| IED ID | IndEnz0010001939 |
| Enzyme Type ID | esterase001939 |
| 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 | Rattus norvegicus (Rat) |
| 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 Rattus Rattus norvegicus (Rat) |
| Enzyme Sequence | MKPRRPISFTREITAMEPSSTSVSRPEWRPEAQQTLTDYPGSRELQEFGIPQKQSLPNEATAQQGAEFQQEQGVQQSTLLQKLLTPLAFPVPQQSFPSHKVHSDQQEATSQNGPGAGKVHTTQKELEHRDEHVGTAESGPAEPPPATEVEATSIAQAVSGPDKKLPTQTDLVSQERAEQSDPTAQQTPLVQGVKSDQGSLIESGILARLQKLAIQQPSQEWKTFLDCVTESDMEKYLNSSSKSNPPEPSGGTVIPGTLPSKQKPDCGKMSGYGGKLPHGKKGILQKHKHYWDTASAFSHSMDLRTMTQSLVALAEDNMAFFSSQGPGETARRLSNVFAGVREQALGLEPTLGQLLGVAHHFDLDTETPANGYRSLVHTARCCLAHLLHKSRYVASNRRSIFFRASHNLAELEAYLAALTQLRALAYYAQRLLTINRPGVLFFEGDEGLSADFLQDYVTLHKGCFYGRCLGFQFTPAIRPFLQTLSIGLVSFGEHYKRNETGLSVTASSLFTGGRFAIDPELRGAEFERIIQNLDVHFWKAFWNITEIEVLSSLANMASTTVRVSRLLSLPPEAFEMPLTSDPKLTVTISPPLAHTGPGPVLARLISYDLREGQDSKMLNSLAKSEGPRLELRPRPQQAPRSRALVVHIHGGGFVAQTSKSHEPYLKNWAQELGVPIISIDYSLAPEAPFPRALEECFFAYCWAVKHCELLGSTGERICLAGDSAGGNLCITVSLRAAAYGVRVPDGIMAAYPVTTLQSSASPSRLLSLMDPLLPLSVLSKCVSAYSGTETEDHFDSDQKALGVMGLVQRDTSLFLRDLRLGASSWLNSFLELSGRKPHKTPLPATETLRPTDSGRLTESMRRSVSEAALAQPEGLLGTDSLKKLTIKDLSFKGNSEPSDSPEMSQSMETLGPSTPSDVNFFLRSGNSQEEAETRDDISPMDGIPRVRAAFPDGFHPRRSSQGVLHMPLYSSPIVKNPFMSPLLAPDVMLKTLPPVHLVACALDPMLDDSVMFARRLKDLGQPVTLKVVEDLPHGFLSLAALCRETRQAAELCVQRIRLILTPPAAPLT |
| Enzyme Length | 1068 |
| Uniprot Accession Number | P15304 |
| Absorption | |
| Active Site | ACT_SITE 723; /evidence=ECO:0000255|PROSITE-ProRule:PRU10038; ACT_SITE 1003; /evidence=ECO:0000250|UniProtKB:Q5NUF3; ACT_SITE 1033; /evidence=ECO:0000250|UniProtKB:Q5NUF3 |
| Activity Regulation | ACTIVITY REGULATION: Rapidly activated by cAMP-dependent phosphorylation under the influence of catecholamines (PubMed:6374655). Dephosphorylation and inactivation are controlled by insulin (PubMed:6374655). cAMP stimulates its retinyl ester hydrolase activity (PubMed:9162045). {ECO:0000269|PubMed:6374655, ECO:0000269|PubMed:9162045}. |
| 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:6643478}; 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:6643478, ECO:0000269|PubMed:9162045}; 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:6643478, ECO:0000305|PubMed:6374655}; CATALYTIC ACTIVITY: Reaction=Hydrolyzes glycerol monoesters of long-chain fatty acids.; EC=3.1.1.23; Evidence={ECO:0000250|UniProtKB:P54310}; 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:10694408, ECO:0000269|PubMed:9162045};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33876; Evidence={ECO:0000305|PubMed:9162045}; 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:9162045};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13934; Evidence={ECO:0000305|PubMed:9162045}; 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:0000269|PubMed:6643478};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38660; Evidence={ECO:0000305|PubMed:6643478}; 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:6643478};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38488; Evidence={ECO:0000305|PubMed:6643478}; 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:0000269|PubMed:6643478};PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38381; Evidence={ECO:0000305|PubMed:6643478}; 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 + (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:0000250|UniProtKB:P54310};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38456; Evidence={ECO:0000250|UniProtKB:P54310}; 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:0000250|UniProtKB:P54310};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26133; Evidence={ECO:0000250|UniProtKB:P54310}; 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:0000250|UniProtKB:P54310};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38492; Evidence={ECO:0000250|UniProtKB:P54310}; 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:0000250|UniProtKB:P54310};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38564; Evidence={ECO:0000250|UniProtKB:P54310}; 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:0000250|UniProtKB:P54310};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39936; Evidence={ECO:0000250|UniProtKB:P54310}; 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:0000250|UniProtKB:P54310};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39940; Evidence={ECO:0000250|UniProtKB:P54310}; |
