MGLL_HUMAN
ID MGLL_HUMAN Reviewed; 303 AA.
AC Q99685; B3KRC2; B7Z9D1; Q6IBG9; Q96AA5;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2004, sequence version 2.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Monoglyceride lipase {ECO:0000303|PubMed:11470505};
DE Short=MGL {ECO:0000312|HGNC:HGNC:17038};
DE EC=3.1.1.23 {ECO:0000269|PubMed:19029917, ECO:0000269|PubMed:20079333, ECO:0000269|PubMed:21049984, ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};
DE AltName: Full=HU-K5 {ECO:0000303|PubMed:9495531};
DE AltName: Full=Lysophospholipase homolog;
DE AltName: Full=Lysophospholipase-like;
DE AltName: Full=Monoacylglycerol lipase {ECO:0000303|PubMed:20079333};
DE Short=MAGL {ECO:0000303|PubMed:20079333};
GN Name=MGLL {ECO:0000312|HGNC:HGNC:17038};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=9495531; DOI=10.1016/s0168-1702(97)00122-6;
RA Wall E.M., Cao J.X., Chen N., Buller R.M.L., Upton C.;
RT "A novel poxvirus gene and its human homolog are similar to an E. coli
RT lysophospholipase.";
RL Virus Res. 52:157-167(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Adipose tissue;
RX PubMed=11470505; DOI=10.1016/s0378-1119(01)00559-5;
RA Karlsson M., Reue K., Xia Y.-R., Lusis A.J., Langin D., Tornqvist H.,
RA Holm C.;
RT "Exon-intron organization and chromosomal localization of the mouse
RT monoglyceride lipase gene.";
RL Gene 272:11-18(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Uterus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Lung;
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 175-303.
RC TISSUE=Rectum tumor;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [9]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=19029917; DOI=10.1038/nchembio.129;
RA Long J.Z., Li W., Booker L., Burston J.J., Kinsey S.G., Schlosburg J.E.,
RA Pavon F.J., Serrano A.M., Selley D.E., Parsons L.H., Lichtman A.H.,
RA Cravatt B.F.;
RT "Selective blockade of 2-arachidonoylglycerol hydrolysis produces
RT cannabinoid behavioral effects.";
RL Nat. Chem. Biol. 5:37-44(2009).
RN [10]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=20079333; DOI=10.1016/j.cell.2009.11.027;
RA Nomura D.K., Long J.Z., Niessen S., Hoover H.S., Ng S.W., Cravatt B.F.;
RT "Monoacylglycerol lipase regulates a fatty acid network that promotes
RT cancer pathogenesis.";
RL Cell 140:49-61(2010).
RN [11]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=21049984; DOI=10.1021/tx1002194;
RA Xie S., Borazjani A., Hatfield M.J., Edwards C.C., Potter P.M., Ross M.K.;
RT "Inactivation of lipid glyceryl ester metabolism in human THP1
RT monocytes/macrophages by activated organophosphorus insecticides: role of
RT carboxylesterases 1 and 2.";
RL Chem. Res. Toxicol. 23:1890-1904(2010).
RN [12]
RP CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=22969151; DOI=10.1194/jlr.m030411;
RA Navia-Paldanius D., Savinainen J.R., Laitinen J.T.;
RT "Biochemical and pharmacological characterization of human alpha/beta-
RT hydrolase domain containing 6 (ABHD6) and 12 (ABHD12).";
RL J. Lipid Res. 53:2413-2424(2012).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 2-303, SUBUNIT, ACTIVE SITE, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=19957260; DOI=10.1002/cbic.200900621;
RA Labar G., Bauvois C., Borel F., Ferrer J.L., Wouters J., Lambert D.M.;
RT "Crystal structure of the human monoacylglycerol lipase, a key actor in
RT endocannabinoid signaling.";
RL ChemBioChem 11:218-227(2010).
RN [16]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF TYR-194; CYS-201; CYS-208 AND CYS-242.
RX PubMed=24368842; DOI=10.1124/mol.113.090795;
RA Laitinen T., Navia-Paldanius D., Rytilahti R., Marjamaa J.J., Karizkova J.,
RA Parkkari T., Pantsar T., Poso A., Laitinen J.T., Savinainen J.R.;
RT "Mutation of Cys242 of human monoacylglycerol lipase disrupts balanced
RT hydrolysis of 1- and 2-monoacylglycerols and selectively impairs inhibitor
RT potency.";
RL Mol. Pharmacol. 85:510-519(2014).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH SYNTHETIC INHIBITOR
RP SAR629, AND ACTIVE SITE.
