IED Industry Enzyme Database

Detail Information for IndEnz0005000694
IED ID IndEnz0005000694
Enzyme Type ID lipase000694
Protein Name Monoglyceride lipase
MGL
EC 3.1.1.23
HU-K5
Lysophospholipase homolog
Lysophospholipase-like
Monoacylglycerol lipase
MAGL
Gene Name MGLL
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 MPEESSPRRTPQSIPYQDLPHLVNADGQYLFCRYWKPTGTPKALIFVSHGAGEHSGRYEELARMLMGLDLLVFAHDHVGHGQSEGERMVVSDFHVFVRDVLQHVDSMQKDYPGLPVFLLGHSMGGAIAILTAAERPGHFAGMVLISPLVLANPESATTFKVLAAKVLNLVLPNLSLGPIDSSVLSRNKTEVDIYNSDPLICRAGLKVCFGIQLLNAVSRVERALPKLTVPFLLLQGSADRLCDSKGAYLLMELAKSQDKTLKIYEGAYHVLHKELPEVTNSVFHEINMWVSQRTATAGTASPP
Enzyme Length 303
Uniprot Accession Number Q99685
Absorption
Active Site ACT_SITE 122; /note=Nucleophile; /evidence=ECO:0000269|PubMed:19957260; ACT_SITE 239; /note=Charge relay system; /evidence=ECO:0000305|PubMed:19957260; ACT_SITE 269; /note=Charge relay system; /evidence=ECO:0000305|PubMed:19957260
Activity Regulation
Binding Site
Calcium Binding
catalytic Activity CATALYTIC ACTIVITY: Reaction=Hydrolyzes glycerol monoesters of long-chain fatty acids.; EC=3.1.1.23; Evidence={ECO:0000269|PubMed:19029917, ECO:0000269|PubMed:20079333, ECO:0000269|PubMed:21049984, ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842}; CATALYTIC ACTIVITY: Reaction=1-octanoylglycerol + H2O = glycerol + H(+) + octanoate; Xref=Rhea:RHEA:44328, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:25646, ChEBI:CHEBI:85241; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44329; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842}; 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:19029917, ECO:0000269|PubMed:20079333, ECO:0000269|PubMed:21049984, ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26133; Evidence={ECO:0000269|PubMed:19029917, ECO:0000269|PubMed:20079333, ECO:0000269|PubMed:21049984, ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842}; CATALYTIC ACTIVITY: Reaction=1-decanoylglycerol + H2O = decanoate + glycerol + H(+); Xref=Rhea:RHEA:44320, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:27689, ChEBI:CHEBI:75547; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44321; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842}; CATALYTIC ACTIVITY: Reaction=1-dodecanoylglycerol + H2O = dodecanoate + glycerol + H(+); Xref=Rhea:RHEA:44316, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:18262, ChEBI:CHEBI:75539; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44317; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842}; CATALYTIC ACTIVITY: Reaction=1-tetradecanoylglycerol + H2O = glycerol + H(+) + tetradecanoate; Xref=Rhea:RHEA:44312, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30807, ChEBI:CHEBI:75562; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44313; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842}; CATALYTIC ACTIVITY: Reaction=2-hexadecanoylglycerol + H2O = glycerol + H(+) + hexadecanoate; Xref=Rhea:RHEA:39963, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:75455; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39964; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842}; 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:20079333, ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38488; Evidence={ECO:0000269|PubMed:20079333, ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842}; 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:22969151, ECO:0000269|PubMed:24368842};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38492; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842}; CATALYTIC ACTIVITY: Reaction=2-(9Z,12Z-octadecadienoyl)-glycerol + H2O = (9Z,12Z)-octadecadienoate + glycerol + H(+); Xref=Rhea:RHEA:44732, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30245, ChEBI:CHEBI:75457; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44733; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842}; CATALYTIC ACTIVITY: Reaction=1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + glycerol + H(+); Xref=Rhea:RHEA:44728, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:32395, ChEBI:CHEBI:75612; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44729; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842}; CATALYTIC ACTIVITY: Reaction=1-(9Z,12Z-octadecadienoyl)-glycerol + H2O = (9Z,12Z)-octadecadienoate + glycerol + H(+); Xref=Rhea:RHEA:48428, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30245, ChEBI:CHEBI:75568; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48429; Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842}; CATALYTIC ACTIVITY: Reaction=(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + glycerol + H(+); Xref=Rhea:RHEA:39955, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30823, ChEBI:CHEBI:75937; Evidence={ECO:0000250|UniProtKB:O35678}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoylglycerol + H2O = glycerol + H(+) + hexadecanoate; Xref=Rhea:RHEA:39959, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:69081; Evidence={ECO:0000269|PubMed:20079333};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39960; Evidence={ECO:0000269|PubMed:20079333}; CATALYTIC ACTIVITY: Reaction=1-octadecanoylglycerol + H2O = glycerol + H(+) + octadecanoate; Xref=Rhea:RHEA:38363, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:25629, ChEBI:CHEBI:75555; Evidence={ECO:0000269|PubMed:20079333};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38364; Evidence={ECO:0000269|PubMed:20079333}; CATALYTIC ACTIVITY: Reaction=H2O + prostaglandin E2 1-glyceryl ester = glycerol + H(+) + prostaglandin E2; Xref=Rhea:RHEA:48296, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:90230, ChEBI:CHEBI:606564; Evidence={ECO:0000269|PubMed:21049984, ECO:0000269|PubMed:24368842};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48297; Evidence={ECO:0000269|PubMed:21049984, ECO:0000269|PubMed:24368842}; CATALYTIC ACTIVITY: Reaction=H2O + prostaglandin D2-1-glycerol ester = glycerol + H(+) + prostaglandin D2; Xref=Rhea:RHEA:45412, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:57406, ChEBI:CHEBI:85232; Evidence={ECO:0000269|PubMed:24368842};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45413; Evidence={ECO:0000269|PubMed:24368842}; CATALYTIC ACTIVITY: Reaction=11-oxo-5Z,9,12E,14E-prostatetraenoate + H2O = 15-deoxy-Delta(12,14)-prostaglandin J2 + glycerol + H(+); Xref=Rhea:RHEA:45416, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:85236, ChEBI:CHEBI:85238; Evidence={ECO:0000269|PubMed:24368842};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45417; Evidence={ECO:0000269|PubMed:24368842}; CATALYTIC ACTIVITY: Reaction=H2O + prostaglandin F2alpha 1-glyceryl ester = glycerol + H(+) + prostaglandin F2alpha; Xref=Rhea:RHEA:48300, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:57404, ChEBI:CHEBI:90233; Evidence={ECO:0000269|PubMed:21049984};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48301; Evidence={ECO:0000269|PubMed:21049984};
DNA Binding
EC Number 3.1.1.23
Enzyme Function FUNCTION: Converts monoacylglycerides to free fatty acids and glycerol (PubMed:19029917, PubMed:20079333, PubMed:21049984, PubMed:22969151, PubMed:24368842). Hydrolyzes the endocannabinoid 2-arachidonoylglycerol, and thereby contributes to the regulation of endocannabinoid signaling, nociperception and perception of pain (PubMed:19029917, PubMed:20079333, PubMed:21049984, PubMed:22969151, PubMed:24368842). Regulates the levels of fatty acids that serve as signaling molecules and promote cancer cell migration, invasion and tumor growth (PubMed:20079333). {ECO:0000269|PubMed:19029917, ECO:0000269|PubMed:20079333, ECO:0000269|PubMed:21049984, ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842}.
Temperature Dependency
PH Dependency
Pathway PATHWAY: Glycerolipid metabolism; triacylglycerol degradation. {ECO:0000250|UniProtKB:O35678}.
nucleotide Binding
Features Active site (3); Alternative sequence (2); Beta strand (11); Chain (1); Erroneous initiation (7); Helix (13); Modified residue (2); Mutagenesis (4); Sequence conflict (1); Turn (1)
Keywords 3D-structure;Alternative splicing;Cytoplasm;Fatty acid biosynthesis;Fatty acid metabolism;Hydrolase;Lipid biosynthesis;Lipid degradation;Lipid metabolism;Membrane;Nitration;Phosphoprotein;Reference proteome;Serine esterase
Interact With P07550
Induction
Subcellular Location SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250|UniProtKB:O35678}. Membrane {ECO:0000250|UniProtKB:O35678}; Peripheral membrane protein {ECO:0000250|UniProtKB:O35678}.
Modified Residue MOD_RES 10; /note=Phosphothreonine; /evidence=ECO:0000250|UniProtKB:O35678; MOD_RES 58; /note=3'-nitrotyrosine; /evidence=ECO:0000250|UniProtKB:O35678
Post Translational Modification
Signal Peptide
Structure 3D X-ray crystallography (8)
Cross Reference PDB 3HJU; 3JW8; 3JWE; 3PE6; 4UUQ; 5ZUN; 6AX1; 6BQ0;
Mapped Pubmed ID 1249056; 15272052; 16169070; 17621164; 18096503; 18452279; 18721756; 19014633; 19233690; 19913121; 20464001; 20628086; 20711500; 20855465; 20976246; 21118518; 21308848; 21543155; 21802006; 22349814; 22664939; 22827915; 23455058; 23553709; 24593280; 24633487; 25078047; 25120746; 25560837; 25636199; 26000748; 26555264; 26595473; 26948343; 26997225; 27366945; 27767105; 27884159; 28088576; 28213089; 29148769; 29379013; 29498843; 29968710; 30251836; 30978461; 31357777; 31695165; 31734989; 32483456; 32532977; 33973101; 3955067; 7295321;
Motif
Gene Encoded By
Mass 33,261
Kinetics BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=110 uM for 2-arachidonoyglycerol {ECO:0000269|PubMed:22969151}; KM=15 uM for 2-glyceryl-15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ(2)-G) {ECO:0000269|PubMed:24368842}; Vmax=120 nmol/min/mg enzyme toward 2-arachidonoyglycerol {ECO:0000269|PubMed:22969151}; Vmax=89 nmol/min/mg enzyme toward 2-glyceryl-15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ(2)-G) {ECO:0000269|PubMed:24368842};
Metal Binding
Rhea ID RHEA:44328; RHEA:44329; RHEA:26132; RHEA:26133; RHEA:44320; RHEA:44321; RHEA:44316; RHEA:44317; RHEA:44312; RHEA:44313; RHEA:39963; RHEA:39964; RHEA:38487; RHEA:38488; RHEA:38491; RHEA:38492; RHEA:44732; RHEA:44733; RHEA:44728; RHEA:44729; RHEA:48428; RHEA:48429; RHEA:39955; RHEA:39959; RHEA:39960; RHEA:38363; RHEA:38364; RHEA:48296; RHEA:48297; RHEA:45412; RHEA:45413; RHEA:45416; RHEA:45417; RHEA:48300; RHEA:48301
Cross Reference Brenda 3.1.1.23;