ID   LIPS_HUMAN              Reviewed;        1076 AA.
AC   Q05469; Q3LRT2; Q6NSL7;
DT   01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT   17-APR-2007, sequence version 4.
DT   27-MAR-2024, entry version 200.
DE   RecName: Full=Hormone-sensitive lipase;
DE            Short=HSL;
DE            EC=3.1.1.79 {ECO:0000269|PubMed:15955102, ECO:0000269|PubMed:19800417, ECO:0000269|PubMed:8812477};
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:15955102};
DE            Short=REH;
GN   Name=LIPE;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8506334; DOI=10.1073/pnas.90.11.4897;
RA   Langin D., Laurell H., Stenson Holst L., Belfrage P., Holm C.;
RT   "Gene organization and primary structure of human hormone-sensitive lipase:
RT   possible significance of a sequence homology with a lipase of Moraxella
RT   TA144, an antarctic bacterium.";
RL   Proc. Natl. Acad. Sci. U.S.A. 90:4897-4901(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, AND
RP   TISSUE SPECIFICITY.
RC   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   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-100; HIS-127; SER-146;
RP   THR-177; VAL-194; GLN-217; ASN-497; HIS-499 AND SER-938.
RG   SeattleSNPs variation discovery resource;
RL   Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Testis;
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   [5]
RP   FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX   PubMed=15955102; DOI=10.1111/j.0022-202x.2005.23761.x;
RA   Gao J., Simon M.;
RT   "Identification of a novel keratinocyte retinyl ester hydrolase as a
RT   transacylase and lipase.";
RL   J. Invest. Dermatol. 124:1259-1266(2005).
RN   [6]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=15716583; DOI=10.1194/jlr.m400509-jlr200;
RA   Ali Y.B., Carriere F., Verger R., Petry S., Muller G., Abousalham A.;
RT   "Continuous monitoring of cholesterol oleate hydrolysis by hormone-
RT   sensitive lipase and other cholesterol esterases.";
RL   J. Lipid Res. 46:994-1000(2005).
RN   [7]
RP   INTERACTION WITH CAVIN1, AND SUBCELLULAR LOCATION.
RX   PubMed=17026959; DOI=10.1016/j.bbrc.2006.09.094;
RA   Aboulaich N., Oertegren U., Vener A.V., Stralfors P.;
RT   "Association and insulin regulated translocation of hormone-sensitive
RT   lipase with PTRF.";
RL   Biochem. Biophys. Res. Commun. 350:657-661(2006).
RN   [8]
RP   SUBCELLULAR LOCATION.
RX   PubMed=16803459; DOI=10.1111/j.1742-4658.2006.05345.x;
RA   Oertegren U., Yin L., Oest A., Karlsson H., Nystrom F.H., Stralfors P.;
RT   "Separation and characterization of caveolae subclasses in the plasma
RT   membrane of primary adipocytes; segregation of specific proteins and
RT   functions.";
RL   FEBS J. 273:3381-3392(2006).
RN   [9]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Leukemic T-cell;
RX   PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA   Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA   Rodionov V., Han D.K.;
RT   "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT   reveals system-wide modulation of protein-protein interactions.";
RL   Sci. Signal. 2:RA46-RA46(2009).
RN   [10]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=19800417; DOI=10.1016/j.bbalip.2009.09.020;
RA   Rodriguez J.A., Ben Ali Y., Abdelkafi S., Mendoza L.D., Leclaire J.,
RA   Fotiadu F., Buono G., Carriere F., Abousalham A.;
RT   "In vitro stereoselective hydrolysis of diacylglycerols by hormone-
RT   sensitive lipase.";
RL   Biochim. Biophys. Acta 1801:77-83(2010).
RN   [11]
RP   INVOLVEMENT IN FPLD6.
