ACOT11

ACOT11
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3FO5
Identifiers
Aliases	ACOT11 , BFIT, STARD14, THEA, THEM1, acyl-CoA thioesterase 11
External IDs	OMIM: 606803; MGI: 1913736; HomoloGene: 11977; GeneCards: ACOT11; OMA:ACOT11 - orthologs
Gene location (Human) Chr. Chromosome 1 (human) [1] Band 1p32.3 Start 54,542,257 bp [1] End 54,639,192 bp [1]
Gene location (Mouse) Chr. Chromosome 4 (mouse) [2] Band 4|4 C7 Start 106,601,752 bp [2] End 106,662,195 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in apex of heart mucosa of transverse colon buccal mucosa cell duodenum jejunal mucosa left ventricle mucosa of ileum renal medulla mucosa of pharynx human kidney Top expressed in gastrula deep cerebellar nuclei median eminence medial vestibular nucleus retinal pigment epithelium inferior colliculi Epithelium of choroid plexus dorsal tegmental nucleus superior colliculus pontine nuclei More reference expression data BioGPS More reference expression data
Gene ontology Molecular function hydrolase activity lipid binding acyl-CoA hydrolase activity carboxylic ester hydrolase activity fatty-acyl-CoA binding palmitoyl-CoA hydrolase activity thiolester hydrolase activity long-chain fatty acyl-CoA binding myristoyl-CoA hydrolase activity Cellular component extracellular exosome cytoplasm cytosol mitochondrion mitochondrial matrix Biological process intracellular signal transduction response to temperature stimulus response to cold fatty acid metabolic process acyl-CoA metabolic process negative regulation of cold-induced thermogenesis palmitic acid biosynthetic process lipid metabolism Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 26027 329910 Ensembl ENSG00000162390 ENSMUSG00000034853 UniProt Q8WXI4 Q8VHQ9 RefSeq (mRNA) NM_147161 NM_015547 NM_025590 NM_001347159 RefSeq (protein) NP_056362 NP_671517 NP_001334088 NP_079866 Location (UCSC) Chr 1: 54.54 – 54.64 Mb Chr 4: 106.6 – 106.66 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/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. ^{[5] [6] [7] [8]} 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. ^[8]

Structure

The ACOT11 gene is located on the 1st chromosome, with its specific localization being 1p32.3. It contains 18 exons. ^[8]

The protein encoded by this gene contains 258 amino acids, and forms a homodimer with another chain. Its theoretical weight is 26.67 kDa. ^[9] 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. ^[10]

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. ^[11] 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, ^[12] hexokinase IV, ^[13] 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. ^[14] 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. ^{[15] [16] [17]} Acyl-CoAs also mediate protein targeting to various membranes and regulation of G protein α subunits, because they are substrates for protein acylation. ^[18] 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. ^[19] 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. ^[20]

References

1. GRCh38: Ensembl release 89: ENSG00000162390 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000034853 – 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. 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   1222210 . PMID   11696000.
6. 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.
7. 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.
8. "Entrez Gene: ACOT11 acyl-CoA thioesterase 11".
9. "Human START domain of Acyl-coenzyme A thioesterase 11 (ACOT11)". Protein Data Bank in Europe. Retrieved 19 May 2015.
10. 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. Bibcode:2011PLoSO...619521T. doi: 10.1371/journal.pone.0019521 . PMC   3127847 . PMID   21738568.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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 ACOT11 genome location and ACOT11 gene details page in the UCSC Genome Browser .

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.