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Protein

Carboxylesterase 3

Gene

CES3

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 low catalytic efficiency for hydrolysis of CPT-11 (7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin), a prodrug for camptothecin used in cancer therapeutics.

Catalytic activityi

A carboxylic ester + H2O = an alcohol + a carboxylate.PROSITE-ProRule annotation

Kineticsi

  1. KM=137 µM for 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin1 Publication
  2. KM=460 µM for 7-ethyl-10-[4-(1-piperidino)-1-amino]-carbonyloxycamptothecin1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei229Acyl-ester intermediatePROSITE-ProRule annotation1
    Active sitei347Charge relay systemBy similarity1
    Active sitei460Charge relay systemBy similarity1

    GO - Molecular functioni

    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase, Serine esterase

    Enzyme and pathway databases

    BioCyciMetaCyc:HS10576-MONOMER.
    ZFISH:HS10576-MONOMER.
    SABIO-RKQ6UWW8.

    Protein family/group databases

    ESTHERihuman-CES3. Carb_B_Chordata.
    MEROPSiS09.958.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Carboxylesterase 3 (EC:3.1.1.1)
    Alternative name(s):
    Liver carboxylesterase 31 homolog
    Gene namesi
    Name:CES3
    ORF Names:UNQ869/PRO1887
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 16

    Organism-specific databases

    HGNCiHGNC:1865. CES3.

    Subcellular locationi

    GO - Cellular componenti

    • endoplasmic reticulum lumen Source: UniProtKB-SubCell
    • extracellular exosome Source: UniProtKB
    • extracellular space Source: GO_Central
    Complete GO annotation...

    Keywords - Cellular componenti

    Endoplasmic reticulum

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi23491.
    OpenTargetsiENSG00000172828.
    PharmGKBiPA26418.

    Polymorphism and mutation databases

    BioMutaiCES3.
    DMDMi74758561.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Signal peptidei1 – 26Sequence analysisAdd BLAST26
    ChainiPRO_000030519127 – 571Carboxylesterase 3Add BLAST545

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Disulfide bondi97 ↔ 124By similarity
    Glycosylationi105N-linked (GlcNAc...)1 Publication1
    Disulfide bondi281 ↔ 292By similarity

    Post-translational modificationi

    N-glycosylated.2 Publications

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    EPDiQ6UWW8.
    MaxQBiQ6UWW8.
    PaxDbiQ6UWW8.
    PeptideAtlasiQ6UWW8.
    PRIDEiQ6UWW8.

    PTM databases

    iPTMnetiQ6UWW8.
    PhosphoSitePlusiQ6UWW8.

    Expressioni

    Tissue specificityi

    Expressed in liver, colon and small intestine.3 Publications

    Gene expression databases

    BgeeiENSG00000172828.
    CleanExiHS_CES3.
    ExpressionAtlasiQ6UWW8. baseline and differential.
    GenevisibleiQ6UWW8. HS.

    Organism-specific databases

    HPAiHPA041008.
    HPA041307.

    Interactioni

    Protein-protein interaction databases

    BioGridi117043. 6 interactors.
    IntActiQ6UWW8. 1 interactor.
    STRINGi9606.ENSP00000304782.

    Structurei

    3D structure databases

    ProteinModelPortaliQ6UWW8.
    SMRiQ6UWW8.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Motif

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Motifi568 – 571Prevents secretion from ERSequence analysis4

    Sequence similaritiesi

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiKOG1516. Eukaryota.
    COG2272. LUCA.
    GeneTreeiENSGT00760000118946.
    HOGENOMiHOG000091866.
    HOVERGENiHBG008839.
    InParanoidiQ6UWW8.
    KOiK15743.
    OMAiLFPISED.
    OrthoDBiEOG091G03ZC.
    PhylomeDBiQ6UWW8.
    TreeFamiTF315470.

