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O00748 (EST2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 119. 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:
Cocaine esterase

EC=3.1.1.84
Alternative name(s):
Carboxylesterase 2
Short name=CE-2
Short name=hCE-2
EC=3.1.1.1
Methylumbelliferyl-acetate deacetylase 2
EC=3.1.1.56
Gene names
Name:CES2
Synonyms:ICE
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length559 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 high catalytic efficiency for hydrolysis of cocaine, 4-methylumbelliferyl acetate, heroin and 6-monoacetylmorphine. Ref.2

Catalytic activity

Cocaine + H2O = ecgonine methyl ester + benzoate. Ref.2

A carboxylic ester + H2O = an alcohol + a carboxylate. Ref.2

4-methylumbelliferyl acetate + H2O = 4-methylumbelliferone + acetate. Ref.2

Subunit structure

Monomer. Ref.2

Subcellular location

Endoplasmic reticulum lumen By similarity.

Tissue specificity

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. Ref.1

Post-translational modification

Glycosylated. Ref.2

Sequence similarities

Belongs to the type-B carboxylesterase/lipase family.

Biophysicochemical properties

Kinetic parameters:

KM=0.39 mM for cocaine Ref.2

KM=0.15 mM for 4-methylumbelliferyl acetate

KM=6.8 mM for heroin

KM=0.13 mM for 6-monoacetylmorphine

Sequence caution

The sequence AAH32095.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence AAW29943.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence CAD28531.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence CAD98009.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O00748-1)

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: O00748-2)

The sequence of this isoform differs from the canonical sequence as follows:
     458-474: GDELPFVFRSFFGGNYI → V

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626 Ref.2
Chain27 – 559533Cocaine esterase
PRO_0000008572

Regions

Motif556 – 5594Prevents secretion from ER Potential

Sites

Active site2281Acyl-ester intermediate By similarity
Active site3451Charge relay system By similarity
Active site4571Charge relay system By similarity

Amino acid modifications

Modified residue271Pyrrolidone carboxylic acid By similarity
Glycosylation1111N-linked (GlcNAc...) Ref.8
Glycosylation2761N-linked (GlcNAc...) Potential
Disulfide bond95 ↔ 123 By similarity
Disulfide bond280 ↔ 291 By similarity

Natural variations

Alternative sequence458 – 47417GDELP…GGNYI → V in isoform 2.
VSP_010161
Natural variant341R → W. Ref.11
VAR_018396
Natural variant2061R → H. Ref.10
VAR_018397

Experimental info

Sequence conflict2 – 109Missing AA sequence Ref.2
Sequence conflict3851F → S in CAD98009. Ref.4
Sequence conflict5191Q → R in CAD98009. Ref.4

Sequences

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

Last modified July 1, 1997. Version 1.
Checksum: E2EBCABA2995339A

FASTA55961,807
        10         20         30         40         50         60 
MRLHRLRARL SAVACGLLLL LVRGQGQDSA SPIRTTHTGQ VLGSLVHVKG ANAGVQTFLG 

        70         80         90        100        110        120 
IPFAKPPLGP LRFAPPEPPE SWSGVRDGTT HPAMCLQDLT AVESEFLSQF NMTFPSDSMS 

       130        140        150        160        170        180 
EDCLYLSIYT PAHSHEGSNL PVMVWIHGGA LVFGMASLYD GSMLAALENV VVVIIQYRLG 

       190        200        210        220        230        240 
VLGFFSTGDK HATGNWGYLD QVAALRWVQQ NIAHFGGNPD RVTIFGESAG GTSVSSLVVS 

       250        260        270        280        290        300 
PISQGLFHGA IMESGVALLP GLIASSADVI STVVANLSAC DQVDSEALVG CLRGKSKEEI 

       310        320        330        340        350        360 
LAINKPFKMI PGVVDGVFLP RHPQELLASA DFQPVPSIVG VNNNEFGWLI PKVMRIYDTQ 

       370        380        390        400        410        420 
KEMDREASQA ALQKMLTLLM LPPTFGDLLR EEYIGDNGDP QTLQAQFQEM MADSMFVIPA 

       430        440        450        460        470        480 
LQVAHFQCSR APVYFYEFQH QPSWLKNIRP PHMKADHGDE LPFVFRSFFG GNYIKFTEEE 

       490        500        510        520        530        540 
EQLSRKMMKY WANFARNGNP NGEGLPHWPL FDQEEQYLQL NLQPAVGRAL KAHRLQFWKK 

       550 
ALPQKIQELE EPEERHTEL 

« Hide

Isoform 2 [UniParc].