RX   PubMed=24848981; DOI=10.1056/nejmoa1315496;
RA   Albert J.S., Yerges-Armstrong L.M., Horenstein R.B., Pollin T.I.,
RA   Sreenivasan U.T., Chai S., Blaner W.S., Snitker S., O'Connell J.R.,
RA   Gong D.W., Breyer R.J., Ryan A.S., McLenithan J.C., Shuldiner A.R.,
RA   Sztalryd C., Damcott C.M.;
RT   "Null mutation in hormone-sensitive lipase gene and risk of type 2
RT   diabetes.";
RL   N. Engl. J. Med. 370:2307-2315(2014).
RN   [12]
RP   VARIANT [LARGE SCALE ANALYSIS] GLN-146.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
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:8812477, PubMed:15955102, PubMed:15716583, PubMed:19800417).
CC       Shows a preferential hydrolysis of DAGs over TAGs and MAGs and
CC       preferentially hydrolyzes the fatty acid (FA) esters at the sn-3
CC       position of the glycerol backbone in DAGs (PubMed:19800417).
CC       Preferentially hydrolyzes FA esters at the sn-1 and sn-2 positions of
CC       the glycerol backbone in TAGs (By similarity). Catalyzes the hydrolysis
CC       of 2-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 (By similarity). {ECO:0000250|UniProtKB:P15304,
CC       ECO:0000250|UniProtKB:P54310, ECO:0000269|PubMed:15716583,
CC       ECO:0000269|PubMed:15955102, ECO:0000269|PubMed:19800417,
CC       ECO:0000269|PubMed:8812477}.
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:19800417, ECO:0000269|PubMed:8812477};
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:15955102, ECO:0000269|PubMed:19800417};
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:0000250|UniProtKB:P15304};
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=(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:19800417};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38381;
CC         Evidence={ECO:0000305|PubMed:19800417};
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:0000269|PubMed:19800417};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38384;
CC         Evidence={ECO:0000305|PubMed:19800417};
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:15716583};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33876;
CC         Evidence={ECO:0000305|PubMed:15716583};
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:0000269|PubMed:15955102};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38576;
CC         Evidence={ECO:0000305|PubMed:15955102};
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:15955102};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13934;
CC         Evidence={ECO:0000305|PubMed:15955102};
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=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:0000250|UniProtKB:P54310};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38488;
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   -!- 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   -!- ACTIVITY REGULATION: Retinyl ester hydrolase is inhibited by bis-p-
CC       nitrophenyl phosphate. {ECO:0000269|PubMed:15955102}.
CC   -!- PATHWAY: Glycerolipid metabolism; triacylglycerol degradation.
CC   -!- SUBUNIT: Monomer and homodimer (By similarity). Interacts with CAVIN1
CC       in the adipocyte cytoplasm (PubMed:17026959). Interacts with PLIN5 (By
CC       similarity). {ECO:0000250|UniProtKB:P15304,
CC       ECO:0000250|UniProtKB:P54310, ECO:0000269|PubMed:17026959}.
CC   -!- INTERACTION:
CC       Q05469; Q3SY00: TSGA10IP; NbExp=3; IntAct=EBI-721601, EBI-10241197;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17026959}.
CC       Membrane, caveola {ECO:0000269|PubMed:16803459,
CC       ECO:0000269|PubMed:17026959}. Cytoplasm, cytosol
CC       {ECO:0000269|PubMed:17026959}. Lipid droplet
CC       {ECO:0000250|UniProtKB:P54310}. Note=Found in the high-density
CC       caveolae. Translocates to the cytoplasm from the caveolae upon insulin
CC       stimulation (PubMed:17026959). Phosphorylation by AMPK reduces its
CC       translocation towards the lipid droplets (By similarity).
CC       {ECO:0000250|UniProtKB:P54310, ECO:0000269|PubMed:17026959}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1; Synonyms=Testicular;
CC         IsoId=Q05469-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q05469-2; Sequence=VSP_017116;
CC   -!- TISSUE SPECIFICITY: Testis. {ECO:0000269|PubMed:8812477}.
CC   -!- PTM: Phosphorylation by AMPK reduces its translocation towards the
CC       lipid droplets. {ECO:0000250|UniProtKB:P54310}.
