Affinage

CES1

Metallothionein-2 · UniProt P02795

Length
61 aa
Mass
6.0 kDa
Annotated
2026-06-09
100 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CES1 is a serine hydrolase of the α/β-hydrolase fold whose catalytic triad mediates the stereoselective hydrolysis of ester and related bonds in a broad range of xenobiotics and endogenous lipids (PMID:15082749, PMID:25462813). It is the principal enzyme for activating or clearing numerous drugs, including methylphenidate (PMID:15082749), the anticancer prodrug irinotecan (CPT-11) to SN-38 (PMID:15100172), the prodrugs sacubitril (PMID:26817948) and multiple ACE-inhibitors such as enalapril (PMID:26076923, PMID:33963573), and oseltamivir (PMID:27895113). Catalytic competence is strongly governed by coding variation: the p.Gly143Glu (G143E) variant retains only ~20% of wild-type efficiency and the p.Asp260fs frameshift abolishes activity, with G143E producing clinically measurable reductions in prodrug activation and blunted pharmacodynamic responses (PMID:18485328, PMID:26817948, PMID:26076923, PMID:33963573). Beyond drug metabolism, CES1 shapes hepatic lipid homeostasis—limiting triacylglycerol accumulation by redirecting fatty acids toward β-oxidation and modulating VLDL secretion and lipogenic gene expression (PMID:19651238, PMID:29631096)—and influences whole-body cholesterol balance, atherosclerosis, and macrophage foam-cell formation/cholesterol efflux (PMID:29259301, PMID:29803178). In immune cells it catabolizes anti-inflammatory prostaglandin glyceryl esters such as PGD2-G, tuning inflammatory cytokine output and PPARγ signaling (PMID:33225149). CES1 expression is transcriptionally controlled by Sp1/C/EBPα (PMID:18305377, PMID:18328811), PXR (PMID:26340669), Nrf2 (PMID:31076985, PMID:36695375), the histone methyltransferase G9a in competition with FXR (PMID:37042626), and miR-155 (PMID:29803178), and its dysregulation contributes to lipid-driven phenotypes in kidney injury and several cancers (PMID:37042626, PMID:34185414, PMID:36472914, PMID:39472448).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2004 High

    Established CES1 as the specific carboxylesterase isoform responsible for metabolizing key clinical substrates, distinguishing it functionally from CES2 and CES3.

    Evidence In vitro kinetics with purified recombinant CES1A1, CES2, CES3 on methylphenidate enantiomers and on irinotecan/metabolites

    PMID:15082749 PMID:15100172

    Open questions at the time
    • Did not address regulation of CES1 levels in vivo
    • Substrate range limited to the tested drugs
  2. 2008 High

    Defined the molecular basis of interindividual variation by showing specific coding mutations cripple catalytic function, and identified promoter elements driving CES1 expression.

    Evidence Mutagenesis and enzymatic kinetics of G143E and Asp260fs; reporter/EMSA assays of Sp1/C/EBPα promoter elements

    PMID:18305377 PMID:18328811 PMID:18485328

    Open questions at the time
    • Functional consequence of G143E shown only for limited substrates at the time
    • Promoter regulation tested in vitro, not in native chromatin
  3. 2009 Medium

    Demonstrated a metabolic role beyond xenobiotic clearance—limiting hepatic triacylglycerol accumulation by shifting fatty acids toward β-oxidation rather than via direct TG hydrolysis.

    Evidence Gain-of-function in McArdle-RH7777 hepatocytes with esterase-inhibitor dissection of mouse ortholog Es-x/Ces1

    PMID:19651238

    Open questions at the time
    • Mechanism by which non-hydrolytic activity drives β-oxidation unclear
    • Mouse ortholog rather than human CES1
  4. 2015 Medium

    Mapped upstream transcriptional control of CES1 to nuclear receptor PXR and broadened its prodrug-activation portfolio to ACE-inhibitors.

    Evidence PXR overexpression/knockdown in HepG2; ACEI prodrug activation in human liver S9 and recombinant CES1 with G143E comparison

    PMID:26076923 PMID:26340669

    Open questions at the time
    • PXR-CES1 link shown in a single cell model
    • Direct PXR binding to CES1 promoter not resolved
  5. 2016 High

    Confirmed CES1-selective activation of sacubitril and quantified developmental scaling of CES1 abundance with enzymatic activity.

    Evidence Human liver/intestine/kidney S9 and recombinant enzyme assays for sacubitril; targeted proteomics across pediatric/adult livers correlated to oseltamivir carboxylase activity

    PMID:26817948 PMID:27895113

    Open questions at the time
    • Ontogenic regulators of the ~5-fold abundance increase not identified
  6. 2018 Medium

    Causally tied the G143E variant to altered systemic lipid metabolism and linked CES1 to macrophage cholesterol handling and atheroprotection.

