| IED ID | IndEnz0005000401 |
| Enzyme Type ID | lipase000401 |
| Protein Name |
Liver carboxylesterase 1 Acyl-coenzyme A:cholesterol acyltransferase ACAT Brain carboxylesterase hBr1 Carboxylesterase 1 CE-1 hCE-1 EC 3.1.1.1 Cholesteryl ester hydrolase CEH EC 3.1.1.13 Cocaine carboxylesterase Egasyn HMSE Methylumbelliferyl-acetate deacetylase 1 EC 3.1.1.56 Monocyte/macrophage serine esterase Retinyl ester hydrolase REH Serine esterase 1 Triacylglycerol hydrolase TGH |
| Gene Name | CES1 CES2 SES1 |
| 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 | MWLRAFILATLSASAAWGHPSSPPVVDTVHGKVLGKFVSLEGFAQPVAIFLGIPFAKPPLGPLRFTPPQPAEPWSFVKNATSYPPMCTQDPKAGQLLSELFTNRKENIPLKLSEDCLYLNIYTPADLTKKNRLPVMVWIHGGGLMVGAASTYDGLALAAHENVVVVTIQYRLGIWGFFSTGDEHSRGNWGHLDQVAALRWVQDNIASFGGNPGSVTIFGESAGGESVSVLVLSPLAKNLFHRAISESGVALTSVLVKKGDVKPLAEQIAITAGCKTTTSAVMVHCLRQKTEEELLETTLKMKFLSLDLQGDPRESQPLLGTVIDGMLLLKTPEELQAERNFHTVPYMVGINKQEFGWLIPMQLMSYPLSEGQLDQKTAMSLLWKSYPLVCIAKELIPEATEKYLGGTDDTVKKKDLFLDLIADVMFGVPSVIVARNHRDAGAPTYMYEFQYRPSFSSDMKPKTVIGDHGDELFSVFGAPFLKEGASEEEIRLSKMVMKFWANFARNGNPNGEGLPHWPEYNQKEGYLQIGANTQAAQKLKDKEVAFWTNLFAKKAVEKPPQTEHIEL |
| Enzyme Length | 567 |
| Uniprot Accession Number | P23141 |
| Absorption | |
| Active Site | ACT_SITE 221; /note="Acyl-ester intermediate"; /evidence="ECO:0000255|PROSITE-ProRule:PRU10039, ECO:0000269|PubMed:12022871"; ACT_SITE 354; /note="Charge relay system"; /evidence="ECO:0000269|PubMed:12022871"; ACT_SITE 468; /note="Charge relay system"; /evidence="ECO:0000269|PubMed:12022871" |
| Activity Regulation | ACTIVITY REGULATION: Activated by CHAPS (PubMed:9490062). Inhibited by chlorpyrifos oxon (IC(50)=0.21 nM), paraoxon (IC(50)=0.29 nM), or methyl paraoxon (IC(50)=49 nM) (PubMed:18762277). {ECO:0000269|PubMed:18762277, ECO:0000269|PubMed:9490062}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | 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:7980644, ECO:0000269|PubMed:9169443, ECO:0000269|PubMed:9490062}; 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:18762277, ECO:0000269|PubMed:9169443}; CATALYTIC ACTIVITY: Reaction=a cholesterol ester + H2O = a fatty acid + cholesterol + H(+); Xref=Rhea:RHEA:36403, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16113, ChEBI:CHEBI:17002, ChEBI:CHEBI:28868; EC=3.1.1.13; Evidence={ECO:0000269|PubMed:11015575, ECO:0000269|PubMed:16024911, ECO:0000269|PubMed:16971496, ECO:0000269|PubMed:18762277};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36404; Evidence={ECO:0000305|PubMed:18762277}; CATALYTIC ACTIVITY: Reaction=cholesteryl (9Z-octadecenoate) + H2O = (9Z)-octadecenoate + cholesterol + H(+); Xref=Rhea:RHEA:33875, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16113, ChEBI:CHEBI:30823, ChEBI:CHEBI:46898; Evidence={ECO:0000269|PubMed:11015575, ECO:0000269|PubMed:16024911, ECO:0000269|PubMed:16971496, ECO:0000269|PubMed:18762277};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33876; Evidence={ECO:0000305|PubMed:11015575}; 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 | 3.1.1.1; 3.1.1.13; 3.1.1.56 |
| Enzyme Function | FUNCTION: Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs (PubMed:7980644, PubMed:9169443, PubMed:9490062, PubMed:18762277). Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester (PubMed:7980644, PubMed:9169443, PubMed:9490062, PubMed:18762277). Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine (PubMed:7980644). Catalyzes the transesterification of cocaine to form cocaethylene (PubMed:7980644). Displays fatty acid ethyl ester synthase activity, catalyzing the ethyl esterification of oleic acid to ethyloleate (PubMed:7980644). Converts monoacylglycerides to free fatty acids and glycerol. Hydrolyzes of 2-arachidonoylglycerol and prostaglandins (PubMed:21049984). Hydrolyzes cellular cholesteryl esters to free cholesterols and promotes reverse cholesterol transport (RCT) by facilitating both the initial and final steps in the process (PubMed:18762277, PubMed:16024911, PubMed:11015575, PubMed:16971496). First of all, allows free cholesterol efflux from macrophages to extracellular cholesterol acceptors and secondly, releases free cholesterol from lipoprotein-delivered cholesteryl esters in the liver for bile acid synthesis or direct secretion into the bile (PubMed:18762277, PubMed:18599737, PubMed:16971496). {ECO:0000269|PubMed:11015575, ECO:0000269|PubMed:16024911, ECO:0000269|PubMed:16971496, ECO:0000269|PubMed:18599737, ECO:0000269|PubMed:18762277, ECO:0000269|PubMed:21049984, ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443, ECO:0000269|PubMed:9490062}. |
| Temperature Dependency | |
| PH Dependency | BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 6.5. {ECO:0000269|PubMed:18485328, ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443, ECO:0000269|PubMed:9490062}; |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Alternative sequence (2); Beta strand (23); Chain (1); Disulfide bond (2); Frameshift (1); Glycosylation (1); Helix (27); Modified residue (1); Mutagenesis (5); Natural variant (5); Sequence conflict (44); Signal peptide (1); Turn (7) |
| Keywords | 3D-structure;Alternative splicing;Cytoplasm;Direct protein sequencing;Disulfide bond;Endoplasmic reticulum;Glycoprotein;Hydrolase;Lipid droplet;Lipid metabolism;Phosphoprotein;Reference proteome;Serine esterase;Signal |
| Interact With | Q8IVF2-3; A8MQ03; Q15125; Q5T7V8; Q5T749; Q13113; Q9NRQ2; Q9NR31; O95231 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Endoplasmic reticulum lumen {ECO:0000269|PubMed:10562416}. Cytoplasm {ECO:0000269|PubMed:16024911}. Lipid droplet {ECO:0000269|PubMed:16024911}. Note=Moves from cytoplasm to lipid droplets upon lipid loading. Associates with lipid droplets independently of triglycerides (TG) content of the droplets and hydrolyzes cholesteryl esters more efficiently from mixed droplets. {ECO:0000269|PubMed:16024911}. |
| Modified Residue | MOD_RES 380; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:24275569 |
| Post Translational Modification | PTM: Contains sialic acid.; PTM: Cleavage of the signal sequence can occur at 2 positions, either between Trp-17 and Gly-18 or between Gly-18 and His-19. |
| Signal Peptide | SIGNAL 1..17; /evidence="ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9490062" |
| Structure 3D | X-ray crystallography (18) |
| Cross Reference PDB | 1MX1; 1MX5; 1MX9; 1YA4; 1YA8; 1YAH; 1YAJ; 2DQY; 2DQZ; 2DR0; 2H7C; 2HRQ; 2HRR; 3K9B; 4AB1; 5A7F; 5A7G; 5A7H; |
