Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Cocaine esterase

Gene

CES2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs (PubMed:9169443). Shows high catalytic efficiency for hydrolysis of cocaine, 4-methylumbelliferyl acetate, heroin and 6-monoacetylmorphine (PubMed:9169443). Hydrolyzes aspirin, substrates with large alcohol group and small acyl group and endogenous lipids such as triacylglycerol (PubMed:28677105).1 Publication1 Publication

Catalytic activityi

Cocaine + H2O = ecgonine methyl ester + benzoate.1 Publication
A carboxylic ester + H2O = an alcohol + a carboxylate.PROSITE-ProRule annotation1 Publication
4-methylumbelliferyl acetate + H2O = 4-methylumbelliferone + acetate.1 Publication

Kineticsi

  1. KM=0.39 mM for cocaine1 Publication
  2. KM=0.15 mM for 4-methylumbelliferyl acetate1 Publication
  3. KM=6.8 mM for heroin1 Publication
  4. KM=0.13 mM for 6-monoacetylmorphine1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei228Acyl-ester intermediatePROSITE-ProRule annotation1
    Active sitei345Charge relay systemBy similarity1
    Active sitei457Charge relay systemBy similarity1

    GO - Molecular functioni

    GO - Biological processi

    • catabolic process Source: ProtInc
    • prostaglandin metabolic process Source: BHF-UCL
    • xenobiotic metabolic process Source: Reactome

    Keywordsi

    Molecular functionHydrolase, Serine esterase

    Enzyme and pathway databases

    BRENDAi3.1.1.1 2681
    3.1.1.84 2681
    ReactomeiR-HSA-211945 Phase I - Functionalization of compounds
    SABIO-RKiO00748

    Protein family/group databases

    ESTHERihuman-CES2 Carb_B_Chordata
    MEROPSiS09.984

    Chemistry databases

    SwissLipidsiSLP:000001424

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cocaine esterase (EC:3.1.1.84)
    Alternative name(s):
    Carboxylesterase 2 (EC:3.1.1.1)
    Short name:
    CE-2
    Short name:
    hCE-2
    Methylumbelliferyl-acetate deacetylase 2 (EC:3.1.1.56)
    Gene namesi
    Name:CES2
    Synonyms:ICE
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 16

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000172831.11
    HGNCiHGNC:1864 CES2
    MIMi605278 gene
    neXtProtiNX_O00748

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Endoplasmic reticulum

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi8824
    OpenTargetsiENSG00000172831
    PharmGKBiPA377

    Chemistry databases

    ChEMBLiCHEMBL3180
    DrugBankiDB06695 Dabigatran etexilate
    DB00762 Irinotecan
    DB00688 Mycophenolate mofetil
    DB06209 Prasugrel

    Polymorphism and mutation databases

    BioMutaiCES2

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Signal peptidei1 – 261 PublicationAdd BLAST26
    ChainiPRO_000000857227 – 559Cocaine esteraseAdd BLAST533

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei27Pyrrolidone carboxylic acidBy similarity1
    Disulfide bondi95 ↔ 123By similarity
    Glycosylationi111N-linked (GlcNAc...) asparagine1 Publication1
    Glycosylationi276N-linked (GlcNAc...) asparagineSequence analysis1
    Disulfide bondi280 ↔ 291By similarity

    Post-translational modificationi

    Glycosylated.2 Publications

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Pyrrolidone carboxylic acid

    Proteomic databases

    EPDiO00748
    MaxQBiO00748
    PaxDbiO00748
    PeptideAtlasiO00748
    PRIDEiO00748
    ProteomicsDBi48014
    48015 [O00748-2]

    PTM databases

    iPTMnetiO00748
    PhosphoSitePlusiO00748

    Expressioni

    Tissue specificityi

    Preferentially expressed in intestine with moderate expression in liver. Within the intestine, highest expression is found in small intestine with lower expression in colon and rectum.1 Publication

    Gene expression databases

    BgeeiENSG00000172831 Expressed in 236 organ(s), highest expression level in jejunal mucosa
    CleanExiHS_CES2
    ExpressionAtlasiO00748 baseline and differential
    GenevisibleiO00748 HS

