O00748 (EST2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	559 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal
Molecular function	Hydrolase Serine esterase
PTM	Disulfide bond Glycoprotein Pyrrolidone carboxylic acid
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	catabolic process Traceable author statement Ref.2. Source: ProtInc
Cellular_component	endoplasmic reticulum Traceable author statement Ref.1. Source: ProtInc endoplasmic reticulum lumen Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	carboxylesterase activity Inferred from Biological aspect of Ancestor. Source: RefGenome methyl indole-3-acetate esterase activity Inferred from electronic annotation. Source: EC methyl jasmonate esterase activity Inferred from electronic annotation. Source: EC methyl salicylate esterase activity Inferred from electronic annotation. Source: EC methylumbelliferyl-acetate deacetylase activity Inferred from electronic annotation. Source: EC retinyl-palmitate esterase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 26	26	Ref.2
	Chain	27 – 559	533	Cocaine esterase		PRO_0000008572
Regions
	Motif	556 – 559	4	Prevents secretion from ER Potential
Sites
	Active site	228	1	Acyl-ester intermediate By similarity
	Active site	345	1	Charge relay system By similarity
	Active site	457	1	Charge relay system By similarity
Amino acid modifications
	Modified residue	27	1	Pyrrolidone carboxylic acid By similarity
	Glycosylation	111	1	N-linked (GlcNAc...) Ref.8
	Glycosylation	276	1	N-linked (GlcNAc...) Potential
	Disulfide bond	95 ↔ 123		By similarity
	Disulfide bond	280 ↔ 291		By similarity
Natural variations
	Alternative sequence	458 – 474	17	GDELP…GGNYI → V in isoform 2.		VSP_010161
	Natural variant	34	1	R → W. Ref.11		VAR_018396
	Natural variant	206	1	R → H. Ref.10		VAR_018397
Experimental info
	Sequence conflict	2 – 10	9	Missing AA sequence Ref.2
	Sequence conflict	385	1	F → S in CAD98009. Ref.4
	Sequence conflict	519	1	Q → R in CAD98009. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: E2EBCABA2995339A	FASTA	559	61,807
	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
	Isoform 2 [UniParc]. Checksum: 4F14FE06766F0F7E	FASTA	543	59,959
	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 PHMKADHVKF TEEEEQLSRK MMKYWANFAR 490 500 510 520 530 540 NGNPNGEGLP HWPLFDQEEQ YLQLNLQPAV GRALKAHRLQ FWKKALPQKI QELEEPEERH TEL

References

	« Hide 'large scale' referencesShow '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. , 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, MASS SPECTROMETRY. 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

NIEHS-SNPs

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.
IPI	IPI00332828. IPI00419920.
PIR	JC5408.
RefSeq	NP_003860.2. NM_003869.5. NP_932327.1. NM_198061.2.
UniGene	Hs.282975.
3D structure databases
ProteinModelPortal	O00748.
ModBase	Search...
Protein-protein interaction databases
IntAct	O00748. 1 interaction.
STRING	9606.ENSP00000317842.
Protein family/group databases
MEROPS	S09.984.
PTM databases
PhosphoSite	O00748.
Proteomic databases
PaxDb	O00748.
PRIDE	O00748.
Protocols and materials databases
DNASU	8824.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000317091; ENSP00000317842; ENSG00000172831. ENST00000417689; ENSP00000394452; ENSG00000172831.
GeneID	8824.
KEGG	hsa:8824.
UCSC	uc002eqs.3. human.
Organism-specific databases
CTD	8824.
GeneCards	GC16P066969.
HGNC	HGNC:1864. CES2.
HPA	HPA018897.
MIM	605278. gene.
neXtProt	NX_O00748.
PharmGKB	PA377.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2272.
HOVERGEN	HBG008839.
InParanoid	O00748.
KO	K03927.
OrthoDB	EOG466VM9.
Enzyme and pathway databases
BRENDA	3.1.1.1. 2681.
SABIO-RK	O00748.
Gene expression databases
ArrayExpress	O00748.
Bgee	O00748.
CleanEx	HS_CES2.
Genevestigator	O00748.
GermOnline	ENSG00000172831. Homo sapiens.
Family and domain databases
InterPro	IPR002018. CarbesteraseB. IPR019826. Carboxylesterase_B_AS. IPR019819. Carboxylesterase_B_CS. [Graphical view]
Pfam	PF00135. COesterase. 1 hit. [Graphical view]
PROSITE	PS00122. CARBOXYLESTERASE_B_1. 1 hit. PS00941. CARBOXYLESTERASE_B_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	O00748.
ChEMBL	CHEMBL3180.
ChiTaRS	CES2. human.
GenomeRNAi	8824.
NextBio	33104.
SOURCE	Search...

Entry information

Entry name

EST2_HUMAN

Accession

Primary (citable) accession number: O00748
Secondary accession number(s): Q16859 , Q5MAB8, Q7Z366, Q8IUP4, Q8TCP8

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 26, 2004
Last sequence update:	July 1, 1997
Last modified:	May 1, 2013
This is version 111 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.