RX PubMed=19962385; DOI=10.1016/j.jmb.2009.11.060;
RA Bertrand T., Auge F., Houtmann J., Rak A., Vallee F., Mikol V., Berne P.F.,
RA Michot N., Cheuret D., Hoornaert C., Mathieu M.;
RT "Structural basis for human monoglyceride lipase inhibition.";
RL J. Mol. Biol. 396:663-673(2010).
CC -!- FUNCTION: Converts monoacylglycerides to free fatty acids and glycerol
CC (PubMed:19029917, PubMed:20079333, PubMed:21049984, PubMed:22969151,
CC PubMed:24368842). Hydrolyzes the endocannabinoid 2-
CC arachidonoylglycerol, and thereby contributes to the regulation of
CC endocannabinoid signaling, nociperception and perception of pain
CC (PubMed:19029917, PubMed:20079333, PubMed:21049984, PubMed:22969151,
CC PubMed:24368842). Regulates the levels of fatty acids that serve as
CC signaling molecules and promote cancer cell migration, invasion and
CC tumor growth (PubMed:20079333). {ECO:0000269|PubMed:19029917,
CC ECO:0000269|PubMed:20079333, ECO:0000269|PubMed:21049984,
CC ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolyzes glycerol monoesters of long-chain fatty acids.;
CC EC=3.1.1.23; Evidence={ECO:0000269|PubMed:19029917,
CC ECO:0000269|PubMed:20079333, ECO:0000269|PubMed:21049984,
CC ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};
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:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44329;
CC Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};
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:19029917, ECO:0000269|PubMed:20079333,
CC ECO:0000269|PubMed:21049984, ECO:0000269|PubMed:22969151,
CC ECO:0000269|PubMed:24368842};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26133;
CC Evidence={ECO:0000269|PubMed:19029917, ECO:0000269|PubMed:20079333,
CC ECO:0000269|PubMed:21049984, ECO:0000269|PubMed:22969151,
CC ECO:0000269|PubMed:24368842};
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:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44321;
CC Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};
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:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44317;
CC Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};
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:0000269|PubMed:22969151,
CC ECO:0000269|PubMed:24368842};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44313;
CC Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};
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:0000269|PubMed:22969151,
CC ECO:0000269|PubMed:24368842};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39964;
CC Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};
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:0000269|PubMed:20079333,
CC ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38488;
CC Evidence={ECO:0000269|PubMed:20079333, ECO:0000269|PubMed:22969151,
CC ECO:0000269|PubMed:24368842};
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:0000269|PubMed:22969151,
CC ECO:0000269|PubMed:24368842};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38492;
CC Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};
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:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44733;
CC Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};
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:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44729;
CC Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};
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:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48429;
CC Evidence={ECO:0000269|PubMed:22969151, ECO:0000269|PubMed:24368842};
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:0000269|PubMed:20079333};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39960;
CC Evidence={ECO:0000269|PubMed:20079333};
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:0000269|PubMed:20079333};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38364;
CC Evidence={ECO:0000269|PubMed:20079333};
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:0000269|PubMed:21049984,
CC ECO:0000269|PubMed:24368842};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48297;
CC Evidence={ECO:0000269|PubMed:21049984, ECO:0000269|PubMed:24368842};
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:0000269|PubMed:24368842};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45413;
CC Evidence={ECO:0000269|PubMed:24368842};
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:0000269|PubMed:24368842};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45417;
CC Evidence={ECO:0000269|PubMed:24368842};
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:0000269|PubMed:21049984};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48301;
CC Evidence={ECO:0000269|PubMed:21049984};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=110 uM for 2-arachidonoyglycerol {ECO:0000269|PubMed:22969151};
CC KM=15 uM for 2-glyceryl-15-deoxy-Delta(12,14)-prostaglandin J2 (15d-
CC PGJ(2)-G) {ECO:0000269|PubMed:24368842};
CC Vmax=120 nmol/min/mg enzyme toward 2-arachidonoyglycerol
CC {ECO:0000269|PubMed:22969151};
CC Vmax=89 nmol/min/mg enzyme toward 2-glyceryl-15-deoxy-Delta(12,14)-
CC prostaglandin J2 (15d-PGJ(2)-G) {ECO:0000269|PubMed:24368842};
CC -!- PATHWAY: Glycerolipid metabolism; triacylglycerol degradation.
