UniProtKB - O00748 (EST2_HUMAN)
Cocaine esterase
CES2
Functioni
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs (PubMed:9169443).
Shows high catalytic efficiency for hydrolysis of cocaine, 4-methylumbelliferyl acetate, heroin and 6-monoacetylmorphine (PubMed:9169443).
Hydrolyzes aspirin, substrates with large alcohol group and small acyl group and endogenous lipids such as triacylglycerol (PubMed:28677105).
Converts monoacylglycerides to free fatty acids and glycerol. Hydrolyzes of 2-arachidonoylglycerol and prostaglandins (PubMed:21049984).
1 Publication2 PublicationsCatalytic activityi
- EC:3.1.1.841 Publication
- EC:3.1.1.1PROSITE-ProRule annotation1 Publication
- EC:3.1.1.561 Publication
- 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + glycerol + H+1 PublicationThis reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
Kineticsi
- KM=0.39 mM for cocaine1 Publication
- KM=0.15 mM for 4-methylumbelliferyl acetate1 Publication
- KM=6.8 mM for heroin1 Publication
- KM=46 µM for 2-arachidonoylglycerol1 Publication
- KM=750 µM for prostaglandin E2 1-glyceryl ester1 Publication
- KM=35 µM for prostaglandin F2alpha 1-glyceryl ester1 Publication
- KM=0.13 mM for 6-monoacetylmorphine1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 228 | Acyl-ester intermediatePROSITE-ProRule annotation | 1 | |
Active sitei | 345 | Charge relay systemBy similarity | 1 | |
Active sitei | 457 | Charge relay systemBy similarity | 1 |
GO - Molecular functioni
- carboxylic ester hydrolase activity Source: BHF-UCL
- methyl indole-3-acetate esterase activity Source: UniProtKB-EC
- methylumbelliferyl-acetate deacetylase activity Source: UniProtKB-EC
GO - Biological processi
- catabolic process Source: ProtInc
- prostaglandin metabolic process Source: BHF-UCL
Keywordsi
Molecular function | Hydrolase, Serine esterase |
Biological process | Lipid metabolism |
Enzyme and pathway databases
BRENDAi | 3.1.1.1, 2681 3.1.1.84, 2681 |
PathwayCommonsi | O00748 |
Reactomei | R-HSA-211945, Phase I - Functionalization of compounds |
SABIO-RKi | O00748 |
SignaLinki | O00748 |
Protein family/group databases
ESTHERi | human-CES2, Carb_B_Chordata |
MEROPSi | S09.984 |
Chemistry databases
SwissLipidsi | SLP:000001424 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:1864, CES2 |
MIMi | 605278, gene |
neXtProti | NX_O00748 |
VEuPathDBi | HostDB:ENSG00000172831 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum lumen 1 Publication
Endoplasmic reticulum
- endoplasmic reticulum Source: ProtInc
- endoplasmic reticulum lumen Source: Reactome
Other locations
- intracellular membrane-bounded organelle Source: GO_Central
Keywords - Cellular componenti
Endoplasmic reticulumPathology & Biotechi
Organism-specific databases
DisGeNETi | 8824 |
OpenTargetsi | ENSG00000172831 |
PharmGKBi | PA377 |
Miscellaneous databases
Pharosi | O00748, Tchem |
Chemistry databases
ChEMBLi | CHEMBL3180 |
DrugBanki | DB06695, Dabigatran etexilate DB14845, Filgotinib DB00762, Irinotecan DB06209, Prasugrel |
DrugCentrali | O00748 |
Genetic variation databases
BioMutai | CES2 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 26 | 1 PublicationAdd BLAST | 26 | |
ChainiPRO_0000008572 | 27 – 559 | Cocaine esteraseAdd BLAST | 533 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 27 | Pyrrolidone carboxylic acidBy similarity | 1 | |
Disulfide bondi | 95 ↔ 123 | By similarity | ||
Glycosylationi | 111 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 276 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 280 ↔ 291 | By similarity |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, Glycoprotein, Pyrrolidone carboxylic acidProteomic databases
EPDi | O00748 |
jPOSTi | O00748 |
MassIVEi | O00748 |
MaxQBi | O00748 |
PaxDbi | O00748 |
PeptideAtlasi | O00748 |
PRIDEi | O00748 |
ProteomicsDBi | 48014 [O00748-1] 48015 [O00748-2] |
PTM databases
GlyGeni | O00748, 2 sites |
iPTMneti | O00748 |
PhosphoSitePlusi | O00748 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000172831, Expressed in jejunal mucosa and 249 other tissues |
ExpressionAtlasi | O00748, baseline and differential |
Genevisiblei | O00748, HS |
Organism-specific databases
HPAi | ENSG00000172831, Tissue enhanced (intestine, liver) |
Interactioni
Subunit structurei
Monomer.
