LOCUS       NP_001352334             559 aa            linear   PRI 28-APR-2025
DEFINITION  cocaine esterase isoform 1 precursor [Homo sapiens].
ACCESSION   NP_001352334
VERSION     NP_001352334.1
DBSOURCE    REFSEQ: accession NM_001365405.1
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 559)
  AUTHORS   Chen,X., Liu,Q., Chen,Y., Wang,L., Yang,R., Zhang,W., Pan,X.,
            Zhang,S., Chen,C., Wu,T., Xia,J., Cheng,B., Chen,X. and Ren,X.
  TITLE     Carboxylesterase 2 induces mitochondrial dysfunction via disrupting
            lipid homeostasis in oral squamous cell carcinoma
  JOURNAL   Mol Metab 65, 101600 (2022)
   PUBMED   36113774
  REMARK    GeneRIF: Carboxylesterase 2 induces mitochondrial dysfunction via
            disrupting lipid homeostasis in oral squamous cell carcinoma.
REFERENCE   2  (residues 1 to 559)
  AUTHORS   Shen,Y., Eades,W., Liu,W. and Yan,B.
  TITLE     The COVID-19 Oral Drug Molnupiravir Is a CES2 Substrate: Potential
            Drug-Drug Interactions and Impact of CES2 Genetic Polymorphism In
            Vitro
  JOURNAL   Drug Metab Dispos 50 (9), 1151-1160 (2022)
   PUBMED   35790245
  REMARK    GeneRIF: The COVID-19 Oral Drug Molnupiravir Is a CES2 Substrate:
            Potential Drug-Drug Interactions and Impact of CES2 Genetic
            Polymorphism In Vitro.
REFERENCE   3  (residues 1 to 559)
  AUTHORS   Song,Y.Q., Guan,X.Q., Weng,Z.M., Liu,J.L., Chen,J., Wang,L.,
            Cui,L.T., Fang,S.Q., Hou,J. and Ge,G.B.
  TITLE     Discovery of hCES2A inhibitors from Glycyrrhiza inflata via
            combination of docking-based virtual screening and
            fluorescence-based inhibition assays
  JOURNAL   Food Funct 12 (1), 162-176 (2021)
   PUBMED   33291124
  REMARK    GeneRIF: Discovery of hCES2A inhibitors from Glycyrrhiza inflata
            via combination of docking-based virtual screening and
            fluorescence-based inhibition assays.
REFERENCE   4  (residues 1 to 559)
  AUTHORS   Pei,J., Sun,X., Yang,G. and Zhang,S.
  TITLE     LncRNA KCNQ1OT1 ameliorates the liver injury induced by
            acetaminophen through the regulation of miR-122-5p/CES2 axis
  JOURNAL   Mol Cell Biochem 475 (1-2), 107-118 (2020)
   PUBMED   32779042
  REMARK    GeneRIF: LncRNA KCNQ1OT1 ameliorates the liver injury induced by
            acetaminophen through the regulation of miR-122-5p/CES2 axis.
REFERENCE   5  (residues 1 to 559)
  AUTHORS   Zhang,Y., Sun,L., Sun,Y., Chen,Y., Wang,X., Xu,M., Chi,P., Xu,Z.
            and Lu,X.
  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
  JOURNAL   Exp Cell Res 389 (1), 111856 (2020)
   PUBMED   31981591
  REMARK    GeneRIF: Overexpressed CES2 has prognostic value in CRC and
            knockdown CES2 reverses L-OHP-resistance in CRC cells by inhibition
            of the PI3K signaling pathway.
REFERENCE   6  (residues 1 to 559)
  AUTHORS   Saito,S., Iida,A., Sekine,A., Kawauchi,S., Higuchi,S., Ogawa,C. and
            Nakamura,Y.
  TITLE     Catalog of 680 variations among eight cytochrome p450 (CYP) genes,
            nine esterase genes, and two other genes in the Japanese population
  JOURNAL   J Hum Genet 48 (5), 249-270 (2003)
   PUBMED   12721789
REFERENCE   7  (residues 1 to 559)
  AUTHORS   Chagnon,P., Michaud,J., Mitchell,G., Mercier,J., Marion,J.F.,
            Drouin,E., Rasquin-Weber,A., Hudson,T.J. and Richter,A.
  TITLE     A missense mutation (R565W) in cirhin (FLJ14728) in North American
            Indian childhood cirrhosis
  JOURNAL   Am J Hum Genet 71 (6), 1443-1449 (2002)
   PUBMED   12417987
REFERENCE   8  (residues 1 to 559)
  AUTHORS   Yan,B., Matoney,L. and Yang,D.
