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Q6UWW8 (EST3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 92. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Carboxylesterase 3

EC=3.1.1.1
Alternative name(s):
Liver carboxylesterase 31 homolog
Gene names
Name:CES3
ORF Names:UNQ869/PRO1887
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length571 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 activity

A carboxylic ester + H2O = an alcohol + a carboxylate.

Subcellular location

Endoplasmic reticulum lumen By similarity.

Tissue specificity

Expressed in liver, colon and small intestine. Ref.1 Ref.8 Ref.9

Post-translational modification

N-glycosylated. Ref.1

Sequence similarities

Belongs to the type-B carboxylesterase/lipase family.

Biophysicochemical properties

Kinetic parameters:

KM=137 µM for 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin Ref.1

KM=460 µM for 7-ethyl-10-[4-(1-piperidino)-1-amino]-carbonyloxycamptothecin

Ontologies

Keywords
   Cellular componentEndoplasmic reticulum
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal
   Molecular functionHydrolase
Serine esterase
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Cellular_componentendoplasmic reticulum lumen

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular vesicular exosome

Inferred from direct assay PubMed 19199708. Source: UniProt

   Molecular_functioncarboxylic ester hydrolase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q6UWW8-1)

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.
Isoform 2 (identifier: Q6UWW8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-361: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626 Potential
Chain27 – 571545Carboxylesterase 3
PRO_0000305191

Regions

Motif568 – 5714Prevents secretion from ER Potential

Sites

Active site2291Acyl-ester intermediate By similarity
Active site3471Charge relay system By similarity
Active site4601Charge relay system By similarity

Amino acid modifications

Glycosylation1051N-linked (GlcNAc...) Ref.10
Disulfide bond97 ↔ 124 By similarity
Disulfide bond281 ↔ 292 By similarity

Natural variations

Alternative sequence1 – 361361Missing in isoform 2.
VSP_044994
Natural variant1291V → I. Ref.4
Corresponds to variant rs61745806 [ dbSNP | Ensembl ].
VAR_060699
Natural variant1511A → T. Ref.4
Corresponds to variant rs71647891 [ dbSNP | Ensembl ].
VAR_060700
Natural variant1601Y → H. Ref.4
Corresponds to variant rs71647892 [ dbSNP | Ensembl ].
VAR_060701
Natural variant1911E → K. Ref.4
Corresponds to variant rs61742964 [ dbSNP | Ensembl ].
VAR_060702
Natural variant2131I → N. Ref.4
Corresponds to variant rs71647894 [ dbSNP | Ensembl ].
VAR_060703
Natural variant3671R → W. Ref.4
Corresponds to variant rs61743167 [ dbSNP | Ensembl ].
VAR_060704
Natural variant5231A → V. Ref.4
VAR_060705
Natural variant5551I → V. Ref.4
Corresponds to variant rs8059252 [ dbSNP | Ensembl ].
VAR_060706

Experimental info

Sequence conflict3721A → S in BAB15123. Ref.3
Sequence conflict481 – 4833Missing in AAH53670. Ref.7

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 5, 2004. Version 1.
Checksum: F2200968FDE072D2

FASTA57162,282
        10         20         30         40         50         60 
MERAVRVESG VLVGVVCLLL ACPATATGPE VAQPEVDTTL GRVRGRQVGV KGTDRLVNVF 

        70         80         90        100        110        120 
LGIPFAQPPL GPDRFSAPHP AQPWEGVRDA STAPPMCLQD VESMNSSRFV LNGKQQIFSV 

       130        140        150        160        170        180 
SEDCLVLNVY SPAEVPAGSG RPVMVWVHGG ALITGAATSY DGSALAAYGD VVVVTVQYRL 

       190        200        210        220        230        240 
GVLGFFSTGD EHAPGNQGFL DVVAALRWVQ ENIAPFGGDL NCVTVFGGSA GGSIISGLVL 

       250        260        270        280        290        300 
SPVAAGLFHR AITQSGVITT PGIIDSHPWP LAQKIANTLA CSSSSPAEMV QCLQQKEGEE 

