic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 122970 171282 Ensembl ENSG00000177465 ENSMUSG00000052392 UniProt Q8N9L9 Q8BWN8 RefSeq (mRNA) NM_152331 NM_134247 RefSeq (protein) NP_689544 NP_599008 Location (UCSC) Chr 14: 73.59 – 73.6 Mb Chr 12: 84.09 – 84.1 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Acyl-coenzyme A thioesterase 4 is an enzyme that in humans is encoded by the ACOT4 gene.

Function

The protein encoded by the ACOT4 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: ENSG00000177465 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000052392 – 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. 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.
6. 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.
7. "Entrez Gene: ACOT4 acyl-CoA thioesterase 4".
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 ACOT4 genome location and ACOT4 gene details page in the UCSC Genome Browser.
• Overview of all the structural information available in the PDB for UniProt: Q8N9L9 (Peroxisomal succinyl-coenzyme A thioesterase) at the PDBe-KB.

Further reading

• Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M, Chi H, Lin C, Li G, Holman K, Tsuda T, Mar L, Foncin JF, Bruni AC, Montesi MP, Sorbi S, Rainero I, Pinessi L, Nee L, Chumakov I, Pollen D, Brookes A, Sanseau P, Polinsky RJ, Wasco W, Da Silva HA, Haines JL, Perkicak-Vance MA, Tanzi RE, Roses AD, Fraser PE, Rommens JM, St George-Hyslop PH (Jun 1995). "Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease". Nature. 375 (6534): 754–60. Bibcode:1995Natur.375..754S. doi:10.1038/375754a0. PMID 7596406. S2CID 4308372.
• Hunt MC, Nousiainen SE, Huttunen MK, Orii KE, Svensson LT, Alexson SE (Nov 1999). "Peroxisome proliferator-induced long chain acyl-CoA thioesterases comprise a highly conserved novel multi-gene family involved in lipid metabolism". The Journal of Biological Chemistry. 274 (48): 34317–26. doi:10.1074/jbc.274.48.34317. PMID 10567408.
• Jones JM, Gould SJ (Aug 2000). "Identification of PTE2, a human peroxisomal long-chain acyl-CoA thioesterase". Biochemical and Biophysical Research Communications. 275 (1): 233–40. doi:10.1006/bbrc.2000.3285. PMID 10944470.
• Westin MA, Hunt MC, Alexson SE (Nov 2005). "The identification of a succinyl-CoA thioesterase suggests a novel pathway for succinate production in peroxisomes". The Journal of Biological Chemistry. 280 (46): 38125–32. doi:10.1074/jbc.M508479200. PMID 16141203.

This article on a gene on human chromosome 14 is a stub. You can help Misplaced Pages by expanding it.

• v
• t
• e

• Genes on human chromosome 14
• Human proteins
• Human chromosome 14 gene stubs