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O00748

- EST2_HUMAN

UniProt

O00748 - EST2_HUMAN

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Protein
Cocaine esterase
Gene
CES2, ICE
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 high catalytic efficiency for hydrolysis of cocaine, 4-methylumbelliferyl acetate, heroin and 6-monoacetylmorphine.1 Publication

Catalytic activityi

Cocaine + H2O = ecgonine methyl ester + benzoate.1 Publication
A carboxylic ester + H2O = an alcohol + a carboxylate.1 Publication
4-methylumbelliferyl acetate + H2O = 4-methylumbelliferone + acetate.1 Publication

Kineticsi

  1. KM=0.39 mM for cocaine1 Publication
  2. KM=0.15 mM for 4-methylumbelliferyl acetate
  3. KM=6.8 mM for heroin
  4. KM=0.13 mM for 6-monoacetylmorphine

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei228 – 2281Acyl-ester intermediate By similarity
Active sitei345 – 3451Charge relay system By similarity
Active sitei457 – 4571Charge relay system By similarity

GO - Molecular functioni

  1. carboxylic ester hydrolase activity Source: ProtInc
  2. methylumbelliferyl-acetate deacetylase activity Source: UniProtKB-EC
Complete GO annotation...

GO - Biological processi

  1. catabolic process Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Serine esterase

Enzyme and pathway databases

BRENDAi3.1.1.1. 2681.
SABIO-RKO00748.

Protein family/group databases

MEROPSiS09.984.

Names & Taxonomyi

Protein namesi
Recommended name:
Cocaine esterase (EC:3.1.1.84)
Alternative name(s):
Carboxylesterase 2 (EC:3.1.1.1)
Short name:
CE-2
Short name:
hCE-2
Methylumbelliferyl-acetate deacetylase 2 (EC:3.1.1.56)
Gene namesi
Name:CES2
Synonyms:ICE
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 16

Organism-specific databases

HGNCiHGNC:1864. CES2.

Subcellular locationi

GO - Cellular componenti

  1. endoplasmic reticulum Source: ProtInc
  2. endoplasmic reticulum lumen Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA377.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 26261 Publication
Add
BLAST
Chaini27 – 559533Cocaine esterase
PRO_0000008572Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei27 – 271Pyrrolidone carboxylic acid By similarity
Disulfide bondi95 ↔ 123 By similarity
Glycosylationi111 – 1111N-linked (GlcNAc...)1 Publication
Glycosylationi276 – 2761N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi280 ↔ 291 By similarity

Post-translational modificationi

Glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Pyrrolidone carboxylic acid

Proteomic databases

MaxQBiO00748.
PaxDbiO00748.
PRIDEiO00748.

PTM databases

PhosphoSiteiO00748.

Expressioni

Tissue specificityi

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.1 Publication

Gene expression databases

ArrayExpressiO00748.
BgeeiO00748.
CleanExiHS_CES2.
GenevestigatoriO00748.

Organism-specific databases

HPAiHPA018897.

Interactioni

Subunit structurei

Monomer.1 Publication

Protein-protein interaction databases

IntActiO00748. 1 interaction.
STRINGi9606.ENSP00000317842.

Structurei

3D structure databases

ProteinModelPortaliO00748.
SMRiO00748. Positions 3-546.

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi556 – 5594Prevents secretion from ER Reviewed prediction

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiCOG2272.
HOVERGENiHBG008839.
InParanoidiO00748.
KOiK03927.
OrthoDBiEOG7RBZ7R.
PhylomeDBiO00748.
TreeFamiTF315470.

Family and domain databases

Gene3Di3.40.50.1820. 1 hit.
InterProiIPR029058. AB_hydrolase.
IPR002018. CarbesteraseB.
IPR019826. Carboxylesterase_B_AS.
IPR019819. Carboxylesterase_B_CS.
[Graphical view]
PfamiPF00135. COesterase. 1 hit.
[Graphical view]
SUPFAMiSSF53474. SSF53474. 1 hit.
PROSITEiPS00122. CARBOXYLESTERASE_B_1. 1 hit.
PS00941. CARBOXYLESTERASE_B_2. 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: O00748-1) [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

MRLHRLRARL SAVACGLLLL LVRGQGQDSA SPIRTTHTGQ VLGSLVHVKG    50
ANAGVQTFLG IPFAKPPLGP LRFAPPEPPE SWSGVRDGTT HPAMCLQDLT 100
AVESEFLSQF NMTFPSDSMS EDCLYLSIYT PAHSHEGSNL PVMVWIHGGA 150
LVFGMASLYD GSMLAALENV VVVIIQYRLG VLGFFSTGDK HATGNWGYLD 200
QVAALRWVQQ NIAHFGGNPD RVTIFGESAG GTSVSSLVVS PISQGLFHGA 250
IMESGVALLP GLIASSADVI STVVANLSAC DQVDSEALVG CLRGKSKEEI 300
LAINKPFKMI PGVVDGVFLP RHPQELLASA DFQPVPSIVG VNNNEFGWLI 350
PKVMRIYDTQ KEMDREASQA ALQKMLTLLM LPPTFGDLLR EEYIGDNGDP 400
QTLQAQFQEM MADSMFVIPA LQVAHFQCSR APVYFYEFQH QPSWLKNIRP 450
PHMKADHGDE LPFVFRSFFG GNYIKFTEEE EQLSRKMMKY WANFARNGNP 500
NGEGLPHWPL FDQEEQYLQL NLQPAVGRAL KAHRLQFWKK ALPQKIQELE 550
EPEERHTEL 559
Length:559
Mass (Da):61,807
Last modified:July 1, 1997 - v1
Checksum:iE2EBCABA2995339A
GO
Isoform 2 (identifier: O00748-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:543
Mass (Da):59,959
Checksum:i4F14FE06766F0F7E
GO

