LIPS_HUMAN
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 03-AUG-2022, entry version 191.
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 (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 -!- 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. [Q05469-2]
DR RefSeq; XP_006723281.1; XM_006723218.2. [Q05469-2]
DR RefSeq; XP_016882299.1; XM_017026810.1. [Q05469-2]
DR AlphaFoldDB; Q05469; -.
DR BioGRID; 110179; 11.
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 BioMuta; LIPE; -.
DR DMDM; 145559491; -.
DR EPD; Q05469; -.
DR jPOST; Q05469; -.
DR MassIVE; Q05469; -.
DR MaxQB; Q05469; -.
DR PaxDb; Q05469; -.
DR PeptideAtlas; Q05469; -.
DR PRIDE; Q05469; -.
DR ProteomicsDB; 58326; -. [Q05469-1]
DR ProteomicsDB; 58327; -. [Q05469-2]
DR Antibodypedia; 4327; 497 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 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; FACGNHT; -.
DR PhylomeDB; Q05469; -.
DR TreeFam; TF314423; -.
DR BioCyc; MetaCyc:HS01328-MON; -.
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 1072 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 129 other tissues.
DR ExpressionAtlas; Q05469; baseline and differential.
DR Genevisible; Q05469; HS.
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; -; 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 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
