| IED ID | IndEnz0010001371 |
| Enzyme Type ID | esterase001371 |
| 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 | 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 | MEPGSKSVSRSDWQPEPHQRPITPLEPGPEKTPIAQPESKTLQGSNTQQKPASNQRPLTQQETPAQHDAESQKEPRAQQKSASQEEFLAPQKPAPQQSPYIQRVLLTQQEAASQQGPGLGKESITQQEPALRQRHVAQPGPGPGEPPPAQQEAESTPAAQAKPGAKREPSAPTESTSQETPEQSDKQTTPVQGAKSKQGSLTELGFLTKLQELSIQRSALEWKALSEWVTDSESESDVGSSSDTDSPATMGGMVAQGVKLGFKGKSGYKVMSGYSGTSPHEKTSARNHRHYQDTASRLIHNMDLRTMTQSLVTLAEDNIAFFSSQGPGETAQRLSGVFAGVREQALGLEPALGRLLGVAHLFDLDPETPANGYRSLVHTARCCLAHLLHKSRYVASNRRSIFFRTSHNLAELEAYLAALTQLRALVYYAQRLLVTNRPGVLFFEGDEGLTADFLREYVTLHKGCFYGRCLGFQFTPAIRPFLQTISIGLVSFGEHYKRNETGLSVAASSLFTSGRFAIDPELRGAEFERITQNLDVHFWKAFWNITEMEVLSSLANMASATVRVSRLLSLPPEAFEMPLTADPTLTVTISPPLAHTGPGPVLVRLISYDLREGQDSEELSSLIKSNGQRSLELWPRPQQAPRSRSLIVHFHGGGFVAQTSRSHEPYLKSWAQELGAPIISIDYSLAPEAPFPRALEECFFAYCWAIKHCALLGSTGERICLAGDSAGGNLCFTVALRAAAYGVRVPDGIMAAYPATMLQPAASPSRLLSLMDPLLPLSVLSKCVSAYAGAKTEDHSNSDQKALGMMGLVRRDTALLLRDFRLGASSWLNSFLELSGRKSQKMSEPIAEPMRRSVSEAALAQPQGPLGTDSLKNLTLRDLSLRGNSETSSDTPEMSLSAETLSPSTPSDVNFLLPPEDAGEEAEAKNELSPMDRGLGVRAAFPEGFHPRRSSQGATQMPLYSSPIVKNPFMSPLLAPDSMLKSLPPVHIVACALDPMLDDSVMLARRLRNLGQPVTLRVVEDLPHGFLTLAALCRETRQAAELCVERIRLVLTPPAGAGPSGETGAAGVDGGCGGRH |
| Enzyme Length | 1076 |
| Uniprot Accession Number | Q05469 |
| Absorption | |
| Active Site | ACT_SITE 725; /evidence="ECO:0000250|UniProtKB:Q8BLF1, ECO:0000255|PROSITE-ProRule:PRU10038"; ACT_SITE 994; /evidence="ECO:0000250|UniProtKB:Q8BLF1"; ACT_SITE 1024; /evidence="ECO:0000250|UniProtKB:Q8BLF1" |
| Activity Regulation | ACTIVITY REGULATION: Retinyl ester hydrolase is inhibited by bis-p-nitrophenyl phosphate. {ECO:0000269|PubMed:15955102}. |
| 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:19800417, ECO:0000269|PubMed:8812477}; 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:15955102, ECO:0000269|PubMed:19800417}; 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:0000250|UniProtKB:P15304}; CATALYTIC ACTIVITY: Reaction=Hydrolyzes glycerol monoesters of long-chain fatty acids.; EC=3.1.1.23; Evidence={ECO:0000250|UniProtKB:P54310}; 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:19800417};PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38381; Evidence={ECO:0000305|PubMed:19800417}; 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:0000269|PubMed:19800417};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38384; Evidence={ECO:0000305|PubMed:19800417}; 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:15716583};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33876; Evidence={ECO:0000305|PubMed:15716583}; 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:0000269|PubMed:15955102};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38576; Evidence={ECO:0000305|PubMed:15955102}; 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:15955102};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13934; Evidence={ECO:0000305|PubMed:15955102}; 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=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:0000250|UniProtKB:P54310};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38488; 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}; 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:8812477, PubMed:15955102, PubMed:15716583, PubMed:19800417). Shows a preferential hydrolysis of DAGs over TAGs and MAGs and preferentially hydrolyzes the fatty acid (FA) esters at the sn-3 position of the glycerol backbone in DAGs (PubMed:19800417). Preferentially hydrolyzes FA esters at the sn-1 and sn-2 positions of the glycerol backbone in TAGs (By similarity). 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 (By similarity). {ECO:0000250|UniProtKB:P15304, ECO:0000250|UniProtKB:P54310, ECO:0000269|PubMed:15716583, ECO:0000269|PubMed:15955102, ECO:0000269|PubMed:19800417, ECO:0000269|PubMed:8812477}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Glycerolipid metabolism; triacylglycerol degradation. |
