SOAT1 explained

Sterol O-acyltransferase (acyl-Coenzyme A: cholesterol acyltransferase) 1, also known as SOAT1, is an enzyme that in humans is encoded by the SOAT1 gene.^[1]

Function

Acyl-coenzyme A:cholesterol acyltransferase is an intracellular protein located in the endoplasmic reticulum that forms cholesterol esters from cholesterol. Accumulation of cholesterol esters as cytoplasmic lipid droplets within macrophages and smooth muscle cells is a characteristic feature of the early stages of atherosclerotic plaques (Cadigan et al., 1988).^[1]

Structure and biogenesis

SOAT1 is a polytopic integral membrane protein belonging to the membrane-bound O-acyltransferase (MBOAT) superfamily. The structure of SOAT1 has not yet been solved but that of DltB, a bacterial MBOAT, suggests a complex arrangement of multiple transmembrane domains (TMDs).^[2] Primary sequences of predicted SOAT1 TMDs indicate many unusual TMD features such as the presence of multiple charged residues within the lipid bilayer.^[3] These features can render challenging the integration of a TMD into the hydrophobic phase of the membrane and might therefore require specialised chaperones. A first hint of such a chaperone assisting SOAT1 biogenesis has been the recognition of the involvement of the ER membrane protein complex (EMC), a molecular chaperone and insertase for integral membrane proteins, in maintaining SOAT1 stability.^[4]

