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 27-MAR-2024, entry version 183. 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, RC Spleen, 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 1-(9Z-octadecenoyl)-glycerol + H(+); Xref=Rhea:RHEA:39939, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, CC ChEBI:CHEBI:75342, ChEBI:CHEBI:75735; 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 BioGRID; 201169; 1. 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; 10090-ENSMUSP00000003207; -. DR PeptideAtlas; P54310; -. DR ProteomicsDB; 292097; -. [P54310-1] DR ProteomicsDB; 292098; -. [P54310-2] DR Pumba; P54310; -. DR Antibodypedia; 4327; 549 antibodies from 38 providers. DR DNASU; 16890; -. DR Ensembl; ENSMUST00000003207.11; ENSMUSP00000003207.5; ENSMUSG00000003123.16. [P54310-2] DR Ensembl; ENSMUST00000054301.14; ENSMUSP00000050935.8; ENSMUSG00000003123.16. [P54310-1] DR Ensembl; ENSMUST00000206861.2; ENSMUSP00000145665.2; ENSMUSG00000003123.16. [P54310-1] DR GeneID; 16890; -. DR KEGG; mmu:16890; -. DR UCSC; uc009fsp.1; mouse. [P54310-1] DR UCSC; uc009fsr.1; mouse. [P54310-2] DR AGR; MGI:96790; -. 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; NACITHG; -. DR OrthoDB; 2941058at2759; -. DR TreeFam; TF314423; -. DR BRENDA; 3.1.1.79; 3474. DR UniPathway; UPA00256; -. DR BioGRID-ORCS; 16890; 3 hits in 79 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 143 other cell types or tissues. DR ExpressionAtlas; P54310; baseline and differential. 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 at RNA polymerase I promoter; ISS:UniProtKB. DR GO; GO:0019433; P:triglyceride catabolic process; IDA:MGI. DR Gene3D; 3.40.50.1820; alpha/beta hydrolase; 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 PANTHER; PTHR23025:SF3; HORMONE-SENSITIVE LIPASE; 1. DR PANTHER; PTHR23025; TRIACYLGLYCEROL LIPASE; 1. DR Pfam; PF07859; Abhydrolase_3; 2. DR Pfam; PF06350; HSL_N; 1. DR SUPFAM; SSF53474; alpha/beta-Hydrolases; 1. DR PROSITE; PS01173; LIPASE_GDXG_HIS; 1. DR PROSITE; PS01174; LIPASE_GDXG_SER; 1. DR Genevisible; P54310; MM. 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 //