CES2 (human, recombinant)

Carboxylesterase 2 (CES2) is a serine hydrolase with a major role in endo- and xenobiotic metabolism.¹ It exists as a monomer and is composed of an α/β-hydrolase fold, a regulatory domain, a catalytic domain, and an HTEL endoplasmic reticulum (ER) localization sequence at the C-terminus.^2,1 CES2 is mainly expressed in liver, kidney, and small intestine, but is also found in cardiovascular and reproductive tissues.³ It is involved in the metabolism of several xenobiotics, including anticancer prodrugs and cocaine, and also has triacylglycerol and diacylglycerol hydrolase activity.^4,2,1 Generally, CES2 prefers to hydrolyze esters with a large alcohol moiety and a small acyl group.¹ Knockdown of CES2 decreases fatty acid oxidation, glucose uptake, and glycogen synthesis and increases the expression of genes involved in gluconeogenesis and ER stress in primary human hepatocytes.⁵ Hepatic overexpression of Ces2 decreases hepatic triglyceride and cholesterol levels in db/db mice and in a mouse model of obesity induced by a high-fat diet.⁶ Liver levels of CES2 are decreased in patients with obesity or non-alcoholic steatohepatitis (NASH) and tumoral levels of CES2 decrease with increasing tumor grade in patients with colorectal cancer.^5,6,7 Cayman’s CES2 (human, recombinant) protein can be used for enzyme activity assays. This protein consists of 544 amino acids, has a calculated molecular weight of 60.4 kDa, and a predicted N-terminus of Gln27 after signal peptide cleavage.

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1. Wang, D., Zou, L., Jin, Q., et al. Human carboxylesterases: A comprehensive review. Acta Pharm. Sin. B 8(5), 699-712 (2018).

2. Figueiredo, P.R., González, R.D., and Carvalho, A.T.P. Human carboxylesterase 2 in cocaine metabolism. Mol. Catal. 515, 111938 (2021).

3. Zhang, W., Xu, G., and McLeod, H.L. Comprehensive evaluation of carboxylesterase-2 expression in normal human tissues using tissue array analysis. Appl. Immunohistochem. Mol. Morphol. 10(4), 374-380 (2002).

4. Takai, S., Matsuda, A., Usami, Y., et al. Hydrolytic profile for ester- or amide-linkage by carboxylesterases pI 5.3 and 4.5 from human liver. Bio. Pharm. Bull. 20(8), 869-873 (1997).

5. Ruby, M.A., Massart, J., Hunerdosse, D.M., et al. Human carboxylesterase 2 reverses obesity-induced diacylglycerol accumulation and glucose intolerance. Cell Rep. 18(3), 636-646 (2017).

6. Li, Y., Zalzala, M., Jadhav, K., et al. Carboxylesterase 2 prevents liver steatosis by modulating lipolysis, endoplasmic reticulum stress, and lipogenesis and is regulated by hepatocyte nuclear factor 4 alpha in mice. Hepatology 63(6), 1860-1874 (2016).

7. Tang, X., Wu, H., Wu, Z., et al. Carboxylesterase 2 is downregulated in colorectal cancer following progression of the disease. Cancer Invest. 26(2), 178-181 (2008).