       310        320        330        340        350        360 
LVLSKKLKNT IYPLTVDGTV FPKSPKELLK EKPFHSVPFL MGVNNHEFSW LIPRGWGLLD 

       370        380        390        400        410        420 
TMEQMSREDM LAISTPVLTS LDVPPEMMPT VIDEYLGSNS DAQAKCQAFQ EFMGDVFINV 

       430        440        450        460        470        480 
PTVSFSRYLR DSGSPVFFYE FQHRPSSFAK IKPAWVKADH GAEGAFVFGG PFLMDESSRL 

       490        500        510        520        530        540 
AFPEATEEEK QLSLTMMAQW THFARTGDPN SKALPPWPQF NQAEQYLEIN PVPRAGQKFR 

       550        560        570 
EAWMQFWSET LPSKIQQWHQ KQKNRKAQED L 

« Hide

Isoform 2 [UniParc].

Checksum: 875CDDA899639F65
Show »

FASTA21024,106

References

« Hide 'large scale' references
[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(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), GLYCOSYLATION, TISSUE SPECIFICITY, BIOPHYSICOCHEMICAL PROPERTIES.
Tissue: Liver.
[2]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Colon mucosa.
[4]NIEHS SNPs program
Submitted (MAR-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. expand/collapse author list , 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(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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(2004) [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(2003) [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(2005) [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(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-105.
Tissue: Liver.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001172105.1. NM_001185176.1.
NP_001172106.1. NM_001185177.1.
NP_079198.2. NM_024922.5.
UniGeneHs.268700.

3D structure databases

ProteinModelPortalQ6UWW8.
SMRQ6UWW8. Positions 34-548.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117043. 1 interaction.
IntActQ6UWW8. 1 interaction.
STRING9606.ENSP00000304782.

Protein family/group databases

MEROPSS09.958.

PTM databases

PhosphoSiteQ6UWW8.

Polymorphism databases

DMDM74758561.

Proteomic databases

PaxDbQ6UWW8.
PRIDEQ6UWW8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000303334; ENSP00000304782; ENSG00000172828. [Q6UWW8-1]
ENST00000394037; ENSP00000377602; ENSG00000172828.
ENST00000543856; ENSP00000445559; ENSG00000172828. [Q6UWW8-2]
GeneID23491.
KEGGhsa:23491.
UCSCuc002eqt.3. human. [Q6UWW8-1]

Organism-specific databases

CTD23491.
GeneCardsGC16P066995.
HGNCHGNC:1865. CES3.
HPAHPA041008.
HPA041307.
MIM605279. gene.
neXtProtNX_Q6UWW8.
PharmGKBPA26418.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2272.
HOGENOMHOG000091866.
HOVERGENHBG008839.
InParanoidQ6UWW8.
KOK15743.
OMAQFWSETL.
OrthoDBEOG7RBZ7R.
PhylomeDBQ6UWW8.
TreeFamTF315470.

Enzyme and pathway databases

BioCycMetaCyc:HS10576-MONOMER.
SABIO-RKQ6UWW8.

Gene expression databases

ArrayExpressQ6UWW8.
BgeeQ6UWW8.
CleanExHS_CES3.
GenevestigatorQ6UWW8.

Family and domain databases

InterProIPR002018. CarbesteraseB.
IPR019826. Carboxylesterase_B_AS.
[Graphical view]
PfamPF00135. COesterase. 1 hit.
[Graphical view]
PROSITEPS00122. CARBOXYLESTERASE_B_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCarboxylesterase_3.
GenomeRNAi23491.
NextBio45851.
PROQ6UWW8.
SOURCESearch...

Entry information

Entry nameEST3_HUMAN
AccessionPrimary (citable) accession number: Q6UWW8
Secondary accession number(s): B2Z3W9 expand/collapse secondary AC list , F5H242, Q7Z6J1, Q9H6X7
Entry history
Integrated into UniProtKB/Swiss-Prot: October 2, 2007
Last sequence update: July 5, 2004
Last modified: April 16, 2014
This is version 92 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM