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UniProt functional annotation for P23141 | ||
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| UniProt code: P23141. |
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| Organism: | |
Homo sapiens (Human). |
| Taxonomy: | |
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. |
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| 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}. |
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| 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}; |
| 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}. |
| 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}; pH dependence: Optimum pH is 6.5. {ECO:0000269|PubMed:18485328, ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:9169443, ECO:0000269|PubMed:9490062}; |
| Subunit: | |
Homotrimer and homohexamer. Binds to beta-glucuronidase. {ECO:0000269|PubMed:12679808, ECO:0000269|PubMed:12725862, ECO:0000269|PubMed:7980644, ECO:0000269|PubMed:8597091}. |
| 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}. |
| Tissue specificity: | |
Expressed predominantly in liver with lower levels in heart and lung (PubMed:10562416). Expressed in macrophages (PubMed:11015575, PubMed:21049984, PubMed:18762277). {ECO:0000269|PubMed:10562416, ECO:0000269|PubMed:11015575, ECO:0000269|PubMed:18762277, ECO:0000269|PubMed:21049984}. |
| 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. |
| Polymorphism: | |
Genetic variants in CES1 are associated with clinically significant alterations in pharmacokinetics and drug response of carboxylesterase 1 substrates [MIM:618057]. {ECO:0000269|PubMed:18485328}. |
| Similarity: | |
Belongs to the type-B carboxylesterase/lipase family. {ECO:0000305}. |
| Sequence caution: | |
Sequence=AAA83932.1; Type=Frameshift; Evidence={ECO:0000305}; |
Annotations taken from UniProtKB at the EBI.