LOCUS       NM_001365405            2871 bp    mRNA    linear   PRI 03-APR-2024
DEFINITION  Homo sapiens carboxylesterase 2 (CES2), transcript variant 4, mRNA.
ACCESSION   NM_001365405
VERSION     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  (bases 1 to 2871)
  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  (bases 1 to 2871)
  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  (bases 1 to 2871)
  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  (bases 1 to 2871)
  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  (bases 1 to 2871)
  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  (bases 1 to 2871)
  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  (bases 1 to 2871)
  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  (bases 1 to 2871)
  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  (bases 1 to 2871)
  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 (bases 1 to 2871)
  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##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-2099              BC032095.2         1057-3155
            2100-2871           BX538086.1         3124-3895
FEATURES             Location/Qualifiers
     source          1..2871
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="16"
                     /map="16q22.1"
     gene            1..2871
                     /gene="CES2"
                     /gene_synonym="CE-2; CES2A1; iCE; PCE-2"
                     /note="carboxylesterase 2"
                     /db_xref="GeneID:8824"
                     /db_xref="HGNC:HGNC:1864"
                     /db_xref="MIM:605278"
     exon            1..196
                     /gene="CES2"
                     /gene_synonym="CE-2; CES2A1; iCE; PCE-2"
                     /inference="alignment:Splign:2.1.0"
     CDS             121..1800
                     /gene="CES2"
                     /gene_synonym="CE-2; CES2A1; iCE; PCE-2"
                     /EC_number="3.1.1.1"
                     /EC_number="3.1.1.84"
                     /EC_number="3.1.1.56"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 4; intestinal carboxylesterase; liver
                     carboxylesterase-2; carboxylesterase 2 (intestine, liver);
                     cocaine esterase; methylumbelliferyl-acetate deacetylase
                     2"
                     /codon_start=1
                     /product="cocaine esterase isoform 1 precursor"
                     /protein_id="NP_001352334.1"
                     /db_xref="CCDS:CCDS10825.2"
                     /db_xref="GeneID:8824"
                     /db_xref="HGNC:HGNC:1864"
                     /db_xref="MIM:605278"
                     /translation="MRLHRLRARLSAVACGLLLLLVRGQGQDSASPIRTTHTGQVLGS
                     LVHVKGANAGVQTFLGIPFAKPPLGPLRFAPPEPPESWSGVRDGTTHPAMCLQDLTAV
                     ESEFLSQFNMTFPSDSMSEDCLYLSIYTPAHSHEGSNLPVMVWIHGGALVFGMASLYD
                     GSMLAALENVVVVIIQYRLGVLGFFSTGDKHATGNWGYLDQVAALRWVQQNIAHFGGN
                     PDRVTIFGESAGGTSVSSLVVSPISQGLFHGAIMESGVALLPGLIASSADVISTVVAN
                     LSACDQVDSEALVGCLRGKSKEEILAINKPFKMIPGVVDGVFLPRHPQELLASADFQP
                     VPSIVGVNNNEFGWLIPKVMRIYDTQKEMDREASQAALQKMLTLLMLPPTFGDLLREE
                     YIGDNGDPQTLQAQFQEMMADSMFVIPALQVAHFQCSRAPVYFYEFQHQPSWLKNIRP
                     PHMKADHGDELPFVFRSFFGGNYIKFTEEEEQLSRKMMKYWANFARNGNPNGEGLPHW
                     PLFDQEEQYLQLNLQPAVGRALKAHRLQFWKKALPQKIQELEEPEERHTEL"
     exon            197..401
                     /gene="CES2"
                     /gene_synonym="CE-2; CES2A1; iCE; PCE-2"
                     /inference="alignment:Splign:2.1.0"
     exon            402..543
                     /gene="CES2"
                     /gene_synonym="CE-2; CES2A1; iCE; PCE-2"
                     /inference="alignment:Splign:2.1.0"
     exon            544..677
                     /gene="CES2"
                     /gene_synonym="CE-2; CES2A1; iCE; PCE-2"
                     /inference="alignment:Splign:2.1.0"
     exon            678..936
                     /gene="CES2"
                     /gene_synonym="CE-2; CES2A1; iCE; PCE-2"
                     /inference="alignment:Splign:2.1.0"
     exon            937..1035
                     /gene="CES2"
                     /gene_synonym="CE-2; CES2A1; iCE; PCE-2"
                     /inference="alignment:Splign:2.1.0"
     exon            1036..1176
                     /gene="CES2"
                     /gene_synonym="CE-2; CES2A1; iCE; PCE-2"
                     /inference="alignment:Splign:2.1.0"
     exon            1177..1257
                     /gene="CES2"
                     /gene_synonym="CE-2; CES2A1; iCE; PCE-2"
                     /inference="alignment:Splign:2.1.0"
