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Protein

Cocaine esterase

Gene

CES2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Shows high catalytic efficiency for hydrolysis of cocaine, 4-methylumbelliferyl acetate, heroin and 6-monoacetylmorphine.1 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)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei228 – 2281Acyl-ester intermediatePROSITE-ProRule annotation
    Active sitei345 – 3451Charge relay systemBy similarity
    Active sitei457 – 4571Charge relay systemBy similarity

    GO - Molecular functioni

    GO - Biological processi

    • catabolic process Source: ProtInc
    • xenobiotic metabolic process Source: Reactome
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase, Serine esterase

    Enzyme and pathway databases

    BRENDAi3.1.1.1. 2681.
    3.1.1.84. 2681.
    ReactomeiR-HSA-211945. Phase 1 - Functionalization of compounds.
    SABIO-RKO00748.

    Protein family/group databases

    ESTHERihuman-CES2. Carb_B_Chordata.
    MEROPSiS09.984.

    Chemistry

    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

    HGNCiHGNC:1864. CES2.

    Subcellular locationi

    GO - Cellular componenti

    • endoplasmic reticulum Source: ProtInc
    • endoplasmic reticulum lumen Source: Reactome
    • extracellular space Source: GO_Central
    Complete GO annotation...

    Keywords - Cellular componenti

    Endoplasmic reticulum

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA377.

    Chemistry

    ChEMBLiCHEMBL3180.
    DrugBankiDB06695. Dabigatran etexilate.
    DB00762. Irinotecan.
    DB00688. Mycophenolate mofetil.
    DB06209. Prasugrel.

    Polymorphism and mutation databases

    BioMutaiCES2.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 26261 PublicationAdd
    BLAST
    Chaini27 – 559533Cocaine esterasePRO_0000008572Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei27 – 271Pyrrolidone carboxylic acidBy similarity
    Disulfide bondi95 ↔ 123By similarity
    Glycosylationi111 – 1111N-linked (GlcNAc...)1 Publication
    Glycosylationi276 – 2761N-linked (GlcNAc...)Sequence analysis
    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.

    PTM databases

    iPTMnetiO00748.
    PhosphoSiteiO00748.

    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.
    CleanExiHS_CES2.
    ExpressionAtlasiO00748. baseline and differential.
    GenevisibleiO00748. HS.

    Organism-specific databases

    HPAiHPA018897.

    Interactioni

    Subunit structurei

    Monomer.1 Publication

    Protein-protein interaction databases

    BioGridi114351. 1 interaction.
    IntActiO00748. 1 interaction.
    STRINGi9606.ENSP00000317842.

    Chemistry

    BindingDBiO00748.

    Structurei

    3D structure databases

    ProteinModelPortaliO00748.
    SMRiO00748. Positions 39-559.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi556 – 5594Prevents secretion from ERSequence analysis

    Sequence similaritiesi

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiKOG1516. Eukaryota.
    COG2272. LUCA.
    HOGENOMiHOG000091866.
    HOVERGENiHBG008839.
    InParanoidiO00748.
    KOiK03927.
    PhylomeDBiO00748.
    TreeFamiTF315470.

    Family and domain databases

    Gene3Di3.40.50.1820. 1 hit.
    InterProiIPR029058. AB_hydrolase.
    IPR002018. CarbesteraseB.
    IPR019826. Carboxylesterase_B_AS.
    IPR019819. Carboxylesterase_B_CS.
    [Graphical view]
    PfamiPF00135. COesterase. 1 hit.
    [Graphical view]
    SUPFAMiSSF53474. SSF53474. 1 hit.
    PROSITEiPS00122. CARBOXYLESTERASE_B_1. 1 hit.
    PS00941. CARBOXYLESTERASE_B_2. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

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

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    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

    Sequence cautioni

    The sequence AAH32095 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
    The sequence AAW29943 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
    The sequence CAD28531 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
    The sequence CAD98009 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti2 – 109Missing AA sequence (PubMed:9169443).Curated
    Sequence conflicti180 – 1801G → S in BAF83171 (PubMed:14702039).Curated
    Sequence conflicti239 – 2391V → M in BAF83171 (PubMed:14702039).Curated
    Sequence conflicti385 – 3851F → S in CAD98009 (PubMed:17974005).Curated
    Sequence conflicti519 – 5191Q → R in CAD98009 (PubMed:17974005).Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti34 – 341R → W.1 Publication
    VAR_018396
    Natural varianti206 – 2061R → H.1 Publication
    VAR_018397

