IED ID | IndEnz0005000500 |
Enzyme Type ID | lipase000500 |
Protein Name |
Liver carboxylesterase EC 3.1.1.1 Proline-beta-naphthylamidase Retinyl ester hydrolase REH |
Gene Name | |
Organism | Sus scrofa (Pig) |
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 Laurasiatheria Artiodactyla Suina Suidae (pigs) Sus Sus scrofa (Pig) |
Enzyme Sequence | MWLLPLVLTSLASSATWAGQPASPPVVDTAQGRVLGKYVSLEGLAQPVAVFLGVPFAKPPLGSLRFAPPQPAEPWSFVKNTTSYPPMCCQDPVVEQMTSDLFTNGKERLTLEFSEDCLYLNIYTPADLTKRGRLPVMVWIHGGGLVLGGAPMYDGVVLAAHENVVVVAIQYRLGIWGFFSTGDEHSRGNWGHLDQVAALHWVQENIANFGGDPGSVTIFGESAGGESVSVLVLSPLAKNLFHRAISESGVALTVALVRKDMKAAAKQIAVLAGCKTTTSAVFVHCLRQKSEDELLDLTLKMKFLTLDFHGDQRESHPFLPTVVDGVLLPKMPEEILAEKDFNTVPYIVGINKQEFGWLLPTMMGFPLSEGKLDQKTATSLLWKSYPIANIPEELTPVATDKYLGGTDDPVKKKDLFLDLMGDVVFGVPSVTVARQHRDAGAPTYMYEFQYRPSFSSDKKPKTVIGDHGDEIFSVFGFPLLKGDAPEEEVSLSKTVMKFWANFARSGNPNGEGLPHWPMYDQEEGYLQIGVNTQAAKRLKGEEVAFWNDLLSKEAAKKPPKIKHAEL |
Enzyme Length | 566 |
Uniprot Accession Number | Q29550 |
Absorption | |
Active Site | ACT_SITE 222; /note=Acyl-ester intermediate; /evidence=ECO:0000255|PROSITE-ProRule:PRU10039; ACT_SITE 354; /note=Charge relay system; /evidence=ECO:0000250; ACT_SITE 467; /note=Charge relay system; /evidence=ECO:0000250 |
Activity Regulation | ACTIVITY REGULATION: Activated by CHAPS at concentrations of up to 130 mM, higher concentrations reduce activity. In the presence of CHAPS, activity is stimulated by non-ionic detergents. Inhibited by the esterase inhibitors diisopropylfluorophosphate and phenylmethylsulfonyl fluoride. {ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}. |
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:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; |
DNA Binding | |
EC Number | 3.1.1.1 |
Enzyme Function | FUNCTION: Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Active towards triacylglycerides containing short-chain fatty acids from C2 to C6, and 1(3)-monoacylglycerols containing fatty acids from C2 to C12. Inactive on long-chain triacylglycerols and diacylglycerol. Hydrolyzes aromatic and alkyl esters and vitamin A acetate. The hydrolysis rate depends upon the amino acid promoiety and the esterification site of the prodrug. Aromatic promoieties are favored, highest rates are observed with phenylalanyl progdrugs, hydrolysis of valyl and isoleucyl prodrugs is less efficient. With floxuridine prodrugs, activity is higher on 5' monoesters than on 3' monoesters. With gemcitabine prodrugs, activity is higher on 3' monoesters than on 5' monoesters. {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}. |
Temperature Dependency | |
PH Dependency | BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 8.0 with tributylglycerol as substrate, and 8.2 with retinyl palmitate as substrate. Active from pH 4.5-9.5 with retinyl palmitate as substrate. {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; |
Pathway | |
nucleotide Binding | |
Features | Active site (3); Beta strand (19); Chain (1); Disulfide bond (2); Glycosylation (1); Helix (26); Modified residue (1); Motif (1); Sequence conflict (18); Signal peptide (1); Turn (2) |
Keywords | 3D-structure;Direct protein sequencing;Disulfide bond;Endoplasmic reticulum;Glycoprotein;Hydrolase;Phosphoprotein;Reference proteome;Serine esterase;Signal |
Interact With | |
Induction | |
Subcellular Location | SUBCELLULAR LOCATION: Endoplasmic reticulum lumen. |
Modified Residue | MOD_RES 379; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P23141 |
Post Translational Modification | |
Signal Peptide | SIGNAL 1..18; /evidence=ECO:0000250 |
Structure 3D | X-ray crystallography (1) |
Cross Reference PDB | 5FV4; |
Mapped Pubmed ID | 31664043; |
Motif | MOTIF 563..566; /note=Prevents secretion from ER; /evidence=ECO:0000255 |
Gene Encoded By | |
Mass | 62,016 |
Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=27.5 uM for retinyl palmitate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=0.46 mM for 5'-L-phenylalanyl-floxuridine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=0.44 mM for 5'-D-phenylalanyl-floxuridine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=1.40 mM for 3'-D-phenylalanyl-floxuridine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=0.74 mM for 3'-L-phenylalanyl-floxuridine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=1.87 mM for 5'-L-prolyl-floxuridine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=0.97 mM for 5'-L-leucyl-floxuridine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=4.85 mM for 3'-L-prolyl-floxuridine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=1.46 mM for 3'-L-leucyl-floxuridine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=3.08 mM for 3'-L-lysyl-floxuridine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=6.25 mM for 5'-L-lysyl-floxuridine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=1.11 mM for 3'-L-isoleucyl-floxuridine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=3.00 mM for 5'-L-aspartyl-floxuridine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=0.93 mM for 3'-L-aspartyl-floxuridine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=4.12 mM for 5'-D-valyl-floxuridine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=2.87 mM for 3'-L-valyl-floxuridine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=3.58 mM for 5'-L-valyl-floxuridine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=2.94 mM for 5'-L-isoleucyl-floxuridine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=11.23 mM for 3'-D-valyl-floxuridine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=0.51 mM for 3'-L-phenylalanyl-gemcitabine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=0.97 mM for 