    Organism-specific databases

    HPAiHPA018897

    Interactioni

    Subunit structurei

    Monomer.1 Publication

    Protein-protein interaction databases

    BioGridi114351, 1 interactor
    IntActiO00748, 1 interactor
    STRINGi9606.ENSP00000317842

    Chemistry databases

    BindingDBiO00748

    Structurei

    3D structure databases

    ProteinModelPortaliO00748
    SMRiO00748
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Motif

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Motifi556 – 559Prevents secretion from ERSequence analysis4

    Sequence similaritiesi

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiKOG1516 Eukaryota
    COG2272 LUCA
    GeneTreeiENSGT00760000118946
    HOGENOMiHOG000091866
    HOVERGENiHBG008839
    InParanoidiO00748
    KOiK03927
    OMAiGASAYWP
    OrthoDBiEOG091G03ZC
    PhylomeDBiO00748
    TreeFamiTF315470

    Family and domain databases

    Gene3Di3.40.50.1820, 1 hit
    InterProiView protein in InterPro
    IPR029058 AB_hydrolase
    IPR002018 CarbesteraseB
    IPR019826 Carboxylesterase_B_AS
    IPR019819 Carboxylesterase_B_CS
    PfamiView protein in Pfam
    PF00135 COesterase, 1 hit
    SUPFAMiSSF53474 SSF53474, 1 hit
    PROSITEiView protein in PROSITE
    PS00122 CARBOXYLESTERASE_B_1, 1 hit
    PS00941 CARBOXYLESTERASE_B_2, 1 hit

    Sequences (4+)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 4 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket

    This entry has 4 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

    Isoform 1 (identifier: O00748-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide
            10         20         30         40         50
    MRLHRLRARL SAVACGLLLL LVRGQGQDSA SPIRTTHTGQ VLGSLVHVKG
    60 70 80 90 100
    ANAGVQTFLG IPFAKPPLGP LRFAPPEPPE SWSGVRDGTT HPAMCLQDLT
    110 120 130 140 150
    AVESEFLSQF NMTFPSDSMS EDCLYLSIYT PAHSHEGSNL PVMVWIHGGA
    160 170 180 190 200
    LVFGMASLYD GSMLAALENV VVVIIQYRLG VLGFFSTGDK HATGNWGYLD
    210 220 230 240 250
    QVAALRWVQQ NIAHFGGNPD RVTIFGESAG GTSVSSLVVS PISQGLFHGA
    260 270 280 290 300
    IMESGVALLP GLIASSADVI STVVANLSAC DQVDSEALVG CLRGKSKEEI
    310 320 330 340 350
    LAINKPFKMI PGVVDGVFLP RHPQELLASA DFQPVPSIVG VNNNEFGWLI
    360 370 380 390 400
    PKVMRIYDTQ KEMDREASQA ALQKMLTLLM LPPTFGDLLR EEYIGDNGDP
    410 420 430 440 450
    QTLQAQFQEM MADSMFVIPA LQVAHFQCSR APVYFYEFQH QPSWLKNIRP
    460 470 480 490 500
    PHMKADHGDE LPFVFRSFFG GNYIKFTEEE EQLSRKMMKY WANFARNGNP
    510 520 530 540 550
    NGEGLPHWPL FDQEEQYLQL NLQPAVGRAL KAHRLQFWKK ALPQKIQELE

    EPEERHTEL
    Length:559
    Mass (Da):61,807
    Last modified:July 1, 1997 - v1
    Checksum:iE2EBCABA2995339A
    GO
    Isoform 2 (identifier: O00748-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         458-474: GDELPFVFRSFFGGNYI → V

    Show »
    Length:543
    Mass (Da):59,959
    Checksum:i4F14FE06766F0F7E
    GO
    Isoform 3 (identifier: O00748-4) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-1: M → MTAQSRSPTTPTFPGPSQRTPLTPCPVQTPRLGKALIHCWTDPGQPLGEQQRVRRQRTETSEPTM

