ACOT11

ACOT11
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases ACOT11, BFIT, STARD14, THEA, THEM1, acyl-CoA thioesterase 11
External IDs MGI: 1913736 HomoloGene: 11977 GeneCards: ACOT11
RNA expression pattern


More reference expression data
Orthologs
Species Human Mouse
Entrez

26027

329910

Ensembl

ENSG00000162390

ENSMUSG00000034853

UniProt

Q8WXI4

Q8VHQ9

RefSeq (mRNA)

NM_147161
NM_015547

NM_025590

RefSeq (protein)

NP_056362.1
NP_671517.1

NP_079866.2

Location (UCSC) Chr 1: 54.54 – 54.64 Mb Chr 4: 106.74 – 106.8 Mb
PubMed search [1] [2]
Wikidata
View/Edit HumanView/Edit Mouse

Acyl-coenzyme A thioesterase 11 also known as StAR-related lipid transfer protein 14 (STARD14) is an enzyme that in humans is encoded by the ACOT11 gene.[3][4][5][6] This gene encodes a protein with acyl-CoA thioesterase activity towards medium (C12) and long-chain (C18) fatty acyl-CoA substrates which relies on its StAR-related lipid transfer domain. Expression of a similar murine protein in brown adipose tissue is induced by cold exposure and repressed by warmth. Expression of the mouse protein has been associated with obesity, with higher expression found in obesity-resistant mice compared with obesity-prone mice. Alternative splicing results in two transcript variants encoding different isoforms.[6]

Structure

The ACOT11 gene is located on the 1st chromosome, with its specific localization being 1p32.3. It contains 18 exons.[6]

The protein encoded by this gene contains 258 amino acids, and forms a homodimer with another chain. Its theoretical weight is 26.67 kDa.[7] 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.[8]

Function

The protein encoded by the ACOT11 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]

References

  1. ↑ "Human PubMed Reference:".
  2. ↑ "Mouse PubMed Reference:".
  3. ↑ Adams SH, Chui C, Schilbach SL, Yu XX, Goddard AD, Grimaldi JC, Lee J, Dowd P, Colman S, Lewin DA (Nov 2001). "BFIT, a unique acyl-CoA thioesterase induced in thermogenic brown adipose tissue: cloning, organization of the human gene and assessment of a potential link to obesity". The Biochemical Journal. 360 (Pt 1): 135–42. doi:10.1042/0264-6021:3600135. PMC 1222210Freely accessible. PMID 11696000.
  4. ↑ 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.
  5. ↑ 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.
  6. 1 2 3 "Entrez Gene: ACOT11 acyl-CoA thioesterase 11".
  7. ↑ "Human START domain of Acyl-coenzyme A thioesterase 11 (ACOT11)". Protein Data Bank in Europe. Retrieved 19 May 2015.
  8. ↑ 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. doi:10.1371/journal.pone.0019521. PMID 21738568.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ Srere PA (Dec 1965). "Palmityl-coenzyme A inhibition of the citrate-condensing enzyme". Biochimica et Biophysica Acta. 106 (3): 445–55. doi:10.1016/0005-2760(65)90061-5. PMID 5881327.
  12. ↑ 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.
  13. ↑ Nishizuka Y (Apr 1995). "Protein kinase C and lipid signaling for sustained cellular responses". FASEB Journal. 9 (7): 484–96. PMID 7737456.
  14. ↑ Glick BS, Rothman JE (Mar 1987). "Possible role for fatty acyl-coenzyme A in intracellular protein transport". Nature. 326 (6110): 309–12. doi:10.1038/326309a0. PMID 3821906.
  15. ↑ 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.
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ 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

Further reading

  • Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. 
  • Ishikawa K, Nagase T, Suyama M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Jun 1998). "Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro". DNA Research. 5 (3): 169–76. doi:10.1093/dnares/5.3.169. PMID 9734811. 
This article is issued from Wikipedia - version of the 11/30/2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.