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Q6UWW8

- EST3_HUMAN

UniProt

Q6UWW8 - EST3_HUMAN

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Protein
Carboxylesterase 3
Gene
CES3, UNQ869/PRO1887
Organism
Homo sapiens (Human)
Status
Reviewed - 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.

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]-carbonyloxycamptothecin

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei229 – 2291Acyl-ester intermediate By similarity
Active sitei347 – 3471Charge relay system By similarity
Active sitei460 – 4601Charge relay system By similarity

GO - Molecular functioni

  1. carboxylic ester hydrolase activity Source: UniProtKB-EC
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Serine esterase

Enzyme and pathway databases

BioCyciMetaCyc:HS10576-MONOMER.
SABIO-RKQ6UWW8.

Protein family/group databases

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
ProteomesiUP000005640: Chromosome 16

Organism-specific databases

HGNCiHGNC:1865. CES3.

Subcellular locationi

GO - Cellular componenti

  1. endoplasmic reticulum lumen Source: UniProtKB-SubCell
  2. extracellular vesicular exosome Source: UniProt
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 – 2626 Reviewed prediction
Add
BLAST
Chaini27 – 571545Carboxylesterase 3
PRO_0000305191Add
BLAST

Amino acid modifications

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

Post-translational modificationi

N-glycosylated.1 Publication

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

ArrayExpressiQ6UWW8.
BgeeiQ6UWW8.
CleanExiHS_CES3.
GenevestigatoriQ6UWW8.

Organism-specific databases

HPAiHPA041008.
HPA041307.

Interactioni

Protein-protein interaction databases

BioGridi117043. 1 interaction.
IntActiQ6UWW8. 1 interaction.
STRINGi9606.ENSP00000304782.

Structurei

3D structure databases

ProteinModelPortaliQ6UWW8.
SMRiQ6UWW8. Positions 34-548.

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi568 – 5714Prevents secretion from ER Reviewed prediction

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiCOG2272.
HOGENOMiHOG000091866.
HOVERGENiHBG008839.
InParanoidiQ6UWW8.
KOiK15743.
OMAiQFWSETL.
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. Align

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

MERAVRVESG VLVGVVCLLL ACPATATGPE VAQPEVDTTL GRVRGRQVGV    50
KGTDRLVNVF LGIPFAQPPL GPDRFSAPHP AQPWEGVRDA STAPPMCLQD 100
VESMNSSRFV LNGKQQIFSV SEDCLVLNVY SPAEVPAGSG RPVMVWVHGG 150
ALITGAATSY DGSALAAYGD VVVVTVQYRL GVLGFFSTGD EHAPGNQGFL 200
DVVAALRWVQ ENIAPFGGDL NCVTVFGGSA GGSIISGLVL SPVAAGLFHR 250
AITQSGVITT PGIIDSHPWP LAQKIANTLA CSSSSPAEMV QCLQQKEGEE 300
LVLSKKLKNT IYPLTVDGTV FPKSPKELLK EKPFHSVPFL MGVNNHEFSW 350
LIPRGWGLLD TMEQMSREDM LAISTPVLTS LDVPPEMMPT VIDEYLGSNS 400
DAQAKCQAFQ EFMGDVFINV PTVSFSRYLR DSGSPVFFYE FQHRPSSFAK 450
IKPAWVKADH GAEGAFVFGG PFLMDESSRL AFPEATEEEK QLSLTMMAQW 500
THFARTGDPN SKALPPWPQF NQAEQYLEIN PVPRAGQKFR EAWMQFWSET 550
LPSKIQQWHQ KQKNRKAQED L 571
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

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.
VSP_044994Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti372 – 3721A → S in BAB15123. 1 Publication
Sequence conflicti481 – 4833Missing in AAH53670. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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]
ENST00000394037; ENSP00000377602; ENSG00000172828.
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:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS10826.1. [Q6UWW8-1 ]
CCDS54023.1. [Q6UWW8-2 ]
RefSeqi NP_001172105.1. NM_001185176.1. [Q6UWW8-2 ]
NP_001172106.1. NM_001185177.1.
NP_079198.2. NM_024922.5. [Q6UWW8-1 ]
UniGenei Hs.268700.

3D structure databases

ProteinModelPortali Q6UWW8.
SMRi Q6UWW8. Positions 34-548.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 117043. 1 interaction.
IntActi Q6UWW8. 1 interaction.
STRINGi 9606.ENSP00000304782.

Protein family/group databases

MEROPSi S09.958.

PTM databases

PhosphoSitei Q6UWW8.

Polymorphism databases

DMDMi 74758561.

Proteomic databases

MaxQBi Q6UWW8.
PaxDbi Q6UWW8.
PRIDEi Q6UWW8.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000303334 ; ENSP00000304782 ; ENSG00000172828 . [Q6UWW8-1 ]
ENST00000394037 ; ENSP00000377602 ; ENSG00000172828 .
ENST00000543856 ; ENSP00000445559 ; ENSG00000172828 . [Q6UWW8-2 ]
GeneIDi 23491.
KEGGi hsa:23491.
UCSCi uc002eqt.3. human. [Q6UWW8-1 ]

Organism-specific databases

CTDi 23491.
GeneCardsi GC16P066995.
HGNCi HGNC:1865. CES3.
HPAi HPA041008.
HPA041307.
MIMi 605279. gene.
neXtProti NX_Q6UWW8.
PharmGKBi PA26418.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG2272.
HOGENOMi HOG000091866.
HOVERGENi HBG008839.
InParanoidi Q6UWW8.
KOi K15743.
OMAi QFWSETL.
OrthoDBi EOG7RBZ7R.
PhylomeDBi Q6UWW8.
TreeFami TF315470.

Enzyme and pathway databases

BioCyci MetaCyc:HS10576-MONOMER.
SABIO-RK Q6UWW8.

Miscellaneous databases

GeneWikii Carboxylesterase_3.
GenomeRNAii 23491.
NextBioi 45851.
PROi Q6UWW8.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q6UWW8.
Bgeei Q6UWW8.
CleanExi HS_CES3.
Genevestigatori Q6UWW8.

Family and domain databases

Gene3Di 3.40.50.1820. 1 hit.
InterProi IPR029058. AB_hydrolase.
IPR002018. CarbesteraseB.
IPR019826. Carboxylesterase_B_AS.
[Graphical view ]
Pfami PF00135. COesterase. 1 hit.
[Graphical view ]
SUPFAMi SSF53474. SSF53474. 2 hits.
PROSITEi PS00122. CARBOXYLESTERASE_B_1. 1 hit.
[Graphical view ]
ProtoNeti Search...

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(2004) [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(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.
    , 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. 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.

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: July 9, 2014
This is version 95 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

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