    Note: Probably produced by alternative initiation of isoform 1. Does not contain a signal peptide. The biological function of the extra amino acids in the N-terminus remains to be determined.1 Publication
    Show »
    Length:623
    Mass (Da):68,899
    Checksum:i5220B2965D800EA3
    GO
    Isoform 4 (identifier: O00748-5) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-1: M → MTAQSRSPTTPTFPGPSQRTPLTPCPVQTPRLGKALIHCWTDPGQPLGEQQRVRRQRTETSEPTM
         458-474: GDELPFVFRSFFGGNYI → V

    Note: Probably produced by alternative initiation of isoform 2. Does not contain a signal peptide. The biological function of the extra amino acids in the N-terminus remains to be determined.1 Publication
    Show »
    Length:607
    Mass (Da):67,051
    Checksum:i7FF4E1A2227B6F9C
    GO

    Computationally mapped potential isoform sequencesi

    There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    J3QLP1J3QLP1_HUMAN
    Cocaine esterase
    CES2
    125Annotation score:
    J3QSC0J3QSC0_HUMAN
    Cocaine esterase
    CES2
    201Annotation score:
    H3BUN5H3BUN5_HUMAN
    Cocaine esterase
    CES2
    122Annotation score:
    J3QKN7J3QKN7_HUMAN
    Cocaine esterase
    CES2
    21Annotation score:

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti2 – 10Missing AA sequence (PubMed:9169443).Curated9
    Sequence conflicti180G → S in BAF83171 (PubMed:14702039).Curated1
    Sequence conflicti239V → M in BAF83171 (PubMed:14702039).Curated1
    Sequence conflicti385F → S in CAD98009 (PubMed:17974005).Curated1
    Sequence conflicti519Q → R in CAD98009 (PubMed:17974005).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_01839634R → W1 Publication1
    Natural variantiVAR_018397206R → H1 Publication1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0598041M → MTAQSRSPTTPTFPGPSQRT PLTPCPVQTPRLGKALIHCW TDPGQPLGEQQRVRRQRTET SEPTM in isoform 3 and isoform 4. 1 Publication1
    Alternative sequenceiVSP_010161458 – 474GDELP…GGNYI → V in isoform 2 and isoform 4. 1 PublicationAdd BLAST17

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    Y09616 mRNA Translation: CAA70831.1
    D50579 mRNA Translation: BAA23606.1
    U60553 mRNA Translation: AAB03611.1
    AL713761 mRNA Translation: CAD28531.1
    AK290482 mRNA Translation: BAF83171.1
    BX538086 mRNA Translation: CAD98009.1
    AY851164 Genomic DNA Translation: AAW29943.1
    AC009084 Genomic DNA No translation available.
    CH471092 Genomic DNA Translation: EAW83058.1
    CH471092 Genomic DNA Translation: EAW83059.1
    BC032095 mRNA Translation: AAH32095.1
    CCDSiCCDS10825.1 [O00748-1]
    CCDS45507.1 [O00748-2]
    PIRiJC5408
    RefSeqiNP_003860.2, NM_003869.5 [O00748-4]
    NP_932327.1, NM_198061.2 [O00748-5]
    UniGeneiHs.282975

    Genome annotation databases

    EnsembliENST00000317091; ENSP00000317842; ENSG00000172831 [O00748-4]
    ENST00000417689; ENSP00000394452; ENSG00000172831 [O00748-5]
    GeneIDi8824
    KEGGihsa:8824
    UCSCiuc002eqq.4 human [O00748-1]
    uc002eqr.4 human

    Keywords - Coding sequence diversityi

    Alternative initiation, Alternative splicing, Polymorphism

    Similar proteinsi

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    Y09616 mRNA Translation: CAA70831.1
    D50579 mRNA Translation: BAA23606.1
    U60553 mRNA Translation: AAB03611.1
    AL713761 mRNA Translation: CAD28531.1
    AK290482 mRNA Translation: BAF83171.1
    BX538086 mRNA Translation: CAD98009.1
    AY851164 Genomic DNA Translation: AAW29943.1
    AC009084 Genomic DNA No translation available.
    CH471092 Genomic DNA Translation: EAW83058.1
    CH471092 Genomic DNA Translation: EAW83059.1
    BC032095 mRNA Translation: AAH32095.1
    CCDSiCCDS10825.1 [O00748-1]
    CCDS45507.1 [O00748-2]
    PIRiJC5408
    RefSeqiNP_003860.2, NM_003869.5 [O00748-4]
    NP_932327.1, NM_198061.2 [O00748-5]
    UniGeneiHs.282975