CC {ECO:0000250|UniProtKB:O35678}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:19957260,
CC ECO:0000269|PubMed:19962385}.
CC -!- INTERACTION:
CC Q99685; P07550: ADRB2; NbExp=2; IntAct=EBI-721306, EBI-491169;
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q99685-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99685-2; Sequence=VSP_045138, VSP_045139;
CC -!- TISSUE SPECIFICITY: Detected in adipose tissue, lung, liver, kidney,
CC brain and heart. {ECO:0000269|PubMed:11470505}.
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB39616.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH00551.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH06230.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAG37910.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAG33116.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=EAW79330.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=EAW79331.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U67963; AAB39616.1; ALT_INIT; mRNA.
DR EMBL; AJ270950; CAC43316.1; -; mRNA.
DR EMBL; AK091314; BAG52334.1; -; mRNA.
DR EMBL; AK315529; BAG37910.1; ALT_INIT; mRNA.
DR EMBL; AK304844; BAH14267.1; -; mRNA.
DR EMBL; CR456835; CAG33116.1; ALT_INIT; mRNA.
DR EMBL; AC023593; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC117480; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW79330.1; ALT_INIT; Genomic_DNA.
DR EMBL; CH471052; EAW79331.1; ALT_INIT; Genomic_DNA.
DR EMBL; BC000551; AAH00551.1; ALT_INIT; mRNA.
DR EMBL; BC006230; AAH06230.1; ALT_INIT; mRNA.
DR EMBL; BX640777; CAE45873.1; -; mRNA.
DR CCDS; CCDS43148.1; -. [Q99685-1]
DR CCDS; CCDS58852.1; -. [Q99685-2]
DR RefSeq; NP_001003794.1; NM_001003794.2. [Q99685-1]
DR RefSeq; NP_001243514.1; NM_001256585.1. [Q99685-2]
DR RefSeq; NP_009214.1; NM_007283.6.
DR PDB; 3HJU; X-ray; 2.20 A; A/B=2-303.
DR PDB; 3JW8; X-ray; 2.10 A; A/B=1-303.
DR PDB; 3JWE; X-ray; 2.70 A; A/B=1-303.
DR PDB; 3PE6; X-ray; 1.35 A; A=1-303.
DR PDB; 4UUQ; X-ray; 2.36 A; A/B=1-303.
DR PDB; 5ZUN; X-ray; 1.35 A; A=1-303.
DR PDB; 6AX1; X-ray; 2.26 A; A/B=1-303.
DR PDB; 6BQ0; X-ray; 2.00 A; A/B=1-303.
DR PDB; 7L4T; X-ray; 2.20 A; A/B=1-303.
DR PDB; 7L4U; X-ray; 2.25 A; A/B=1-303.
DR PDB; 7L4W; X-ray; 2.20 A; A/B=1-303.
DR PDB; 7L50; X-ray; 2.30 A; A/B/C/D=1-303.
DR PDB; 7PRM; X-ray; 1.65 A; A=1-303.
DR PDBsum; 3HJU; -.
DR PDBsum; 3JW8; -.
DR PDBsum; 3JWE; -.
DR PDBsum; 3PE6; -.
DR PDBsum; 4UUQ; -.
DR PDBsum; 5ZUN; -.
DR PDBsum; 6AX1; -.
DR PDBsum; 6BQ0; -.
DR PDBsum; 7L4T; -.
DR PDBsum; 7L4U; -.
DR PDBsum; 7L4W; -.
DR PDBsum; 7L50; -.
DR PDBsum; 7PRM; -.
DR AlphaFoldDB; Q99685; -.
DR SMR; Q99685; -.
DR BioGRID; 116471; 37.
DR IntAct; Q99685; 11.
DR MINT; Q99685; -.
DR STRING; 9606.ENSP00000265052; -.
DR BindingDB; Q99685; -.
DR ChEMBL; CHEMBL4191; -.