    Family and domain databases

    Gene3Di3.40.50.1820. 1 hit.
    InterProiIPR029058. AB_hydrolase.
    IPR002018. CarbesteraseB.
    IPR019826. Carboxylesterase_B_AS.
    [Graphical view]
    PfamiPF00135. COesterase. 1 hit.
    [Graphical view]
    SUPFAMiSSF53474. SSF53474. 2 hits.
    PROSITEiPS00122. CARBOXYLESTERASE_B_1. 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: Q6UWW8-1) [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
    MERAVRVESG VLVGVVCLLL ACPATATGPE VAQPEVDTTL GRVRGRQVGV
    60 70 80 90 100
    KGTDRLVNVF LGIPFAQPPL GPDRFSAPHP AQPWEGVRDA STAPPMCLQD
    110 120 130 140 150
    VESMNSSRFV LNGKQQIFSV SEDCLVLNVY SPAEVPAGSG RPVMVWVHGG
    160 170 180 190 200
    ALITGAATSY DGSALAAYGD VVVVTVQYRL GVLGFFSTGD EHAPGNQGFL
    210 220 230 240 250
    DVVAALRWVQ ENIAPFGGDL NCVTVFGGSA GGSIISGLVL SPVAAGLFHR
    260 270 280 290 300
    AITQSGVITT PGIIDSHPWP LAQKIANTLA CSSSSPAEMV QCLQQKEGEE
    310 320 330 340 350
    LVLSKKLKNT IYPLTVDGTV FPKSPKELLK EKPFHSVPFL MGVNNHEFSW
    360 370 380 390 400
    LIPRGWGLLD TMEQMSREDM LAISTPVLTS LDVPPEMMPT VIDEYLGSNS
    410 420 430 440 450
    DAQAKCQAFQ EFMGDVFINV PTVSFSRYLR DSGSPVFFYE FQHRPSSFAK
    460 470 480 490 500
    IKPAWVKADH GAEGAFVFGG PFLMDESSRL AFPEATEEEK QLSLTMMAQW
    510 520 530 540 550
    THFARTGDPN SKALPPWPQF NQAEQYLEIN PVPRAGQKFR EAWMQFWSET
    560 570
    LPSKIQQWHQ KQKNRKAQED L
    Length:571
    Mass (Da):62,282
    Last modified:July 5, 2004 - v1
    Checksum:iF2200968FDE072D2
    GO
    Isoform 2 (identifier: Q6UWW8-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-361: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:210
    Mass (Da):24,106
    Checksum:i875CDDA899639F65
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti372A → S in BAB15123 (PubMed:14702039).Curated1
    Sequence conflicti481 – 483Missing in AAH53670 (PubMed:15489334).Curated3

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_060699129V → I.1 PublicationCorresponds to variant rs61745806dbSNPEnsembl.1
    Natural variantiVAR_060700151A → T.1 PublicationCorresponds to variant rs71647891dbSNPEnsembl.1
    Natural variantiVAR_060701160Y → H.1 PublicationCorresponds to variant rs71647892dbSNPEnsembl.1
    Natural variantiVAR_060702191E → K.1 PublicationCorresponds to variant rs61742964dbSNPEnsembl.1
    Natural variantiVAR_060703213I → N.1 PublicationCorresponds to variant rs71647894dbSNPEnsembl.1
    Natural variantiVAR_060704367R → W.1 PublicationCorresponds to variant rs61743167dbSNPEnsembl.1
    Natural variantiVAR_060705523A → V.1 PublicationCorresponds to variant rs71649615dbSNPEnsembl.1
    Natural variantiVAR_060706555I → V.1 PublicationCorresponds to variant rs8059252dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0449941 – 361Missing in isoform 2. 1 PublicationAdd BLAST361

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY358609 mRNA. Translation: AAQ88972.1.
    AK025389 mRNA. Translation: BAB15123.1.
    EU595874 Genomic DNA. Translation: ACD11491.1.
    AC009084 Genomic DNA. No translation available.
    CH471092 Genomic DNA. Translation: EAW83060.1.
    BC053670 mRNA. Translation: AAH53670.1.
    CCDSiCCDS10826.1. [Q6UWW8-1]
    CCDS54023.1. [Q6UWW8-2]
    RefSeqiNP_001172105.1. NM_001185176.1. [Q6UWW8-2]
    NP_001172106.1. NM_001185177.1.
    NP_079198.2. NM_024922.5. [Q6UWW8-1]
    UniGeneiHs.268700.

