LIPS_MOUSE
ID LIPS_MOUSE Reviewed; 759 AA.
AC P54310; P97866; Q3TE34; Q6GU16; Q8CDI9;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2006, sequence version 2.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Hormone-sensitive lipase;
DE Short=HSL;
DE EC=3.1.1.79 {ECO:0000269|PubMed:15550674, ECO:0000269|PubMed:20625037, ECO:0000269|PubMed:23066022};
DE AltName: Full=Monoacylglycerol lipase LIPE;
DE EC=3.1.1.23 {ECO:0000269|PubMed:21454566};
DE AltName: Full=Retinyl ester hydrolase {ECO:0000303|PubMed:15550674};
DE Short=REH;
GN Name=Lipe;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=7698747; DOI=10.1006/geno.1994.1614;
RA Li Z., Sumida M., Birchbauer A., Schotz M.C., Reue K.;
RT "Isolation and characterization of the gene for mouse hormone-sensitive
RT lipase.";
RL Genomics 24:259-265(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/Sv;
RX PubMed=9060404; DOI=10.1007/s003359900363;
RA Sztrolovics R., Wang S.P., Lapierre P., Chen H.S., Robert M.-F.,
RA Mitchell G.A.;
RT "Hormone-sensitive lipase (Lipe): sequence analysis of the 129Sv mouse Lipe
RT gene.";
RL Mamm. Genome 8:86-89(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Salivary gland;
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 [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=15550674; DOI=10.1126/science.1100747;
RA Zimmermann R., Strauss J.G., Haemmerle G., Schoiswohl G.,
RA Birner-Gruenberger R., Riederer M., Lass A., Neuberger G., Eisenhaber F.,
RA Hermetter A., Zechner R.;
RT "Fat mobilization in adipose tissue is promoted by adipose triglyceride
RT lipase.";
RL Science 306:1383-1386(2004).
RN [7]
RP PHOSPHORYLATION BY AMPK, AND SUBCELLULAR LOCATION.
RX PubMed=15878856; DOI=10.1074/jbc.m414222200;
RA Daval M., Diot-Dupuy F., Bazin R., Hainault I., Viollet B., Vaulont S.,
RA Hajduch E., Ferre P., Foufelle F.;
RT "Anti-lipolytic action of AMP-activated protein kinase in rodent
RT adipocytes.";
RL J. Biol. Chem. 280:25250-25257(2005).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [9]
RP INTERACTION WITH PLIN5.
RX PubMed=19717842; DOI=10.1074/jbc.m109.006726;
RA Wang H., Hu L., Dalen K., Dorward H., Marcinkiewicz A., Russell D.,
RA Gong D., Londos C., Yamaguchi T., Holm C., Rizzo M.A., Brasaemle D.,
RA Sztalryd C.;
RT "Activation of hormone-sensitive lipase requires two steps, protein
RT phosphorylation and binding to the PAT-1 domain of lipid droplet coat
RT proteins.";
RL J. Biol. Chem. 284:32116-32125(2009).
RN [10]
RP PHOSPHORYLATION AT SER-559.
