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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)LengthDescriptionGraphical viewFeature identifierActions
Active sitei229 – 2291Acyl-ester intermediatePROSITE-ProRule annotation
Active sitei347 – 3471Charge relay systemBy similarity
Active sitei460 – 4601Charge relay systemBy similarity

GO - Molecular functioni

  1. carboxylic ester hydrolase activity Source: GO_Central

GO - Biological processi

  1. metabolic process Source: GOC
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Serine esterase

Enzyme and pathway databases

BioCyciMetaCyc:HS10576-MONOMER.
SABIO-RKQ6UWW8.

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
ProteomesiUP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:1865. CES3.

Subcellular locationi

GO - Cellular componenti

  1. endoplasmic reticulum lumen Source: UniProtKB-SubCell
  2. extracellular space Source: GO_Central
  3. extracellular vesicular exosome Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA26418.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2626Sequence AnalysisAdd
BLAST
Chaini27 – 571545Carboxylesterase 3PRO_0000305191Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi97 ↔ 124By similarity
Glycosylationi105 – 1051N-linked (GlcNAc...)1 Publication
Disulfide bondi281 ↔ 292By similarity

Post-translational modificationi

N-glycosylated.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ6UWW8.
PaxDbiQ6UWW8.
PRIDEiQ6UWW8.

PTM databases

PhosphoSiteiQ6UWW8.

Expressioni

Tissue specificityi

Expressed in liver, colon and small intestine.3 Publications

Gene expression databases

BgeeiQ6UWW8.
CleanExiHS_CES3.
ExpressionAtlasiQ6UWW8. baseline and differential.
GenevestigatoriQ6UWW8.

Organism-specific databases

HPAiHPA041008.
HPA041307.

Interactioni

Protein-protein interaction databases

BioGridi117043. 3 interactions.
IntActiQ6UWW8. 1 interaction.
STRINGi9606.ENSP00000304782.

Structurei

3D structure databases

ProteinModelPortaliQ6UWW8.
SMRiQ6UWW8. Positions 34-548.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi568 – 5714Prevents secretion from ERSequence Analysis

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiCOG2272.
GeneTreeiENSGT00760000118946.
HOGENOMiHOG000091866.
HOVERGENiHBG008839.
InParanoidiQ6UWW8.
KOiK15743.
OMAiMQFWAET.
OrthoDBiEOG7RBZ7R.
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti372 – 3721A → S in BAB15123 (PubMed:14702039).Curated
Sequence conflicti481 – 4833Missing in AAH53670 (PubMed:15489334).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti129 – 1291V → I.1 Publication
Corresponds to variant rs61745806 [ dbSNP | Ensembl ].
VAR_060699
Natural varianti151 – 1511A → T.1 Publication
Corresponds to variant rs71647891 [ dbSNP | Ensembl ].
VAR_060700
Natural varianti160 – 1601Y → H.1 Publication
Corresponds to variant rs71647892 [ dbSNP | Ensembl ].
VAR_060701
Natural varianti191 – 1911E → K.1 Publication
Corresponds to variant rs61742964 [ dbSNP | Ensembl ].
VAR_060702
Natural varianti213 – 2131I → N.1 Publication
Corresponds to variant rs71647894 [ dbSNP | Ensembl ].
VAR_060703
Natural varianti367 – 3671R → W.1 Publication
Corresponds to variant rs61743167 [ dbSNP | Ensembl ].
VAR_060704
Natural varianti523 – 5231A → V.1 Publication
VAR_060705
Natural varianti555 – 5551I → V.1 Publication
Corresponds to variant rs8059252 [ dbSNP | Ensembl ].
VAR_060706

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 361361Missing in isoform 2. 1 PublicationVSP_044994Add
BLAST

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.3. human. [Q6UWW8-1]

Polymorphism databases

DMDMi74758561.

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. Positions 34-548.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117043. 3 interactions.
IntActiQ6UWW8. 1 interaction.
STRINGi9606.ENSP00000304782.

PTM databases

PhosphoSiteiQ6UWW8.

Polymorphism databases

DMDMi74758561.

Proteomic databases

MaxQBiQ6UWW8.
PaxDbiQ6UWW8.
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.3. human. [Q6UWW8-1]

Organism-specific databases

CTDi23491.
GeneCardsiGC16P066995.
HGNCiHGNC:1865. CES3.
HPAiHPA041008.
HPA041307.
MIMi605279. gene.
neXtProtiNX_Q6UWW8.
PharmGKBiPA26418.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG2272.
GeneTreeiENSGT00760000118946.
HOGENOMiHOG000091866.
HOVERGENiHBG008839.
InParanoidiQ6UWW8.
KOiK15743.
OMAiMQFWAET.
OrthoDBiEOG7RBZ7R.
PhylomeDBiQ6UWW8.
TreeFamiTF315470.

Enzyme and pathway databases

BioCyciMetaCyc:HS10576-MONOMER.
SABIO-RKQ6UWW8.

Miscellaneous databases

GeneWikiiCarboxylesterase_3.
GenomeRNAii23491.
NextBioi45851.
PROiQ6UWW8.
SOURCEiSearch...

Gene expression databases

BgeeiQ6UWW8.
CleanExiHS_CES3.
ExpressionAtlasiQ6UWW8. baseline and differential.
GenevestigatoriQ6UWW8.

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...

Publicationsi

« Hide 'large scale' publications
  1. "Hydrolysis of irinotecan and its oxidative metabolites, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino] carbonyloxycamptothecin and 7-ethyl-10-[4-(1-piperidino)-1-amino]-carbonyloxycamptothecin, by human carboxylesterases CES1A1, CES2, and a newly expressed carboxylesterase isoenzyme, CES3."
    Sanghani S.P., Quinney S.K., Fredenburg T.B., Davis W.I., Murry D.J., Bosron W.F.
    Drug Metab. Dispos. 32:505-511(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), GLYCOSYLATION, TISSUE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES.
    Tissue: Liver.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Colon mucosa.
  4. NIEHS SNPs program
    Submitted (FEB-2008) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ILE-129; THR-151; HIS-160; LYS-191; ASN-213; TRP-367; VAL-523 AND VAL-555.
  5. "The sequence and analysis of duplication-rich human chromosome 16."
    Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.
    , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
    Nature 432:988-994(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Eye.
  8. "Carboxylesterases expressed in human colon tumor tissue and their role in CPT-11 hydrolysis."
    Sanghani S.P., Quinney S.K., Fredenburg T.B., Sun Z., Davis W.I., Murry D.J., Cummings O.W., Seitz D.E., Bosron W.F.
    Clin. Cancer Res. 9:4983-4991(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  9. "Hydrolysis of capecitabine to 5'-deoxy-5-fluorocytidine by human carboxylesterases and inhibition by loperamide."
    Quinney S.K., Sanghani S.P., Davis W.I., Hurley T.D., Sun Z., Murry D.J., Bosron W.F.
    J. Pharmacol. Exp. Ther. 313:1011-1016(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  10. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
    Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
    J. Proteome Res. 8:651-661(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-105.
    Tissue: Liver.

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: March 4, 2015
This is version 100 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

External Data

Dasty 3

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 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.