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J Biol Chem, Vol. 273, Issue 41, 26765-26771, October 9, 1998
Characterization of Two Human Genes Encoding Acyl Coenzyme
A:Cholesterol Acyltransferase-related Enzymes
Peter
Oelkers ,
Ajay
Behari ,
Debra
Cromley¶,
Jeffrey
T.
Billheimer¶, and
Stephen L.
Sturley
From the Institute of Human Nutrition,
Departments of Pediatrics and Physiology and Molecular
Biophysics, Columbia University College of Physicians and Surgeons, New
York, New York 10032 and ¶ DuPont Pharmaceutical Company,
Experimental Station, Wilmington, Delaware 19880-0400
The enzyme acyl coenzyme A:cholesterol
acyltransferase 1 (ACAT1) mediates sterol esterification, a crucial
component of intracellular lipid homeostasis. Two enzymes catalyze this
activity in Saccharomyces cerevisiae (yeast), and several
lines of evidence suggest multigene families may also exist in mammals.
Using the human ACAT1 sequence to screen data bases of expressed
sequence tags, we identified two novel and distinct partial human
cDNAs. Full-length cDNA clones for these ACAT related gene
products (ARGP) 1 and 2 were isolated from a hepatocyte (HepG2)
cDNA library. ARGP1 was expressed in numerous human adult tissues
and tissue culture cell lines, whereas expression of ARGP2 was more
restricted. In vitro microsomal assays in a yeast strain
deleted for both esterification genes and completely deficient in
sterol esterification indicated that ARGP2 esterified cholesterol while
ARGP1 did not. In contrast to ACAT1 and similar to liver
esterification, the activity of ARGP2 was relatively resistant to a
histidine active site modifier. ARGP2 is therefore a tissue-specific
sterol esterification enzyme which we thus designated ACAT2. We
speculate that ARGP1 participates in the coenzyme
A-dependent acylation of substrate(s) other than
cholesterol. Consistent with this hypothesis, ARGP1, unlike any other
member of this multigene family, possesses a predicted diacylglycerol
binding motif suggesting that it may perform the last acylation in
triglyceride biosynthesis.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.

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C. W. Joyce, G. S. Shelness, M. A. Davis, R. G. Lee, K. Skinner, R. A. Anderson, and L. L. Rudel
ACAT1 and ACAT2 Membrane Topology Segregates a Serine Residue Essential for Activity to Opposite Sides of the Endoplasmic Reticulum Membrane
Mol. Biol. Cell,
November 1, 2000;
11(11):
3675 - 3687.
[Abstract]
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N. N. Izzat, M. E. Deshazer, and D. S. Loose-Mitchell
New Molecular Targets for Cholesterol-Lowering Therapy
J. Pharmacol. Exp. Ther.,
May 1, 2000;
293(2):
315 - 320.
[Abstract]
[Full Text]
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J. Kusunoki, K. Aragane, T. Kitamine, H. Kozono, K. Kano, K. Fujinami, K. Kojima, T. Chiwata, and Y. Sekine
Postprandial Hyperlipidemia in Streptozotocin-Induced Diabetic Rats Is Due to Abnormal Increase in Intestinal Acyl Coenzyme A:Cholesterol Acyltransferase Activity
Arterioscler. Thromb. Vasc. Biol.,
January 1, 2000;
20(1):
171 - 178.
[Abstract]
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N. Sakashita, A. Miyazaki, M. Takeya, S. Horiuchi, C. C. Y. Chang, T.-Y. Chang, and K. Takahashi
Localization of Human Acyl-Coenzyme A:Cholesterol Acyltransferase-1 (ACAT-1) in Macrophages and in Various Tissues
Am. J. Pathol.,
January 1, 2000;
156(1):
227 - 236.
[Abstract]
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C. Yu, J. Chen, S. Lin, J. Liu, C. C. Y. Chang, and T.-Y. Chang
Human Acyl-CoA:Cholesterol Acyltransferase-1 Is a Homotetrameric Enzyme in Intact Cells and in Vitro
J. Biol. Chem.,
December 17, 1999;
274(51):
36139 - 36145.