RX PubMed=19921680; DOI=10.1002/pmic.200800861;
RA Kanshin E., Wang S., Ashmarina L., Fedjaev M., Nifant'ev I., Mitchell G.A.,
RA Pshezhetsky A.V.;
RT "The stoichiometry of protein phosphorylation in adipocyte lipid droplets:
RT analysis by N-terminal isotope tagging and enzymatic dephosphorylation.";
RL Proteomics 9:5067-5077(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-559; THR-574 AND SER-651, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [12]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=20625037; DOI=10.1194/jlr.m004259;
RA Buchebner M., Pfeifer T., Rathke N., Chandak P.G., Lass A., Schreiber R.,
RA Kratzer A., Zimmermann R., Sattler W., Koefeler H., Froehlich E.,
RA Kostner G.M., Birner-Gruenberger R., Chiang K.P., Haemmerle G., Zechner R.,
RA Levak-Frank S., Cravatt B., Kratky D.;
RT "Cholesteryl ester hydrolase activity is abolished in HSL-/- macrophages
RT but unchanged in macrophages lacking KIAA1363.";
RL J. Lipid Res. 51:2896-2908(2010).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=21454566; DOI=10.1074/jbc.m110.215434;
RA Taschler U., Radner F.P., Heier C., Schreiber R., Schweiger M.,
RA Schoiswohl G., Preiss-Landl K., Jaeger D., Reiter B., Koefeler H.C.,
RA Wojciechowski J., Theussl C., Penninger J.M., Lass A., Haemmerle G.,
RA Zechner R., Zimmermann R.;
RT "Monoglyceride lipase deficiency in mice impairs lipolysis and attenuates
RT diet-induced insulin resistance.";
RL J. Biol. Chem. 286:17467-17477(2011).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=23066022; DOI=10.1074/jbc.m112.400416;
RA Eichmann T.O., Kumari M., Haas J.T., Farese R.V. Jr., Zimmermann R.,
RA Lass A., Zechner R.;
RT "Studies on the substrate and stereo/regioselectivity of adipose
RT triglyceride lipase, hormone-sensitive lipase, and diacylglycerol-O-
RT acyltransferases.";
RL J. Biol. Chem. 287:41446-41457(2012).
RN [15]
RP FUNCTION AS LIPOLYTIC ENZYME.
RX PubMed=23291629; DOI=10.1038/nm.3056;
RA Liew C.W., Boucher J., Cheong J.K., Vernochet C., Koh H.J., Mallol C.,
RA Townsend K., Langin D., Kawamori D., Hu J., Tseng Y.H., Hellerstein M.K.,
RA Farmer S.R., Goodyear L., Doria A., Blueher M., Hsu S.I., Kulkarni R.N.;
RT "Ablation of TRIP-Br2, a regulator of fat lipolysis, thermogenesis and
RT oxidative metabolism, prevents diet-induced obesity and insulin
RT resistance.";
RL Nat. Med. 19:217-226(2013).
CC -!- FUNCTION: Lipase with broad substrate specificity, catalyzing the
CC hydrolysis of triacylglycerols (TAGs), diacylglycerols (DAGs),
CC monoacylglycerols (MAGs), cholesteryl esters and retinyl esters
CC (PubMed:15550674, PubMed:20625037, PubMed:21454566, PubMed:23066022,
CC PubMed:23291629). Shows a preferential hydrolysis of DAGs over TAGs and
CC MAGs and of the fatty acid (FA) esters at the sn-1 and sn-2 positions
CC of the glycerol backbone in TAGs (By similarity). Preferentially
CC hydrolyzes FA esters at the sn-3 position of the glycerol backbone in
CC DAGs (PubMed:23066022). Catalyzes the hydrolysis of 2-
CC arachidonoylglycerol, an endocannabinoid and of 2-acetyl
CC monoalkylglycerol ether, the penultimate precursor of the pathway for
CC de novo synthesis of platelet-activating factor (PubMed:20625037,
CC PubMed:21454566). In adipose tissue and heart, it primarily hydrolyzes
CC stored triglycerides to free fatty acids, while in steroidogenic
CC tissues, it principally converts cholesteryl esters to free cholesterol
CC for steroid hormone production (By similarity).
