LIPS_ICTTR
ID LIPS_ICTTR Reviewed; 763 AA.
AC Q9R101;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 02-JUN-2021, entry version 94.
DE RecName: Full=Hormone-sensitive lipase;
DE Short=HSL;
DE EC=3.1.1.79 {ECO:0000250|UniProtKB:P15304};
DE AltName: Full=Monoacylglycerol lipase LIPE;
DE EC=3.1.1.23 {ECO:0000250|UniProtKB:P54310};
DE AltName: Full=Retinyl ester hydrolase {ECO:0000250|UniProtKB:P54310};
DE Short=REH;
GN Name=LIPE;
OS Ictidomys tridecemlineatus (Thirteen-lined ground squirrel) (Spermophilus
OS tridecemlineatus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Sciuromorpha; Sciuridae;
OC Xerinae; Marmotini; Ictidomys.
OX NCBI_TaxID=43179;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=White adipose tissue;
RA Bauer V.W., Andrews M.T.;
RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Lipase with broad substrate specificity, catalyzing the
CC hydrolysis of triacylglycerols (TAGs), diacylglycerols (DAGs),
CC monoacylglycerols (MAGs), cholesteryl esters and retinyl esters (By
CC similarity). Shows a preferential hydrolysis of DAGs over TAGs and MAGs
CC (By similarity). Preferentially hydrolyzes fatty acid (FA) esters at
CC the sn-3 position of the glycerol backbone in DAGs and FA esters at the
CC sn-1 and sn-2 positions of the glycerol backbone in TAGs (By
CC similarity). Catalyzes the hydrolysis of 2-arachidonoylglycerol, an
CC endocannabinoid and of 2-acetyl monoalkylglycerol ether, the
CC penultimate precursor of the pathway for de novo synthesis of platelet-
CC activating factor (By similarity). In adipose tissue and heart, it
CC primarily hydrolyzes stored triglycerides to free fatty acids, while in
CC steroidogenic tissues, it principally converts cholesteryl esters to
CC free cholesterol for steroid hormone production (By similarity).
CC {ECO:0000250|UniProtKB:P15304, ECO:0000250|UniProtKB:P54310,
CC ECO:0000250|UniProtKB:Q05469}.
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:0000250|UniProtKB:P15304};
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:0000250|UniProtKB:P15304};
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:P15304};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoate + 1,2-di-(9Z-octadecenoyl)-glycerol + H(+)
CC = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O; Xref=Rhea:RHEA:38379,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:52323, ChEBI:CHEBI:53753;
CC Evidence={ECO:0000250|UniProtKB:Q05469};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38381;
CC Evidence={ECO:0000250|UniProtKB:Q05469};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2,3-di-(9Z)-octadecenoyl-sn-glycerol + H2O = (9Z)-
CC octadecenoate + 2-(9Z-octadecenoyl)-glycerol + H(+);
CC Xref=Rhea:RHEA:38383, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:73990, ChEBI:CHEBI:75824;
CC Evidence={ECO:0000250|UniProtKB:Q05469};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38384;
CC Evidence={ECO:0000250|UniProtKB:Q05469};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=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:0000250|UniProtKB:Q05469};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33876;
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=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:0000250|UniProtKB:P54310};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13934;
CC Evidence={ECO:0000250|UniProtKB:P54310};
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 -!- PATHWAY: Glycerolipid metabolism; triacylglycerol degradation.
CC -!- SUBUNIT: Monomer and homodimer (By similarity). Interacts with CAVIN1
CC in the adipocyte cytoplasm (By similarity). Interacts with PLIN5 (By
CC similarity). {ECO:0000250|UniProtKB:P15304,
CC ECO:0000250|UniProtKB:P54310, ECO:0000250|UniProtKB:Q05469}.
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:0000250|UniProtKB:P54310}. Note=Found in the high-density
CC caveolae. Translocates to the cytoplasm from the caveolae upon insulin
CC stimulation. Phosphorylation by AMPK reduces its translocation towards
CC the lipid droplets. {ECO:0000250|UniProtKB:P54310,
CC ECO:0000250|UniProtKB:Q05469}.
CC -!- PTM: Phosphorylation by AMPK reduces its translocation towards the
CC lipid droplets. {ECO:0000250|UniProtKB:P54310}.