    Evidence Humanized CES1WT/G143E/S221A mice on high-fat diet; Ces1g knockout in Ldlr-/- mice; miR-155-driven CEH induction in THP-1 macrophages

    PMID:29259301 PMID:29631096 PMID:29803178

    Open questions at the time
    • Human relevance of mouse Ces1g knockout phenotypes uncertain
    • miR-155–CES1 axis shown in a single macrophage model
  7. 2020 Medium

    Identified CES1 as a regulator of bioactive lipid signaling by hydrolyzing prostaglandin glyceryl esters and thereby modulating inflammation.

    Evidence CES1 knockdown plus small-molecule inhibitors in THP-1 cells with LC-MS/MS of PGD2-G/PGE2-G and cytokine readouts

    PMID:33225149

    Open questions at the time
    • In vivo relevance of PG-glyceryl ester catabolism not established
    • Single cell-line system
  8. 2022 Medium

    Resolved the catalytic architecture of the carboxylesterase fold and connected gut-microbial TMAO signaling to CES1-dependent drug response.

    Evidence X-ray structure of mouse Ces2c with comparison to human CES1; TMAO feeding/HepG2 studies dissecting NOX-ROS/Nrf2/CES1 control of clopidogrel activation and platelet function

    PMID:36361897 PMID:36695375

    Open questions at the time
    • Structure is of an ortholog, not human CES1
    • Direct Nrf2 binding to CES1 promoter not shown
  9. 2023 Medium

    Placed CES1 within epigenetic and lipid-signaling circuits driving disease, including G9a/FXR-controlled expression in kidney injury and PPAR-SCD–linked chemoresistance in cancer.

    Evidence Renal G9a knockout with competitive promoter-binding assays and AKI models; genetic/pharmacological CES1 blockade in HCC with lipidomics and xenografts

    PMID:36472914 PMID:37042626

    Open questions at the time
    • G9a/FXR competition characterized by promoter-binding surrogates
    • Causal lipid species mediating chemoresistance not definitively isolated
  10. 2024 Medium

    Confirmed CES1 clinical pharmacogenetics and uncovered receptor-driven control via CHRNA5/MEK-ERK signaling.

    Evidence Prospective enalapril PK/PD study genotyped for G143E; co-IP and CHRNA5 knockdown/overexpression with MEK/ERK phosphorylation analysis in HNSC cells

    PMID:33963573 PMID:39472448

    Open questions at the time
    • CHRNA5-CES1 interaction from single-lab co-IP/docking, no reciprocal structural validation
    • Direct vs indirect nature of physical interaction unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse upstream regulators (PXR, Nrf2, G9a/FXR, Sp1/C/EBPα, miR-155, CHRNA5) are integrated to set tissue- and disease-specific CES1 levels, and how its non-hydrolytic lipid-partitioning role is mechanistically achieved, remain unresolved.
  • No unified model linking transcriptional inputs to context-specific CES1 output
  • Mechanism coupling CES1 activity to fatty acid β-oxidation undefined
  • No experimental structure of human CES1 in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 9 GO:0008289 lipid binding 3 GO:0016740 transferase activity 3
Localization
GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-9748784 Drug ADME 6 R-HSA-1430728 Metabolism 5 R-HSA-74160 Gene expression (Transcription) 5
Partners
CHRNA5

