LIPS_RAT
ID LIPS_RAT Reviewed; 1068 AA.
AC P15304; Q6LCQ2;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2006, sequence version 3.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Hormone-sensitive lipase;
DE Short=HSL;
DE EC=3.1.1.79 {ECO:0000269|PubMed:6643478, ECO:0000269|PubMed:9162045, ECO:0000305|PubMed:6374655};
DE AltName: Full=Monoacylglycerol lipase LIPE;
DE EC=3.1.1.23 {ECO:0000250|UniProtKB:P54310};
DE AltName: Full=Retinyl ester hydrolase {ECO:0000303|PubMed:9162045};
DE Short=REH;
GN Name=Lipe;
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] (ISOFORM 2).
RC TISSUE=Adipose tissue;
RX PubMed=3186461; DOI=10.1093/nar/16.20.9879;
RA Holm C., Kirchgessner T.G., Svenson K.L., Lusis A.J., Belfrage P.,
RA Schotz M.C.;
RT "Nucleotide sequence of rat adipose hormone sensitive lipase cDNA.";
RL Nucleic Acids Res. 16:9879-9879(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Adipose tissue;
RX PubMed=3420405; DOI=10.1126/science.3420405;
RA Holm C., Kirchgessner T.G., Svenson K.L., Fredrikson G., Nilsson S.,
RA Miller C.G., Shively J.E., Heinzmann C., Sparkes R.S., Mohandas T.,
RA Lusis A.J., Belfrage P., Schotz M.C.;
RT "Hormone-sensitive lipase: sequence, expression, and chromosomal
RT localization to 19 cent-q13.3.";
RL Science 241:1503-1506(1988).
RN [3]
RP SEQUENCE REVISION TO 842-855 AND 1046-1068.
RA Holm C.;
RL Submitted (JUL-1995) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Testis;
RX PubMed=8812477; DOI=10.1006/geno.1996.0383;
RA Holst L.S., Langin D., Mulder H., Laurell H., Grober J., Bergh A.,
RA Mohrenweiser H.W., Edgren G., Holm C.;
RT "Molecular cloning, genomic organization, and expression of a testicular
RT isoform of hormone-sensitive lipase.";
RL Genomics 35:441-447(1996).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=6643478; DOI=10.1016/s0021-9258(17)43852-x;
RA Fredrikson G., Belfrage P.;
RT "Positional specificity of hormone-sensitive lipase from rat adipose
RT tissue.";
RL J. Biol. Chem. 258:14253-14256(1983).
RN [6]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND PHOSPHORYLATION.
RX PubMed=6374655; DOI=10.1073/pnas.81.11.3317;
RA Straalfors P., Bjoergell P., Belfrage P.;
RT "Hormonal regulation of hormone-sensitive lipase in intact adipocytes:
RT identification of phosphorylated sites and effects on the phosphorylation
RT by lipolytic hormones and insulin.";
RL Proc. Natl. Acad. Sci. U.S.A. 81:3317-3321(1984).
RN [7]
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=1770312;
RA Kraemer F.B., Tavangar K., Hoffman A.R.;
RT "Developmental regulation of hormone-sensitive lipase mRNA in the rat:
RT changes in steroidogenic tissues.";
RL J. Lipid Res. 32:1303-1310(1991).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=9162045; DOI=10.1074/jbc.272.22.14159;
RA Wei S., Lai K., Patel S., Piantedosi R., Shen H., Colantuoni V.,
RA Kraemer F.B., Blaner W.S.;
RT "Retinyl ester hydrolysis and retinol efflux from BFC-1beta adipocytes.";
RL J. Biol. Chem. 272:14159-14165(1997).
RN [9]
RP PHOSPHORYLATION AT SER-863; SER-959 AND SER-960, AND MUTAGENESIS OF
RP SER-863; SER-865; SER-959 AND SER-960.
RX PubMed=9417067; DOI=10.1074/jbc.273.1.215;
RA Anthonsen M.W., Roennstrand L., Wernstedt C., Degerman E., Holm C.;
RT "Identification of novel phosphorylation sites in hormone-sensitive lipase
RT that are phosphorylated in response to isoproterenol and govern activation
RT properties in vitro.";
RL J. Biol. Chem. 273:215-221(1998).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, PHOSPHORYLATION, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10694408; DOI=10.1021/bi992283h;
RA Shen W.J., Patel S., Hong R., Kraemer F.B.;
RT "Hormone-sensitive lipase functions as an oligomer.";
RL Biochemistry 39:2392-2398(2000).