DR DrugCentral; Q99685; -.
DR GuidetoPHARMACOLOGY; 1399; -.
DR SwissLipids; SLP:000000315; -.
DR ESTHER; human-MGLL; Monoglyceridelipase_lysophospholip.
DR MEROPS; S33.979; -.
DR GlyGen; Q99685; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q99685; -.
DR PhosphoSitePlus; Q99685; -.
DR BioMuta; MGLL; -.
DR DMDM; 47117287; -.
DR EPD; Q99685; -.
DR jPOST; Q99685; -.
DR MassIVE; Q99685; -.
DR MaxQB; Q99685; -.
DR PaxDb; Q99685; -.
DR PeptideAtlas; Q99685; -.
DR PRIDE; Q99685; -.
DR ProteomicsDB; 7025; -.
DR ProteomicsDB; 78397; -. [Q99685-1]
DR Antibodypedia; 1635; 502 antibodies from 36 providers.
DR DNASU; 11343; -.
DR Ensembl; ENST00000398104.6; ENSP00000381176.1; ENSG00000074416.16. [Q99685-1]
DR Ensembl; ENST00000453507.7; ENSP00000404146.2; ENSG00000074416.16. [Q99685-2]
DR GeneID; 11343; -.
DR KEGG; hsa:11343; -.
DR UCSC; uc003ejw.4; human. [Q99685-1]
DR CTD; 11343; -.
DR DisGeNET; 11343; -.
DR GeneCards; MGLL; -.
DR HGNC; HGNC:17038; MGLL.
DR HPA; ENSG00000074416; Low tissue specificity.
DR MIM; 609699; gene.
DR neXtProt; NX_Q99685; -.
DR OpenTargets; ENSG00000074416; -.
DR PharmGKB; PA30789; -.
DR VEuPathDB; HostDB:ENSG00000074416; -.
DR eggNOG; KOG1455; Eukaryota.
DR GeneTree; ENSGT00390000011364; -.
DR HOGENOM; CLU_026209_7_1_1; -.
DR InParanoid; Q99685; -.
DR OMA; FHGFSDH; -.
DR OrthoDB; 919091at2759; -.
DR PhylomeDB; Q99685; -.
DR TreeFam; TF329184; -.
DR BioCyc; MetaCyc:HS01140-MON; -.
DR BRENDA; 3.1.1.23; 2681.
DR PathwayCommons; Q99685; -.
DR Reactome; R-HSA-1482883; Acyl chain remodeling of DAG and TAG.
DR Reactome; R-HSA-163560; Triglyceride catabolism.
DR Reactome; R-HSA-426048; Arachidonate production from DAG.
DR SABIO-RK; Q99685; -.
DR SignaLink; Q99685; -.
DR SIGNOR; Q99685; -.
DR UniPathway; UPA00256; -.
DR BioGRID-ORCS; 11343; 16 hits in 1071 CRISPR screens.
DR ChiTaRS; MGLL; human.
DR EvolutionaryTrace; Q99685; -.
DR GenomeRNAi; 11343; -.
DR Pharos; Q99685; Tchem.
DR PRO; PR:Q99685; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q99685; protein.
DR Bgee; ENSG00000074416; Expressed in decidua and 208 other tissues.
DR ExpressionAtlas; Q99685; baseline and differential.
DR Genevisible; Q99685; HS.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0019898; C:extrinsic component of membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0047372; F:acylglycerol lipase activity; IDA:UniProtKB.
DR GO; GO:0016298; F:lipase activity; IBA:GO_Central.
DR GO; GO:0004622; F:lysophospholipase activity; TAS:ProtInc.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0046464; P:acylglycerol catabolic process; IDA: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:0006954; P:inflammatory response; TAS:ProtInc.
DR GO; GO:0006629; P:lipid metabolic process; TAS:ProtInc.
DR GO; GO:0052651; P:monoacylglycerol catabolic process; ISS:UniProtKB.
DR GO; GO:2000124; P:regulation of endocannabinoid signaling pathway; ISS:UniProtKB.
