Carboxylesterase 1
CES1 | |||
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Gene ontology | |||
Molecular function | |||
Cellular component | |||
Biological process | |||
Sources:Amigo / QuickGO |
Ensembl | |||||||||
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UniProt | |||||||||
RefSeq (mRNA) | |||||||||
RefSeq (protein) | |||||||||
Location (UCSC) | Chr 16: 55.8 – 55.83 Mb | Chr 8: 93.89 – 93.92 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
Liver carboxylesterase 1 also known as carboxylesterase 1 (CES1, hCE-1 or CES1A1) is an
CES1 is present in most tissues with higher levels in the liver and low levels in the gastrointestinal tract.[7]
Function
Carboxylesterase 1 is a serine esterase and member of a large multigene
This enzyme is known to hydrolyze aromatic and aliphatic esters and can manage cellular cholesterol esterification levels. It may also play a role in detoxification in the lung and/or protection of the central nervous system from ester or amide compounds.[6]
The protein contains an amino acid sequence at its N-terminus that sends it into the endoplasmic reticulum where a C-terminal sequence can bind to a KDEL receptor.[7]
Clinical significance
Carboxylesterase 1 deficiency may be associated with
CES1 can activate or deactivate various drugs. CES1 is responsible for the activation of many prodrugs such as angiotensin-converting enzyme (ACE) inhibitors, oseltamivir, and dabigatran.[10][11][12][13] Genetic variants of CES1 can significantly affect both pharmacokinetics and pharmacodynamics of drugs metabolized by CES1, such as methylphenidate and clopidogrel.[14] The ability of CES1 to metabolize heroin and cocaine among other drugs has suggested a therapeutic role for the enzyme.[15]
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.[§ 1]
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Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
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References
- ^ a b c ENSG00000262243 GRCh38: Ensembl release 89: ENSG00000198848, ENSG00000262243 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000056973 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 2070086.
- ^ a b c "Entrez Gene: CES1 carboxylesterase 1 (monocyte/macrophage serine esterase 1)".
- ^ PMID 16858120.
- S2CID 84899499.
- ^ S2CID 32622794.
- PMID 19185566.
- S2CID 206496779.
- S2CID 9277216.
- PMID 23467860.
- PMID 18485328.
- PMID 12773168.
Further reading
- Riddles PW, Richards LJ, Bowles MR, Pond SM (1992). "Cloning and analysis of a cDNA encoding a human liver carboxylesterase". Gene. 108 (2): 289–92. PMID 1748313.
- Munger JS, Shi GP, Mark EA, et al. (1991). "A serine esterase released by human alveolar macrophages is closely related to liver microsomal carboxylesterases". J. Biol. Chem. 266 (28): 18832–8. PMID 1918003.
- Long RM, Calabrese MR, Martin BM, Pohl LR (1991). "Cloning and sequencing of a human liver carboxylesterase isoenzyme". Life Sci. 48 (11): PL43–9. PMID 1997784.
- Ketterman AJ, Bowles MR, Pond SM (1990). "Purification and characterization of two human liver carboxylesterases". Int. J. Biochem. 21 (12): 1303–12. PMID 2612723.
- Becker A, Böttcher A, Lackner KJ, et al. (1994). "Purification, cloning, and expression of a human enzyme with acyl coenzyme A: cholesterol acyltransferase activity, which is identical to liver carboxylesterase". Arterioscler. Thromb. 14 (8): 1346–55. PMID 8049197.
- Kroetz DL, McBride OW, Gonzalez FJ (1993). "Glycosylation-dependent activity of baculovirus-expressed human liver carboxylesterases: cDNA cloning and characterization of two highly similar enzyme forms". Biochemistry. 32 (43): 11606–17. PMID 8218228.
- Shibata F, Takagi Y, Kitajima M, et al. (1993). "Molecular cloning and characterization of a human carboxylesterase gene". Genomics. 17 (1): 76–82. PMID 8406473.
- Langmann T, Becker A, Aslanidis C, et al. (1997). "Structural organization and characterization of the promoter region of a human carboxylesterase gene". Biochim. Biophys. Acta. 1350 (1): 65–74. PMID 9003459.
- Brzezinski MR, Spink BJ, Dean RA, et al. (1997). "Human liver carboxylesterase hCE-1: binding specificity for cocaine, heroin, and their metabolites and analogs". Drug Metab. Dispos. 25 (9): 1089–96. PMID 9311626.
- Yan B, Matoney L, Yang D (1999). "Human carboxylesterases in term placentae: enzymatic characterization, molecular cloning and evidence for the existence of multiple forms". Placenta. 20 (7): 599–607. PMID 10452915.
- Mori M, Hosokawa M, Ogasawara Y, et al. (1999). "cDNA cloning, characterization and stable expression of novel human brain carboxylesterase". FEBS Lett. 458 (1): 17–22. S2CID 5792413.
- Islam MR, Waheed A, Shah GN, et al. (1999). "Human egasyn binds beta-glucuronidase but neither the esterase active site of egasyn nor the C terminus of beta-glucuronidase is involved in their interaction". Arch. Biochem. Biophys. 372 (1): 53–61. PMID 10562416.
- Ghosh S (2001). "Cholesteryl ester hydrolase in human monocyte/macrophage: cloning, sequencing, and expression of full-length cDNA". Physiol. Genomics. 2 (1): 1–8. S2CID 1657010.
- Ghosh S, Natarajan R (2001). "Cloning of the human cholesteryl ester hydrolase promoter: identification of functional peroxisomal proliferator-activated receptor responsive elements". Biochem. Biophys. Res. Commun. 284 (4): 1065–70. PMID 11409902.
- Alam M, Ho S, Vance DE, Lehner R (2002). "Heterologous expression, purification, and characterization of human triacylglycerol hydrolase". Protein Expr. Purif. 24 (1): 33–42. PMID 11812220.
- Satoh T, Taylor P, Bosron WF, et al. (2002). "Current progress on esterases: from molecular structure to function". Drug Metab. Dispos. 30 (5): 488–93. S2CID 5802731.
- Alam M, Vance DE, Lehner R (2002). "Structure-function analysis of human triacylglycerol hydrolase by site-directed mutagenesis: identification of the catalytic triad and a glycosylation site". Biochemistry. 41 (21): 6679–87. PMID 12022871.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. PMID 12477932.
- Bencharit S, Morton CL, Xue Y, et al. (2003). "Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme". Nat. Struct. Biol. 10 (5): 349–56. S2CID 1108060.
- Zhu HJ, Brinda B, Froehlich TE, Markowitz JS (2012). "A discriminative analytical method for detection of CES1A1 and CES1A2/CES1A3 genetic variants". Pharmacogenet Genomics. 22 (3): 215–8. PMID 22237548.