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 CES1A1 (CES1) is the major enzyme responsible for the stereoselective hydrolysis of both d- and l-enantiomers of methylphenidate, with higher catalytic efficiency for l-methylphenidate (kcat/Km = 7.7 mM⁻¹ min⁻¹) than d-methylphenidate (kcat/Km = 1.3–2.1 mM⁻¹ min⁻¹); CES2 and CES3 showed no detectable activity toward either enantiomer. In vitro kinetic assay with purified recombinant CES1A1, CES2, and CES3 expressed in Sf9 cells; LC/MS assay; 3D active-site modeling The Journal of pharmacology and experimental therapeutics High 15082749
2004 CES1A1 hydrolyzes irinotecan (CPT-11) and its oxidative metabolites NPC and APC to the active metabolite SN-38; catalytic efficiency of CES1A1 for CPT-11 is intermediate between CES2 (highest) and CES3 (lowest). CES2 > CES1A1 >> CES3 for all three substrates. In vitro hydrolysis assay with purified recombinant CES1A1, CES2, and CES3; kinetic parameter determination Drug metabolism and disposition: the biological fate of chemicals High 15100172
2008 Two CES1 coding mutations — p.Gly143Glu (exon 4) and p.Asp260fs (exon 6 frameshift) — substantially impair catalytic function: p.Gly143Glu retains only 21.4% catalytic efficiency (Vmax/Km) and p.Asp260fs retains only 0.6% relative to wild-type using p-nitrophenyl acetate as substrate; both mutations result in complete loss of hydrolytic activity toward methylphenidate. In vitro functional assay of recombinant wild-type and mutant CES1 proteins expressed in cell lines; DNA sequencing; enzymatic kinetics American journal of human genetics High 18485328
2008 CES1A1 transcription is regulated by Sp1 and C/EBPalpha binding to responsive elements in its promoter; CES1A2 promoter lacks functional Sp1/C/EBP binding sites, explaining the much higher CES1A1 mRNA expression in liver and lung compared to CES1A2. Reporter gene assay; electrophoretic mobility shift assay (EMSA) in transfected cells Drug metabolism and pharmacokinetics Medium 18305377
2008 A minor haplotype in the CES1A2 promoter (positions -62 to -32) contains two Sp1 binding sites absent in the major haplotype, and the minor haplotype drives higher transcriptional and Sp1 binding activity in vitro, establishing Sp1 binding site variation as a functional determinant of CES1A2 expression. Promoter re-sequencing; reporter gene assay; EMSA; linkage disequilibrium analysis Biochemical and biophysical research communications Medium 18328811
2016 Sacubitril (prodrug) is selectively activated by CES1 in human liver; CES2 does not activate sacubitril. The CES1 G143E variant (rs71647871) is a loss-of-function variant for sacubitril activation, significantly impairing hydrolysis in liver samples carrying G143E. Incubation with human liver/intestine/kidney S9 fractions; CES1 inhibitor (bis-p-nitrophenyl phosphate) studies; recombinant CES1 and CES2 incubation; transfected cell lines expressing wild-type CES1 vs. G143E variant Drug metabolism and disposition: the biological fate of chemicals High 26817948
2015 CES1 selectively activates multiple ACEI prodrugs (enalapril, ramipril, perindopril, moexipril, fosinopril) in human liver; the G143E variant reduces enalapril activation in human livers carrying the variant to approximately one-third of wild-type activity. Incubation of human liver/intestine/kidney S9 fractions with ACEI prodrugs; transfected cell lines expressing wild-type CES1 and G143E variant; activity assays in 102 human liver samples The pharmacogenomics journal High 26076923
2009 Mouse Es-x/Ces1 (ortholog of human CES1) prevents triacylglycerol accumulation in hepatocytes by reducing partitioning of exogenous fatty acids into TG and increasing beta-oxidation, rather than by increasing TG turnover; this effect persists in the presence of esterase/lipase inhibitor E600, indicating the mechanism is independent of direct TG hydrolysis. Stable transfection of McArdle-RH7777 hepatocytes with Es-x cDNA; TG quantification; acid-soluble metabolite measurement (beta-oxidation indicator); esterase inhibitor (E600) treatment; glycerol supplementation experiments Biochimica et biophysica acta Medium 19651238
