Carboxylesterase 2 Explained

Carboxylesterase 2 is an enzyme that in humans is encoded by the CES2 gene.^{[1] [2] [3]} It is a member of the alpha/beta fold hydrolase family.^[4]

Carboxylesterase 2 is a member of a large multigene family. The enzymes encoded by these genes are responsible for the hydrolysis of ester- and amide-bond-containing drugs such as cocaine and heroin. They also hydrolyze long-chain fatty acid esters and thioesters. The specific function of this enzyme has not yet been determined; however, it is speculated that carboxylesterases may play a role in lipid metabolism and/or the blood–brain barrier system. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.^[3]

Further reading

• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–174 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–156 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Yan B, Matoney L, Yang D . Human carboxylesterases in term placentae: enzymatic characterization, molecular cloning and evidence for the existence of multiple forms . Placenta . 20 . 7 . 599–607 . September 1999 . 10452915 . 10.1053/plac.1999.0407 .
• Hartley JL, Temple GF, Brasch MA . DNA cloning using in vitro site-specific recombination . Genome Research . 10 . 11 . 1788–1795 . November 2000 . 11076863 . 310948 . 10.1101/gr.143000 .
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A . 6 . Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs . Genome Research . 11 . 3 . 422–435 . March 2001 . 11230166 . 311072 . 10.1101/gr.GR1547R .
• Chagnon P, Michaud J, Mitchell G, Mercier J, Marion JF, Drouin E, Rasquin-Weber A, Hudson TJ, Richter A . 6 . A missense mutation (R565W) in cirhin (FLJ14728) in North American Indian childhood cirrhosis . American Journal of Human Genetics . 71 . 6 . 1443–1449 . December 2002 . 12417987 . 378590 . 10.1086/344580 .
• Saito S, Iida A, Sekine A, Kawauchi S, Higuchi S, Ogawa C, Nakamura Y . Catalog of 680 variations among eight cytochrome p450 (CYP) genes, nine esterase genes, and two other genes in the Japanese population . Journal of Human Genetics . 48 . 5 . 249–270 . 2003 . 12721789 . 10.1007/s10038-003-0021-7 . free .
• Wu MH, Chen P, Remo BF, Cook EH, Das S, Dolan ME . Characterization of multiple promoters in the human carboxylesterase 2 gene . Pharmacogenetics . 13 . 7 . 425–435 . July 2003 . 12835618 . 10.1097/00008571-200307000-00008 .
• Marsh S, Xiao M, Yu J, Ahluwalia R, Minton M, Freimuth RR, Kwok PY, McLeod HL . 6 . Pharmacogenomic assessment of carboxylesterases 1 and 2 . Genomics . 84 . 4 . 661–668 . October 2004 . 15475243 . 10.1016/j.ygeno.2004.07.008 .
• Wu MH, Chen P, Wu X, Liu W, Strom S, Das S, Cook EH, Rosner GL, Dolan ME . 6 . Determination and analysis of single nucleotide polymorphisms and haplotype structure of the human carboxylesterase 2 gene . Pharmacogenetics . 14 . 9 . 595–605 . September 2004 . 15475733 . 10.1097/00008571-200409000-00004 .
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A . 6 . From ORFeome to biology: a functional genomics pipeline . Genome Research . 14 . 10B . 2136–2144 . October 2004 . 15489336 . 528930 . 10.1101/gr.2576704 .
• Charasson V, Bellott R, Meynard D, Longy M, Gorry P, Robert J . Pharmacogenetics of human carboxylesterase 2, an enzyme involved in the activation of irinotecan into SN-38 . Clinical Pharmacology and Therapeutics . 76 . 6 . 528–535 . December 2004 . 15592324 . 10.1016/j.clpt.2004.08.007 . 23999721 .
• Kim SR, Nakamura T, Saito Y, Sai K, Nakajima T, Saito H, Shirao K, Minami H, Ohtsu A, Yoshida T, Saijo N, Ozawa S, Sawada J . 6 . Twelve novel single nucleotide polymorphisms in the CES2 gene encoding human carboxylesterase 2 (hCE-2) . Drug Metabolism and Pharmacokinetics . 18 . 5 . 327–332 . 2005 . 15618752 . 10.2133/dmpk.18.327 .
• Fox CA, Sapinoso LM, Zhang H, Zhang W, McLeod HL, Petroni GR, Mullick T, Moskaluk CA, Frierson HF, Hampton GM, Powell SM . 6 . Altered expression of TFF-1 and CES-2 in Barrett's Esophagus and associated adenocarcinomas . Neoplasia . 7 . 4 . 407–416 . April 2005 . 15967118 . 1501154 . 10.1593/neo.04715 .
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S . 6 . Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes . Genome Research . 16 . 1 . 55–65 . January 2006 . 16344560 . 1356129 . 10.1101/gr.4039406 .
• Wang D, Zou L, Jin Q, Hou J, Ge G, Yang L . Human carboxylesterases: a comprehensive review . Acta Pharmaceutica Sinica B . 8 . 5 . 699–712 . September 2018 . 30245959 . 6146386 . 10.1016/j.apsb.2018.05.005 .
• Web site: Tissue expression of CES2 - Summary - The Human Protein Atlas . 2022-09-30 . www.proteinatlas.org.

Notes and References

1. Pindel EV, Kedishvili NY, Abraham TL, Brzezinski MR, Zhang J, Dean RA, Bosron WF . Purification and cloning of a broad substrate specificity human liver carboxylesterase that catalyzes the hydrolysis of cocaine and heroin . The Journal of Biological Chemistry . 272 . 23 . 14769–14775 . June 1997 . 9169443 . 10.1074/jbc.272.23.14769 . free .
2. Schwer H, Langmann T, Daig R, Becker A, Aslanidis C, Schmitz G . Molecular cloning and characterization of a novel putative carboxylesterase, present in human intestine and liver . Biochemical and Biophysical Research Communications . 233 . 1 . 117–120 . April 1997 . 9144407 . 10.1006/bbrc.1997.6413 .
3. Web site: Entrez Gene: CES2 carboxylesterase 2 (intestine, liver).
4. Imai T . Human carboxylesterase isozymes: catalytic properties and rational drug design . Drug Metabolism and Pharmacokinetics . 21 . 3 . 173–185 . June 2006 . 16858120 . 10.2133/dmpk.21.173 .