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 3D-structure; Alternative splicing; Cytoplasm; 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_0000191265"
FT ACT_SITE 122
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:19957260"
FT ACT_SITE 239
FT /note="Charge relay system"
FT /evidence="ECO:0000305|PubMed:19957260"
FT ACT_SITE 269
FT /note="Charge relay system"
FT /evidence="ECO:0000305|PubMed:19957260"
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 VAR_SEQ 1
FT /note="M -> METGPEDPSSM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045138"
FT VAR_SEQ 161..190
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045139"
FT MUTAGEN 194
FT /note="Y->F: Does not affect ability to hydrolyze 1- or 2-
FT monoacylglycerol."
FT /evidence="ECO:0000269|PubMed:24368842"
FT MUTAGEN 201
FT /note="C->A: Does not affect ability to hydrolyze 1- or 2-
FT monoacylglycerol."
FT /evidence="ECO:0000269|PubMed:24368842"
FT MUTAGEN 208
FT /note="C->A: Does not affect ability to hydrolyze 1- or 2-
FT monoacylglycerol."
FT /evidence="ECO:0000269|PubMed:24368842"
FT MUTAGEN 242
FT /note="C->A: Reduced 1-monoacylglycerol lipase activity."
FT /evidence="ECO:0000269|PubMed:24368842"
FT CONFLICT 144
FT /note="L -> P (in Ref. 3; BAG52334)"
FT /evidence="ECO:0000305"
FT HELIX 16..18
FT /evidence="ECO:0007829|PDB:3PE6"
FT STRAND 21..23
FT /evidence="ECO:0007829|PDB:3PE6"
FT STRAND 29..35
FT /evidence="ECO:0007829|PDB:3PE6"
FT STRAND 42..48
FT /evidence="ECO:0007829|PDB:3PE6"
FT HELIX 55..58
FT /evidence="ECO:0007829|PDB:3PE6"
FT HELIX 59..67
FT /evidence="ECO:0007829|PDB:3PE6"
FT STRAND 70..75
FT /evidence="ECO:0007829|PDB:3PE6"
FT HELIX 94..110
FT /evidence="ECO:0007829|PDB:3PE6"
FT STRAND 116..121
FT /evidence="ECO:0007829|PDB:3PE6"
FT HELIX 123..134
FT /evidence="ECO:0007829|PDB:3PE6"
FT TURN 136..138
FT /evidence="ECO:0007829|PDB:3PE6"
FT STRAND 140..146
FT /evidence="ECO:0007829|PDB:3PE6"
FT STRAND 148..151
FT /evidence="ECO:0007829|PDB:3PE6"
FT HELIX 153..168
FT /evidence="ECO:0007829|PDB:3PE6"
FT HELIX 181..183
FT /evidence="ECO:0007829|PDB:3PE6"
FT HELIX 188..195
FT /evidence="ECO:0007829|PDB:3PE6"
FT STRAND 198..200
FT /evidence="ECO:0007829|PDB:4UUQ"
FT HELIX 207..223
FT /evidence="ECO:0007829|PDB:3PE6"
FT HELIX 224..226
FT /evidence="ECO:0007829|PDB:3PE6"
FT STRAND 231..236
FT /evidence="ECO:0007829|PDB:3PE6"
FT STRAND 240..242
FT /evidence="ECO:0007829|PDB:3PE6"
FT HELIX 244..253
FT /evidence="ECO:0007829|PDB:3PE6"
FT STRAND 257..264
FT /evidence="ECO:0007829|PDB:3PE6"
FT HELIX 271..273
FT /evidence="ECO:0007829|PDB:3PE6"
FT HELIX 276..292
FT /evidence="ECO:0007829|PDB:3PE6"
SQ SEQUENCE 303 AA; 33261 MW; 80E754F126EE64DE CRC64;
MPEESSPRRT PQSIPYQDLP HLVNADGQYL FCRYWKPTGT PKALIFVSHG AGEHSGRYEE
LARMLMGLDL LVFAHDHVGH GQSEGERMVV SDFHVFVRDV LQHVDSMQKD YPGLPVFLLG
HSMGGAIAIL TAAERPGHFA GMVLISPLVL ANPESATTFK VLAAKVLNLV LPNLSLGPID
SSVLSRNKTE VDIYNSDPLI CRAGLKVCFG IQLLNAVSRV ERALPKLTVP FLLLQGSADR
LCDSKGAYLL MELAKSQDKT LKIYEGAYHV LHKELPEVTN SVFHEINMWV SQRTATAGTA
SPP
