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FLASH GENE
Symbol CES1 contributors: mct/npt - updated : 22-03-2018
HGNC name carboxylesterase 1 (monocyte/macrophage serine esterase 1)
HGNC id 1863
Location 16q12.2      Physical location : 55.836.765 - 55.867.075
Genatlas name egasyn
Synonym name
  • monocyte macrophage serine esterase
  • liver carboxylesterase
  • acyl coenzyme A:cholesterol acyltransferase
  • serine esterase 1
  • brain carboxylesterase hBr1
  • triacylglycerol hydrolase
  • cholesteryl ester hydrolase
  • retinyl ester hydrolase
    • Synonym symbol(s) SES1, CEH, HMSE, EST1, ACAT, CES2, HMSE1, MGC117365, PCE-1, CES1A1, CES1A2
    EC.number 3.1.1.1/3.1.1.56
    DNA
    TYPE functioning gene
    STRUCTURE 30.34 kb     14 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    14 - 2027 - 568 predominantly expressed in liver and lung 2012 22237548
  • CES1A plays an important role in the hydrolysis of endogenous compounds and xenobiotics
    • 14 - 2024 - 567 - 2012 22237548
    14 - 2021 - 566 - 2012 22237548
    - - 30295 - 567 - 2012 22237548
  • signal peptide of CES1A1 posses a motif to direct gene product to endoplasmic reticulum, while that of CES1A2 does not
  • is induced by NFE2L2
    • - - 30275 - 567 - 2012 22237548
    multiple polymorphisms in the promoter including the ones that are likely to be the functional and affect the promoter activity
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
     liver   highly Homo sapiens
    Nervousbrain    
    Respiratoryrespiratory tractlarynx  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmonocyte
    Lymphoid/Immunemacrophage
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a catalytic triad and the ER retention motif
    • conjugated MetalloP
    HOMOLOGY
    Homologene
    FAMILY
  • type-B carboxylesterase/lipase family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,lumen
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    basic FUNCTION
  • catalyzing the hydrolysis of ester and amide-bond containing drugs such as temocapril p-nitrophenyl-acetate, also hydrolyzing long chain acyl-CoA
  • putatively functioning as a blood-brain barrier to protect the CNS from ester or amide compounds
  • involved in metabolic activation of a variety of prodrugs into active derivatives and plays an important role in pharmacokinetics
  • governing both metabolic deactivation and activation of numerous therapeutic agents
  • in the hepatocytes, potentially regulates the synthesis of bile acids and thus the removal of cholesterol from the body (Zhao 2005)
  • key liver microsomal enzyme responsible for detoxification and metabolism of a variety of clinical drugs
  • CES1 and CES2 are important for the disposition of ester- and amide-bond-containing pharmaceuticals and environmental chemicals
  • expression and activity of CES1, CES2 in human induced pluripotent stem (iPS) cell-derived enterocytes are more similar to the human small intestine compared with Caco-2 cells
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS immunity/defense , detoxification
    PATHWAY
    metabolism drug , lipid/lipoprotein
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
    zinc Zn2+
    protein
  • CES1 is a novel transcriptional regulator of GHR gene expression, thereby establishing a unique nonenzymatic role for a carboxyesterase and expanding the potential biological roles of this protein superfamily
  • CES1 had a clear impact not only on the methylation status of RHOA but also RHOA activation and cell morphology
  • activation of NR1H4 induced hepatic CES1, and reduced the levels of hepatic and plasma triglyceride (TG) as well as plasma cholesterol in a CES1-dependent manner
  • liver carboxylesterase 1 (CES1) is a novel SORT1-interacting protein
  • SORT1 may regulate CES1 lysosomal targeting and degradation and SORT1 deficiency resulted in higher liver CES1 protein abundance
    • cell & other
    REGULATION
    activated by thyroid hormones
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in non hodgkin lymphoma, B chronic lymphocytic leukemia
    constitutional     --over  
    associated with obesity and markers of metabolic dysfunction indicating that CES1 plays a role in metabolism (Jernas 2009)
    constitutional     --low  
    in infants younger than 3 weeks of age with significantly lower CES1- and CES2-dependent metabolic clearance compared with older individuals
    Susceptibility
  • to alteration of pharmacokinetics and drug response
  • to resistance to angiotensin-converting enzyme inhibitor (ACEI)
    • Variant & Polymorphism other
  • polymorphisms increasing the risk of drug fatal exposures and overdoses
  • some functional CES1 genetic variants (for example, G143E) may impair angiotensin-converting enzyme inhibitor (ACEI) activation, and consequently affect therapeutic outcomes of ACEI prodrugs
    • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS