| IED ID | IndEnz0005000361 |
| Enzyme Type ID | lipase000361 |
| Protein Name |
Cocaine esterase EC 3.1.1.84 Carboxylesterase 2 CE-2 hCE-2 EC 3.1.1.1 Methylumbelliferyl-acetate deacetylase 2 EC 3.1.1.56 |
| Gene Name | CES2 ICE |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MRLHRLRARLSAVACGLLLLLVRGQGQDSASPIRTTHTGQVLGSLVHVKGANAGVQTFLGIPFAKPPLGPLRFAPPEPPESWSGVRDGTTHPAMCLQDLTAVESEFLSQFNMTFPSDSMSEDCLYLSIYTPAHSHEGSNLPVMVWIHGGALVFGMASLYDGSMLAALENVVVVIIQYRLGVLGFFSTGDKHATGNWGYLDQVAALRWVQQNIAHFGGNPDRVTIFGESAGGTSVSSLVVSPISQGLFHGAIMESGVALLPGLIASSADVISTVVANLSACDQVDSEALVGCLRGKSKEEILAINKPFKMIPGVVDGVFLPRHPQELLASADFQPVPSIVGVNNNEFGWLIPKVMRIYDTQKEMDREASQAALQKMLTLLMLPPTFGDLLREEYIGDNGDPQTLQAQFQEMMADSMFVIPALQVAHFQCSRAPVYFYEFQHQPSWLKNIRPPHMKADHGDELPFVFRSFFGGNYIKFTEEEEQLSRKMMKYWANFARNGNPNGEGLPHWPLFDQEEQYLQLNLQPAVGRALKAHRLQFWKKALPQKIQELEEPEERHTEL |
| Enzyme Length | 559 |
| Uniprot Accession Number | O00748 |
| Absorption | |
| Active Site | ACT_SITE 228; /note=Acyl-ester intermediate; /evidence=ECO:0000255|PROSITE-ProRule:PRU10039; ACT_SITE 345; /note=Charge relay system; /evidence=ECO:0000250|UniProtKB:P23141; ACT_SITE 457; /note=Charge relay system; /evidence=ECO:0000250|UniProtKB:P23141 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=cocaine + H2O = benzoate + ecgonine methyl ester + H(+); Xref=Rhea:RHEA:27506, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16150, ChEBI:CHEBI:59908, ChEBI:CHEBI:60056; EC=3.1.1.84; Evidence={ECO:0000269|PubMed:9169443}; CATALYTIC ACTIVITY: Reaction=a carboxylic ester + H2O = a carboxylate + an alcohol + H(+); Xref=Rhea:RHEA:21164, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29067, ChEBI:CHEBI:30879, ChEBI:CHEBI:33308; EC=3.1.1.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU10039, ECO:0000269|PubMed:9169443}; CATALYTIC ACTIVITY: Reaction=4-methylumbelliferyl acetate + H2O = 4-methylumbelliferone + acetate + H(+); Xref=Rhea:RHEA:12208, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17224, ChEBI:CHEBI:17763, ChEBI:CHEBI:30089; EC=3.1.1.56; Evidence={ECO:0000269|PubMed:9169443}; CATALYTIC ACTIVITY: Reaction=2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + glycerol + H(+); Xref=Rhea:RHEA:26132, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:32395, ChEBI:CHEBI:52392; Evidence={ECO:0000269|PubMed:21049984};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26133; Evidence={ECO:0000305|PubMed:21049984}; CATALYTIC ACTIVITY: Reaction=H2O + prostaglandin E2 1-glyceryl ester = glycerol + H(+) + prostaglandin E2; Xref=Rhea:RHEA:48296, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:90230, ChEBI:CHEBI:606564; Evidence={ECO:0000269|PubMed:21049984};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48297; Evidence={ECO:0000305|PubMed:21049984}; CATALYTIC ACTIVITY: Reaction=H2O + prostaglandin F2alpha 1-glyceryl ester = glycerol + H(+) + prostaglandin F2alpha; Xref=Rhea:RHEA:48300, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:57404, ChEBI:CHEBI:90233; Evidence={ECO:0000269|PubMed:21049984};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48301; Evidence={ECO:0000305|PubMed:21049984}; |
| DNA Binding | |
| EC Number | 3.1.1.84; 3.1.1.1; 3.1.1.56 |
| Enzyme Function | FUNCTION: 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). {ECO:0000269|PubMed:21049984, ECO:0000269|PubMed:9169443, ECO:0000303|PubMed:28677105}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Alternative sequence (2); Chain (1); Disulfide bond (2); Glycosylation (2); Modified residue (1); Motif (1); Natural variant (2); Sequence conflict (5); Signal peptide (1) |
| Keywords | Alternative initiation;Alternative splicing;Direct protein sequencing;Disulfide bond;Endoplasmic reticulum;Glycoprotein;Hydrolase;Lipid metabolism;Pyrrolidone carboxylic acid;Reference proteome;Serine esterase;Signal |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Endoplasmic reticulum lumen {ECO:0000269|PubMed:22446793}. |
| Modified Residue | MOD_RES 27; /note=Pyrrolidone carboxylic acid; /evidence=ECO:0000250|UniProtKB:P14943 |
| Post Translational Modification | PTM: Glycosylated. {ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:9169443}. |
| Signal Peptide | SIGNAL 1..26; /evidence=ECO:0000269|PubMed:9169443 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 12725862; 12835618; 12960109; 15475243; 15475733; 15592324; 15967118; 16690525; 16837570; 16858120; 16943252; 16963839; 17483951; 17537833; 17640957; 17764701; 18259949; 18305377; 18473752; 18794728; 18797458; 18983829; 19274604; 19343046; 19349540; 19367725; 19508181; 19856659; 19956635; 20195289; 20237496; 20379614; 20529763; 20628086; 20649590; 20711500; 22525521; 22674043; 23471941; 23480903; 24195516; 24212379; 25724353; 26025324; 26806650; 26825642; 27149931; 28099843; 28285137; 28532270; 28827188; 29261002; 29263072; 29651325; 30016861; 30867471; 31836607; 31981591; 32779042; 33291124; 5013373; 7206363; 7980644; |
| Motif | MOTIF 556..559; /note=Prevents secretion from ER; /evidence=ECO:0000255 |
| Gene Encoded By | |
| Mass | 61,807 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.39 mM for cocaine {ECO:0000269|PubMed:9169443}; KM=0.15 mM for 4-methylumbelliferyl acetate {ECO:0000269|PubMed:9169443}; KM=6.8 mM for heroin {ECO:0000269|PubMed:9169443}; KM=46 uM for 2-arachidonoylglycerol {ECO:0000269|PubMed:21049984}; KM=750 uM for prostaglandin E2 1-glyceryl ester {ECO:0000269|PubMed:21049984}; KM=35 uM for prostaglandin F2alpha 1-glyceryl ester {ECO:0000269|PubMed:21049984}; KM=0.13 mM for 6-monoacetylmorphine {ECO:0000269|PubMed:9169443}; Note=kcat is 43 min(-1), 49 min(-1), 150 min(-1) with 2-arachidonoylglycerol, prostaglandin F2alpha 1-glyceryl ester and prostaglandin E2 1-glyceryl ester as substrates, respectively. {ECO:0000269|PubMed:21049984}; |
| Metal Binding | |
| Rhea ID | RHEA:27506; RHEA:21164; RHEA:12208; RHEA:26132; RHEA:26133; RHEA:48296; RHEA:48297; RHEA:48300; RHEA:48301 |
| Cross Reference Brenda | 3.1.1.1;3.1.1.84; |