CC {ECO:0000250|UniProtKB:P15304, ECO:0000250|UniProtKB:Q05469,
CC ECO:0000269|PubMed:15550674, ECO:0000269|PubMed:20625037,
CC ECO:0000269|PubMed:21454566, ECO:0000269|PubMed:23066022,
CC ECO:0000269|PubMed:23291629}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a diacylglycerol + H2O = a fatty acid + a monoacylglycerol +
CC H(+); Xref=Rhea:RHEA:32731, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17408, ChEBI:CHEBI:18035, ChEBI:CHEBI:28868; EC=3.1.1.79;
CC Evidence={ECO:0000269|PubMed:20625037, ECO:0000269|PubMed:23066022};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a triacylglycerol + H2O = a diacylglycerol + a fatty acid +
CC H(+); Xref=Rhea:RHEA:12044, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17855, ChEBI:CHEBI:18035, ChEBI:CHEBI:28868; EC=3.1.1.79;
CC Evidence={ECO:0000269|PubMed:15550674};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a monoacylglycerol + H2O = a fatty acid + glycerol + H(+);
CC Xref=Rhea:RHEA:15245, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17408, ChEBI:CHEBI:17754, ChEBI:CHEBI:28868; EC=3.1.1.79;
CC Evidence={ECO:0000269|PubMed:21454566};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolyzes glycerol monoesters of long-chain fatty acids.;
CC EC=3.1.1.23; Evidence={ECO:0000269|PubMed:21454566};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholesteryl (9Z-octadecenoate) + H2O = (9Z)-octadecenoate +
CC cholesterol + H(+); Xref=Rhea:RHEA:33875, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16113, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:46898; Evidence={ECO:0000269|PubMed:15550674,
CC ECO:0000269|PubMed:20625037};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33876;
CC Evidence={ECO:0000305|PubMed:15550674};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-retinyl hexadecanoate + H2O = all-trans-retinol +
CC H(+) + hexadecanoate; Xref=Rhea:RHEA:13933, ChEBI:CHEBI:7896,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17336,
CC ChEBI:CHEBI:17616; Evidence={ECO:0000269|PubMed:15550674};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13934;
CC Evidence={ECO:0000305|PubMed:15550674};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate +
CC (9Z-octadecenoyl)-glycerol + H(+); Xref=Rhea:RHEA:38455,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:52323, ChEBI:CHEBI:75937;
CC Evidence={ECO:0000269|PubMed:20625037, ECO:0000269|PubMed:23066022};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38456;
CC Evidence={ECO:0000305|PubMed:20625037};
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:21454566};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26133;
CC Evidence={ECO:0000305|PubMed:21454566};
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:21454566};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38488;
CC Evidence={ECO:0000305|PubMed:21454566};
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:21454566};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38492;
CC Evidence={ECO:0000305|PubMed:21454566};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-hexadecyl-2-acetyl-sn-glycerol + H2O = 1-O-hexadecyl-sn-
CC glycerol + acetate + H(+); Xref=Rhea:RHEA:38563, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30089, ChEBI:CHEBI:34115,
CC ChEBI:CHEBI:75936; Evidence={ECO:0000269|PubMed:20625037};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38564;
CC Evidence={ECO:0000305|PubMed:20625037};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycerol + H2O = (9Z)-
CC octadecenoate + (9Z-octadecenoyl)-glycerol + H(+);
CC Xref=Rhea:RHEA:39935, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:52333, ChEBI:CHEBI:75937;
CC Evidence={ECO:0000269|PubMed:23066022};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39936;
CC Evidence={ECO:0000305|PubMed:23066022};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,3-di-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate +
CC (9Z-octadecenoyl)-glycerol + H(+); Xref=Rhea:RHEA:39939,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:75735, ChEBI:CHEBI:75937;
CC Evidence={ECO:0000269|PubMed:23066022};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39940;
CC Evidence={ECO:0000305|PubMed:23066022};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoate + 1,2-di-(9Z-octadecenoyl)-glycerol + H(+)
CC = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O; Xref=Rhea:RHEA:38379,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:52323, ChEBI:CHEBI:53753;
CC Evidence={ECO:0000250|UniProtKB:Q05469};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38381;
CC Evidence={ECO:0000250|UniProtKB:Q05469};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2,3-di-(9Z)-octadecenoyl-sn-glycerol + H2O = (9Z)-
CC octadecenoate + 2-(9Z-octadecenoyl)-glycerol + H(+);
CC Xref=Rhea:RHEA:38383, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:73990, ChEBI:CHEBI:75824;
CC Evidence={ECO:0000250|UniProtKB:Q05469};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38384;
CC Evidence={ECO:0000250|UniProtKB:Q05469};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-
CC octadecenoate + di-(9Z)-octadecenoylglycerol + H(+);
CC Xref=Rhea:RHEA:38575, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:53753, ChEBI:CHEBI:75945;
CC Evidence={ECO:0000250|UniProtKB:Q05469};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38576;
CC Evidence={ECO:0000250|UniProtKB:Q05469};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate +
CC 2-(9Z-octadecenoyl)-glycerol + H(+); Xref=Rhea:RHEA:38659,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:52323, ChEBI:CHEBI:73990;
CC Evidence={ECO:0000250|UniProtKB:P15304};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38660;
CC Evidence={ECO:0000250|UniProtKB:P15304};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.25 uM for 1-(9Z-octadecenoyl)-glycerol
CC {ECO:0000269|PubMed:21454566};
CC KM=0.26 uM for 2-(9Z-octadecenoyl)-glycerol
CC {ECO:0000269|PubMed:21454566};
CC KM=0.27 uM for 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol
CC {ECO:0000269|PubMed:21454566};
CC -!- PATHWAY: Glycerolipid metabolism; triacylglycerol degradation.