1 PublicationProtein-protein interaction databases
BioGRIDi | 114351, 26 interactors |
IntActi | O00748, 3 interactors |
STRINGi | 9606.ENSP00000317842 |
Chemistry databases
BindingDBi | O00748 |
Miscellaneous databases
RNActi | O00748, protein |
Family & Domainsi
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 556 – 559 | Prevents secretion from ERSequence analysis | 4 |
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG1516, Eukaryota |
GeneTreei | ENSGT00940000153793 |
HOGENOMi | CLU_006586_13_2_1 |
InParanoidi | O00748 |
OMAi | NIANTVC |
OrthoDBi | 754103at2759 |
PhylomeDBi | O00748 |
TreeFami | TF315470 |
Family and domain databases
Gene3Di | 3.40.50.1820, 1 hit |
InterProi | View protein in InterPro IPR029058, AB_hydrolase IPR002018, CarbesteraseB IPR019826, Carboxylesterase_B_AS IPR019819, Carboxylesterase_B_CS |
Pfami | View protein in Pfam PF00135, COesterase, 1 hit |
SUPFAMi | SSF53474, SSF53474, 1 hit |
PROSITEi | View protein in PROSITE PS00122, CARBOXYLESTERASE_B_1, 1 hit PS00941, CARBOXYLESTERASE_B_2, 1 hit |
s (4+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 4 produced by isoformsialternative splicing and alternative initiation. AlignAdd to basketThis entry has 4 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MRLHRLRARL SAVACGLLLL LVRGQGQDSA SPIRTTHTGQ VLGSLVHVKG
60 70 80 90 100
ANAGVQTFLG IPFAKPPLGP LRFAPPEPPE SWSGVRDGTT HPAMCLQDLT
110 120 130 140 150
AVESEFLSQF NMTFPSDSMS EDCLYLSIYT PAHSHEGSNL PVMVWIHGGA
160 170 180 190 200
LVFGMASLYD GSMLAALENV VVVIIQYRLG VLGFFSTGDK HATGNWGYLD
210 220 230 240 250
QVAALRWVQQ NIAHFGGNPD RVTIFGESAG GTSVSSLVVS PISQGLFHGA
260 270 280 290 300
IMESGVALLP GLIASSADVI STVVANLSAC DQVDSEALVG CLRGKSKEEI
310 320 330 340 350
LAINKPFKMI PGVVDGVFLP RHPQELLASA DFQPVPSIVG VNNNEFGWLI
360 370 380 390 400
PKVMRIYDTQ KEMDREASQA ALQKMLTLLM LPPTFGDLLR EEYIGDNGDP
410 420 430 440 450
QTLQAQFQEM MADSMFVIPA LQVAHFQCSR APVYFYEFQH QPSWLKNIRP
460 470 480 490 500
PHMKADHGDE LPFVFRSFFG GNYIKFTEEE EQLSRKMMKY WANFARNGNP
510 520 530 540 550
NGEGLPHWPL FDQEEQYLQL NLQPAVGRAL KAHRLQFWKK ALPQKIQELE
EPEERHTEL
The sequence of this isoform differs from the canonical sequence as follows:
1-1: M → MTAQSRSPTTPTFPGPSQRTPLTPCPVQTPRLGKALIHCWTDPGQPLGEQQRVRRQRTETSEPTM
The sequence of this isoform differs from the canonical sequence as follows:
1-1: M → MTAQSRSPTTPTFPGPSQRTPLTPCPVQTPRLGKALIHCWTDPGQPLGEQQRVRRQRTETSEPTM
458-474: GDELPFVFRSFFGGNYI → V
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH3BUN5 | H3BUN5_HUMAN | Cocaine esterase | CES2 | 58 | Annotation score: | ||
J3QLP1 | J3QLP1_HUMAN | Cocaine esterase | CES2 | 125 | Annotation score: | ||
J3QSC0 | J3QSC0_HUMAN | Cocaine esterase | CES2 | 201 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 2 – 10 | Missing AA sequence (PubMed:9169443).Curated | 9 | |
Sequence conflicti | 180 | G → S in BAF83171 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 239 | V → M in BAF83171 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 385 | F → S in CAD98009 (PubMed:17974005).Curated | 1 | |