2017 Global inactivation of mouse Ces1/Ces1g reduces plasma cholesterol and TG levels and protects against atherosclerosis in Ldlr⁻/⁻ mice by inhibiting intestinal cholesterol and fat absorption, reducing Niemann-Pick C1-like 1 expression, and increasing macrophage cholesterol efflux via ABCA1 and ABCG1 upregulation; Ces1g⁻/⁻ also promotes M2 macrophage polarization and induces hepatic cholesterol 7α-hydroxylase and sterol 12α-hydroxylase expression. Ces1g⁻/⁻ mouse generation; Ces1g⁻/⁻ Ldlr⁻/⁻ double knockout on Western diet; hepatic Ces1/Ces1g knockdown in Apoe⁻/⁻ mice; plasma lipid measurement; atherosclerotic lesion quantification; gene expression analysis Scientific reports Medium 29259301
2018 The CES1 G143E variant (p.Gly143Glu) exhibits only ~20% of wild-type lipolytic activity; humanized CES1G143E-expressing mice on high-fat diet have reduced liver and plasma TG levels due to decreased VLDL secretion, decreased hepatic lipogenic gene expression, and increased fatty acid oxidation (elevated plasma ketone bodies and hepatic mitochondrial electron transport chain proteins). Humanized mouse model expressing CES1WT, CES1G143E, or catalytically dead CES1S221A in liver; high-fat diet challenge; lipidomics; plasma/liver TG measurement; VLDL secretion assay; gene expression; plasma ketone measurement; protein abundance analysis Biochimica et biophysica acta. Molecular and cell biology of lipids High 29631096
2015 Fluoxetine reduces CES1 expression and hydrolytic activity in HepG2 cells by decreasing pregnane X receptor (PXR), which positively regulates CES1; overexpression of PXR attenuates fluoxetine-induced CES1 decrease, while PXR knockdown abolishes the fluoxetine effect, placing PXR upstream of CES1 transcription. DEC1 upregulation by fluoxetine contributes to PXR repression. PXR overexpression and knockdown in HepG2 cells; DEC1 knockdown; CES1 expression and enzymatic activity measurement; western blot Xenobiotica; the fate of foreign compounds in biological systems Medium 26340669
2019 CES1 expression is upregulated by Nrf2 activation; vitamin E treatment upregulates Nrf2 and CES1 in NAFLD mouse liver, and the Nrf2 inhibitor ML385 reverses CES1 upregulation and the protective lipid-lowering effect, placing CES1 downstream of Nrf2 in lipid metabolism. NAFLD mouse model (fructose-fed); vitamin E treatment in vivo and in vitro; Nrf2 inhibitor (ML385) treatment; histopathology; western blot for Nrf2 and CES1 Digestive diseases and sciences Medium 31076985
2020 CES1 in human monocytic THP-1 cells hydrolyzes prostaglandin D2-glyceryl ester (PGD2-G), accounting for ~50% of its hydrolytic metabolism; CES1 knockdown stabilizes PGD2-G and enhances its anti-inflammatory effects (greater attenuation of IL-6 and TNFα), while PGE2-G pro-inflammatory effects are attenuated by CES1-dependent hydrolysis to PGE2. PGD2-G activates PPARγ. CES1 knockdown (CES1KD) in THP-1 cells; small-molecule CES1 inhibitors (CPO, WWL229, WWL113); LC-MS/MS quantification of PGD2-G and PGD2; cytokine measurement (IL-6, TNFα); PPARγ activation assay ACS omega Medium 33225149
2022 TMAO (trimethylamine N-oxide) increases Ces1 protein expression and activity in mouse liver and CES1 levels in HepG2 cells through the NOX-dependent ROS/Nrf2/CES1 pathway, leading to increased clopidogrel hydrolysis and impaired platelet response; co-treatment with ROS scavenger N-acetyl-L-cysteine or Nrf2 inhibitor ML385 reverses TMAO-induced Ces1 upregulation and restores clopidogrel activity. TMAO/choline feeding in mice; HepG2 cell treatment; ROS measurement; Nrf2 nuclear translocation; Ces1 protein expression; clopidogrel metabolite quantification; platelet aggregation assay; pharmacological pathway inhibitors Journal of thrombosis and haemostasis : JTH Medium 36695375
2023 G9a (Ehmt2-encoded histone methyltransferase) suppresses Ces1 transcription by binding to Ces1 promoter regions; G9a and farnesoid X receptor (FXR) competitively bind the same Ces1 promoter regions. Renal tubular G9a knockout increases Ces1 expression, reduces lipid accumulation, and alleviates AKI; pharmacological Ces1 inhibition reverses these beneficial effects. Renal tubular-specific G9a knockout mice (Ehmt2Ksp); pharmacological G9a inhibition; Ces1 pharmacological inhibition; ChIP-like promoter binding competition assays; lipid quantification; AKI model (I/R injury, cisplatin); Ces1 expression in patient kidneys EMBO reports Medium 37042626
