IED Industry Enzyme Database

Detail Information for IndEnz0005000030
IED ID IndEnz0005000030
Enzyme Type ID lipase000030
Protein Name Hormone-sensitive lipase
HSL
EC 3.1.1.79
Monoacylglycerol lipase LIPE
EC 3.1.1.23
Retinyl ester hydrolase
REH
Gene Name Lipe
Organism Mus musculus (Mouse)
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 Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse)
Enzyme Sequence MDLRTMTQSLVTLAEDNMAFFSSQGPGETARRLSNVFAGVREQALGLEPTLGQLLGVAHHFDLDTETPANGYRSLVHTARCCLAHLLHKSRYVASNRKSIFFRASHNLAELEAYLAALTQLRAMAYYAQRLLTINRPGVLFFEGDEGLTADFLQEYVTLHKGCFYGRCLGFQFTPAIRPFLQTLSIGLVSFGEHYKRNETGLSVTASSLFTGGRFAIDPELRGAEFERIIQNLDVHFWKAFWNITEIEVLSSLANMASTTVRVSRLLSLPPEAFEMPLTSDPRLTVTISPPLAHTGPAPVLARLISYDLREGQDSKVLNSLAKSEGPRLELRPRPHQAPRSRALVVHIHGGGFVAQTSKSHEPYLKNWAQELGVPIFSIDYSLAPEAPFPRALEECFFAYCWAVKHCDLLGSTGERICLAGDSAGGNLCITVSLRAAAYGVRVPDGIMAAYPVTTLQSSASPSRLLSLMDPLLPLSVLSKCVSAYSGTEAEDHFDSDQKALGVMGLVQRDTSLFLRDLRLGASSWLNSFLELSGRKPQKTTSPTAESVRPTESMRRSVSEAALAQPEGLLGTDTLKKLTIKDLSNSEPSDSPEMSQSMETLGPSTPSDVNFFLRPGNSQEEAEAKDEVRPMDGVPRVRAAFPEGFHPRRSSQGVLHMPLYTSPIVKNPFMSPLLAPDSMLKTLPPVHLVACALDPMLDDSVMFARRLRDLGQPVTLKVVEDLPHGFLSLAALCRETRQATEFCVQRIRLILTPPAAPLN
Enzyme Length 759
Uniprot Accession Number P54310
Absorption
Active Site ACT_SITE 423; /evidence="ECO:0000250|UniProtKB:Q8BLF1, ECO:0000255|PROSITE-ProRule:PRU10038"; ACT_SITE 694; /evidence="ECO:0000250|UniProtKB:Q8BLF1"; ACT_SITE 724; /evidence="ECO:0000250|UniProtKB:Q8BLF1"
Activity Regulation
Binding Site
Calcium Binding
catalytic Activity CATALYTIC ACTIVITY: Reaction=a diacylglycerol + H2O = a fatty acid + a monoacylglycerol + H(+); Xref=Rhea:RHEA:32731, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17408, ChEBI:CHEBI:18035, ChEBI:CHEBI:28868; EC=3.1.1.79; Evidence={ECO:0000269|PubMed:20625037, ECO:0000269|PubMed:23066022}; CATALYTIC ACTIVITY: Reaction=a triacylglycerol + H2O = a diacylglycerol + a fatty acid + H(+); Xref=Rhea:RHEA:12044, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17855, ChEBI:CHEBI:18035, ChEBI:CHEBI:28868; EC=3.1.1.79; Evidence={ECO:0000269|PubMed:15550674}; CATALYTIC ACTIVITY: Reaction=a monoacylglycerol + H2O = a fatty acid + glycerol + H(+); Xref=Rhea:RHEA:15245, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17408, ChEBI:CHEBI:17754, ChEBI:CHEBI:28868; EC=3.1.1.79; Evidence={ECO:0000269|PubMed:21454566}; CATALYTIC ACTIVITY: Reaction=Hydrolyzes glycerol monoesters of long-chain fatty acids.; EC=3.1.1.23; Evidence={ECO:0000269|PubMed:21454566}; 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:15550674, ECO:0000269|PubMed:20625037};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33876; Evidence={ECO:0000305|PubMed:15550674}; CATALYTIC ACTIVITY: Reaction=all-trans-retinyl hexadecanoate + H2O = all-trans-retinol + H(+) + hexadecanoate; Xref=Rhea:RHEA:13933, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17336, ChEBI:CHEBI:17616; Evidence={ECO:0000269|PubMed:15550674};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13934; Evidence={ECO:0000305|PubMed:15550674}; CATALYTIC ACTIVITY: Reaction=1,2-di-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + (9Z-octadecenoyl)-glycerol + H(+); Xref=Rhea:RHEA:38455, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:52323, ChEBI:CHEBI:75937; Evidence={ECO:0000269|PubMed:20625037, ECO:0000269|PubMed:23066022};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38456; Evidence={ECO:0000305|PubMed:20625037}; 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:21454566};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26133; Evidence={ECO:0000305|PubMed:21454566}; CATALYTIC ACTIVITY: Reaction=1-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + glycerol + H(+); Xref=Rhea:RHEA:38487, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30823, ChEBI:CHEBI:75342; Evidence={ECO:0000269|PubMed:21454566};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38488; Evidence={ECO:0000305|PubMed:21454566}; CATALYTIC ACTIVITY: Reaction=2-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + glycerol + H(+); Xref=Rhea:RHEA:38491, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30823, ChEBI:CHEBI:73990; Evidence={ECO:0000269|PubMed:21454566};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38492; Evidence={ECO:0000305|PubMed:21454566}; CATALYTIC ACTIVITY: Reaction=1-O-hexadecyl-2-acetyl-sn-glycerol + H2O = 1-O-hexadecyl-sn-glycerol + acetate + H(+); Xref=Rhea:RHEA:38563, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30089, ChEBI:CHEBI:34115, ChEBI:CHEBI:75936; Evidence={ECO:0000269|PubMed:20625037};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38564; Evidence={ECO:0000305|PubMed:20625037}; CATALYTIC ACTIVITY: Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycerol + H2O = (9Z)-octadecenoate + (9Z-octadecenoyl)-glycerol + H(+); Xref=Rhea:RHEA:39935, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:52333, ChEBI:CHEBI:75937; Evidence={ECO:0000269|PubMed:23066022};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39936; Evidence={ECO:0000305|PubMed:23066022}; CATALYTIC ACTIVITY: Reaction=1,3-di-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + (9Z-octadecenoyl)-glycerol + H(+); Xref=Rhea:RHEA:39939, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:75735, ChEBI:CHEBI:75937; Evidence={ECO:0000269|PubMed:23066022};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39940; Evidence={ECO:0000305|PubMed:23066022}; CATALYTIC ACTIVITY: Reaction=(9Z)-octadecenoate + 1,2-di-(9Z-octadecenoyl)-glycerol + H(+) = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O; Xref=Rhea:RHEA:38379, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:52323, ChEBI:CHEBI:53753; Evidence={ECO:0000250|UniProtKB:Q05469};PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38381; Evidence={ECO:0000250|UniProtKB:Q05469}; CATALYTIC ACTIVITY: Reaction=2,3-di-(9Z)-octadecenoyl-sn-glycerol + H2O = (9Z)-octadecenoate + 2-(9Z-octadecenoyl)-glycerol + H(+); Xref=Rhea:RHEA:38383, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:73990, ChEBI:CHEBI:75824; Evidence={ECO:0000250|UniProtKB:Q05469};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38384; Evidence={ECO:0000250|UniProtKB:Q05469}; CATALYTIC ACTIVITY: Reaction=1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + di-(9Z)-octadecenoylglycerol + H(+); Xref=Rhea:RHEA:38575, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:53753, ChEBI:CHEBI:75945; Evidence={ECO:0000250|UniProtKB:Q05469};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38576; Evidence={ECO:0000250|UniProtKB:Q05469}; CATALYTIC ACTIVITY: Reaction=1,2-di-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + 2-(9Z-octadecenoyl)-glycerol + H(+); Xref=Rhea:RHEA:38659, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:52323, ChEBI:CHEBI:73990; Evidence={ECO:0000250|UniProtKB:P15304};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38660; Evidence={ECO:0000250|UniProtKB:P15304};
DNA Binding
EC Number 3.1.1.79; 3.1.1.23
Enzyme Function FUNCTION: Lipase with broad substrate specificity, catalyzing the hydrolysis of triacylglycerols (TAGs), diacylglycerols (DAGs), monoacylglycerols (MAGs), cholesteryl esters and retinyl esters (PubMed:15550674, PubMed:20625037, PubMed:21454566, PubMed:23066022, PubMed:23291629). Shows a preferential hydrolysis of DAGs over TAGs and MAGs and of the fatty acid (FA) esters at the sn-1 and sn-2 positions of the glycerol backbone in TAGs (By similarity). Preferentially hydrolyzes FA esters at the sn-3 position of the glycerol backbone in DAGs (PubMed:23066022). Catalyzes the hydrolysis of 2-arachidonoylglycerol, an endocannabinoid and of 2-acetyl monoalkylglycerol ether, the penultimate precursor of the pathway for de novo synthesis of platelet-activating factor (PubMed:20625037, PubMed:21454566). In adipose tissue and heart, it primarily hydrolyzes stored triglycerides to free fatty acids, while in steroidogenic tissues, it principally converts cholesteryl esters to free cholesterol for steroid hormone production (By similarity). {ECO:0000250|UniProtKB:P15304, ECO:0000250|UniProtKB:Q05469, ECO:0000269|PubMed:15550674, ECO:0000269|PubMed:20625037, ECO:0000269|PubMed:21454566, ECO:0000269|PubMed:23066022, ECO:0000269|PubMed:23291629}.