CC -!- SUBUNIT: Monomer and homodimer (By similarity). Interacts with CAVIN1
CC in the adipocyte cytoplasm (By similarity). Interacts with PLIN5
CC (PubMed:19717842). {ECO:0000250|UniProtKB:P15304,
CC ECO:0000250|UniProtKB:Q05469, ECO:0000269|PubMed:19717842}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:15550674}.
CC Membrane, caveola {ECO:0000250|UniProtKB:Q05469}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:15550674}. Lipid droplet
CC {ECO:0000269|PubMed:15878856}. Note=Found in the high-density caveolae
CC (By similarity). Translocates to the cytoplasm from the caveolae upon
CC insulin stimulation (By similarity). Phosphorylation by AMPK reduces
CC its translocation towards the lipid droplets.
CC {ECO:0000250|UniProtKB:Q05469, ECO:0000269|PubMed:15878856}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P54310-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P54310-2; Sequence=VSP_053335;
CC -!- PTM: Phosphorylation by AMPK reduces its translocation towards the
CC lipid droplets. {ECO:0000269|PubMed:15878856,
CC ECO:0000269|PubMed:19921680}.
CC -!- DISRUPTION PHENOTYPE: Total acylglycerol levels are unaltered whereas
CC diacylglycerol concentrations are drastically increased in white
CC adipose tissue of knockout mice when compared to wild-type littermates.
CC {ECO:0000269|PubMed:23066022}.
CC -!- SIMILARITY: Belongs to the 'GDXG' lipolytic enzyme family.
CC {ECO:0000305}.
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DR EMBL; U08188; AAC52163.1; -; mRNA.
DR EMBL; AF179427; AAC53069.1; -; Genomic_DNA.
DR EMBL; AC162443; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC169209; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK029984; BAC26716.1; -; mRNA.
DR EMBL; AK169858; BAE41414.1; -; mRNA.
DR EMBL; BC021642; AAH21642.1; -; mRNA.
DR CCDS; CCDS20981.1; -. [P54310-2]
DR CCDS; CCDS20982.1; -. [P54310-1]
DR PIR; I49007; I49007.
DR RefSeq; NP_001034596.1; NM_001039507.2. [P54310-1]
DR RefSeq; NP_034849.2; NM_010719.5. [P54310-2]
DR RefSeq; XP_006539634.1; XM_006539571.2.
DR RefSeq; XP_006539635.1; XM_006539572.3. [P54310-1]
DR AlphaFoldDB; P54310; -.
DR STRING; 10090.ENSMUSP00000003207; -.
DR ChEMBL; CHEMBL5935; -.
DR SwissLipids; SLP:000000313; -.
DR SwissLipids; SLP:000000314; -.
DR ESTHER; mouse-hslip; Hormone-sensitive_lipase_like.
DR MEROPS; S09.993; -.
DR iPTMnet; P54310; -.
DR PhosphoSitePlus; P54310; -.
DR jPOST; P54310; -.
DR MaxQB; P54310; -.
DR PaxDb; P54310; -.