Further reading

• Chang TY, Chang CC, Lin S, Yu C, Li BL, Miyazaki A . Roles of acyl-coenzyme A:cholesterol acyltransferase-1 and -2 . Current Opinion in Lipidology . 12 . 3 . 289–96 . June 2001 . 11353332 . 10.1097/00041433-200106000-00008 . 7310225 .
• Chang CC, Noll WW, Nutile-McMenemy N, Lindsay EA, Baldini A, Chang W, Chang TY . Localization of acyl coenzyme A:cholesterol acyltransferase gene to human chromosome 1q25 . Somatic Cell and Molecular Genetics . 20 . 1 . 71–4 . January 1994 . 8197480 . 10.1007/BF02257489 . 20146117 .
• Chang CC, Huh HY, Cadigan KM, Chang TY . Molecular cloning and functional expression of human acyl-coenzyme A:cholesterol acyltransferase cDNA in mutant Chinese hamster ovary cells . The Journal of Biological Chemistry . 268 . 28 . 20747–55 . October 1993 . 8407899 . 10.1074/jbc.273.52.35132 . free .
• Chang CC, Huh HY, Cadigan KM, Chang TY . Molecular cloning and functional expression of human acyl-coenzyme A:cholesterol acyltransferase cDNA in mutant Chinese hamster ovary cells . The Journal of Biological Chemistry . 268 . 28 . 20747–55 . October 1993 . 8407899 . 10.1074/jbc.273.52.35132 . free .
• Oelkers P, Behari A, Cromley D, Billheimer JT, Sturley SL . Characterization of two human genes encoding acyl coenzyme A:cholesterol acyltransferase-related enzymes . The Journal of Biological Chemistry . 273 . 41 . 26765–71 . October 1998 . 9756920 . 10.1074/jbc.273.41.26765 . free .
• Li BL, Li XL, Duan ZJ, Lee O, Lin S, Ma ZM, Chang CC, Yang XY, Park JP, Mohandas TK, Noll W, Chan L, Chang TY . Human acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) gene organization and evidence that the 4.3-kilobase ACAT-1 mRNA is produced from two different chromosomes . The Journal of Biological Chemistry . 274 . 16 . 11060–71 . April 1999 . 10196189 . 10.1074/jbc.274.16.11060 . free .
• Lin S, Cheng D, Liu MS, Chen J, Chang TY . Human acyl-CoA:cholesterol acyltransferase-1 in the endoplasmic reticulum contains seven transmembrane domains . The Journal of Biological Chemistry . 274 . 33 . 23276–85 . August 1999 . 10438503 . 10.1074/jbc.274.33.23276 . free .
• Sakashita N, Miyazaki A, Takeya M, Horiuchi S, Chang CC, Chang TY, Takahashi K . Localization of human acyl-coenzyme A: cholesterol acyltransferase-1 (ACAT-1) in macrophages and in various tissues . The American Journal of Pathology . 156 . 1 . 227–36 . January 2000 . 10623671 . 1868616 . 10.1016/S0002-9440(10)64723-2 .
• Guo Z, Cromley D, Billheimer JT, Sturley SL . Identification of potential substrate-binding sites in yeast and human acyl-CoA sterol acyltransferases by mutagenesis of conserved sequences . Journal of Lipid Research . 42 . 8 . 1282–91 . August 2001 . 10.1016/S0022-2275(20)31579-0 . 11483630 . free .
• Zhang Y, Yu C, Liu J, Spencer TA, Chang CC, Chang TY . Cholesterol is superior to 7-ketocholesterol or 7 alpha-hydroxycholesterol as an allosteric activator for acyl-coenzyme A:cholesterol acyltransferase 1 . The Journal of Biological Chemistry . 278 . 13 . 11642–7 . March 2003 . 12533546 . 10.1074/jbc.M211559200 . free .
• Wollmer MA, Streffer JR, Tsolaki M, Grimaldi LM, Lütjohann D, Thal D, von Bergmann K, Nitsch RM, Hock C, Papassotiropoulos A . Genetic association of acyl-coenzyme A: cholesterol acyltransferase with cerebrospinal fluid cholesterol levels, brain amyloid load, and risk for Alzheimer's disease . Molecular Psychiatry . 8 . 6 . 635–8 . June 2003 . 12851640 . 10.1038/sj.mp.4001296 . free .
• Smith JL, Rangaraj K, Simpson R, Maclean DJ, Nathanson LK, Stuart KA, Scott SP, Ramm GA, de Jersey J . Quantitative analysis of the expression of ACAT genes in human tissues by real-time PCR . Journal of Lipid Research . 45 . 4 . 686–96 . April 2004 . 14729857 . 10.1194/jlr.M300365-JLR200 . free .
• Hori M, Miyazaki A, Tamagawa H, Satoh M, Furukawa K, Hakamata H, Sasaki Y, Horiuchi S . Up-regulation of acyl-coenzyme A:cholesterol acyltransferase-1 by transforming growth factor-beta1 during differentiation of human monocytes into macrophages . Biochemical and Biophysical Research Communications . 320 . 2 . 501–5 . July 2004 . 15219857 . 10.1016/j.bbrc.2004.05.190 . 2019-09-17 . 2017-09-21 . https://web.archive.org/web/20170921225138/http://reposit.lib.kumamoto-u.ac.jp/bitstream/2298/2610/14/22-1480.pdf . dead .
• Yang L, Chen J, Chang CC, Yang XY, Wang ZZ, Chang TY, Li BL . A stable upstream stem-loop structure enhances selection of the first 5'-ORF-AUG as a main start codon for translation initiation of human ACAT1 mRNA . Acta Biochimica et Biophysica Sinica . 36 . 4 . 259–68 . April 2004 . 15253151 . 10.1093/abbs/36.4.259 .
• Liang JJ, Oelkers P, Guo C, Chu PC, Dixon JL, Ginsberg HN, Sturley SL . Overexpression of human diacylglycerol acyltransferase 1, acyl-coa:cholesterol acyltransferase 1, or acyl-CoA:cholesterol acyltransferase 2 stimulates secretion of apolipoprotein B-containing lipoproteins in McA-RH7777 cells . The Journal of Biological Chemistry . 279 . 43 . 44938–44 . October 2004 . 15308631 . 10.1074/jbc.M408507200 . free .
• Yang L, Lee O, Chen J, Chen J, Chang CC, Zhou P, Wang ZZ, Ma HH, Sha HF, Feng JX, Wang Y, Yang XY, Wang L, Dong R, Ornvold K, Li BL, Chang TY . Human acyl-coenzyme A:cholesterol acyltransferase 1 (acat1) sequences located in two different chromosomes (7 and 1) are required to produce a novel ACAT1 isoenzyme with additional sequence at the N terminus . The Journal of Biological Chemistry . 279 . 44 . 46253–62 . October 2004 . 15319423 . 10.1074/jbc.M408155200 . free .
• Yang L, Yang JB, Chen J, Yu GY, Zhou P, Lei L, Wang ZZ, Cy Chang C, Yang XY, Chang TY, Li BL . Enhancement of human ACAT1 gene expression to promote the macrophage-derived foam cell formation by dexamethasone . Cell Research . 14 . 4 . 315–23 . August 2004 . 15353128 . 10.1038/sj.cr.7290231 . free .
• Bertram L, Hsiao M, Mullin K, Parkinson M, Menon R, Moscarillo TJ, Blacker D, Tanzi RE . ACAT1 is not associated with Alzheimer's disease in two independent family-based samples . Molecular Psychiatry . 10 . 6 . 522–4 . June 2005 . 15768051 . 10.1038/sj.mp.4001646 . free .

Notes and References

1. Web site: Entrez Gene: SOAT1 sterol O-acyltransferase (acyl-Coenzyme A: cholesterol acyltransferase) 1.
2. Ma D, Wang Z, Merrikh CN, Lang KS, Lu P, Li X, Merrikh H, Rao Z, Xu W . Crystal structure of a membrane-bound O-acyltransferase . Nature . 562 . 7726 . 286–290 . October 2018 . 30283133 . 6529733 . 10.1038/s41586-018-0568-2 . 2018Natur.562..286M .
3. Lin S, Cheng D, Liu MS, Chen J, Chang TY . Human acyl-CoA:cholesterol acyltransferase-1 in the endoplasmic reticulum contains seven transmembrane domains . The Journal of Biological Chemistry . 274 . 33 . 23276–85 . August 1999 . 10438503 . 10.1074/jbc.274.33.23276 . free .
4. Volkmar N, Thezenas ML, Louie SM, Juszkiewicz S, Nomura DK, Hegde RS, Kessler BM, Christianson JC . The ER membrane protein complex promotes biogenesis of sterol-related enzymes maintaining cholesterol homeostasis . Journal of Cell Science . 132 . 2 . jcs223453 . January 2019 . 30578317 . 6362398 . 10.1242/jcs.223453 .