HGNC Approved Gene Symbol: ACOT1
Cytogenetic location: 14q24.3 Genomic coordinates (GRCh38): 14:73,490,933-73,543,796 (from NCBI)
Acyl-CoA thioesterases (ACOTs; EC 3.1.2.2), such as ACOT1, hydrolyze acyl-CoAs to the free fatty acid and CoA. ACOTs therefore play key roles in maintaining the intracellular ratio between CoA esters of various lipids and free fatty acids (summary by Hunt et al., 2006).
By searching a database for orthologs of mouse Acot genes, Hunt et al. (2006) identified human ACOT1. The deduced 421-amino acid protein has a putative catalytic site and a possible C-terminal peroxisome-targeting signal. ACOT1 shares 98.6% amino acid identity with the corresponding 421 amino acids of ACOT2 (609972); however, ACOT2 has a 62-amino acid mitochondrial targeting signal at its N-terminal end that is absent in ACOT1. Fluorescence-tagged ACOT1 showed a diffuse pattern of expression in transfected human skin fibroblasts.
Brocker et al. (2010) reviewed the ACOT gene family. They stated that ACOT1 contains an N-terminal acyl-CoA thioester hydrolase domain and a C-terminal esterase-lipase domain. The N-terminal domain does not participate directly in catalysis but appears to regulate enzyme activity. The C-terminal domain, also known as an alpha/beta-hydrolase fold, contains all residues required for catalysis. ACOT2 and ACOT4 (614314) have the same protein structure.
By assaying recombinant human proteins, Hunt et al. (2006) found that ACOT1 and ACOT2 had similar substrate specificities, with both enzymes showing highest activity on long-chain saturated acyl-CoAs of 12 to 20 carbon atoms and long-chain unsaturated acyl-CoAs, such as C16:1-CoA and C18:1-CoA. No activity was detected for ACOT1 or ACOT2 with acyl-CoAs of 8 carbons or less.
Hunt et al. (2006) determined that the ACOT1 gene contains 3 exons.
By genomic sequence analysis, Hunt et al. (2006) mapped the ACOT1 gene to an 80-kb ACOT gene cluster on chromosome 14q24.3. The order of the genes, from centromere to telomere, is ACOT1, ACOT2, ACOT4 (614314), and ACOT6 (614267). They mapped the mouse Acot1 gene to a similar Acot gene cluster on chromosome 12D3, except that the mouse Acot cluster has 6 genes. The mouse Acot3 and Acot5 genes do not have human orthologs.
Brocker, C., Carpenter, C., Nebert, D. W., Vasiliou, V. Evolutionary divergence and functions of the human acyl-CoA thioesterase gene (ACOT) family. Hum. Genomics 4: 411-420, 2010. [PubMed: 20846931] [Full Text: https://doi.org/10.1186/1479-7364-4-6-411]
Hunt, M. C., Rautanen, A., Westin, M. A. K., Svensson, L. T., Alexson, S. E. H. 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 J. 20: 1855-1864, 2006. [PubMed: 16940157] [Full Text: https://doi.org/10.1096/fj.06-6042com]