| nucleotide Binding | |
| Features | Active site (3); Alternative sequence (1); Chain (1); Compositional bias (6); Modified residue (6); Motif (1); Natural variant (10); Region (4); Sequence conflict (5) |
| Keywords | Alternative splicing;Cell membrane;Cholesterol metabolism;Cytoplasm;Diabetes mellitus;Hydrolase;Lipid degradation;Lipid droplet;Lipid metabolism;Membrane;Obesity;Phosphoprotein;Reference proteome;Steroid metabolism;Sterol metabolism |
| Interact With | Q3SY00 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17026959}. Membrane, caveola {ECO:0000269|PubMed:16803459, ECO:0000269|PubMed:17026959}. Cytoplasm, cytosol {ECO:0000269|PubMed:17026959}. Lipid droplet {ECO:0000250|UniProtKB:P54310}. Note=Found in the high-density caveolae. Translocates to the cytoplasm from the caveolae upon insulin stimulation (PubMed:17026959). Phosphorylation by AMPK reduces its translocation towards the lipid droplets (By similarity). {ECO:0000250|UniProtKB:P54310, ECO:0000269|PubMed:17026959}. |
| Modified Residue | MOD_RES 853; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P16386; MOD_RES 855; /note=Phosphoserine; by AMPK; /evidence=ECO:0000250|UniProtKB:P16386; MOD_RES 897; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P15304; MOD_RES 929; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P15304; MOD_RES 950; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P15304; MOD_RES 951; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P15304 |
| Post Translational Modification | PTM: Phosphorylation by AMPK reduces its translocation towards the lipid droplets. {ECO:0000250|UniProtKB:P54310}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10318917; 10671541; 10694408; 10940339; 11574428; 11682468; 11731226; 11850754; 11979403; 12514936; 12518034; 12534454; 12701046; 12727985; 12730334; 12765952; 12832420; 12970365; 14984467; 15231718; 15260473; 15308678; 15345679; 15456755; 15609025; 15871848; 16169070; 16188906; 16243839; 16534522; 16690773; 16752181; 16822962; 16940551; 17074755; 17318300; 17327373; 17356053; 17587400; 18249203; 18383440; 18398140; 18660489; 18820256; 18824087; 18996102; 19018281; 19164092; 19336475; 19369647; 19433586; 19491387; 19695247; 19755426; 19913121; 19996383; 20017959; 20495294; 20628086; 20855565; 20926921; 21042876; 21081692; 21186937; 21241784; 21338323; 21498783; 21543206; 21680814; 21826994; 21919688; 21933124; 22166756; 22493722; 22553833; 22982310; 23576171; 23688034; 23907381; 23940618; 2537200; 25475467; 25790476; 25819461; 26514267; 27862896; 28123934; 29500454; 31150775; 31427606; 33445064; 3345839; 33502468; 33725252; 33758172; 6643478; 7240206; 9417067; |
| Motif | MOTIF 651..653; /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 | 116,598 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:32731; RHEA:12044; RHEA:15245; RHEA:38379; RHEA:38381; RHEA:38383; RHEA:38384; RHEA:33875; RHEA:33876; RHEA:38575; RHEA:38576; 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:38659; RHEA:38660 |
| Cross Reference Brenda | 3.1.1.79; |