    Genome annotation databases

    EnsembliENST00000303334; ENSP00000304782; ENSG00000172828. [Q6UWW8-1]
    ENST00000543856; ENSP00000445559; ENSG00000172828. [Q6UWW8-2]
    GeneIDi23491.
    KEGGihsa:23491.
    UCSCiuc002eqt.4. human. [Q6UWW8-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY358609 mRNA. Translation: AAQ88972.1.
    AK025389 mRNA. Translation: BAB15123.1.
    EU595874 Genomic DNA. Translation: ACD11491.1.
    AC009084 Genomic DNA. No translation available.
    CH471092 Genomic DNA. Translation: EAW83060.1.
    BC053670 mRNA. Translation: AAH53670.1.
    CCDSiCCDS10826.1. [Q6UWW8-1]
    CCDS54023.1. [Q6UWW8-2]
    RefSeqiNP_001172105.1. NM_001185176.1. [Q6UWW8-2]
    NP_001172106.1. NM_001185177.1.
    NP_079198.2. NM_024922.5. [Q6UWW8-1]
    UniGeneiHs.268700.

    3D structure databases

    ProteinModelPortaliQ6UWW8.
    SMRiQ6UWW8.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi117043. 6 interactors.
    IntActiQ6UWW8. 1 interactor.
    STRINGi9606.ENSP00000304782.

    Protein family/group databases

    ESTHERihuman-CES3. Carb_B_Chordata.
    MEROPSiS09.958.

    PTM databases

    iPTMnetiQ6UWW8.
    PhosphoSitePlusiQ6UWW8.

    Polymorphism and mutation databases

    BioMutaiCES3.
    DMDMi74758561.

    Proteomic databases

    EPDiQ6UWW8.
    MaxQBiQ6UWW8.
    PaxDbiQ6UWW8.
    PeptideAtlasiQ6UWW8.
    PRIDEiQ6UWW8.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000303334; ENSP00000304782; ENSG00000172828. [Q6UWW8-1]
    ENST00000543856; ENSP00000445559; ENSG00000172828. [Q6UWW8-2]
    GeneIDi23491.
    KEGGihsa:23491.
    UCSCiuc002eqt.4. human. [Q6UWW8-1]

    Organism-specific databases

    CTDi23491.
    DisGeNETi23491.
    GeneCardsiCES3.
    HGNCiHGNC:1865. CES3.
    HPAiHPA041008.
    HPA041307.
    MIMi605279. gene.
    neXtProtiNX_Q6UWW8.
    OpenTargetsiENSG00000172828.
    PharmGKBiPA26418.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1516. Eukaryota.
    COG2272. LUCA.
    GeneTreeiENSGT00760000118946.
    HOGENOMiHOG000091866.
    HOVERGENiHBG008839.
    InParanoidiQ6UWW8.
    KOiK15743.
    OMAiLFPISED.
    OrthoDBiEOG091G03ZC.
    PhylomeDBiQ6UWW8.
    TreeFamiTF315470.

    Enzyme and pathway databases

    BioCyciMetaCyc:HS10576-MONOMER.
    ZFISH:HS10576-MONOMER.
    SABIO-RKQ6UWW8.

    Miscellaneous databases

    GeneWikiiCarboxylesterase_3.
    GenomeRNAii23491.
    PROiQ6UWW8.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000172828.
    CleanExiHS_CES3.
    ExpressionAtlasiQ6UWW8. baseline and differential.
    GenevisibleiQ6UWW8. HS.

    Family and domain databases

    Gene3Di3.40.50.1820. 1 hit.
    InterProiIPR029058. AB_hydrolase.
    IPR002018. CarbesteraseB.
    IPR019826. Carboxylesterase_B_AS.
    [Graphical view]
    PfamiPF00135. COesterase. 1 hit.
    [Graphical view]
    SUPFAMiSSF53474. SSF53474. 2 hits.
    PROSITEiPS00122. CARBOXYLESTERASE_B_1. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiEST3_HUMAN
    AccessioniPrimary (citable) accession number: Q6UWW8
    Secondary accession number(s): B2Z3W9
    , F5H242, Q7Z6J1, Q9H6X7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 2, 2007
    Last sequence update: July 5, 2004
    Last modified: November 2, 2016
    This is version 114 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, 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.