Temperature Dependency
PH Dependency
Pathway PATHWAY: Glycerolipid metabolism; triacylglycerol degradation.
nucleotide Binding
Features Active site (3); Alternative sequence (1); Chain (1); Modified residue (7); Motif (1); Region (2); Sequence conflict (4)
Keywords Alternative splicing;Cell membrane;Cholesterol metabolism;Cytoplasm;Hydrolase;Lipid degradation;Lipid droplet;Lipid metabolism;Membrane;Phosphoprotein;Reference proteome;Steroid metabolism;Sterol metabolism
Interact With
Induction
Subcellular Location SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:15550674}. Membrane, caveola {ECO:0000250|UniProtKB:Q05469}. Cytoplasm, cytosol {ECO:0000269|PubMed:15550674}. Lipid droplet {ECO:0000269|PubMed:15878856}. Note=Found in the high-density caveolae (By similarity). Translocates to the cytoplasm from the caveolae upon insulin stimulation (By similarity). Phosphorylation by AMPK reduces its translocation towards the lipid droplets. {ECO:0000250|UniProtKB:Q05469, ECO:0000269|PubMed:15878856}.
Modified Residue MOD_RES 557; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:P16386"; MOD_RES 559; /note="Phosphoserine; by AMPK"; /evidence="ECO:0000305|PubMed:19921680, ECO:0007744|PubMed:21183079"; MOD_RES 574; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:21183079"; MOD_RES 597; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:P15304"; MOD_RES 618; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:P15304"; MOD_RES 650; /note="Phosphoserine"; /evidence="ECO:0000250|UniProtKB:P15304"; MOD_RES 651; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:21183079"
Post Translational Modification PTM: Phosphorylation by AMPK reduces its translocation towards the lipid droplets. {ECO:0000269|PubMed:15878856, ECO:0000269|PubMed:19921680}.
Signal Peptide
Structure 3D
Cross Reference PDB -
Mapped Pubmed ID 10639158; 11063252; 11076952; 11217851; 11316346; 11440986; 11522661; 11551864; 11564684; 11717312; 11751901; 11809748; 12193545; 12466851; 12482847; 12832420; 12835327; 12865325; 12923228; 12954598; 13129924; 14643795; 14657254; 14752112; 15142983; 15220197; 15242332; 15271647; 15292223; 15345679; 15701680; 15961788; 16091387; 16199803; 16243839; 16765472; 16804080; 16818490; 16985254; 17026959; 17074755; 17114792; 17134676; 17215164; 17711991; 17886267; 18335062; 18337240; 18480494; 18492774; 18572100; 18664600; 18804448; 18824087; 19023560; 19246492; 19491295; 19515989; 19619509; 19706782; 19723498; 19755426; 19785415; 20107043; 20143880; 20435159; 20534721; 20950707; 21111707; 21180279; 21241784; 21267068; 21464445; 21505145; 21543206; 21566206; 21677750; 21680814; 21738729; 21857651; 21969372; 22842588; 22988039; 23362264; 23369366; 23431266; 23471217; 23878361; 24086110; 24194600; 24196706; 24265455; 24273196; 24440819; 24797631; 24891333; 24945349; 25100058; 25351614; 25535287; 25677823; 25732851; 25879679; 26122391; 26143381; 26220403; 26724218; 27185876; 27355565; 27489310; 27596982; 27626380; 27754788; 27920259; 27974211; 28364022; 28459858; 28488768; 28851734; 29232702; 29728617; 30086728; 30352954; 30862682; 30937958; 31558710; 32361002; 33059001; 33372146; 33549847; 33692445; 33732701; 34461308; 34638755; 7560076; 7698777; 8104872; 8105016; 8263420; 8288233; 8660658; 8798769; 8812477; 8827514; 9077551; 9173930; 9446609; 9582279; 9615220;
Motif MOTIF 349..351; /note=Involved in the stabilization of the negatively charged intermediate by the formation of the oxyanion hole; /evidence=ECO:0000250|UniProtKB:Q5NUF3
Gene Encoded By
Mass 83,348
Kinetics BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.25 uM for 1-(9Z-octadecenoyl)-glycerol {ECO:0000269|PubMed:21454566}; KM=0.26 uM for 2-(9Z-octadecenoyl)-glycerol {ECO:0000269|PubMed:21454566}; KM=0.27 uM for 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol {ECO:0000269|PubMed:21454566};
Metal Binding
Rhea ID RHEA:32731; RHEA:12044; RHEA:15245; RHEA:33875; RHEA:33876; RHEA:13933; RHEA:13934; RHEA:38455; RHEA:38456; RHEA:26132; RHEA:26133; RHEA:38487; RHEA:38488; RHEA:38491; RHEA:38492; RHEA:38563; RHEA:38564; RHEA:39935; RHEA:39936; RHEA:39939; RHEA:39940; RHEA:38379; RHEA:38381; RHEA:38383; RHEA:38384; RHEA:38575; RHEA:38576; RHEA:38659; RHEA:38660
Cross Reference Brenda 3.1.1.79;