2021 Melatonin treatment restores CES1 expression in CRPC through epigenetic modification of the CES1 gene; restored CES1 expression reduces lipid droplet accumulation, induces apoptosis by increasing ER stress, and reduces de novo intratumoral androgen synthesis. Ces1-knockout (Ces1⁻/⁻) mice confirmed the role of endogenous Ces1 in prostate cancer progression. Animal CRPC models; melatonin treatment; PCa cell lines; Ces1-knockout mice; lipid droplet quantification; ER stress markers; androgen synthesis measurement; mechanistic investigations of CES1 epigenetic regulation Clinical and translational medicine Medium 34185414
2023 CES1 inhibition in hepatocellular carcinoma (HCC) cells alters lipid profiles by dramatically reducing polyunsaturated fatty acids (PUFAs), which activate PPARα/γ; reduced PPARα/γ activation downregulates SCD (a lipogenic/chemoresistance gene), sensitizing HCC cells to cisplatin. CES1 acts upstream of PPARα/γ-SCD axis. Pharmacological and genetic CES1 blockade in HCC cells; lipidomic analyses; PPARα/γ activity measurement; SCD expression analysis; HCC xenograft mouse model with cisplatin co-treatment JCI insight Medium 36472914
2021 The CES1 G143E variant significantly impairs enalapril activation in a multi-dose steady-state clinical study: G143E carriers had 30.9% lower enalaprilat Cmax, 27.5% lower AUCo-∞, and 32.3% lower enalaprilat-to-enalapril AUC ratio compared to non-carriers; non-carriers showed significant systolic BP reduction while G143E carriers did not. Prospective multi-dose clinical pharmacokinetic/pharmacodynamic study; LC-MS/MS plasma concentration measurement; genotyping for G143E British journal of clinical pharmacology High 33963573
2016 Hepatic CES1 protein abundance increases approximately 5-fold from neonates to adults in human liver microsomes; CES1 protein abundance in pediatric liver microsomes correlates with oseltamivir carboxylase activity, establishing a direct relationship between CES1 expression level and enzymatic function during ontogeny. LC-MS/MS targeted proteomics with purified protein standards; hepatic microsomal and cytosolic fractionation from 136 pediatric and 35 adult donors; oseltamivir carboxylase activity assay; PBPK modeling Drug metabolism and disposition: the biological fate of chemicals High 27895113
2022 Crystal structure of mouse Ces2c shows that the core domain adopts an α/β hydrolase-fold with S230, E347, and H459 forming a catalytic triad; conserved gate (M417) and switch (F418) residues are proposed to function in product release, similar to human CES1; the protein is a monomer in solution. X-ray crystallography (2.12 Å resolution); biophysical characterization; structural comparison to human CES1 International journal of molecular sciences Medium 36361897
2014 Recombinant human CES1 expressed in E. coli and refolded from inclusion bodies retains its biological hydrolytic activity after refolding in Tris-HCl pH 7.5 with 1% glycerol and 2 mM β-mercaptoethanol; other additive combinations (trehalose, sorbitol, sucrose) failed to recover functional protein. Recombinant CES1 expression in E. coli; in vitro refolding; immobilized-metal affinity purification; enzymatic activity assay Protein expression and purification Medium 25462813
2018 MiR-155 upregulates CEH (CES1) expression in THP-1 macrophages in a dose- and time-dependent manner; CEH upregulation by miR-155 inhibits foam cell formation, reduces intracellular cholesterol ester accumulation, and enhances cholesterol efflux. Knockdown of CEH (siCEH) reverses these anti-foam cell effects. Tim-3 overexpression attenuates miR-155-mediated CEH induction. miR-155 mimic transfection in THP-1 macrophages; siRNA knockdown of CEH; foam cell formation assay; cholesterol ester and free cholesterol measurement; Tim-3 overexpression Biomedicine & pharmacotherapy Medium 29803178
2024 CHRNA5 and CES1 physically interact in HNSC cells (co-immunoprecipitation); nicotine-induced CHRNA5 activation upregulates CES1 expression via the MEK/ERK pathway; CHRNA5 knockdown reduces CES1 mRNA and protein levels, p-MEK/MEK, and p-ERK/ERK, effects reversible by nicotine. Co-immunoprecipitation; molecular docking; immunofluorescence; CHRNA5 knockdown and overexpression; western blot for MEK/ERK phosphorylation; transcriptomics pathway enrichment; in vivo tumor formation in nude mice Cell death & disease Medium 39472448