RN [11]
RP PHOSPHORYLATION AT SER-865 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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-865; SER-906; SER-927;
RP SER-938 AND THR-1068, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [13]
RP INTERACTION WITH PLIN5.
RX PubMed=24303154; DOI=10.1002/phy2.84;
RA Macpherson R.E., Vandenboom R., Roy B.D., Peters S.J.;
RT "Skeletal muscle PLIN3 and PLIN5 are serine phosphorylated at rest and
RT following lipolysis during adrenergic or contractile stimulation.";
RL Physiol. Rep. 1:E00084-E00084(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:6643478, PubMed:9162045, PubMed:10694408). Shows a preferential
CC hydrolysis of DAGs over TAGs and MAGs and preferentially hydrolyzes the
CC fatty acid (FA) esters at the sn-3 position of DAGs (By similarity).
CC Preferentially hydrolyzes fatty acids at the sn-1 and sn-2 positions of
CC TAGs (PubMed:6643478). 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 (By similarity). In
CC adipose tissue and heart, it primarily hydrolyzes stored triglycerides
CC to free fatty acids, while in steroidogenic tissues, it principally
CC converts cholesteryl esters to free cholesterol for steroid hormone
CC production (PubMed:1770312). {ECO:0000250|UniProtKB:P54310,
CC ECO:0000269|PubMed:10694408, ECO:0000269|PubMed:6643478,
CC ECO:0000269|PubMed:9162045, ECO:0000303|PubMed:1770312}.
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:6643478};
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:6643478, ECO:0000269|PubMed:9162045};
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:6643478, ECO:0000305|PubMed:6374655};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolyzes glycerol monoesters of long-chain fatty acids.;
CC EC=3.1.1.23; Evidence={ECO:0000250|UniProtKB:P54310};
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:10694408,
CC ECO:0000269|PubMed:9162045};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33876;
CC Evidence={ECO:0000305|PubMed:9162045};
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:9162045};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13934;
CC Evidence={ECO:0000305|PubMed:9162045};
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:0000269|PubMed:6643478};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38660;
CC Evidence={ECO:0000305|PubMed:6643478};
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:6643478};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38488;
CC Evidence={ECO:0000305|PubMed:6643478};
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:0000269|PubMed:6643478};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38381;
CC Evidence={ECO:0000305|PubMed:6643478};
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 (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:0000250|UniProtKB:P54310};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38456;
CC Evidence={ECO:0000250|UniProtKB:P54310};
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:0000250|UniProtKB:P54310};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26133;
CC Evidence={ECO:0000250|UniProtKB:P54310};
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:P54310};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38492;
CC Evidence={ECO:0000250|UniProtKB:P54310};
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:0000250|UniProtKB:P54310};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38564;
CC Evidence={ECO:0000250|UniProtKB:P54310};
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:0000250|UniProtKB:P54310};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39936;
CC Evidence={ECO:0000250|UniProtKB:P54310};
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:0000250|UniProtKB:P54310};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39940;
CC Evidence={ECO:0000250|UniProtKB:P54310};
CC -!- ACTIVITY REGULATION: Rapidly activated by cAMP-dependent
CC phosphorylation under the influence of catecholamines (PubMed:6374655).
CC Dephosphorylation and inactivation are controlled by insulin
CC (PubMed:6374655). cAMP stimulates its retinyl ester hydrolase activity
CC (PubMed:9162045). {ECO:0000269|PubMed:6374655,
CC ECO:0000269|PubMed:9162045}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=161 uM for retinyl palmitate {ECO:0000269|PubMed:9162045};
CC KM=33 uM for 1,2-dioleoylglycerol {ECO:0000269|PubMed:6643478};
CC KM=33 uM for 1,3-dioleoylglycerol {ECO:0000269|PubMed:6643478};
CC KM=2.2 uM for cholesteryl (9Z-octadecenoate) (dimeric form)
CC {ECO:0000269|PubMed:10694408};
CC KM=2.2 uM for cholesteryl (9Z-octadecenoate) (monomeric form)
CC {ECO:0000269|PubMed:10694408};
CC Vmax=0.141 nmol/h/mg enzyme with cholesteryl (9Z-octadecenoate) as
CC substrate (dimeric form) {ECO:0000269|PubMed:10694408};
CC Vmax=0.003 nmol/h/mg enzyme with cholesteryl (9Z-octadecenoate) as
CC substrate (monomeric form) {ECO:0000269|PubMed:10694408};
CC -!- PATHWAY: Glycerolipid metabolism; triacylglycerol degradation.