Sequence cautioni

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.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti34 – 341R → W.1 Publication
VAR_018396
Natural varianti206 – 2061R → H.1 Publication
VAR_018397

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei458 – 47417GDELP…GGNYI → V in isoform 2.
VSP_010161Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti2 – 109Missing AA sequence 1 Publication
Sequence conflicti180 – 1801G → S in BAF83171. 1 Publication
Sequence conflicti239 – 2391V → M in BAF83171. 1 Publication
Sequence conflicti385 – 3851F → S in CAD98009. 1 Publication
Sequence conflicti519 – 5191Q → R in CAD98009. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Y09616 mRNA. Translation: CAA70831.1.
D50579 mRNA. Translation: BAA23606.1.
U60553 mRNA. Translation: AAB03611.1.
AL713761 mRNA. Translation: CAD28531.1. Different initiation.
AK290482 mRNA. Translation: BAF83171.1.
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.
PIRiJC5408.
RefSeqiNP_003860.2. NM_003869.5.
NP_932327.1. NM_198061.2.
UniGeneiHs.282975.

Genome annotation databases

EnsembliENST00000317091; ENSP00000317842; ENSG00000172831.
ENST00000417689; ENSP00000394452; ENSG00000172831.
GeneIDi8824.
KEGGihsa:8824.
UCSCiuc002eqs.3. human. [O00748-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Y09616 mRNA. Translation: CAA70831.1 .
D50579 mRNA. Translation: BAA23606.1 .
U60553 mRNA. Translation: AAB03611.1 .
AL713761 mRNA. Translation: CAD28531.1 . Different initiation.
AK290482 mRNA. Translation: BAF83171.1 .
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.
PIRi JC5408.
RefSeqi NP_003860.2. NM_003869.5.
NP_932327.1. NM_198061.2.
UniGenei Hs.282975.

3D structure databases

ProteinModelPortali O00748.
SMRi O00748. Positions 3-546.
ModBasei Search...

Protein-protein interaction databases

IntActi O00748. 1 interaction.
STRINGi 9606.ENSP00000317842.

Chemistry

BindingDBi O00748.
ChEMBLi CHEMBL3180.

Protein family/group databases

MEROPSi S09.984.

PTM databases

PhosphoSitei O00748.

Proteomic databases

MaxQBi O00748.
PaxDbi O00748.
PRIDEi O00748.

Protocols and materials databases

DNASUi 8824.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000317091 ; ENSP00000317842 ; ENSG00000172831 .
ENST00000417689 ; ENSP00000394452 ; ENSG00000172831 .
GeneIDi 8824.
KEGGi hsa:8824.
UCSCi uc002eqs.3. human. [O00748-1 ]

Organism-specific databases

CTDi 8824.
GeneCardsi GC16P066969.
HGNCi HGNC:1864. CES2.
HPAi HPA018897.
MIMi 605278. gene.
neXtProti NX_O00748.
PharmGKBi PA377.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG2272.
HOVERGENi HBG008839.
InParanoidi O00748.
KOi K03927.
OrthoDBi EOG7RBZ7R.
PhylomeDBi O00748.
TreeFami TF315470.

Enzyme and pathway databases

BRENDAi 3.1.1.1. 2681.
SABIO-RK O00748.

Miscellaneous databases

ChiTaRSi CES2. human.
GeneWikii Carboxylesterase_2.
GenomeRNAii 8824.
NextBioi 33104.
PROi O00748.
SOURCEi Search...

Gene expression databases

ArrayExpressi O00748.
Bgeei O00748.
CleanExi HS_CES2.
Genevestigatori O00748.

Family and domain databases

Gene3Di 3.40.50.1820. 1 hit.
InterProi IPR029058. AB_hydrolase.
IPR002018. CarbesteraseB.
IPR019826. Carboxylesterase_B_AS.
IPR019819. Carboxylesterase_B_CS.
[Graphical view ]
Pfami PF00135. COesterase. 1 hit.
[Graphical view ]
SUPFAMi SSF53474. SSF53474. 1 hit.
PROSITEi PS00122. CARBOXYLESTERASE_B_1. 1 hit.
PS00941. CARBOXYLESTERASE_B_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. "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 1).
    Tissue: Brain.
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Endometrial adenocarcinoma and Testis.
  6. NIEHS SNPs program
    Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  7. "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].
  8. "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.
  9. "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.
  10. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  11. "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.
  12. "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.

Entry informationi

Entry nameiEST2_HUMAN
AccessioniPrimary (citable) accession number: O00748
Secondary accession number(s): A8K367
, Q16859, Q5MAB8, Q7Z366, Q8IUP4, Q8TCP8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: July 1, 1997
Last modified: July 9, 2014
This is version 122 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, Direct protein sequencing, 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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