DR PeptideAtlas; P54310; -.
DR PRIDE; P54310; -.
DR ProteomicsDB; 292097; -. [P54310-1]
DR ProteomicsDB; 292098; -. [P54310-2]
DR Antibodypedia; 4327; 497 antibodies from 38 providers.
DR DNASU; 16890; -.
DR Ensembl; ENSMUST00000003207; ENSMUSP00000003207; ENSMUSG00000003123. [P54310-2]
DR Ensembl; ENSMUST00000054301; ENSMUSP00000050935; ENSMUSG00000003123. [P54310-1]
DR Ensembl; ENSMUST00000206861; ENSMUSP00000145665; ENSMUSG00000003123. [P54310-1]
DR GeneID; 16890; -.
DR KEGG; mmu:16890; -.
DR UCSC; uc009fsp.1; mouse. [P54310-1]
DR UCSC; uc009fsr.1; mouse. [P54310-2]
DR CTD; 3991; -.
DR MGI; MGI:96790; Lipe.
DR VEuPathDB; HostDB:ENSMUSG00000003123; -.
DR eggNOG; KOG4388; Eukaryota.
DR GeneTree; ENSGT00730000111056; -.
DR HOGENOM; CLU_010288_1_0_1; -.
DR InParanoid; P54310; -.
DR OMA; FACGNHT; -.
DR TreeFam; TF314423; -.
DR BRENDA; 3.1.1.79; 3474.
DR UniPathway; UPA00256; -.
DR BioGRID-ORCS; 16890; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Lipe; mouse.
DR PRO; PR:P54310; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P54310; protein.
DR Bgee; ENSMUSG00000003123; Expressed in brown adipose tissue and 140 other tissues.
DR ExpressionAtlas; P54310; baseline and differential.
DR Genevisible; P54310; MM.
DR GO; GO:0005901; C:caveola; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0005811; C:lipid droplet; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0102259; F:1,2-diacylglycerol acylhydrolase activity; IDA:UniProtKB.
DR GO; GO:0102258; F:1,3-diacylglycerol acylhydrolase activity; IDA:UniProtKB.
DR GO; GO:0047372; F:acylglycerol lipase activity; IDA:UniProtKB.
DR GO; GO:0047376; F:all-trans-retinyl-palmitate hydrolase, all-trans-retinol forming activity; IEA:RHEA.
DR GO; GO:0033878; F:hormone-sensitive lipase activity; ISO:MGI.
DR GO; GO:0016788; F:hydrolase activity, acting on ester bonds; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0050253; F:retinyl-palmitate esterase activity; IDA:UniProtKB.
DR GO; GO:0042134; F:rRNA primary transcript binding; ISS:UniProtKB.
DR GO; GO:0017171; F:serine hydrolase activity; IDA:MGI.
DR GO; GO:0004771; F:sterol esterase activity; IDA:UniProtKB.
DR GO; GO:0004806; F:triglyceride lipase activity; IDA:UniProtKB.
DR GO; GO:0070417; P:cellular response to cold; IDA:MGI.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0046340; P:diacylglycerol catabolic process; IDA:UniProtKB.
DR GO; GO:0046485; P:ether lipid metabolic process; IDA:UniProtKB.
DR GO; GO:0016042; P:lipid catabolic process; IDA:UniProtKB.
DR GO; GO:0042758; P:long-chain fatty acid catabolic process; IDA:MGI.
DR GO; GO:0006363; P:termination of RNA polymerase I transcription; ISS:UniProtKB.
DR GO; GO:0006361; P:transcription initiation from RNA polymerase I promoter; ISS:UniProtKB.
DR GO; GO:0019433; P:triglyceride catabolic process; IDA:MGI.
DR Gene3D; 3.40.50.1820; -; 2.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR013094; AB_hydrolase_3.
DR InterPro; IPR010468; HSL_N.
DR InterPro; IPR002168; Lipase_GDXG_HIS_AS.
DR InterPro; IPR033140; Lipase_GDXG_put_SER_AS.
DR Pfam; PF07859; Abhydrolase_3; 2.
