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   27-MAR-2024, entry version 171.
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         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: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   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; 10116-ENSRNOP00000027911; -.
DR   GeneID; 25330; -.
DR   KEGG; rno:25330; -.
DR   UCSC; RGD:3010; rat. [P15304-1]
DR   AGR; RGD:3010; -.
DR   CTD; 3991; -.
DR   RGD; 3010; Lipe.
DR   eggNOG; KOG4388; Eukaryota.
DR   InParanoid; P15304; -.
DR   OrthoDB; 2941058at2759; -.
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; ISS:UniProtKB.
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 at RNA polymerase I promoter; ISS:UniProtKB.
DR   GO; GO:0019433; P:triglyceride catabolic process; IDA:RGD.
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.
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
//