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 A regulatory cascade of three homeobox genes, ceh-10, ttx-3 and ceh-23, controls cell fate specification of a defined interneuron class in C. elegans. Development (Cambridge, England) 249 11493519
2008 Two CES1 gene mutations lead to dysfunctional carboxylesterase 1 activity in man: clinical significance and molecular basis. American journal of human genetics 189 18485328
2004 Methylphenidate is stereoselectively hydrolyzed by human carboxylesterase CES1A1. The Journal of pharmacology and experimental therapeutics 155 15082749
2004 Hydrolysis of irinotecan and its oxidative metabolites, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino] carbonyloxycamptothecin and 7-ethyl-10-[4-(1-piperidino)-1-amino]-carbonyloxycamptothecin, by human carboxylesterases CES1A1, CES2, and a newly expressed carboxylesterase isoenzyme, CES3. Drug metabolism and disposition: the biological fate of chemicals 107 15100172
1999 The C. elegans cell death specification gene ces-1 encodes a snail family zinc finger protein. Molecular cell 102 10518212
2009 Human carboxylesterases: an update on CES1, CES2 and CES3. Protein and peptide letters 100 19508181
2003 The Snail-like CES-1 protein of C. elegans can block the expression of the BH3-only cell-death activator gene egl-1 by antagonizing the function of bHLH proteins. Development (Cambridge, England) 99 12874127
2016 Age-Dependent Absolute Abundance of Hepatic Carboxylesterases (CES1 and CES2) by LC-MS/MS Proteomics: Application to PBPK Modeling of Oseltamivir In Vivo Pharmacokinetics in Infants. Drug metabolism and disposition: the biological fate of chemicals 87 27895113
2014 The pharmacogenetics of carboxylesterases: CES1 and CES2 genetic variants and their clinical effect. Drug metabolism and drug interactions 86 24988246
1997 The POU gene ceh-18 promotes gonadal sheath cell differentiation and function required for meiotic maturation and ovulation in Caenorhabditis elegans. Developmental biology 79 9405097
1994 Targeted mutations in the Caenorhabditis elegans POU homeo box gene ceh-18 cause defects in oocyte cell cycle arrest, gonad migration, and epidermal differentiation. Genes & development 75 7958868
2000 Overlapping roles of two Hox genes and the exd ortholog ceh-20 in diversification of the C. elegans postembryonic mesoderm. Development (Cambridge, England) 72 11060243
2011 The homeobox protein CEH-23 mediates prolonged longevity in response to impaired mitochondrial electron transport chain in C. elegans. PLoS biology 70 21713031
2000 The LIM homeobox gene ceh-14 confers thermosensory function to the AFD neurons in Caenorhabditis elegans. Neuron 70 10774727
2007 The C. elegans protein CEH-30 protects male-specific neurons from apoptosis independently of the Bcl-2 homolog CED-9. Genes & development 69 18056428
2006 Wnt signaling and CEH-22/tinman/Nkx2.5 specify a stem cell niche in C. elegans. Current biology : CB 69 16461282
2002 Roles of the Homothorax/Meis/Prep homolog UNC-62 and the Exd/Pbx homologs CEH-20 and CEH-40 in C. elegans embryogenesis. Development (Cambridge, England) 65 12399316
1995 The C. elegans neuronally expressed homeobox gene ceh-10 is closely related to genes expressed in the vertebrate eye. Development (Cambridge, England) 63 7789259
2007 Control of sex-specific apoptosis in C. elegans by the BarH homeodomain protein CEH-30 and the transcriptional repressor UNC-37/Groucho. Genes & development 62 18056429
1999 Anterior organization of the Caenorhabditis elegans embryo by the labial-like Hox gene ceh-13. Development (Cambridge, England) 62 10068646
2016 Sacubitril Is Selectively Activated by Carboxylesterase 1 (CES1) in the Liver and the Activation Is Affected by CES1 Genetic Variation. Drug metabolism and disposition: the biological fate of chemicals 60 26817948
2000 The homeodomain protein CePHOX2/CEH-17 controls antero-posterior axonal growth in C. elegans. Development (Cambridge, England) 60 10887091
2005 Distinct molecular alterations in complex endometrial hyperplasia (CEH) with and without immature squamous metaplasia (squamous morules). The American journal of surgical pathology 59 16160475
2009 Regulation of carboxylesterase 1 (CES1) in human adipose tissue. Biochemical and biophysical research communications 57 19332024
2015 CES1 genetic variation affects the activation of angiotensin-converting enzyme inhibitors. The pharmacogenomics journal 53 26076923
2006 Direct regulation of egl-1 and of programmed cell death by the Hox protein MAB-5 and by CEH-20, a C. elegans homolog of Pbx1. Development (Cambridge, England) 53 16421192
2002 Conserved regulation of the Caenorhabditis elegans labial/Hox1 gene ceh-13. Developmental biology 53 11820809
2016 Age-Dependent Human Hepatic Carboxylesterase 1 (CES1) and Carboxylesterase 2 (CES2) Postnatal Ontogeny. Drug metabolism and disposition: the biological fate of chemicals 50 26825642
2010 A dysregulation in CES1, APOE and other lipid metabolism-related genes is associated to cardiovascular risk factors linked to obesity. Obesity facts 49 20975297
2007 UNC-4 represses CEH-12/HB9 to specify synaptic inputs to VA motor neurons in C. elegans. Genes & development 49 17289921
2019 Synthesis of clathrate cerium superhydride CeH9 at 80-100 GPa with atomic hydrogen sublattice. Nature communications 48 31575861
2005 ceh-16/engrailed patterns the embryonic epidermis of Caenorhabditis elegans. Development (Cambridge, England) 48 15659483
2001 Regulation of ectodermal and excretory function by the C. elegans POU homeobox gene ceh-6. Development (Cambridge, England) 45 11171402
2019 CEH-60/PBX and UNC-62/MEIS Coordinate a Metabolic Switch that Supports Reproduction in C. elegans. Developmental cell 44 30956009