Sequence conflicti | 519 | Q → R in CAD98009 (PubMed:17974005).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_018396 | 34 | R → W1 PublicationCorresponds to variant dbSNP:rs72547531Ensembl. | 1 | |
Natural variantiVAR_018397 | 206 | R → H1 PublicationCorresponds to variant dbSNP:rs8192924Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_059804 | 1 | M → MTAQSRSPTTPTFPGPSQRT PLTPCPVQTPRLGKALIHCW TDPGQPLGEQQRVRRQRTET SEPTM in isoform 3 and isoform 4. 1 Publication | 1 | |
Alternative sequenceiVSP_010161 | 458 – 474 | GDELP…GGNYI → V in isoform 2 and isoform 4. 1 PublicationAdd BLAST | 17 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Y09616 mRNA Translation: CAA70831.1 D50579 mRNA Translation: BAA23606.1 U60553 mRNA Translation: AAB03611.1 AL713761 mRNA Translation: CAD28531.1 AK290482 mRNA Translation: BAF83171.1 BX538086 mRNA Translation: CAD98009.1 AY851164 Genomic DNA Translation: AAW29943.1 AC009084 Genomic DNA No translation available. CH471092 Genomic DNA Translation: EAW83058.1 CH471092 Genomic DNA Translation: EAW83059.1 BC032095 mRNA Translation: AAH32095.1 |
CCDSi | CCDS10825.1 [O00748-1] CCDS45507.1 [O00748-2] |
PIRi | JC5408 |
RefSeqi | NP_003860.2, NM_003869.5 [O00748-1] NP_932327.1, NM_198061.2 [O00748-2] |
Genome annotation databases
Ensembli | ENST00000317091; ENSP00000317842; ENSG00000172831 ENST00000417689; ENSP00000394452; ENSG00000172831 [O00748-2] |
GeneIDi | 8824 |
KEGGi | hsa:8824 |
MANE-Selecti | ENST00000317091.10; ENSP00000317842.5; NM_001365405.1; NP_001352334.1 |
UCSCi | uc002eqq.4, human [O00748-1] uc002eqr.4, human |
Keywords - Coding sequence diversityi
Alternative initiation, Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
NIEHS-SNPs |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Y09616 mRNA Translation: CAA70831.1 D50579 mRNA Translation: BAA23606.1 U60553 mRNA Translation: AAB03611.1 AL713761 mRNA Translation: CAD28531.1 AK290482 mRNA Translation: BAF83171.1 BX538086 mRNA Translation: CAD98009.1 AY851164 Genomic DNA Translation: AAW29943.1 AC009084 Genomic DNA No translation available. CH471092 Genomic DNA Translation: EAW83058.1 CH471092 Genomic DNA Translation: EAW83059.1 BC032095 mRNA Translation: AAH32095.1 |
CCDSi | CCDS10825.1 [O00748-1] CCDS45507.1 [O00748-2] |
PIRi | JC5408 |
RefSeqi | NP_003860.2, NM_003869.5 [O00748-1] NP_932327.1, NM_198061.2 [O00748-2] |
3D structure databases
SMRi | O00748 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 114351, 26 interactors |
IntActi | O00748, 3 interactors |
STRINGi | 9606.ENSP00000317842 |
Chemistry databases
BindingDBi | O00748 |
ChEMBLi | CHEMBL3180 |
DrugBanki | DB06695, Dabigatran etexilate DB14845, Filgotinib DB00762, Irinotecan DB06209, Prasugrel |
DrugCentrali | O00748 |
SwissLipidsi | SLP:000001424 |
Protein family/group databases