CC   -!- DISEASE: Lipodystrophy, familial partial, 6 (FPLD6) [MIM:615980]: A
CC       form of lipodystrophy characterized by abnormal subcutaneous fat
CC       distribution. Affected individuals have increased visceral fat,
CC       impaired lipolysis, dyslipidemia, hepatic steatosis, systemic insulin
CC       resistance, and diabetes. Some patients manifest muscular dystrophy.
CC       {ECO:0000269|PubMed:24848981}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the 'GDXG' lipolytic enzyme family.
CC       {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=SeattleSNPs;
CC       URL="http://pga.gs.washington.edu/data/lipe/";
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; L11706; AAA69810.1; -; Genomic_DNA.
DR   EMBL; U40001; AAC50666.1; -; mRNA.
DR   EMBL; DQ188033; ABA03168.1; -; Genomic_DNA.
DR   EMBL; BC070041; AAH70041.1; -; mRNA.
DR   CCDS; CCDS12607.1; -. [Q05469-1]
DR   RefSeq; NP_005348.2; NM_005357.3. [Q05469-1]
DR   RefSeq; XP_005258997.1; XM_005258940.3.
DR   RefSeq; XP_006723281.1; XM_006723218.2. [Q05469-2]
DR   RefSeq; XP_016882299.1; XM_017026810.1.
DR   AlphaFoldDB; Q05469; -.
DR   BioGRID; 110179; 12.
DR   IntAct; Q05469; 4.
DR   STRING; 9606.ENSP00000244289; -.
DR   BindingDB; Q05469; -.
DR   ChEMBL; CHEMBL3590; -.
DR   GuidetoPHARMACOLOGY; 2593; -.
DR   SwissLipids; SLP:000000316; -.
DR   ESTHER; human-LIPE; Hormone-sensitive_lipase_like.
DR   MEROPS; S09.993; -.
DR   iPTMnet; Q05469; -.
DR   PhosphoSitePlus; Q05469; -.
DR   SwissPalm; Q05469; -.
DR   BioMuta; LIPE; -.
DR   DMDM; 145559491; -.
DR   EPD; Q05469; -.
DR   jPOST; Q05469; -.
DR   MassIVE; Q05469; -.
DR   MaxQB; Q05469; -.
DR   PaxDb; 9606-ENSP00000244289; -.
DR   PeptideAtlas; Q05469; -.
DR   ProteomicsDB; 58326; -. [Q05469-1]
DR   ProteomicsDB; 58327; -. [Q05469-2]
DR   Pumba; Q05469; -.
DR   Antibodypedia; 4327; 549 antibodies from 38 providers.
DR   DNASU; 3991; -.
DR   Ensembl; ENST00000244289.9; ENSP00000244289.3; ENSG00000079435.10. [Q05469-1]
DR   GeneID; 3991; -.
DR   KEGG; hsa:3991; -.
DR   MANE-Select; ENST00000244289.9; ENSP00000244289.3; NM_005357.4; NP_005348.2.
DR   UCSC; uc002otr.4; human. [Q05469-1]
DR   AGR; HGNC:6621; -.
DR   CTD; 3991; -.
DR   DisGeNET; 3991; -.
DR   GeneCards; LIPE; -.
DR   HGNC; HGNC:6621; LIPE.
DR   HPA; ENSG00000079435; Group enriched (adipose tissue, breast).
DR   MalaCards; LIPE; -.
DR   MIM; 151750; gene.
DR   MIM; 615980; phenotype.
DR   neXtProt; NX_Q05469; -.
DR   OpenTargets; ENSG00000079435; -.
DR   Orphanet; 435660; LIPE-related familial partial lipodystrophy.
DR   PharmGKB; PA30393; -.
DR   VEuPathDB; HostDB:ENSG00000079435; -.
DR   eggNOG; KOG4388; Eukaryota.
DR   GeneTree; ENSGT00730000111056; -.
DR   HOGENOM; CLU_010288_0_0_1; -.
DR   InParanoid; Q05469; -.
DR   OMA; NACITHG; -.
DR   OrthoDB; 2941058at2759; -.
DR   PhylomeDB; Q05469; -.
DR   TreeFam; TF314423; -.