     exon            1258..1402
                     /gene="CES2"
                     /gene_synonym="CE-2; CES2A1; iCE; PCE-2"
                     /inference="alignment:Splign:2.1.0"
     exon            1403..1540
                     /gene="CES2"
                     /gene_synonym="CE-2; CES2A1; iCE; PCE-2"
                     /inference="alignment:Splign:2.1.0"
     exon            1541..1613
                     /gene="CES2"
                     /gene_synonym="CE-2; CES2A1; iCE; PCE-2"
                     /inference="alignment:Splign:2.1.0"
     exon            1614..2871
                     /gene="CES2"
                     /gene_synonym="CE-2; CES2A1; iCE; PCE-2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2855..2860
                     /regulatory_class="polyA_signal_sequence"
                     /gene="CES2"
                     /gene_synonym="CE-2; CES2A1; iCE; PCE-2"
                     /note="hexamer: AATAAA"
     polyA_site      2871
                     /gene="CES2"
                     /gene_synonym="CE-2; CES2A1; iCE; PCE-2"
                     /note="major polyA site"
ORIGIN      
        1 tgcccagtcc aaactccaag gctgggcaag gcactgatcc actgctggac agacccgggg
       61 cagcctctgg gtgaacagca gcgtgtccgc cggcagcgaa ccgagaccag cgagccgacc
      121 atgcggctgc acagacttcg tgcgcggctg agcgcggtgg cctgtgggct tctgctgctt
      181 cttgtccggg gccagggcca ggactcagcc agtcccatcc ggaccacaca cacggggcag
      241 gtgctgggga gtcttgtcca tgtgaagggc gccaatgccg gggtccaaac cttcctggga
      301 attccatttg ccaagccacc tctaggtccg ctgcgatttg caccccctga gccccctgaa
      361 tcttggagtg gtgtgaggga tggaaccacc catccggcca tgtgtctaca ggacctcacc
      421 gcagtggagt cagagtttct tagccagttc aacatgacct tcccttccga ctccatgtct
      481 gaggactgcc tgtacctcag catctacacg ccggcccata gccatgaagg ctctaacctg
      541 ccggtgatgg tgtggatcca cggtggtgcg cttgtttttg gcatggcttc cttgtatgat
      601 ggttccatgc tggctgcctt ggagaacgtg gtggtggtca tcatccagta ccgcctgggt
      661 gtcctgggct tcttcagcac tggagacaag cacgcaaccg gcaactgggg ctacctggac
      721 caagtggctg cactacgctg ggtccagcag aatatcgccc actttggagg caaccctgac
      781 cgtgtcacca tttttggcga gtctgcgggt ggcacgagtg tgtcttcgct tgttgtgtcc
      841 cccatatccc aaggactctt ccacggagcc atcatggaga gtggcgtggc cctcctgccc
      901 ggcctcattg ccagctcagc tgatgtcatc tccacggtgg tggccaacct gtctgcctgt
      961 gaccaagttg actctgaggc cctggtgggc tgcctgcggg gcaagagtaa agaggagatt
     1021 cttgcaatta acaagccttt caagatgatc cccggagtgg tggatggggt cttcctgccc
     1081 aggcaccccc aggagctgct ggcctctgcc gactttcagc ctgtccctag cattgttggt
     1141 gtcaacaaca atgaattcgg ctggctcatc cccaaggtca tgaggatcta tgatacccag
     1201 aaggaaatgg acagagaggc ctcccaggct gctctgcaga aaatgttaac gctgctgatg
     1261 ttgcctccta catttggtga cctgctgagg gaggagtaca ttggggacaa tggggatccc
     1321 cagaccctcc aagcgcagtt ccaggagatg atggcggact ccatgtttgt gatccctgca
     1381 ctccaagtag cacattttca gtgttcccgg gcccctgtgt acttctacga gttccagcat
     1441 cagcccagct ggctcaagaa catcaggcca ccgcacatga aggcagacca tggtgatgag
     1501 cttccttttg ttttcagaag tttctttggg ggcaactaca ttaaattcac tgaggaagag
     1561 gagcagctaa gcaggaagat gatgaagtac tgggccaact ttgcgagaaa tgggaacccc
     1621 aatggcgagg gtctgccaca ctggccgctg ttcgaccagg aggagcaata cctgcagctg
     1681 aacctacagc ctgcggtggg ccgggctctg aaggcccaca ggctccagtt ctggaagaag
     1741 gcgctgcccc aaaagatcca ggagctcgag gagcctgaag agagacacac agagctgtag
     1801 ctccctgtgc cggggaggag ggggtgggtt cgctgacagg cgagggtcag cctgctgtgc
     1861 ccacacacac ccactaagga gaaagaagtt gattccttca ttcacttcgc cattcattca
     1921 tacttccgtc catccattca gaaagcattt attaagaatt tactcaggca tgatggccca
     1981 tacttgtaat cccagctatt gggaaggatg agatgggagg atggcttgag gccagaggtt
     2041 tgagaccgac cagccagggc aacacagtga gaccccttct caaaaaaaaa aaaaaaaaag
     2101 agagagtgtg tgattagaag ctaaatagga aagttttgag cttcaagtca gtgaggagta
     2161 aaaaagattt ttaaaaagca aagaaaacaa aatataaggg aaaaatatga gaaaaataaa
     2221 aataaaaaga gaataatagg ccaggcactg tggctcatgc ccctaatccc agcacttttg
     2281 ggaggtcaag gtgagcagaa cacctgagga caggagtttg agaccagcct gcccaacgtg
     2341 gtgaaacccc atctctatga aaaatacaaa aatcagacgg gcacagtggt ggtgcccacc
     2401 tgtgatccca gctactcagg aggctgaggc aggagaatta cttgaacctg ggaggcagag
     2461 gttgcagtga gctgagattg tgccactgta ctccagcctg ggcaacaaga gcgagactcc
     2521 gtttccaaaa aaataagaga gaatagaaga agctactgca tgatgttagt taccaagcct
     2581 gccatgggtc ctctcttgct agacacactc catagatccc cccactgagc tgtggatggg
     2641 caaaccccgg tggaatccca ccctccccaa caccccactg agccctgggc cccctcctcc
     2701 cttcctcacc tccaccttct ccctgccttc tctcttctct cgtctgagcc cccaggcctt
     2761 ttccactttg agggaggtgc ttcgaagaat gttgcccaca cctaagtgtt agaagcctat
     2821 gtccgttcat ccctgagagg tctgaaagaa taaaaataaa ttctaaaaaa a
//
