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CES2 carboxylesterase 2 [ Homo sapiens (human) ]

Gene ID: 8824, updated on 5-Mar-2024

Summary

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Official Symbol
CES2provided by HGNC
Official Full Name
carboxylesterase 2provided by HGNC
Primary source
HGNC:HGNC:1864
See related
Ensembl:ENSG00000172831 MIM:605278; AllianceGenome:HGNC:1864
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
iCE; CE-2; PCE-2; CES2A1
Summary
This gene encodes a member of the carboxylesterase large family. The family members are responsible for the hydrolysis or transesterification of various xenobiotics, such as cocaine and heroin, and endogenous substrates with ester, thioester, or amide bonds. They may participate in fatty acyl and cholesterol ester metabolism, and may play a role in the blood-brain barrier system. The protein encoded by this gene is the major intestinal enzyme and functions in intestine drug clearance. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Oct 2010]
Expression
Biased expression in duodenum (RPKM 209.7), small intestine (RPKM 176.0) and 8 other tissues See more
Orthologs
all
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Genomic context

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Location:
16q22.1
Exon count:
12
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (66934471..66945096)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (72728771..72739396)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (66968374..66978999)

Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:66955545-66956068 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:66956069-66956592 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7571 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7572 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr16:66961058-66962257 Neighboring gene RRAD, Ras related glycolysis inhibitor and calcium channel regulator Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10945 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10946 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:66969029-66969641 Neighboring gene cytosolic iron-sulfur assembly component 2B Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:66974461-66974960 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr16:66975020-66976219 Neighboring gene uncharacterized LOC107984881 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7573 Neighboring gene MPRA-validated peak2620 silencer Neighboring gene MPRA-validated peak2621 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10947 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10948 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:66994865-66995366 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:66997641-66998558 Neighboring gene carboxylesterase 3 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr16:67004920-67006119 Neighboring gene Sharpr-MPRA regulatory region 4953

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Carboxylesterase 2 induces mitochondrial dysfunction via disrupting lipid homeostasis in oral squamous cell carcinoma. Chen X, et al. Mol Metab, 2022 Nov. PMID 36113774, Free PMC Article
  2. The COVID-19 Oral Drug Molnupiravir Is a CES2 Substrate: Potential Drug-Drug Interactions and Impact of CES2 Genetic Polymorphism In Vitro. Shen Y, et al. Drug Metab Dispos, 2022 Sep. PMID 35790245, Free PMC Article
  3. Discovery of hCES2A inhibitors from Glycyrrhiza inflata via combination of docking-based virtual screening and fluorescence-based inhibition assays. Song YQ, et al. Food Funct, 2021 Jan 7. PMID 33291124
  4. Overexpressed CES2 has prognostic value in CRC and knockdown CES2 reverses L-OHP-resistance in CRC cells by inhibition of the PI3K signaling pathway. Zhang Y, et al. Exp Cell Res, 2020 Apr 1. PMID 31981591
  5. Prognostic Impact of Carboxylesterase 2 in Cholangiocarcinoma. Goeppert B, et al. Sci Rep, 2019 Mar 13. PMID 30867471, Free PMC Article

See all (82) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Carboxylesterase 2 induces mitochondrial dysfunction via disrupting lipid homeostasis in oral squamous cell carcinoma.
    Title: Carboxylesterase 2 induces mitochondrial dysfunction via disrupting lipid homeostasis in oral squamous cell carcinoma.
  2. The COVID-19 Oral Drug Molnupiravir Is a CES2 Substrate: Potential Drug-Drug Interactions and Impact of CES2 Genetic Polymorphism In Vitro.
    Title: The COVID-19 Oral Drug Molnupiravir Is a CES2 Substrate: Potential Drug-Drug Interactions and Impact of CES2 Genetic Polymorphism In Vitro.
  3. LncRNA KCNQ1OT1 ameliorates the liver injury induced by acetaminophen through the regulation of miR-122-5p/CES2 axis.
    Title: LncRNA KCNQ1OT1 ameliorates the liver injury induced by acetaminophen through the regulation of miR-122-5p/CES2 axis.
  4. Discovery of hCES2A inhibitors from Glycyrrhiza inflata via combination of docking-based virtual screening and fluorescence-based inhibition assays.
    Title: Discovery of hCES2A inhibitors from Glycyrrhiza inflata via combination of docking-based virtual screening and fluorescence-based inhibition assays.
  5. Identification and Characterization of a New Carboxylesterase 2 Isozyme, mfCES2C, in the Small Intestine of Cynomolgus Monkeys.
    Title: Identification and Characterization of a New Carboxylesterase 2 Isozyme, mfCES2C, in the Small Intestine of Cynomolgus Monkeys.
  6. Overexpressed CES2 has prognostic value in CRC and knockdown CES2 reverses L-OHP-resistance in CRC cells by inhibition of the PI3K signaling pathway.
    Title: Overexpressed CES2 has prognostic value in CRC and knockdown CES2 reverses L-OHP-resistance in CRC cells by inhibition of the PI3K signaling pathway.
  7. Prognostic Impact of Carboxylesterase 2 in Cholangiocarcinoma.
    Title: Prognostic Impact of Carboxylesterase 2 in Cholangiocarcinoma.
  8. The T/T genotype of the polymorphism rs2241409 in CES2 gene is associated with graft rejection during kidney transplantation.
    Title: Polymorphisms in IMPDH2, UGT2B7, and CES2 genes influence the risk of graft rejection in kidney transplant recipients taking mycophenolate mofetil.
  9. Effect of genetic variation of NAT2 on isoniazid and SLCO1B1 and CES2 on rifampin pharmacokinetics in Ghanaian children with tuberculosis has been reported.
    Title: Effect of Genetic Variation of NAT2 on Isoniazid and SLCO1B1 and CES2 on Rifampin Pharmacokinetics in Ghanaian Children with Tuberculosis.
  10. High expression of TOPO-1 and CES-2 are correlated with longer progression free and overall survival in irinotecan treated metastatic colorectal cancer patients.
    Title: Expression of Topoisomerase 1 and carboxylesterase 2 correlates with irinotecan treatment response in metastatic colorectal cancer.
Submit: New GeneRIF Correction See all GeneRIFs (53)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables carboxylesterase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables carboxylesterase activity TAS
Traceable Author Statement
more info
  