ESTHERi | human-CES2, Carb_B_Chordata |
MEROPSi | S09.984 |
PTM databases
GlyGeni | O00748, 2 sites |
iPTMneti | O00748 |
PhosphoSitePlusi | O00748 |
Genetic variation databases
BioMutai | CES2 |
Proteomic databases
EPDi | O00748 |
jPOSTi | O00748 |
MassIVEi | O00748 |
MaxQBi | O00748 |
PaxDbi | O00748 |
PeptideAtlasi | O00748 |
PRIDEi | O00748 |
ProteomicsDBi | 48014 [O00748-1] 48015 [O00748-2] |
Protocols and materials databases
Antibodypediai | 15599, 367 antibodies from 34 providers |
DNASUi | 8824 |
Genome annotation databases
Ensembli | ENST00000317091; ENSP00000317842; ENSG00000172831 ENST00000417689; ENSP00000394452; ENSG00000172831 [O00748-2] |
GeneIDi | 8824 |
KEGGi | hsa:8824 |
MANE-Selecti | ENST00000317091.10; ENSP00000317842.5; NM_001365405.1; NP_001352334.1 |
UCSCi | uc002eqq.4, human [O00748-1] uc002eqr.4, human |
Organism-specific databases
CTDi | 8824 |
DisGeNETi | 8824 |
GeneCardsi | CES2 |
HGNCi | HGNC:1864, CES2 |
HPAi | ENSG00000172831, Tissue enhanced (intestine, liver) |
MIMi | 605278, gene |
neXtProti | NX_O00748 |
OpenTargetsi | ENSG00000172831 |
PharmGKBi | PA377 |
VEuPathDBi | HostDB:ENSG00000172831 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1516, Eukaryota |
GeneTreei | ENSGT00940000153793 |
HOGENOMi | CLU_006586_13_2_1 |
InParanoidi | O00748 |
OMAi | NIANTVC |
OrthoDBi | 754103at2759 |
PhylomeDBi | O00748 |
TreeFami | TF315470 |
Enzyme and pathway databases
BRENDAi | 3.1.1.1, 2681 3.1.1.84, 2681 |
PathwayCommonsi | O00748 |
Reactomei | R-HSA-211945, Phase I - Functionalization of compounds |
SABIO-RKi | O00748 |
SignaLinki | O00748 |
Miscellaneous databases
BioGRID-ORCSi | 8824, 8 hits in 1046 CRISPR screens |
ChiTaRSi | CES2, human |
GeneWikii | Carboxylesterase_2 |
GenomeRNAii | 8824 |
Pharosi | O00748, Tchem |
PROi | PR:O00748 |
RNActi | O00748, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000172831, Expressed in jejunal mucosa and 249 other tissues |
ExpressionAtlasi | O00748, baseline and differential |
Genevisiblei | O00748, HS |
Family and domain databases
Gene3Di | 3.40.50.1820, 1 hit |
InterProi | View protein in InterPro IPR029058, AB_hydrolase IPR002018, CarbesteraseB IPR019826, Carboxylesterase_B_AS IPR019819, Carboxylesterase_B_CS |
Pfami | View protein in Pfam PF00135, COesterase, 1 hit |
SUPFAMi | SSF53474, SSF53474, 1 hit |
PROSITEi | View protein in PROSITE PS00122, CARBOXYLESTERASE_B_1, 1 hit PS00941, CARBOXYLESTERASE_B_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | EST2_HUMAN | |
Accessioni | O00748Primary (citable) accession number: O00748 Secondary accession number(s): A0A024R6X1 Q8TCP8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 26, 2004 |
Last sequence update: | July 1, 1997 | |
Last modified: | February 23, 2022 | |
This is version 171 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 16
Human chromosome 16: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families