Alternative titles; symbols
HGNC Approved Gene Symbol: SOAT2
Cytogenetic location: 12q13.13 Genomic coordinates (GRCh38): 12:53,103,486-53,124,535 (from NCBI)
Acyl-CoA:cholesterol acyltransferase (ACAT; EC 2.3.1.26), also known as sterol O-acyltransferase (SOAT), catalyzes the formation of cholesterol esters from long-chain fatty acyl CoA and cholesterol (Chang et al., 1997).
The esterification of intracellular sterol by the membrane-bound SOAT1 enzyme (102642) is a critical determinant of eukaryotic cell membrane fluidity and function. Using a consensus sequence found in human and yeast sterol O-acyltransferase genes, Yang et al. (1996) cloned the partial sequence of a second distinct human gene of the SOAT family (GenBank R07932). The second human gene, designated SOAT2, shares 47% identity with the gene encoding human SOAT1 as well as with 2 yeast sterol O-acyltransferase genes.
The human SOAT2 gene maps to chromosome 12q13 (Cases et al., 1998; Lee et al., 2000).
Song et al. (2001) found that the ACAT2 gene is linked to the insulin-like growth factor binding protein-6 gene (IGFBP6; 146735) in a head-to-tail manner with a small intergenic region of about 1.2 kb.
Song et al. (2001) determined that the ACAT2 gene spans over 18 kb and contains 15 exons. The 5-prime flanking region of the gene contains many cis-acting elements for multiple transcriptional regulatory factors but lacks TATA and CCAAT boxes.
Deficiency of Soat2 (Acat2) in mice results in a reduction in cholesterol ester synthesis in the small intestine and liver, which in turn limits intestinal cholesterol absorption, hepatic cholesterol gallstone formation, and the accumulation of cholesterol esters in the plasma lipoproteins. Willner et al. (2003) examined the contribution of Soat2-derived cholesterol esters to atherosclerosis by crossing Soat2-deficient mice with apolipoprotein E (Apoe; 107741)-deficient mice, an atherosclerosis-susceptible strain that has impaired apoE-mediated clearance of apoB (107730)-containing lipoproteins. Doubly deficient mice and Soat2 +/+/apoE -/- control mice had similar elevations of plasma apoB and total plasma lipids; however, the lipid cores of the apoB-containing lipoproteins in doubly-null mice contained primarily triglycerides rather than cholesterol esters. At 30 weeks of age, only the control mice had significant atherosclerosis, which was nearly absent in doubly-null mice. The results demonstrated the crucial role of Soat2-derived cholesterol esters in the development of atherosclerosis in mice and suggested that triglyceride-rich apoB-containing lipoproteins are not as atherogenic as those containing cholesterol esters. The results also supported the rationale of pharmacologic inhibition of SOAT2 as a therapy for atherosclerosis.
Cases, S., Novak, S., Zheng, Y.-W., Myers, H. M., Lear, S. R., Sande, E., Welch, C. B., Lusis, A. J., Spencer, T. A., Krause, B. R., Erickson, S. K., Farese, R. V., Jr. ACAT-2, a second mammalian acyl-CoA:cholesterol acyltransferase: its cloning, expression, and characterization. J. Biol. Chem. 273: 26755-26764, 1998. [PubMed: 9756919] [Full Text: https://doi.org/10.1074/jbc.273.41.26755]
Chang, T. Y., Chang, C. C. Y., Cheng, D. Acyl-coenzyme A:cholesterol acyltransferase. Annu. Rev. Biochem. 66: 613-638, 1997. [PubMed: 9242919] [Full Text: https://doi.org/10.1146/annurev.biochem.66.1.613]
Lee, H., Choi, E., Seomun, Y., Montgomery, K., Huebner, A., Lee, E., Lau, S., Joo, C.-K., Kucherlapati, R., Yoon, S.-J. K. High-resolution transcript map of the region spanning D12S1629 and D12S312 at chromosome 12q13: triple A syndrome-linked region. Genome Res. 10: 1561-1567, 2000. [PubMed: 11042153] [Full Text: https://doi.org/10.1101/gr.142100]
Song, B.-L., Qi, W., Yang, X.-Y., Chang, C. C. Y., Zhu, J.-Q., Chang, T.-Y., Li, B.-L. Organization of human ACAT-2 gene and its cell-type-specific promoter activity. Biochem. Biophys. Res. Commun. 282: 580-588, 2001. [PubMed: 11401500] [Full Text: https://doi.org/10.1006/bbrc.2001.4612]
Willner, E. L., Tow, B., Buhman, K. K., Wilson, M., Sanan, D. A., Rudel, L. L., Farese, R. V., Jr. Deficiency of acyl CoA:cholesterol acyltransferase 2 prevents atherosclerosis in apolipoprotein E-deficient mice. Proc. Nat. Acad. Sci. 100: 1262-1267, 2003. [PubMed: 12538880] [Full Text: https://doi.org/10.1073/pnas.0336398100]
Yang, H., Bard, M., Bruner, D. A., Gleeson, A., Deckelbaum, R. J., Aljinovic, G., Pohl, T. M., Rothstein, R., Sturley, S. L. Sterol esterification in yeast: a two-gene process. Science 272: 1353-1356, 1996. [PubMed: 8650549] [Full Text: https://doi.org/10.1126/science.272.5266.1353]