CC -!- SUBUNIT: Monomer and homodimer (PubMed:10694408). Interacts with CAVIN1
CC in the adipocyte cytoplasm (By similarity). Interacts with PLIN5
CC (PubMed:24303154). {ECO:0000250|UniProtKB:Q05469,
CC ECO:0000269|PubMed:10694408, ECO:0000269|PubMed:24303154}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q05469}.
CC Membrane, caveola {ECO:0000250|UniProtKB:Q05469}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q05469}. 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; Synonyms=Testicular;
CC IsoId=P15304-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P15304-2; Sequence=VSP_017117;
CC -!- TISSUE SPECIFICITY: Highly expressed in the adipose tissue
CC (PubMed:1770312). Also expressed in the heart, adrenal gland and testis
CC (PubMed:1770312, PubMed:8812477). {ECO:0000269|PubMed:1770312,
CC ECO:0000269|PubMed:8812477}.
CC -!- DEVELOPMENTAL STAGE: Levels do not vary in adipose tissue from
CC epididymal fat pads between 3 weeks and 2 years of age
CC (PubMed:1770312). In heart, levels are lowest in the fetus, increase
CC rapidly within the first day postnatally, and then gradually increase
CC to stable adult levels by 2 months that are 3-fold higher than observed
CC in fetal rats (PubMed:1770312). Levels in the adrenals are lowest in
CC fetal rats, increase 4-fold during the first day and peak at levels
CC that are 9-fold higher by the end of the first week (PubMed:1770312).
CC Thereafter, levels fall and remain 3-to 4-fold higher than at birth
CC throughout adult life (PubMed:1770312). Undetectable in testis before 4
CC weeks of age and increase 25-fold to stable adult levels between 4 and
CC 12 weeks (PubMed:1770312). {ECO:0000269|PubMed:1770312}.
CC -!- PTM: Phosphorylation by AMPK reduces its translocation towards the
CC lipid droplets. {ECO:0000269|PubMed:15878856}.
CC -!- SIMILARITY: Belongs to the 'GDXG' lipolytic enzyme family.
CC {ECO:0000305}.
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DR EMBL; X51415; CAA35777.1; -; mRNA.
DR EMBL; U40001; AAC52771.1; -; mRNA.
DR PIR; S03672; LIRTH.
DR RefSeq; NP_036991.1; NM_012859.1. [P15304-1]
DR RefSeq; XP_006228456.1; XM_006228394.3. [P15304-2]
DR AlphaFoldDB; P15304; -.
DR BioGRID; 247369; 2.
DR IntAct; P15304; 1.
DR MINT; P15304; -.
DR STRING; 10116.ENSRNOP00000027911; -.
DR BindingDB; P15304; -.
DR ChEMBL; CHEMBL5582; -.
DR DrugCentral; P15304; -.
DR SwissLipids; SLP:000000320; -.
DR ESTHER; ratno-hslip; Hormone-sensitive_lipase_like.
DR MEROPS; S09.993; -.
DR iPTMnet; P15304; -.
DR PhosphoSitePlus; P15304; -.
DR PaxDb; P15304; -.
DR PRIDE; P15304; -.
DR GeneID; 25330; -.
DR KEGG; rno:25330; -.
DR UCSC; RGD:3010; rat. [P15304-1]
DR CTD; 3991; -.
DR RGD; 3010; Lipe.
DR eggNOG; KOG4388; Eukaryota.
DR InParanoid; P15304; -.
DR OrthoDB; 1263520at2759; -.
DR PhylomeDB; P15304; -.
DR BRENDA; 3.1.1.79; 5301.
DR UniPathway; UPA00256; -.
DR PRO; PR:P15304; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005901; C:caveola; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005811; C:lipid droplet; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISS: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; ISS:UniProtKB.
DR GO; GO:0102258; F:1,3-diacylglycerol acylhydrolase activity; ISS:UniProtKB.
DR GO; GO:0047372; F:acylglycerol lipase activity; IDA:RGD.
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; IDA:UniProtKB.
DR GO; GO:0016788; F:hydrolase activity, acting on ester bonds; IDA:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
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; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0046340; P:diacylglycerol catabolic process; ISS:UniProtKB.
DR GO; GO:0046485; P:ether lipid metabolic process; ISS:UniProtKB.
DR GO; GO:0007565; P:female pregnancy; IEP:RGD.
DR GO; GO:0016042; P:lipid catabolic process; ISS:UniProtKB.
DR GO; GO:0042758; P:long-chain fatty acid catabolic process; ISO:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
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:RGD.