Checksum: 4F14FE06766F0F7E
Show »

FASTA54359,959

References

« Hide 'large scale' references
[1]"Molecular cloning and characterization of a novel putative carboxylesterase, present in human intestine and liver."
Schwer H., Langmann T., Daig R., Becker A., Aslanidis C., Schmitz G.
Biochem. Biophys. Res. Commun. 233:117-120(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Small intestine.
[2]"Purification and cloning of a broad substrate specificity human liver carboxylesterase that catalyzes the hydrolysis of cocaine and heroin."
Pindel E.V., Kedishvili N.Y., Abraham T.L., Brzezinski M.R., Zhang J., Dean R.A., Bosron W.F.
J. Biol. Chem. 272:14769-14775(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 27-34; 57-70; 227-235; 300-305; 346-351; 447-454; 458-466; 535-540 AND 546-551, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, GLYCOSYLATION, BIOPHYSICOCHEMICAL PROPERTIES.
Tissue: Liver.
[3]"Molecular cloning and expression of a human liver cDNA encoding a novel carboxylesterase."
Sone T., Ishida Y., Takabatake E., Wang C., Pohl L., Isobe M.
Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Liver.
[4]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Endometrial adenocarcinoma and Testis.
[5]NIEHS SNPs program
Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]"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].
[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: Skin.
[8]"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-111.
Tissue: Liver.
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Catalog of 680 variations among eight cytochrome p450 (CYP) genes, nine esterase genes, and two other genes in the Japanese population."
Saito S., Iida A., Sekine A., Kawauchi S., Higuchi S., Ogawa C., Nakamura Y.
J. Hum. Genet. 48:249-270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HIS-206.
[11]"Twelve novel single nucleotide polymorphisms in the CES2 gene encoding human carboxylesterase 2 (hCE-2)."
Kim S.-R., Nakamura T., Saito Y., Sai K., Nakajima T., Saito H., Shirao K., Minami H., Ohtsu A., Yoshida T., Saijo N., Ozawa S., Sawada J.
Drug Metab. Pharmacokinet. 18:327-332(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TRP-34.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y09616 mRNA. Translation: CAA70831.1.
D50579 mRNA. Translation: BAA23606.1.
U60553 mRNA. Translation: AAB03611.1.
AL713761 mRNA. Translation: CAD28531.1. Different initiation.
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.
PIRJC5408.
RefSeqNP_003860.2. NM_003869.5.
NP_932327.1. NM_198061.2.
UniGeneHs.282975.

3D structure databases

ProteinModelPortalO00748.
SMRO00748. Positions 32-544.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActO00748. 1 interaction.
STRING9606.ENSP00000317842.

Chemistry

BindingDBO00748.
ChEMBLCHEMBL3180.

Protein family/group databases

MEROPSS09.984.

PTM databases

PhosphoSiteO00748.

Proteomic databases

PaxDbO00748.
PRIDEO00748.

Protocols and materials databases

DNASU8824.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000317091; ENSP00000317842; ENSG00000172831.
ENST00000417689; ENSP00000394452; ENSG00000172831.
GeneID8824.
KEGGhsa:8824.
UCSCuc002eqs.3. human. [O00748-1]

Organism-specific databases

CTD8824.
GeneCardsGC16P066969.
HGNCHGNC:1864. CES2.
HPAHPA018897.
MIM605278. gene.
neXtProtNX_O00748.
PharmGKBPA377.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2272.
HOVERGENHBG008839.
InParanoidO00748.
KOK03927.
OrthoDBEOG7RBZ7R.
PhylomeDBO00748.
TreeFamTF315470.

Enzyme and pathway databases

BRENDA3.1.1.1. 2681.
SABIO-RKO00748.

Gene expression databases

ArrayExpressO00748.
BgeeO00748.
CleanExHS_CES2.
GenevestigatorO00748.

Family and domain databases

InterProIPR002018. CarbesteraseB.
IPR019826. Carboxylesterase_B_AS.
IPR019819. Carboxylesterase_B_CS.
[Graphical view]
PfamPF00135. COesterase. 1 hit.
[Graphical view]
PROSITEPS00122. CARBOXYLESTERASE_B_1. 1 hit.
PS00941. CARBOXYLESTERASE_B_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCES2. human.
GeneWikiCarboxylesterase_2.
GenomeRNAi8824.
NextBio33104.
PROO00748.
SOURCESearch...

Entry information

Entry nameEST2_HUMAN
AccessionPrimary (citable) accession number: O00748
Secondary accession number(s): Q16859 expand/collapse secondary AC list , Q5MAB8, Q7Z366, Q8IUP4, Q8TCP8
Entry history
Integrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: July 1, 1997
Last modified: April 16, 2014
This is version 119 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