2018 The impact of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) gene polymorphisms on dabigatran equilibrium peak concentration in patients after total knee arthroplasty. Pharmacogenomics and personalized medicine 43 30100750
2008 Structural organization and characterization of the regulatory element of the human carboxylesterase (CES1A1 and CES1A2) genes. Drug metabolism and pharmacokinetics 43 18305377
2021 Melatonin inhibits lipid accumulation to repress prostate cancer progression by mediating the epigenetic modification of CES1. Clinical and translational medicine 42 34185414
2009 The NK-2 class homeodomain factor CEH-51 and the T-box factor TBX-35 have overlapping function in C. elegans mesoderm development. Development (Cambridge, England) 42 19605496
2008 Functional polymorphisms in carboxylesterase1A2 (CES1A2) gene involves specific protein 1 (Sp1) binding sites. Biochemical and biophysical research communications 41 18328811
2017 The impact of CES1 genotypes on the pharmacokinetics of methylphenidate in healthy Danish subjects. British journal of clinical pharmacology 39 28087982
2004 The C. elegans ceh-36 gene encodes a putative homemodomain transcription factor involved in chemosensory functions of ASE and AWC neurons. Journal of molecular biology 39 15095973
2001 The Caenorhabditis elegans Six/sine oculis class homeobox gene ceh-32 is required for head morphogenesis. Developmental biology 38 11476572
1997 The expression of the C. elegans labial-like Hox gene ceh-13 during early embryogenesis relies on cell fate and on anteroposterior cell polarity. Development (Cambridge, England) 38 9334268
2010 The HMX/NKX homeodomain protein MLS-2 specifies the identity of the AWC sensory neuron type via regulation of the ceh-36 Otx gene in C. elegans. Development (Cambridge, England) 37 20150279
2023 Interfering with lipid metabolism through targeting CES1 sensitizes hepatocellular carcinoma for chemotherapy. JCI insight 36 36472914
2010 Depot-specific expression of lipolytic genes in human adipose tissues--association among CES1 expression, triglyceride lipase activity and adiposity. Journal of atherosclerosis and thrombosis 35 21081832
2009 Es-x/Ces1 prevents triacylglycerol accumulation in McArdle-RH7777 hepatocytes. Biochimica et biophysica acta 35 19651238
2023 Loss of renal tubular G9a benefits acute kidney injury by lowering focal lipid accumulation via CES1. EMBO reports 33 37042626
2018 Presence and inter-individual variability of carboxylesterases (CES1 and CES2) in human lung. Biochemical pharmacology 33 29407485
2019 Vitamin E Ameliorates Lipid Metabolism in Mice with Nonalcoholic Fatty Liver Disease via Nrf2/CES1 Signaling Pathway. Digestive diseases and sciences 32 31076985
2015 The Bicoid class homeodomain factors ceh-36/OTX and unc-30/PITX cooperate in C. elegans embryonic progenitor cells to regulate robust development. PLoS genetics 29 25738873
2015 CYP2C19 and CES1 polymorphisms and efficacy of clopidogrel and aspirin dual antiplatelet therapy in patients with symptomatic intracranial atherosclerotic disease. Journal of neurosurgery 29 26587656
2013 Methylphenidate side effect profile is influenced by genetic variation in the attention-deficit/hyperactivity disorder-associated CES1 gene. Journal of child and adolescent psychopharmacology 29 24350812
2003 The Caenorhabditis elegans ems class homeobox gene ceh-2 is required for M3 pharynx motoneuron function. Development (Cambridge, England) 29 12810585
2018 Genetic variation in human carboxylesterase CES1 confers resistance to hepatic steatosis. Biochimica et biophysica acta. Molecular and cell biology of lipids 28 29631096
2022 The enteric nervous system of the C. elegans pharynx is specified by the Sine oculis-like homeobox gene ceh-34. eLife 27 35324425
2020 Natural Products as Modulators of CES1 Activity. Drug metabolism and disposition: the biological fate of chemicals 24 32591414
2009 The C. elegans engrailed homolog ceh-16 regulates the self-renewal expansion division of stem cell-like seam cells. Developmental biology 24 19607822
2019 Influence of CYP450 Enzymes, CES1, PON1, ABCB1, and P2RY12 Polymorphisms on Clopidogrel Response in Patients Subjected to a Percutaneous Neurointervention. Clinical therapeutics 23 31128980
2017 Transcription factors CEP-1/p53 and CEH-23 collaborate with AAK-2/AMPK to modulate longevity in Caenorhabditis elegans. Aging cell 23 28560849
2017 Global inactivation of carboxylesterase 1 (Ces1/Ces1g) protects against atherosclerosis in Ldlr -/- mice. Scientific reports 22 29259301
2007 Transcriptional regulation of AQP-8, a Caenorhabditis elegans aquaporin exclusively expressed in the excretory system, by the POU homeobox transcription factor CEH-6. The Journal of biological chemistry 22 17660295
2024 Nicotine-induced CHRNA5 activation modulates CES1 expression, impacting head and neck squamous cell carcinoma recurrence and metastasis via MEK/ERK pathway. Cell death & disease 21 39472448
2018 MiR-155 inhibits transformation of macrophages into foam cells via regulating CEH expression. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 21 29803178
2010 Carboxylesterase 1 (Ces1): from monocyte marker to major player. Journal of clinical pathology 21 21177752
2015 Individualization of treatments with drugs metabolized by CES1: combining genetics and metabolomics. Pharmacogenomics 20 25896426
2023 The homeodomain transcription factor CEH-37 regulates PMK-1/p38 MAPK pathway to protect against intestinal infection via the phosphatase VHP-1. Cellular and molecular life sciences : CMLS 19 37796333
2020 Effect of Sex, Use of Pantoprazole and Polymorphisms in SLC22A1, ABCB1, CES1, CYP3A5 and CYP2D6 on the Pharmacokinetics and Safety of Dabigatran. Advances in therapy 19 32564268