DR Pfam; PF06350; HSL_N; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS01173; LIPASE_GDXG_HIS; 1.
DR PROSITE; PS01174; LIPASE_GDXG_SER; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cholesterol metabolism; Cytoplasm;
KW Hydrolase; Lipid degradation; Lipid droplet; Lipid metabolism; Membrane;
KW Phosphoprotein; Reference proteome; Steroid metabolism; Sterol metabolism.
FT CHAIN 1..759
FT /note="Hormone-sensitive lipase"
FT /id="PRO_0000071548"
FT REGION 534..553
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 583..604
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 349..351
FT /note="Involved in the stabilization of the negatively
FT charged intermediate by the formation of the oxyanion hole"
FT /evidence="ECO:0000250|UniProtKB:Q5NUF3"
FT ACT_SITE 423
FT /evidence="ECO:0000250|UniProtKB:Q8BLF1,
FT ECO:0000255|PROSITE-ProRule:PRU10038"
FT ACT_SITE 694
FT /evidence="ECO:0000250|UniProtKB:Q8BLF1"
FT ACT_SITE 724
FT /evidence="ECO:0000250|UniProtKB:Q8BLF1"
FT MOD_RES 557
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16386"
FT MOD_RES 559
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000305|PubMed:19921680,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 574
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 597
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15304"
FT MOD_RES 618
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15304"
FT MOD_RES 650
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15304"
FT MOD_RES 651
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1
FT /note="M -> MEPAVESAPVGAQASKQGKEGSKNRSRRRWRKGKIKASAFSHSM
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_053335"
FT CONFLICT 113
FT /note="A -> T (in Ref. 3; BAE41414)"
FT /evidence="ECO:0000305"
FT CONFLICT 311
FT /note="E -> D (in Ref. 3; BAE41414)"
FT /evidence="ECO:0000305"
FT CONFLICT 330..331
FT /note="EL -> DV (in Ref. 1; AAC52163)"
FT /evidence="ECO:0000305"
FT CONFLICT 530
FT /note="L -> P (in Ref. 1; AAC52163)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 759 AA; 83348 MW; 3419AF52F6C85FF4 CRC64;
MDLRTMTQSL VTLAEDNMAF FSSQGPGETA RRLSNVFAGV REQALGLEPT LGQLLGVAHH
FDLDTETPAN GYRSLVHTAR CCLAHLLHKS RYVASNRKSI FFRASHNLAE LEAYLAALTQ
LRAMAYYAQR LLTINRPGVL FFEGDEGLTA DFLQEYVTLH KGCFYGRCLG FQFTPAIRPF
LQTLSIGLVS FGEHYKRNET GLSVTASSLF TGGRFAIDPE LRGAEFERII QNLDVHFWKA
FWNITEIEVL SSLANMASTT VRVSRLLSLP PEAFEMPLTS DPRLTVTISP PLAHTGPAPV
LARLISYDLR EGQDSKVLNS LAKSEGPRLE LRPRPHQAPR SRALVVHIHG GGFVAQTSKS
HEPYLKNWAQ ELGVPIFSID YSLAPEAPFP RALEECFFAY CWAVKHCDLL GSTGERICLA
GDSAGGNLCI TVSLRAAAYG VRVPDGIMAA YPVTTLQSSA SPSRLLSLMD PLLPLSVLSK
CVSAYSGTEA EDHFDSDQKA LGVMGLVQRD TSLFLRDLRL GASSWLNSFL ELSGRKPQKT
TSPTAESVRP TESMRRSVSE AALAQPEGLL GTDTLKKLTI KDLSNSEPSD SPEMSQSMET
LGPSTPSDVN FFLRPGNSQE EAEAKDEVRP MDGVPRVRAA FPEGFHPRRS SQGVLHMPLY
TSPIVKNPFM SPLLAPDSML KTLPPVHLVA CALDPMLDDS VMFARRLRDL GQPVTLKVVE
DLPHGFLSLA ALCRETRQAT EFCVQRIRLI LTPPAAPLN