enables carboxylic ester hydrolase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables methylumbelliferyl-acetate deacetylase activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in catabolic process TAS
Traceable Author Statement
more info
 PubMed 
involved_in prostaglandin metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in xenobiotic metabolic process TAS
Traceable Author Statement
more info
  
Component Evidence Code Pubs
located_in endoplasmic reticulum TAS
Traceable Author Statement
more info
 PubMed 
located_in endoplasmic reticulum lumen TAS
Traceable Author Statement
more info
  
is_active_in intracellular membrane-bounded organelle IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
cocaine esterase
Names
carboxylesterase 2 (intestine, liver)
intestinal carboxylesterase; liver carboxylesterase-2
methylumbelliferyl-acetate deacetylase 2
NP_001352334.1
NP_001352335.1
NP_001352336.1
NP_001352337.1
NP_003860.3
NP_932327.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001365405.1 → NP_001352334.1  cocaine esterase isoform 1 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) contains the same exon structure as variant 1, but contains a shorter 5' UTR. This represents use of a different promoter, relative to variant 1. This promoter is the dominant promoter used in some tissue types.
    Source sequence(s)
    BC032095, BX538086
    Consensus CDS
    CCDS10825.2
    UniProtKB/Swiss-Prot
    A0A024R6X1, A8K367, O00748, Q16859, Q5MAB8, Q7Z366, Q8IUP4, Q8TCP8
    UniProtKB/TrEMBL
    Q53H57
    Related
    ENSP00000317842.5, ENST00000317091.10
    Conserved Domains (1) summary
    pfam00135
    Location:30 → 538
    COesterase; Carboxylesterase family

  2. NM_001365406.1 → NP_001352335.1  cocaine esterase isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR, resulting in the use of a downtream start codon, relative to variant 1. The encoded isoform (3) has a shorter N-terminus than isoform 1.
    Source sequence(s)
    AK095522, BC032095, BX538086
    UniProtKB/TrEMBL
    Q53H57
    Conserved Domains (1) summary
    pfam00135
    Location:1 → 445
    COesterase; Carboxylesterase family

  3. NM_001365407.1 → NP_001352336.1  cocaine esterase isoform 3

    Status: REVIEWED

    Source sequence(s)
    AC009084
    UniProtKB/TrEMBL
    Q53H57
    Conserved Domains (1) summary
    pfam00135
    Location:1 → 445
    COesterase; Carboxylesterase family

  4. NM_001365408.1 → NP_001352337.1  cocaine esterase isoform 4

    Status: REVIEWED

    Source sequence(s)
    AC009084
    Conserved Domains (1) summary
    pfam00135
    Location:1 → 429
    COesterase; Carboxylesterase family

  5. NM_003869.6 → NP_003860.3  cocaine esterase isoform 1 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1) and contains a longer 5' UTR than some of the other variants. This variant represent use of an alternate promote that is used in some tissues, and uses a downstream start codon. The upstream start codon is not well conserved.
    Source sequence(s)
    BC032095, BX538086
    Consensus CDS
    CCDS10825.2
    UniProtKB/Swiss-Prot
    A0A024R6X1, A8K367, O00748, Q16859, Q5MAB8, Q7Z366, Q8IUP4, Q8TCP8
    UniProtKB/TrEMBL
    Q53H57
    Conserved Domains (1) summary
    pfam00135
    Location:30 → 538
    COesterase; Carboxylesterase family

  6. NM_198061.3 → NP_932327.2  cocaine esterase isoform 2 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) has a shorter 5' UTR and lacks an internal in-frame segment in the coding region, as compared to variant 1. The encoded isoform (2) is thus shorter than isoform 1.
    Source sequence(s)
    BC032095, BX538086
    Consensus CDS
    CCDS45507.2
    UniProtKB/TrEMBL
    Q53H57
    Related
    ENSP00000394452.2, ENST00000417689.6
    Conserved Domains (1) summary
    pfam00135
    Location:30 → 522
    COesterase; Carboxylesterase family

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000016.10 Reference GRCh38.p14 Primary Assembly

    Range
    66934471..66945096
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060940.1 Alternate T2T-CHM13v2.0

    Range
    72728771..72739396
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O00748.1 GenPept UniProtKB/Swiss-Prot:O00748

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