CC -!- SIMILARITY: Belongs to the 'GDXG' lipolytic enzyme family.
CC {ECO:0000305}.
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DR EMBL; AF177401; AAD51122.1; -; mRNA.
DR RefSeq; NP_001269179.1; NM_001282250.1.
DR STRING; 43179.ENSSTOP00000010392; -.
DR ESTHER; spetr-hslip; Hormone-sensitive_lipase_like.
DR MEROPS; S09.993; -.
DR GeneID; 101976389; -.
DR CTD; 3991; -.
DR eggNOG; KOG4388; Eukaryota.
DR InParanoid; Q9R101; -.
DR OrthoDB; 1263520at2759; -.
DR UniPathway; UPA00256; -.
DR Proteomes; UP000005215; Unassembled WGS sequence.
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: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; 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; IEA:UniProtKB-EC.
DR GO; GO:0050253; F:retinyl-palmitate esterase activity; ISS:UniProtKB.
DR GO; GO:0042134; F:rRNA primary transcript binding; ISS:UniProtKB.
DR GO; GO:0004771; F:sterol esterase activity; ISS:UniProtKB.
DR GO; GO:0004806; F:triglyceride lipase activity; ISS: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: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; IEA:UniProtKB-UniPathway.
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 2: Evidence at transcript level;
KW Cell membrane; Cholesterol metabolism; Cytoplasm; Hydrolase;
KW Lipid degradation; Lipid droplet; Lipid metabolism; Membrane;
KW Phosphoprotein; Reference proteome; Steroid metabolism; Sterol metabolism.
FT CHAIN 1..763
FT /note="Hormone-sensitive lipase"
FT /id="PRO_0000071551"
FT REGION 614..652
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 350..352
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 614..628
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 424
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10038"
FT ACT_SITE 692
FT /evidence="ECO:0000250|UniProtKB:Q5NUF3"
FT ACT_SITE 722
FT /evidence="ECO:0000250|UniProtKB:Q5NUF3"
FT MOD_RES 552
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16386"
FT MOD_RES 554
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000250|UniProtKB:P16386"
FT MOD_RES 595
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15304"
FT MOD_RES 627
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15304"
FT MOD_RES 649
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P15304"
SQ SEQUENCE 763 AA; 83129 MW; E5516B02EFB8BE4D CRC64;
MDLRTMTQSL VTLAEDNMAF FSSQGPGETA RRLSNVFAGV REQALGLEPA LGSLLSVAHL
FDLDPETPAN GYRSLVHTAR CCLAHLLHKS RYVASNRRSI FFRTSHNLAE LEAYLAALTQ
LRALAYYAQR LLATNRPGGL FFEGDEGLTA DFLREYVTLH KGCFYGRCLG FQFTPSIRPF
LQTISIGLVS FGEHYKRNES GLGVTASSLF TSGRFAIDPE LRGAEFERIT QNLDVHFWKA
FWNITEIEVL SSLANMASAT VRVSRLISLP PEAFEMPLTS DPKLTVTISP PLAHTGPGPV
LIRLISYDLR EGQDSEELNS MVKSEGPRIL ELRPRPQQTS RSRSLVVXFH GGGFVAQTSK
SHEPYLKSWA QELGAPIISI DYSLAPEAPF PRALEECFFA YCWAVKHCAL LGSTGERICL
AGDSAGGNLC FTVALRAAAY GVRVPDGIMA AYPATMLQSA ASPSRLLSLM DPLLPLSVLS
KCVSAYAGAE TEEHPNSDEK ALGMMGLVRR DTSLLLRDLR LGASSWLNSF LEFSGQKSQK
TSAPTVESMR RSVSEAALAQ PEGPVGTDSL KILTLKDLNL KSSSETSETP EMSLSVETLG
PSTPSDVNFF LRPEDAREEA EAKEGLSAKD GSSRVSNAFP EGFHPRRTSQ GATQMPLYSS
PIVKNPFMSP LLAPDNMLKT LPPVHIVACA LDPMLDDSXM FARRLRALGQ PVTLRVVEDL
PHGFLSLASL CRETRQAAEL CVERIRLILT PPAAAAAAAP PPL