| 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:6643478, PubMed:9162045, PubMed:10694408). Shows a preferential hydrolysis of DAGs over TAGs and MAGs and preferentially hydrolyzes the fatty acid (FA) esters at the sn-3 position of DAGs (By similarity). Preferentially hydrolyzes fatty acids at the sn-1 and sn-2 positions of TAGs (PubMed:6643478). 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 (By similarity). 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 (PubMed:1770312). {ECO:0000250|UniProtKB:P54310, ECO:0000269|PubMed:10694408, ECO:0000269|PubMed:6643478, ECO:0000269|PubMed:9162045, ECO:0000303|PubMed:1770312}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Glycerolipid metabolism; triacylglycerol degradation. |
| nucleotide Binding | |
| Features | Active site (3); Alternative sequence (1); Chain (1); Compositional bias (8); Modified residue (8); Motif (1); Mutagenesis (5); Region (5) |
| 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:0000250|UniProtKB:Q05469}. Membrane, caveola {ECO:0000250|UniProtKB:Q05469}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q05469}. 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 863; /note="Phosphoserine; by PKA"; /evidence="ECO:0000269|PubMed:9417067"; MOD_RES 865; /note="Phosphoserine"; /evidence="ECO:0000269|PubMed:15878856, ECO:0007744|PubMed:22673903"; MOD_RES 906; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:22673903"; MOD_RES 927; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:22673903"; MOD_RES 938; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:22673903"; MOD_RES 959; /note="Phosphoserine; by PKA"; /evidence="ECO:0000269|PubMed:9417067"; MOD_RES 960; /note="Phosphoserine; by PKA"; /evidence="ECO:0000269|PubMed:9417067"; MOD_RES 1068; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:22673903" |
| Post Translational Modification | PTM: Phosphorylation by AMPK reduces its translocation towards the lipid droplets. {ECO:0000269|PubMed:15878856}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10064727; 10318917; 11016888; 11581251; 12925534; 14739077; 15627655; 15654127; 15697220; 16328496; 16906479; 17712951; 18180326; 18413675; 19664063; 20621463; 2165906; 22951290; 26506094; 32967199; 9636039; |
| Motif | MOTIF 649..651; /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 | 116,812 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=161 uM for retinyl palmitate {ECO:0000269|PubMed:9162045}; KM=33 uM for 1,2-dioleoylglycerol {ECO:0000269|PubMed:6643478}; KM=33 uM for 1,3-dioleoylglycerol {ECO:0000269|PubMed:6643478}; KM=2.2 uM for cholesteryl (9Z-octadecenoate) (dimeric form) {ECO:0000269|PubMed:10694408}; KM=2.2 uM for cholesteryl (9Z-octadecenoate) (monomeric form) {ECO:0000269|PubMed:10694408}; Vmax=0.141 nmol/h/mg enzyme with cholesteryl (9Z-octadecenoate) as substrate (dimeric form) {ECO:0000269|PubMed:10694408}; Vmax=0.003 nmol/h/mg enzyme with cholesteryl (9Z-octadecenoate) as substrate (monomeric form) {ECO:0000269|PubMed:10694408}; |
| Metal Binding | |
| Rhea ID | RHEA:32731; RHEA:12044; RHEA:15245; RHEA:33875; RHEA:33876; RHEA:13933; RHEA:13934; RHEA:38659; RHEA:38660; RHEA:38487; RHEA:38488; RHEA:38379; RHEA:38381; RHEA:38383; RHEA:38384; RHEA:38575; RHEA:38576; RHEA:38455; RHEA:38456; RHEA:26132; RHEA:26133; RHEA:38491; RHEA:38492; RHEA:38563; RHEA:38564; RHEA:39935; RHEA:39936; RHEA:39939; RHEA:39940 |
| Cross Reference Brenda | 3.1.1.79; |