| Mapped Pubmed ID | 12773168; 12960109; 15475243; 15475733; 15931389; 16081098; 16282638; 16419644; 16837570; 16858120; 16943252; 16962139; 17407327; 17537833; 17764701; 18305377; 18328811; 18794728; 18983829; 19185566; 19332024; 19343046; 19508181; 19658107; 19715681; 19733552; 19932971; 20051531; 20529763; 20530478; 20649590; 20975297; 21081832; 21516116; 21994455; 22237548; 22442219; 22525521; 22588607; 22674043; 22688218; 22700792; 22943824; 23111421; 23275066; 23468884; 23658012; 23936796; 24141856; 24170778; 24212379; 24350812; 24563511; 25704243; 26076923; 26340669; 26587656; 26657071; 26825642; 26871237; 26915813; 27075303; 27130352; 27228223; 27450232; 27614009; 27638507; 28139840; 28473326; 28532270; 28639420; 28677105; 28775293; 28786738; 28838926; 28990360; 29321244; 29457755; 29631096; 30833288; 30850966; 31128980; 31698983; 31717501; 31871135; 33206527; 33791812; 33878036; 34234263; 5013373; 7206363; 9144407; |
| Motif | |
| Gene Encoded By | |
| Mass | 62,521 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=106.6 uM for p-nitrophenyl acetate {ECO:0000269|PubMed:18485328, ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443, ECO:0000269|PubMed:9490062}; KM=775.7 uM for L-methylphenidate {ECO:0000269|PubMed:18485328, ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443, ECO:0000269|PubMed:9490062}; KM=663.5 uM for D-methylphenidate {ECO:0000269|PubMed:18485328, ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443, ECO:0000269|PubMed:9490062}; KM=116 uM for cocaine {ECO:0000269|PubMed:18485328, ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443, ECO:0000269|PubMed:9490062}; KM=43 mM for ethanol {ECO:0000269|PubMed:18485328, ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443, ECO:0000269|PubMed:9490062}; KM=0.8 mM for 4-methylumbelliferyl acetate {ECO:0000269|PubMed:18485328, ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443, ECO:0000269|PubMed:9490062}; KM=6.3 mM for heroin {ECO:0000269|PubMed:18485328, ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443, ECO:0000269|PubMed:9490062}; KM=8.3 mM for 6-monoacetylmorphine {ECO:0000269|PubMed:18485328, ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443, ECO:0000269|PubMed:9490062}; KM=49 uM for 2-arachidonoylglycerol {ECO:0000269|PubMed:21049984}; KM=250 uM for prostaglandin E2 1-glyceryl ester {ECO:0000269|PubMed:21049984}; KM=93 uM for prostaglandin F2alpha 1-glyceryl ester {ECO:0000269|PubMed:21049984}; Vmax=493.9 nmol/min/mg enzyme with p-nitrophenyl acetate as substrate {ECO:0000269|PubMed:18485328, ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443, ECO:0000269|PubMed:9490062}; Vmax=1701.1 pmol/min/mg enzyme with L-methylphenidate as substrate {ECO:0000269|PubMed:18485328, ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443, ECO:0000269|PubMed:9490062}; Vmax=177.2 pmol/min/mg enzyme with D-methylphenidate as substrate {ECO:0000269|PubMed:18485328, ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443, ECO:0000269|PubMed:9490062}; Note=kcat is 59 min(-1), 29 min(-1), 90 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:21164; RHEA:12208; RHEA:36403; RHEA:36404; RHEA:33875; RHEA:33876; RHEA:26132; RHEA:26133; RHEA:48296; RHEA:48297; RHEA:48300; RHEA:48301 |
| Cross Reference Brenda | 3.1.1.1; |