MGLL_RAT
ID MGLL_RAT Reviewed; 303 AA.
AC Q8R431; Q32PZ2;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Monoglyceride lipase {ECO:0000305};
DE Short=MGL;
DE EC=3.1.1.23 {ECO:0000269|PubMed:17649977};
DE AltName: Full=Monoacylglycerol lipase;
DE Short=MAGL;
GN Name=Mgll {ECO:0000312|RGD:71039}; Synonyms=Mgl2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=12136125; DOI=10.1073/pnas.152334899;
RA Dinh T.P., Carpenter D., Leslie F.M., Freund T.F., Katona I., Sensi S.L.,
RA Kathuria S., Piomelli D.;
RT "Brain monoglyceride lipase participating in endocannabinoid
RT inactivation.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:10819-10824(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PROTEIN SEQUENCE OF 9-16; 34-41; 99-109; 179-183; 187-197; 227-240 AND
RP 263-273, AND TISSUE SPECIFICITY.
RX PubMed=9341166; DOI=10.1074/jbc.272.43.27218;
RA Karlsson M., Contreras J.A., Hellman U., Tornqvist H., Holm C.;
RT "cDNA cloning, tissue distribution, and identification of the catalytic
RT triad of monoglyceride lipase. Evolutionary relationship to esterases,
RT lysophospholipases, and haloperoxidases.";
RL J. Biol. Chem. 272:27218-27223(1997).
RN [4]
RP PROTEIN SEQUENCE OF 227-240, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Spinal cord;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (DEC-2006) to UniProtKB.
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=17649977; DOI=10.1021/bi7005898;
RA Vila A., Rosengarth A., Piomelli D., Cravatt B., Marnett L.J.;
RT "Hydrolysis of prostaglandin glycerol esters by the endocannabinoid-
RT hydrolyzing enzymes, monoacylglycerol lipase and fatty acid amide
RT hydrolase.";
RL Biochemistry 46:9578-9585(2007).
CC -!- FUNCTION: Converts monoacylglycerides to free fatty acids and glycerol
CC (PubMed:12136125). Hydrolyzes the endocannabinoid 2-
CC arachidonoylglycerol, and thereby contributes to the regulation of
CC endocannabinoid signaling, nociperception and perception of pain
CC (PubMed:12136125, PubMed:17649977). Regulates the levels of fatty acids
CC that serve as signaling molecules and promote cancer cell migration,
CC invasion and tumor growth (By similarity).
CC {ECO:0000250|UniProtKB:O35678, ECO:0000269|PubMed:12136125,
CC ECO:0000269|PubMed:17649977}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolyzes glycerol monoesters of long-chain fatty acids.;
CC EC=3.1.1.23; Evidence={ECO:0000269|PubMed:17649977};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octanoylglycerol + H2O = glycerol + H(+) + octanoate;
CC Xref=Rhea:RHEA:44328, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17754, ChEBI:CHEBI:25646, ChEBI:CHEBI:85241;
CC Evidence={ECO:0000250|UniProtKB:Q99685};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O =
CC (5Z,8Z,11Z,14Z)-eicosatetraenoate + glycerol + H(+);
CC Xref=Rhea:RHEA:26132, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17754, ChEBI:CHEBI:32395, ChEBI:CHEBI:52392;
CC Evidence={ECO:0000269|PubMed:17649977};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26133;
CC Evidence={ECO:0000269|PubMed:17649977};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-decanoylglycerol + H2O = decanoate + glycerol + H(+);
CC Xref=Rhea:RHEA:44320, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17754, ChEBI:CHEBI:27689, ChEBI:CHEBI:75547;
CC Evidence={ECO:0000250|UniProtKB:Q99685};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-dodecanoylglycerol + H2O = dodecanoate + glycerol + H(+);
CC Xref=Rhea:RHEA:44316, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17754, ChEBI:CHEBI:18262, ChEBI:CHEBI:75539;
CC Evidence={ECO:0000250|UniProtKB:Q99685};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-tetradecanoylglycerol + H2O = glycerol + H(+) +
CC tetradecanoate; Xref=Rhea:RHEA:44312, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30807,
CC ChEBI:CHEBI:75562; Evidence={ECO:0000250|UniProtKB:Q99685};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-hexadecanoylglycerol + H2O = glycerol + H(+) +
CC hexadecanoate; Xref=Rhea:RHEA:39963, ChEBI:CHEBI:7896,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754,
CC ChEBI:CHEBI:75455; Evidence={ECO:0000250|UniProtKB:Q99685};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate +
CC glycerol + H(+); Xref=Rhea:RHEA:38487, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:75342; Evidence={ECO:0000250|UniProtKB:Q99685};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate +
CC glycerol + H(+); Xref=Rhea:RHEA:38491, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:73990; Evidence={ECO:0000250|UniProtKB:Q99685};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-(9Z,12Z-octadecadienoyl)-glycerol + H2O = (9Z,12Z)-
CC octadecadienoate + glycerol + H(+); Xref=Rhea:RHEA:44732,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754,
CC ChEBI:CHEBI:30245, ChEBI:CHEBI:75457;
CC Evidence={ECO:0000250|UniProtKB:Q99685};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O =
CC (5Z,8Z,11Z,14Z)-eicosatetraenoate + glycerol + H(+);
CC Xref=Rhea:RHEA:44728, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17754, ChEBI:CHEBI:32395, ChEBI:CHEBI:75612;
CC Evidence={ECO:0000250|UniProtKB:Q99685};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z,12Z-octadecadienoyl)-glycerol + H2O = (9Z,12Z)-
CC octadecadienoate + glycerol + H(+); Xref=Rhea:RHEA:48428,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754,
CC ChEBI:CHEBI:30245, ChEBI:CHEBI:75568;
CC Evidence={ECO:0000250|UniProtKB:Q99685};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate +
CC glycerol + H(+); Xref=Rhea:RHEA:39955, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:75937; Evidence={ECO:0000250|UniProtKB:O35678};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoylglycerol + H2O = glycerol + H(+) +
CC hexadecanoate; Xref=Rhea:RHEA:39959, ChEBI:CHEBI:7896,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17754,
CC ChEBI:CHEBI:69081; Evidence={ECO:0000250|UniProtKB:O35678};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoylglycerol + H2O = glycerol + H(+) +
CC octadecanoate; Xref=Rhea:RHEA:38363, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:25629,
CC ChEBI:CHEBI:75555; Evidence={ECO:0000250|UniProtKB:Q99685};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + prostaglandin E2 1-glyceryl ester = glycerol + H(+) +
CC prostaglandin E2; Xref=Rhea:RHEA:48296, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:90230,
CC ChEBI:CHEBI:606564; Evidence={ECO:0000250|UniProtKB:Q99685};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + prostaglandin D2-1-glycerol ester = glycerol + H(+) +
CC prostaglandin D2; Xref=Rhea:RHEA:45412, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:57406,
CC ChEBI:CHEBI:85232; Evidence={ECO:0000250|UniProtKB:Q99685};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=11-oxo-5Z,9,12E,14E-prostatetraenoate + H2O = 15-deoxy-
CC Delta(12,14)-prostaglandin J2 + glycerol + H(+);
CC Xref=Rhea:RHEA:45416, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17754, ChEBI:CHEBI:85236, ChEBI:CHEBI:85238;
CC Evidence={ECO:0000250|UniProtKB:Q99685};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + prostaglandin F2alpha 1-glyceryl ester = glycerol + H(+)
CC + prostaglandin F2alpha; Xref=Rhea:RHEA:48300, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17754, ChEBI:CHEBI:57404,
CC ChEBI:CHEBI:90233; Evidence={ECO:0000250|UniProtKB:Q99685};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=10 uM for 2-arachidonoylglycerol (2-(5Z,8Z,11Z,14Z-
CC eicosatetraenoyl)-glycerol) {ECO:0000269|PubMed:17649977};
CC Note=kcat is 21 min(-1) with 2-arachidonoylglycerol (2-
CC (5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol).
CC {ECO:0000269|PubMed:17649977};
CC -!- PATHWAY: Glycerolipid metabolism; triacylglycerol degradation.
CC {ECO:0000250|UniProtKB:O35678}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q99685}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:O35678}. Membrane
CC {ECO:0000250|UniProtKB:O35678}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:O35678}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed in adipose tissue,
CC adrenal gland, ovary, heart, spleen, lung, skeletal muscle, kidney and
CC testis. Highly expressed throughout the brain.
CC {ECO:0000269|PubMed:12136125, ECO:0000269|PubMed:9341166}.
CC -!- MISCELLANEOUS: Requires non-ionic detergent for solubilization.
CC -!- MISCELLANEOUS: Short-term inhibition causes analgesia, while long-term
CC inhibition causes tolerance to endocannabinoids acting on brain
CC cannabinoid receptor CNR1, and a reduction in brain cannabinoid
CC receptor CNR1 activity. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Monoacylglycerol
CC lipase family. {ECO:0000305}.
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DR EMBL; AY081195; AAL87453.1; -; mRNA.
DR EMBL; BC107920; AAI07921.1; -; mRNA.
DR RefSeq; NP_612511.1; NM_138502.2.
DR AlphaFoldDB; Q8R431; -.
DR SMR; Q8R431; -.
DR STRING; 10116.ENSRNOP00000030271; -.
DR BindingDB; Q8R431; -.