  TITLE     Human carboxylesterases in term placentae: enzymatic
            characterization, molecular cloning and evidence for the existence
            of multiple forms
  JOURNAL   Placenta 20 (7), 599-607 (1999)
   PUBMED   10452915
REFERENCE   9  (residues 1 to 559)
  AUTHORS   Pindel,E.V., Kedishvili,N.Y., Abraham,T.L., Brzezinski,M.R.,
            Zhang,J., Dean,R.A. and Bosron,W.F.
  TITLE     Purification and cloning of a broad substrate specificity human
            liver carboxylesterase that catalyzes the hydrolysis of cocaine and
            heroin
  JOURNAL   J Biol Chem 272 (23), 14769-14775 (1997)
   PUBMED   9169443
REFERENCE   10 (residues 1 to 559)
  AUTHORS   Schwer,H., Langmann,T., Daig,R., Becker,A., Aslanidis,C. and
            Schmitz,G.
  TITLE     Molecular cloning and characterization of a novel putative
            carboxylesterase, present in human intestine and liver
  JOURNAL   Biochem Biophys Res Commun 233 (1), 117-120 (1997)
   PUBMED   9144407
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BC032095.2 and BX538086.1.
            
            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].
            
            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.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1660805.244837.1,
                                           SRR1803617.77025.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000317091.10/ ENSP00000317842.5
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..559
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="16"
                     /map="16q22.1"
     Protein         1..559
                     /product="cocaine esterase isoform 1 precursor"
                     /EC_number="3.1.1.1"
                     /EC_number="3.1.1.84"
                     /EC_number="3.1.1.56"
                     /note="intestinal carboxylesterase; liver
                     carboxylesterase-2; carboxylesterase 2 (intestine, liver);
                     cocaine esterase; methylumbelliferyl-acetate deacetylase
                     2"
                     /calculated_mol_wt=58952
     sig_peptide     1..26
                     /inference="COORDINATES: ab initio prediction:SignalP:6.0"
                     /calculated_mol_wt=2874
     mat_peptide     27..559
                     /product="Cocaine esterase. /id=PRO_0000008572"
                     /note="propagated from UniProtKB/Swiss-Prot (O00748.1)"
                     /calculated_mol_wt=58952
     Site            27
                     /site_type="pyrrolidone-carboxylic-acid"
                     /note="Pyrrolidone carboxylic acid.
                     /evidence=ECO:0000250|UniProtKB:P14943; propagated from
                     UniProtKB/Swiss-Prot (O00748.1)"
     Region          30..538
                     /region_name="COesterase"
                     /note="Carboxylesterase family; pfam00135"
                     /db_xref="CDD:395084"
     Site            111
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:19159218; propagated from
                     UniProtKB/Swiss-Prot (O00748.1)"
     Site            order(148..150,227..229,232,374,378..379,411,458,461)
                     /site_type="other"
                     /note="substrate binding pocket [chemical binding]"
                     /db_xref="CDD:238191"
     Site            order(228,345,457)
                     /site_type="active"
                     /note="catalytic triad [active]"
                     /db_xref="CDD:238191"
     Site            276
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (O00748.1)"
     Region          556..559
                     /region_name="Prevents secretion from ER.
                     /evidence=ECO:0000255"
                     /note="propagated from UniProtKB/Swiss-Prot (O00748.1)"
     CDS             1..559
                     /gene="CES2"
                     /gene_synonym="CE-2; CES2A1; iCE; PCE-2"
                     /coded_by="NM_001365405.1:121..1800"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 4"
                     /db_xref="CCDS:CCDS10825.2"
                     /db_xref="GeneID:8824"
                     /db_xref="HGNC:HGNC:1864"
                     /db_xref="MIM:605278"
ORIGIN      
        1 mrlhrlrarl savacgllll lvrgqgqdsa spirtthtgq vlgslvhvkg anagvqtflg
       61 ipfakpplgp lrfappeppe swsgvrdgtt hpamclqdlt aveseflsqf nmtfpsdsms
      121 edclylsiyt pahshegsnl pvmvwihgga lvfgmaslyd gsmlaalenv vvviiqyrlg
      181 vlgffstgdk hatgnwgyld qvaalrwvqq niahfggnpd rvtifgesag gtsvsslvvs
      241 pisqglfhga imesgvallp gliassadvi stvvanlsac dqvdsealvg clrgkskeei
      301 lainkpfkmi pgvvdgvflp rhpqellasa dfqpvpsivg vnnnefgwli pkvmriydtq
      361 kemdreasqa alqkmltllm lpptfgdllr eeyigdngdp qtlqaqfqem madsmfvipa
      421 lqvahfqcsr apvyfyefqh qpswlknirp phmkadhgde lpfvfrsffg gnyikfteee
      481 eqlsrkmmky wanfarngnp ngeglphwpl fdqeeqylql nlqpavgral kahrlqfwkk
      541 alpqkiqele epeerhtel
//