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..1068
FT /note="Hormone-sensitive lipase"
FT /id="PRO_0000071550"
FT REGION 1..76
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 91..195
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 236..278
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 836..862
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 890..913
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 649..651
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 COMPBIAS 13..41
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 48..76
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 96..118
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 121..136
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 162..195
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 236..250
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 846..860
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 891..913
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 723
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10038"
FT ACT_SITE 1003
FT /evidence="ECO:0000250|UniProtKB:Q5NUF3"
FT ACT_SITE 1033
FT /evidence="ECO:0000250|UniProtKB:Q5NUF3"
FT MOD_RES 863
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:9417067"
FT MOD_RES 865
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:15878856,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 906
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 927
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 938
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 959
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:9417067"
FT MOD_RES 960
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:9417067"
FT MOD_RES 1068
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT VAR_SEQ 1..300
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:3186461,
FT ECO:0000303|PubMed:3420405"
FT /id="VSP_017117"
FT MUTAGEN 863
FT /note="S->A,E: No effect on activation by PKA."
FT /evidence="ECO:0000269|PubMed:9417067"
FT MUTAGEN 865
FT /note="S->A: Increases activation by PKA."
FT /evidence="ECO:0000269|PubMed:9417067"
FT MUTAGEN 865
FT /note="S->E: No effect on activation by PKA."
FT /evidence="ECO:0000269|PubMed:9417067"
FT MUTAGEN 959
FT /note="S->A: Slightly decreases activation by PKA.
FT Abolishes activation by PKA; when associated with A-960."
FT /evidence="ECO:0000269|PubMed:9417067"
FT MUTAGEN 960
FT /note="S->A: No effect on activation by PKA. Abolishes
FT activation by PKA; when associated with A-959."
FT /evidence="ECO:0000269|PubMed:9417067"
SQ SEQUENCE 1068 AA; 116812 MW; 13B10C9315AC87F1 CRC64;
MKPRRPISFT REITAMEPSS TSVSRPEWRP EAQQTLTDYP GSRELQEFGI PQKQSLPNEA
TAQQGAEFQQ EQGVQQSTLL QKLLTPLAFP VPQQSFPSHK VHSDQQEATS QNGPGAGKVH
TTQKELEHRD EHVGTAESGP AEPPPATEVE ATSIAQAVSG PDKKLPTQTD LVSQERAEQS
DPTAQQTPLV QGVKSDQGSL IESGILARLQ KLAIQQPSQE WKTFLDCVTE SDMEKYLNSS
SKSNPPEPSG GTVIPGTLPS KQKPDCGKMS GYGGKLPHGK KGILQKHKHY WDTASAFSHS
MDLRTMTQSL VALAEDNMAF FSSQGPGETA RRLSNVFAGV REQALGLEPT LGQLLGVAHH
FDLDTETPAN GYRSLVHTAR CCLAHLLHKS RYVASNRRSI FFRASHNLAE LEAYLAALTQ
LRALAYYAQR LLTINRPGVL FFEGDEGLSA DFLQDYVTLH KGCFYGRCLG FQFTPAIRPF
LQTLSIGLVS FGEHYKRNET GLSVTASSLF TGGRFAIDPE LRGAEFERII QNLDVHFWKA
FWNITEIEVL SSLANMASTT VRVSRLLSLP PEAFEMPLTS DPKLTVTISP PLAHTGPGPV
LARLISYDLR EGQDSKMLNS LAKSEGPRLE LRPRPQQAPR SRALVVHIHG GGFVAQTSKS
HEPYLKNWAQ ELGVPIISID YSLAPEAPFP RALEECFFAY CWAVKHCELL GSTGERICLA
GDSAGGNLCI TVSLRAAAYG VRVPDGIMAA YPVTTLQSSA SPSRLLSLMD PLLPLSVLSK
CVSAYSGTET EDHFDSDQKA LGVMGLVQRD TSLFLRDLRL GASSWLNSFL ELSGRKPHKT
PLPATETLRP TDSGRLTESM RRSVSEAALA QPEGLLGTDS LKKLTIKDLS FKGNSEPSDS
PEMSQSMETL GPSTPSDVNF FLRSGNSQEE AETRDDISPM DGIPRVRAAF PDGFHPRRSS
QGVLHMPLYS SPIVKNPFMS PLLAPDVMLK TLPPVHLVAC ALDPMLDDSV MFARRLKDLG
QPVTLKVVED LPHGFLSLAA LCRETRQAAE LCVQRIRLIL TPPAAPLT