    3D structure databases

    ProteinModelPortaliO00748
    SMRiO00748
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi114351, 1 interactor
    IntActiO00748, 1 interactor
    STRINGi9606.ENSP00000317842

    Chemistry databases

    BindingDBiO00748
    ChEMBLiCHEMBL3180
    DrugBankiDB06695 Dabigatran etexilate
    DB00762 Irinotecan
    DB00688 Mycophenolate mofetil
    DB06209 Prasugrel
    SwissLipidsiSLP:000001424

    Protein family/group databases

    ESTHERihuman-CES2 Carb_B_Chordata
    MEROPSiS09.984

    PTM databases

    iPTMnetiO00748
    PhosphoSitePlusiO00748

    Polymorphism and mutation databases

    BioMutaiCES2

    Proteomic databases

    EPDiO00748
    MaxQBiO00748
    PaxDbiO00748
    PeptideAtlasiO00748
    PRIDEiO00748
    ProteomicsDBi48014
    48015 [O00748-2]

    Protocols and materials databases

    DNASUi8824
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000317091; ENSP00000317842; ENSG00000172831 [O00748-4]
    ENST00000417689; ENSP00000394452; ENSG00000172831 [O00748-5]
    GeneIDi8824
    KEGGihsa:8824
    UCSCiuc002eqq.4 human [O00748-1]
    uc002eqr.4 human

    Organism-specific databases

    CTDi8824
    DisGeNETi8824
    EuPathDBiHostDB:ENSG00000172831.11
    GeneCardsiCES2
    HGNCiHGNC:1864 CES2
    HPAiHPA018897
    MIMi605278 gene
    neXtProtiNX_O00748
    OpenTargetsiENSG00000172831
    PharmGKBiPA377
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1516 Eukaryota
    COG2272 LUCA
    GeneTreeiENSGT00760000118946
    HOGENOMiHOG000091866
    HOVERGENiHBG008839
    InParanoidiO00748
    KOiK03927
    OMAiGASAYWP
    OrthoDBiEOG091G03ZC
    PhylomeDBiO00748
    TreeFamiTF315470

    Enzyme and pathway databases

    BRENDAi3.1.1.1 2681
    3.1.1.84 2681
    ReactomeiR-HSA-211945 Phase I - Functionalization of compounds
    SABIO-RKiO00748

    Miscellaneous databases

    ChiTaRSiCES2 human
    GeneWikiiCarboxylesterase_2
    GenomeRNAii8824
    PROiPR:O00748
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000172831 Expressed in 236 organ(s), highest expression level in jejunal mucosa
    CleanExiHS_CES2
    ExpressionAtlasiO00748 baseline and differential
    GenevisibleiO00748 HS

    Family and domain databases

    Gene3Di3.40.50.1820, 1 hit
    InterProiView protein in InterPro
    IPR029058 AB_hydrolase
    IPR002018 CarbesteraseB
    IPR019826 Carboxylesterase_B_AS
    IPR019819 Carboxylesterase_B_CS
    PfamiView protein in Pfam
    PF00135 COesterase, 1 hit
    SUPFAMiSSF53474 SSF53474, 1 hit
    PROSITEiView protein in PROSITE
    PS00122 CARBOXYLESTERASE_B_1, 1 hit
    PS00941 CARBOXYLESTERASE_B_2, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiEST2_HUMAN
    AccessioniPrimary (citable) accession number: O00748
    Secondary accession number(s): A0A024R6X1
    , A8K367, Q16859, Q5MAB8, Q7Z366, Q8IUP4, Q8TCP8
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 26, 2004
    Last sequence update: July 1, 1997
    Last modified: November 7, 2018
    This is version 151 of the entry and version 1 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    2. Human chromosome 16
      Human chromosome 16: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health

    We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

    Do not show this banner again