3'-D-phenylalanyl-gemcitabine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=0.17 mM for 5'-L-phenylalanyl-gemcitabine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=0.22 mM for 5'-D-phenylalanyl-gemcitabine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=0.90 mM for 3'-L-valyl-gemcitabine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=0.94 mM for 3'-L-isoleucyl-gemcitabine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=1.43 mM for 3'-D-valyl-gemcitabine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=0.85 mM for 5'-L-isoleucyl-gemcitabine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=1.16 mM for 5'-D-valyl-gemcitabine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=0.96 mM for 5'-L-valyl-gemcitabine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=0.91 mM for 5'-L-phenylalanyl-BDCRB {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=0.90 mM for 5'-D-phenylalanyl-BDCRB {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=0.14 mM for pNPB {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=0.52 mM for pNPA {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=1.18 mM for PHEE {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=0.08 mM for PHBE {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=0.40 mM for AcPHEE {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=0.63 mM for 5' cinn-floxuridine {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=4.21 mM for CPT-11 {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; KM=8.81 mM for VACV {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=530 nmol/h/mg enzyme with retinyl palmitate as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=1.82 nmol/min/ug enzyme with 5'-L-phenylalanyl-floxuridine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=1.63 nmol/min/ug enzyme with 5'-D-phenylalanyl-floxuridine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=4.05 nmol/min/ug enzyme with 3'-D-phenylalanyl-floxuridine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=1.55 nmol/min/ug enzyme with 3'-L-phenylalanyl-floxuridine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=1.97 nmol/min/ug enzyme with 5'-L-prolyl-floxuridine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=0.92 nmol/min/ug enzyme with 5'-L-leucyl-floxuridine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=4.53 nmol/min/ug enzyme with 3'-L-prolyl-floxuridine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=0.70 nmol/min/ug enzyme with 3'-L-leucyl-floxuridine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=0.59 nmol/min/ug enzyme with 3'-L-lysyl-floxuridine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=1.11 nmol/min/ug enzyme with 5'-L-lysyl-floxuridine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=0.16 nmol/min/ug enzyme with 3'-L-isoleucyl-floxuridine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=0.33 nmol/min/ug enzyme with 5'-L-aspartyl-floxuridine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=0.10 nmol/min/ug enzyme with 3'-L-aspartyl-floxuridine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=0.30 nmol/min/ug enzyme with 5'-D-valyl-floxuridine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=0.19 nmol/min/ug enzyme with 3'-L-valyl-floxuridine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=0.21 nmol/min/ug enzyme with 5'-L-valyl-floxuridine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=0.15 nmol/min/ug enzyme with 5'-L-isoleucyl-floxuridine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=0.27 nmol/min/ug enzyme with 3'-D-valyl-floxuridine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=283.52 nmol/min/ug enzyme with 3'-L-phenylalanyl-gemcitabine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=406.92 nmol/min/ug enzyme with 3'-D-phenylalanyl-gemcitabine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=3.25 nmol/min/ug enzyme with 5'-L-phenylalanyl-gemcitabine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=3.19 nmol/min/ug enzyme with 5'-D-phenylalanyl-gemcitabine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=0.35 nmol/min/ug enzyme with 3'-L-valyl-gemcitabine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=0.24 nmol/min/ug enzyme with 3'-L-isoleucyl-gemcitabine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=0.32 nmol/min/ug enzyme with 3'-D-valyl-gemcitabine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=0.09 nmol/min/ug enzyme with 5'-L-isoleucyl-gemcitabine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=0.13 nmol/min/ug enzyme with 5'-D-valyl-gemcitabine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=0.12 nmol/min/ug enzyme with 5'-L-valyl-gemcitabine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=2.33 nmol/min/ug enzyme with 5'-L-phenylalanyl-BDCRB as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=1.60 nmol/min/ug enzyme with 5'-D-phenylalanyl-BDCRB as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=82.25 nmol/min/ug enzyme with pNPB as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=60.45 nmol/min/ug enzyme with pNPA as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=11859.78 nmol/min/ug enzyme with PHEE as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=7.24 nmol/min/ug enzyme with PHBE as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=1.29 nmol/min/ug enzyme with AcPHEE as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=4.00 nmol/min/ug enzyme with 5' cinn-floxuridine as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; Vmax=0.03 nmol/min/ug enzyme with CPT-11 as substrate {ECO:0000269|PubMed:16223870, ECO:0000269|PubMed:9490062, ECO:0000269|PubMed:9799112}; |
Metal Binding | |
Rhea ID | RHEA:21164 |
Cross Reference Brenda |