DR   BioCyc; MetaCyc:HS01328-MONOMER; -.
DR   BRENDA; 3.1.1.79; 2681.
DR   PathwayCommons; Q05469; -.
DR   Reactome; R-HSA-163560; Triglyceride catabolism.
DR   SABIO-RK; Q05469; -.
DR   SignaLink; Q05469; -.
DR   SIGNOR; Q05469; -.
DR   UniPathway; UPA00256; -.
DR   BioGRID-ORCS; 3991; 18 hits in 1154 CRISPR screens.
DR   ChiTaRS; LIPE; human.
DR   GeneWiki; Hormone-sensitive_lipase; -.
DR   GenomeRNAi; 3991; -.
DR   Pharos; Q05469; Tchem.
DR   PRO; PR:Q05469; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; Q05469; Protein.
DR   Bgee; ENSG00000079435; Expressed in omental fat pad and 131 other cell types or tissues.
DR   ExpressionAtlas; Q05469; baseline and differential.
DR   GO; GO:0005901; C:caveola; IEA:UniProtKB-SubCell.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005811; C:lipid droplet; ISS:UniProtKB.
DR   GO; GO:0016020; C:membrane; 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; ISS: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; IDA:UniProtKB.
DR   GO; GO:0050253; F:retinyl-palmitate esterase activity; IDA:UniProtKB.
DR   GO; GO:0004771; F:sterol esterase activity; IDA:UniProtKB.
DR   GO; GO:0004806; F:triglyceride lipase activity; IDA:UniProtKB.
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:0016042; P:lipid catabolic process; ISS:UniProtKB.
DR   GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc.
DR   GO; GO:0019433; P:triglyceride catabolic process; IBA:GO_Central.
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; Q05469; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell membrane; Cholesterol metabolism; Cytoplasm;
KW   Diabetes mellitus; Hydrolase; Lipid degradation; Lipid droplet;
KW   Lipid metabolism; Membrane; Obesity; Phosphoprotein; Reference proteome;
KW   Steroid metabolism; Sterol metabolism.
FT   CHAIN           1..1076
FT                   /note="Hormone-sensitive lipase"
FT                   /id="PRO_0000071547"
FT   REGION          1..198
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          229..250
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          838..930
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1055..1076
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           651..653
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        1..16
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        36..66
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        95..132
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        170..198
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        229..249
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        866..909
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        725
FT                   /evidence="ECO:0000250|UniProtKB:Q8BLF1,
FT                   ECO:0000255|PROSITE-ProRule:PRU10038"
FT   ACT_SITE        994
FT                   /evidence="ECO:0000250|UniProtKB:Q8BLF1"
FT   ACT_SITE        1024
FT                   /evidence="ECO:0000250|UniProtKB:Q8BLF1"
FT   MOD_RES         853
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P16386"
FT   MOD_RES         855
FT                   /note="Phosphoserine; by AMPK"
FT                   /evidence="ECO:0000250|UniProtKB:P16386"
FT   MOD_RES         897
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P15304"
FT   MOD_RES         929
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P15304"
FT   MOD_RES         950
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P15304"
FT   MOD_RES         951
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P15304"