2016 Regulatory effects of genomic translocations at the human carboxylesterase-1 (CES1) gene locus. Pharmacogenetics and genomics 19 26871237
2010 The C. elegans Hox gene ceh-13 regulates cell migration and fusion in a non-colinear way. Implications for the early evolution of Hox clusters. BMC developmental biology 19 20667114
2009 Two Hox cofactors, the Meis/Hth homolog UNC-62 and the Pbx/Exd homolog CEH-20, function together during C. elegans postembryonic mesodermal development. Developmental biology 19 19643105
2020 Effect of CES1 and ABCB1 genotypes on the pharmacokinetics and clinical outcomes of dabigatran etexilate in patients with atrial fibrillation and chronic kidney disease. Drug metabolism and personalized therapy 18 32134727
2020 Inactivation of CES1 Blocks Prostaglandin D2 Glyceryl Ester Catabolism in Monocytes/Macrophages and Enhances Its Anti-inflammatory Effects, Whereas the Pro-inflammatory Effects of Prostaglandin E2 Glyceryl Ester Are Attenuated. ACS omega 18 33225149
2013 The LIM homeobox gene ceh-14 is required for phasmid function and neurite outgrowth. Developmental biology 18 23608457
2021 Enhancer RNA lnc-CES1-1 inhibits decidual cell migration by interacting with RNA-binding protein FUS and activating PPARγ in URPL. Molecular therapy. Nucleic acids 17 33738142
2019 The impact of human CES1 genetic variation on enzyme activity assessed by ritalinic acid/methylphenidate ratios. Basic & clinical pharmacology & toxicology 17 30801959
2017 The Pharmacokinetics of Enalapril in Relation to CES1 Genotype in Healthy Danish Volunteers. Basic & clinical pharmacology & toxicology 17 28639420
2015 Fluoxetine reduces CES1, CES2, and CYP3A4 expression through decreasing PXR and increasing DEC1 in HepG2 cells. Xenobiotica; the fate of foreign compounds in biological systems 17 26340669
2013 Coordination of cell proliferation and cell fate determination by CES-1 snail. PLoS genetics 17 24204299
2001 The Caenorhabditis elegans distal-less ortholog ceh-43 is required for development of the anterior hypodermis. Developmental dynamics : an official publication of the American Association of Anatomists 17 11747075
1998 Effects of deletion mutations in the yeast Ces1 protein on cell growth and morphology and on high copy suppression of mutations in mRNA capping enzyme and translation initiation factor 4A. Nucleic acids research 17 9443973
2022 Choline and trimethylamine N-oxide impair metabolic activation of and platelet response to clopidogrel through activation of the NOX/ROS/Nrf2/CES1 pathway. Journal of thrombosis and haemostasis : JTH 16 36695375
2009 Exploring the diabetogenicity of the HLA-B18-DR3 CEH: independent association with T1D genetic risk close to HLA-DOA. Genes and immunity 16 19458622
2004 An early pharyngeal muscle enhancer from the Caenorhabditis elegans ceh-22 gene is targeted by the Forkhead factor PHA-4. Developmental biology 16 14738885
2003 Sequence-specific binding to telomeric DNA by CEH-37, a homeodomain protein in the nematode Caenorhabditis elegans. The Journal of biological chemistry 16 12711598
2020 Genetic Analysis Reveals a Significant Contribution of CES1 to Prostate Cancer Progression in Taiwanese Men. Cancers 15 32466188
2020 PIG-1 MELK-dependent phosphorylation of nonmuscle myosin II promotes apoptosis through CES-1 Snail partitioning. PLoS genetics 15 32946434
2019 CEH-60/PBX regulates vitellogenesis and cuticle permeability through intestinal interaction with UNC-62/MEIS in Caenorhabditis elegans. PLoS biology 15 31675356
2023 CES1-Triggered Liver-Specific Cargo Release of CRISPR/Cas9 Elements by Cationic Triadic Copolymeric Nanoparticles Targeting Gene Editing of PCSK9 for Hyperlipidemia Amelioration. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 14 37083231
2001 Multiple enhancers contribute to expression of the NK-2 homeobox gene ceh-22 in C. elegans pharyngeal muscle. Genesis (New York, N.Y. : 2000) 14 11783006
2022 The anterior Hox gene ceh-13 and elt-1/GATA activate the posterior Hox genes nob-1 and php-3 to specify posterior lineages in the C. elegans embryo. PLoS genetics 13 35500030
2022 The Crystal Structure of Mouse Ces2c, a Potential Ortholog of Human CES2, Shows Structural Similarities in Substrate Regulation and Product Release to Human CES1. International journal of molecular sciences 13 36361897
2021 Effect of CES1 genetic variation on enalapril steady-state pharmacokinetics and pharmacodynamics in healthy subjects. British journal of clinical pharmacology 13 33963573
2014 Efficient in vitro refolding and functional characterization of recombinant human liver carboxylesterase (CES1) expressed in E. coli. Protein expression and purification 13 25462813
2014 Regulation of C. elegans neuronal differentiation by the ZEB-family factor ZAG-1 and the NK-2 homeodomain factor CEH-28. PloS one 13 25474681
2013 CEH-20/Pbx and UNC-62/Meis function upstream of rnt-1/Runx to regulate asymmetric divisions of the C. elegans stem-like seam cells. Biology open 13 23862020
2012 A discriminative analytical method for detection of CES1A1 and CES1A2/CES1A3 genetic variants. Pharmacogenetics and genomics 13 22237548
2008 Behavioral and synaptic defects in C. elegans lacking the NK-2 homeobox gene ceh-28. Developmental neurobiology 13 18161854
2008 Mesodermal expression of the C. elegans HMX homolog mls-2 requires the PBC homolog CEH-20. Mechanisms of development 13 18316179
2020 cnd-1/NeuroD1 Functions with the Homeobox Gene ceh-5/Vax2 and Hox Gene ceh-13/labial To Specify Aspects of RME and DD Neuron Fate in Caenorhabditis elegans. G3 (Bethesda, Md.) 12 32601060

Missed literature

Know a paper Affinage missed for CES1? Flag it for the maintainers and the community.

No submissions yet.