| IED ID | IndEnz0010000026 |
| Enzyme Type ID | esterase000026 |
| Protein Name |
Lysosomal acid lipase/cholesteryl ester hydrolase Acid cholesteryl ester hydrolase LAL EC 3.1.1.13 Cholesteryl esterase Lipase A Sterol esterase |
| Gene Name | LIPA |
| 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 | MKMRFLGLVVCLVLWTLHSEGSGGKLTAVDPETNMNVSEIISYWGFPSEEYLVETEDGYILCLNRIPHGRKNHSDKGPKPVVFLQHGLLADSSNWVTNLANSSLGFILADAGFDVWMGNSRGNTWSRKHKTLSVSQDEFWAFSYDEMAKYDLPASINFILNKTGQEQVYYVGHSQGTTIGFIAFSQIPELAKRIKMFFALGPVASVAFCTSPMAKLGRLPDHLIKDLFGDKEFLPQSAFLKWLGTHVCTHVILKELCGNLCFLLCGFNERNLNMSRVDVYTTHSPAGTSVQNMLHWSQAVKFQKFQAFDWGSSAKNYFHYNQSYPPTYNVKDMLVPTAVWSGGHDWLADVYDVNILLTQITNLVFHESIPEWEHLDFIWGLDAPWRLYNKIINLMRKYQ |
| Enzyme Length | 399 |
| Uniprot Accession Number | P38571 |
| Absorption | |
| Active Site | ACT_SITE 174; /note=Charge relay system; /evidence=ECO:0000255|PROSITE-ProRule:PRU10037; ACT_SITE 374; /note=Charge relay system; /evidence=ECO:0000255|PROSITE-ProRule:PRU10037 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=a sterol ester + H2O = a fatty acid + a sterol + H(+); Xref=Rhea:RHEA:10100, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15889, ChEBI:CHEBI:28868, ChEBI:CHEBI:35915; EC=3.1.1.13; Evidence={ECO:0000269|PubMed:15269241, ECO:0000269|PubMed:7204383, ECO:0000269|PubMed:8112342}; 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:1718995, ECO:0000269|PubMed:9633819};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33876; Evidence={ECO:0000305|PubMed:1718995}; |
| DNA Binding | |
| EC Number | 3.1.1.13 |
| Enzyme Function | FUNCTION: Catalyzes the deacylation of triacylglyceryl and cholesteryl ester core lipids of endocytosed low density lipoproteins to generate free fatty acids and cholesterol. {ECO:0000269|PubMed:15269241, ECO:0000269|PubMed:1718995, ECO:0000269|PubMed:7204383, ECO:0000269|PubMed:8112342, ECO:0000269|PubMed:9633819}. |
| Temperature Dependency | |
| PH Dependency | BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 4.5-5 (PubMed:8112342). Optimum pH is 4.4 with either cholesterol oleate or trioleoylglycerol as substrate (PubMed:7204383). {ECO:0000269|PubMed:7204383, ECO:0000269|PubMed:8112342}; |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Alternative sequence (2); Beta strand (13); Chain (1); Domain (1); Glycosylation (6); Helix (22); Mutagenesis (2); Natural variant (7); Propeptide (1); Sequence conflict (1); Signal peptide (1); Turn (3) |
| Keywords | 3D-structure;Alternative splicing;Direct protein sequencing;Disease variant;Glycoprotein;Hydrolase;Lipid degradation;Lipid metabolism;Lysosome;Reference proteome;Signal |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Lysosome {ECO:0000250|UniProtKB:Q64194}. |
| Modified Residue | |
| Post Translational Modification | PTM: Glycosylation is not essential for catalytic activity. {ECO:0000269|PubMed:8112342}. |
| Signal Peptide | SIGNAL 1..27; /evidence=ECO:0000269|PubMed:8112342 |
| Structure 3D | X-ray crystallography (1) |
| Cross Reference PDB | 6V7N; |
| Mapped Pubmed ID | 15465627; 16385451; 16730122; 18996102; 25699256; 32482718; 7773732; 8566968; 9365051; 9705237; |
| Motif | |
| Gene Encoded By | |
| Mass | 45,419 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.142 mM for cholesteryl oleate {ECO:0000269|PubMed:8112342}; KM=0.8 mM for cholesteryl oleate {ECO:0000269|PubMed:7204383}; KM=0.138 mM for trioleoylglycerol {ECO:0000269|PubMed:8112342}; KM=0.8 mM for trioleoylglycerol {ECO:0000269|PubMed:7204383}; KM=899 uM for trioleoylglycerol {ECO:0000269|PubMed:15269241}; KM=0.9 mM for 1,2-dioleoylglycerol {ECO:0000269|PubMed:7204383}; KM=1.2 mM for 1,3-dioleoylglycerol {ECO:0000269|PubMed:7204383}; Vmax=4390 nmol/min/mg enzyme with cholesteryl oleate as substrate {ECO:0000269|PubMed:8112342}; Vmax=1400 nmol/min/mg enzyme with cholesteryl oleate as substrate {ECO:0000269|PubMed:7204383}; Vmax=4756 mmol/min/mg enzyme with trioleoylglycerol as substrate {ECO:0000269|PubMed:8112342}; Vmax=5400 nmol/min/mg enzyme with trioleoylglycerol as substrate {ECO:0000269|PubMed:7204383}; Vmax=19400 nmol/min/mg enzyme with 1,2-dioleoylglycerol as substrate {ECO:0000269|PubMed:7204383}; Vmax=22100 nmol/min/mg enzyme with 1,3-dioleoylglycerol as substrate {ECO:0000269|PubMed:7204383}; |
| Metal Binding | |
| Rhea ID | RHEA:10100; RHEA:33875; RHEA:33876 |
| Cross Reference Brenda |