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei458 – 47417GDELP…GGNYI → V in isoform 2. 1 PublicationVSP_010161Add
    BLAST

    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. Different initiation.
    AK290482 mRNA. Translation: BAF83171.1.
    BX538086 mRNA. Translation: CAD98009.1. Different initiation.
    AY851164 Genomic DNA. Translation: AAW29943.1. Different initiation.
    AC009084 Genomic DNA. No translation available.
    BC032095 mRNA. Translation: AAH32095.1. Different initiation.
    PIRiJC5408.
    RefSeqiNP_003860.2. NM_003869.5.
    NP_932327.1. NM_198061.2.
    UniGeneiHs.282975.

    Genome annotation databases

    EnsembliENST00000417689; ENSP00000394452; ENSG00000172831.
    GeneIDi8824.
    KEGGihsa:8824.
    UCSCiuc002eqq.4. human. [O00748-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    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. Different initiation.
    AK290482 mRNA. Translation: BAF83171.1.
    BX538086 mRNA. Translation: CAD98009.1. Different initiation.
    AY851164 Genomic DNA. Translation: AAW29943.1. Different initiation.
    AC009084 Genomic DNA. No translation available.
    BC032095 mRNA. Translation: AAH32095.1. Different initiation.
    PIRiJC5408.
    RefSeqiNP_003860.2. NM_003869.5.
    NP_932327.1. NM_198061.2.
    UniGeneiHs.282975.

    3D structure databases

    ProteinModelPortaliO00748.
    SMRiO00748. Positions 39-559.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi114351. 1 interaction.
    IntActiO00748. 1 interaction.
    STRINGi9606.ENSP00000317842.

    Chemistry

    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.
    PhosphoSiteiO00748.

    Polymorphism and mutation databases

    BioMutaiCES2.

    Proteomic databases

    EPDiO00748.
    MaxQBiO00748.
    PaxDbiO00748.
    PeptideAtlasiO00748.
    PRIDEiO00748.

    Protocols and materials databases

    DNASUi8824.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000417689; ENSP00000394452; ENSG00000172831.
    GeneIDi8824.
    KEGGihsa:8824.
    UCSCiuc002eqq.4. human. [O00748-1]

    Organism-specific databases

    CTDi8824.
    GeneCardsiCES2.
    HGNCiHGNC:1864. CES2.
    HPAiHPA018897.
    MIMi605278. gene.
    neXtProtiNX_O00748.
    PharmGKBiPA377.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1516. Eukaryota.
    COG2272. LUCA.
    HOGENOMiHOG000091866.
    HOVERGENiHBG008839.
    InParanoidiO00748.
    KOiK03927.
    PhylomeDBiO00748.
    TreeFamiTF315470.

    Enzyme and pathway databases

    BRENDAi3.1.1.1. 2681.
    3.1.1.84. 2681.
    ReactomeiR-HSA-211945. Phase 1 - Functionalization of compounds.
    SABIO-RKO00748.

    Miscellaneous databases

    ChiTaRSiCES2. human.
    GeneWikiiCarboxylesterase_2.
    GenomeRNAii8824.
    PROiO00748.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000172831.
    CleanExiHS_CES2.
    ExpressionAtlasiO00748. baseline and differential.
    GenevisibleiO00748. HS.

    Family and domain databases

    Gene3Di3.40.50.1820. 1 hit.
    InterProiIPR029058. AB_hydrolase.
    IPR002018. CarbesteraseB.
    IPR019826. Carboxylesterase_B_AS.
    IPR019819. Carboxylesterase_B_CS.
    [Graphical view]
    PfamiPF00135. COesterase. 1 hit.
    [Graphical view]
    SUPFAMiSSF53474. SSF53474. 1 hit.
    PROSITEiPS00122. CARBOXYLESTERASE_B_1. 1 hit.
    PS00941. CARBOXYLESTERASE_B_2. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiEST2_HUMAN
    AccessioniPrimary (citable) accession number: O00748
    Secondary accession number(s): A8K367
    , Q16859, Q5MAB8, Q7Z366, Q8IUP4, Q8TCP8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 26, 2004
    Last sequence update: July 1, 1997
    Last modified: September 7, 2016
    This is version 140 of the entry and version 1 of the sequence. [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. Human chromosome 16
      Human chromosome 16: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.