DR ChEMBL; CHEMBL3321; -.
DR GuidetoPHARMACOLOGY; 1399; -.
DR SwissLipids; SLP:000001427; -.
DR ESTHER; ratno-MGLL; Monoglyceridelipase_lysophospholip.
DR iPTMnet; Q8R431; -.
DR PhosphoSitePlus; Q8R431; -.
DR SwissPalm; Q8R431; -.
DR PaxDb; Q8R431; -.
DR PRIDE; Q8R431; -.
DR ABCD; Q8R431; 1 sequenced antibody.
DR Ensembl; ENSRNOT00000029125; ENSRNOP00000030271; ENSRNOG00000014508.
DR GeneID; 29254; -.
DR KEGG; rno:29254; -.
DR UCSC; RGD:71039; rat.
DR CTD; 11343; -.
DR RGD; 71039; Mgll.
DR eggNOG; KOG1455; Eukaryota.
DR GeneTree; ENSGT00390000011364; -.
DR HOGENOM; CLU_026209_7_1_1; -.
DR InParanoid; Q8R431; -.
DR OrthoDB; 919091at2759; -.
DR PhylomeDB; Q8R431; -.
DR BRENDA; 3.1.1.23; 5301.
DR Reactome; R-RNO-1482883; Acyl chain remodeling of DAG and TAG.
DR Reactome; R-RNO-426048; Arachidonate production from DAG.
DR UniPathway; UPA00256; -.
DR PRO; PR:Q8R431; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000014508; Expressed in adult mammalian kidney and 19 other tissues.
DR ExpressionAtlas; Q8R431; baseline and differential.
DR Genevisible; Q8R431; RN.
DR GO; GO:0030424; C:axon; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0019898; C:extrinsic component of membrane; ISS:UniProtKB.
DR GO; GO:0005811; C:lipid droplet; TAS:Reactome.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0045202; C:synapse; IDA:RGD.
DR GO; GO:0043196; C:varicosity; ISO:RGD.
DR GO; GO:0047372; F:acylglycerol lipase activity; IDA:UniProtKB.
DR GO; GO:0016787; F:hydrolase activity; IDA:RGD.
DR GO; GO:0016298; F:lipase activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0046464; P:acylglycerol catabolic process; ISS:UniProtKB.
DR GO; GO:0019369; P:arachidonic acid metabolic process; ISS:UniProtKB.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0060292; P:long-term synaptic depression; ISO:RGD.
DR GO; GO:0052651; P:monoacylglycerol catabolic process; IDA:UniProtKB.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; IMP:RGD.
DR GO; GO:0030516; P:regulation of axon extension; ISO:RGD.
DR GO; GO:2000124; P:regulation of endocannabinoid signaling pathway; ISO:RGD.
DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0051930; P:regulation of sensory perception of pain; ISS:UniProtKB.
DR GO; GO:0009966; P:regulation of signal transduction; ISS:UniProtKB.
DR GO; GO:0019433; P:triglyceride catabolic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR000073; AB_hydrolase_1.
DR InterPro; IPR022742; Hydrolase_4.
DR Pfam; PF12146; Hydrolase_4; 1.
DR PRINTS; PR00111; ABHYDROLASE.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS00120; LIPASE_SER; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Direct protein sequencing; Fatty acid biosynthesis;
KW Fatty acid metabolism; Hydrolase; Lipid biosynthesis; Lipid degradation;
KW Lipid metabolism; Membrane; Nitration; Phosphoprotein; Reference proteome;
KW Serine esterase.
FT CHAIN 1..303
FT /note="Monoglyceride lipase"
FT /id="PRO_0000191267"
FT ACT_SITE 122
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:O35678"
FT ACT_SITE 239
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:O35678"
FT ACT_SITE 269
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:O35678"
FT MOD_RES 10
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O35678"
FT MOD_RES 58
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O35678"
FT MOD_RES 189
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35678"
SQ SEQUENCE 303 AA; 33500 MW; 49CD407D97A1A971 CRC64;
MPEASSPRRT PQNVPYQDLP HLVNADGQYL FCRYWKPSGT PKALIFVSHG AGEHCGRYDE
LAQMLKRLDM LVFAHDHVGH GQSEGERMVV SDFQVFVRDL LQHVNTVQKD YPEVPVFLLG
HSMGGAISIL AAAERPTHFS GMILISPLIL ANPESASTLK VLAAKLLNFV LPNISLGRID
SSVLSRNKSE VDLYNSDPLI CHAGVKVCFG IQLLNAVSRV ERAMPRLTLP FLLLQGSADR
LCDSKGAYLL MESSPSQDKT LKMYEGAYHV LHKELPEVTN SVLHEINTWV SHRIAVAGAR
CLP