FT   VAR_SEQ         1..301
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_017116"
FT   VARIANT         100
FT                   /note="Y -> H (in dbSNP:rs16975750)"
FT                   /evidence="ECO:0000269|Ref.3"
FT                   /id="VAR_025108"
FT   VARIANT         127
FT                   /note="Q -> H (in dbSNP:rs34080774)"
FT                   /evidence="ECO:0000269|Ref.3"
FT                   /id="VAR_025109"
FT   VARIANT         146
FT                   /note="P -> Q (in a breast cancer sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_036539"
FT   VARIANT         146
FT                   /note="P -> S (in dbSNP:rs34348028)"
FT                   /evidence="ECO:0000269|Ref.3"
FT                   /id="VAR_025110"
FT   VARIANT         177
FT                   /note="S -> T (in dbSNP:rs16975748)"
FT                   /evidence="ECO:0000269|Ref.3"
FT                   /id="VAR_025111"
FT   VARIANT         194
FT                   /note="A -> V (in dbSNP:rs34996020)"
FT                   /evidence="ECO:0000269|Ref.3"
FT                   /id="VAR_025112"
FT   VARIANT         217
FT                   /note="R -> Q (in dbSNP:rs3745238)"
FT                   /evidence="ECO:0000269|Ref.3"
FT                   /id="VAR_025113"
FT   VARIANT         497
FT                   /note="K -> N (in dbSNP:rs35938529)"
FT                   /evidence="ECO:0000269|Ref.3"
FT                   /id="VAR_025114"
FT   VARIANT         499
FT                   /note="N -> H (in dbSNP:rs33921216)"
FT                   /evidence="ECO:0000269|Ref.3"
FT                   /id="VAR_025115"
FT   VARIANT         938
FT                   /note="R -> S (in dbSNP:rs7246232)"
FT                   /evidence="ECO:0000269|Ref.3"
FT                   /id="VAR_025116"
FT   CONFLICT        230
FT                   /note="T -> A (in Ref. 1; AAA69810, 2; AAC50666 and 3;
FT                   ABA03168)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        486
FT                   /note="S -> Y (in Ref. 4; AAH70041)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        608
FT                   /note="Y -> C (in Ref. 4; AAH70041)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1076 AA;  116598 MW;  1CC0E3880FF64D74 CRC64;
     MEPGSKSVSR SDWQPEPHQR PITPLEPGPE KTPIAQPESK TLQGSNTQQK PASNQRPLTQ
     QETPAQHDAE SQKEPRAQQK SASQEEFLAP QKPAPQQSPY IQRVLLTQQE AASQQGPGLG
     KESITQQEPA LRQRHVAQPG PGPGEPPPAQ QEAESTPAAQ AKPGAKREPS APTESTSQET
     PEQSDKQTTP VQGAKSKQGS LTELGFLTKL QELSIQRSAL EWKALSEWVT DSESESDVGS
     SSDTDSPATM GGMVAQGVKL GFKGKSGYKV MSGYSGTSPH EKTSARNHRH YQDTASRLIH
     NMDLRTMTQS LVTLAEDNIA FFSSQGPGET AQRLSGVFAG VREQALGLEP ALGRLLGVAH
     LFDLDPETPA NGYRSLVHTA RCCLAHLLHK SRYVASNRRS IFFRTSHNLA ELEAYLAALT
     QLRALVYYAQ RLLVTNRPGV LFFEGDEGLT ADFLREYVTL HKGCFYGRCL GFQFTPAIRP
     FLQTISIGLV SFGEHYKRNE TGLSVAASSL FTSGRFAIDP ELRGAEFERI TQNLDVHFWK
     AFWNITEMEV LSSLANMASA TVRVSRLLSL PPEAFEMPLT ADPTLTVTIS PPLAHTGPGP
     VLVRLISYDL REGQDSEELS SLIKSNGQRS LELWPRPQQA PRSRSLIVHF HGGGFVAQTS
     RSHEPYLKSW AQELGAPIIS IDYSLAPEAP FPRALEECFF AYCWAIKHCA LLGSTGERIC
     LAGDSAGGNL CFTVALRAAA YGVRVPDGIM AAYPATMLQP AASPSRLLSL MDPLLPLSVL
     SKCVSAYAGA KTEDHSNSDQ KALGMMGLVR RDTALLLRDF RLGASSWLNS FLELSGRKSQ
     KMSEPIAEPM RRSVSEAALA QPQGPLGTDS LKNLTLRDLS LRGNSETSSD TPEMSLSAET
     LSPSTPSDVN FLLPPEDAGE EAEAKNELSP MDRGLGVRAA FPEGFHPRRS SQGATQMPLY
     SSPIVKNPFM SPLLAPDSML KSLPPVHIVA CALDPMLDDS VMLARRLRNL GQPVTLRVVE
     DLPHGFLTLA ALCRETRQAA ELCVERIRLV LTPPAGAGPS GETGAAGVDG GCGGRH
//