[Abstract]
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K. A. H. Abo-Hashema, M. H. Cake, G. W. Power, and D. Clarke
Evidence for Triacylglycerol Synthesis in the Lumen of Microsomes via a Lipolysis-Esterification Pathway Involving Carnitine Acyltransferases
J. Biol. Chem.,
December 10, 1999;
274(50):
35577 - 35582.
[Abstract]
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S. Lin, D. Cheng, M.-S. Liu, J. Chen, and T.-Y. Chang
Human Acyl-CoA:Cholesterol Acyltransferase-1 in the Endoplasmic Reticulum Contains Seven Transmembrane Domains
J. Biol. Chem.,
August 13, 1999;
274(33):
23276 - 23285.
[Abstract]
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J. R. Burnett, L. J. Wilcox, D. E. Telford, S. J. Kleinstiver, P. H. R. Barrett, R. S. Newton, and M. W. Huff
Inhibition of ACAT by avasimibe decreases both VLDL and LDL apolipoprotein B production in miniature pigs
J. Lipid Res.,
July 1, 1999;
40(7):
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[Abstract]
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R. L. Hamilton, A. Moorehouse, S. R. Lear, J. S. Wong, and S. K. Erickson
A rapid calcium precipitation method of recovering large amounts of highly pure hepatocyte rough endoplasmic reticulum
J. Lipid Res.,
June 1, 1999;
40(6):
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[Abstract]
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D. Warnecke, R. Erdmann, A. Fahl, B. Hube, F. Muller, T. Zank, U. Zahringer, and E. Heinz
Cloning and Functional Expression of UGT Genes Encoding Sterol Glucosyltransferases from Saccharomyces cerevisiae, Candida albicans, Pichia pastoris, and Dictyostelium discoideum
J. Biol. Chem.,
May 7, 1999;
274(19):
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B.-L. Li, X.-L. Li, Z.-J. Duan, O. Lee, S. Lin, Z.-M. Ma, C. C. Y. Chang, X.-Y. Yang, J. P. Park, T. K. Mohandas, et al.
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
J. Biol. Chem.,
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S. Cases, S. Novak, Y.-W. Zheng, H. M. Myers, S. R. Lear, E. Sande, C. B. Welch, A. J. Lusis, T. A. Spencer, B. R. Krause, et al.
ACAT-2, A Second Mammalian Acyl-CoA:Cholesterol Acyltransferase. ITS CLONING, EXPRESSION, AND CHARACTERIZATION
J. Biol. Chem.,
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P. Oelkers, A. Tinkelenberg, N. Erdeniz, D. Cromley, J. T. Billheimer, and S. L. Sturley
A Lecithin Cholesterol Acyltransferase-like Gene Mediates Diacylglycerol Esterification in Yeast
J. Biol. Chem.,
May 19, 2000;
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H. Yagyu, T. Kitamine, J.-i. Osuga, R.-i. Tozawa, Z. Chen, Y. Kaji, T. Oka, S. Perrey, Y. Tamura, K. Ohashi, et al.
Absence of ACAT-1 Attenuates Atherosclerosis but Causes Dry Eye and Cutaneous Xanthomatosis in Mice with Congenital Hyperlipidemia
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July 7, 2000;
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C. C. Y. Chang, N. Sakashita, K. Ornvold, O. Lee, E. T. Chang, R. Dong, S. Lin, C.-Y. G. Lee, S. C. Strom, R. Kashyap, et al.
Immunological Quantitation and Localization of ACAT-1 and ACAT-2 in Human Liver and Small Intestine
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J.-B. Yang, Z.-J. Duan, W. Yao, O. Lee, L. Yang, X.-Y. Yang, X. Sun, C. C. Y. Chang, T.-Y. Chang, and B.-L. Li
Synergistic Transcriptional Activation of Human Acyl-coenzyme A: Cholesterol Acyltransterase-1 Gene by Interferon-gamma and All-trans-Retinoic Acid THP-1 Cells
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K. K. Buhman, H. C. Chen, and R. V. Farese Jr.
The Enzymes of Neutral Lipid Synthesis
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Copyright © 1998 by the American Society for Biochemistry and Molecular Biology.
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