ID A0A455AB62_PHYMC Unreviewed; 888 AA.
AC A0A455AB62;
DT 05-JUN-2019, integrated into UniProtKB/TrEMBL.
DT 05-JUN-2019, sequence version 1.
DT 27-MAR-2024, entry version 24.
DE RecName: Full=Hormone-sensitive lipase {ECO:0000256|ARBA:ARBA00015845};
DE EC=3.1.1.23 {ECO:0000256|ARBA:ARBA00013254};
DE EC=3.1.1.79 {ECO:0000256|ARBA:ARBA00013088};
DE AltName: Full=Monoacylglycerol lipase LIPE {ECO:0000256|ARBA:ARBA00031112};
DE AltName: Full=Retinyl ester hydrolase {ECO:0000256|ARBA:ARBA00030031};
GN Name=LIPE {ECO:0000313|RefSeq:XP_028333275.1};
OS Physeter macrocephalus (Sperm whale) (Physeter catodon).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Whippomorpha; Cetacea; Odontoceti;
OC Physeteridae; Physeter.
OX NCBI_TaxID=9755 {ECO:0000313|Proteomes:UP000248484, ECO:0000313|RefSeq:XP_028333275.1};
RN [1] {ECO:0000313|RefSeq:XP_028333275.1}
RP IDENTIFICATION.
RC TISSUE=Muscle {ECO:0000313|RefSeq:XP_028333275.1};
RG RefSeq;
RL Submitted (NOV-2023) to UniProtKB.
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:0000256|ARBA:ARBA00023334};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38381;
CC Evidence={ECO:0000256|ARBA:ARBA00023334};
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:0000256|ARBA:ARBA00000652};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38576;
CC Evidence={ECO:0000256|ARBA:ARBA00000652};
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:0000256|ARBA:ARBA00023366};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38456;
CC Evidence={ECO:0000256|ARBA:ARBA00023366};
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:0000256|ARBA:ARBA00023353};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38660;
CC Evidence={ECO:0000256|ARBA:ARBA00023353};
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:0000256|ARBA:ARBA00023356};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39936;
CC Evidence={ECO:0000256|ARBA:ARBA00023356};
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:0000256|ARBA:ARBA00023393};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39940;
CC Evidence={ECO:0000256|ARBA:ARBA00023393};
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:0000256|ARBA:ARBA00023407};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38488;
CC Evidence={ECO:0000256|ARBA:ARBA00023407};
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:0000256|ARBA:ARBA00023406};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38564;
CC Evidence={ECO:0000256|ARBA:ARBA00023406};
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:0000256|ARBA:ARBA00023360};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38384;
CC Evidence={ECO:0000256|ARBA:ARBA00023360};
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:0000256|ARBA:ARBA00000361};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26133;
CC Evidence={ECO:0000256|ARBA:ARBA00000361};
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:0000256|ARBA:ARBA00023382};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38492;
CC Evidence={ECO:0000256|ARBA:ARBA00023382};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolyzes glycerol monoesters of long-chain fatty acids.;
CC EC=3.1.1.23; Evidence={ECO:0000256|ARBA:ARBA00001613};
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:0000256|ARBA:ARBA00000354};
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:0000256|ARBA:ARBA00001413};
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:0000256|ARBA:ARBA00000803};
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:0000256|ARBA:ARBA00023384};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13934;
CC Evidence={ECO:0000256|ARBA:ARBA00023384};
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:0000256|ARBA:ARBA00023350};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33876;
CC Evidence={ECO:0000256|ARBA:ARBA00023350};
CC -!- PATHWAY: Glycerolipid metabolism; triacylglycerol degradation.
CC {ECO:0000256|ARBA:ARBA00004879}.
CC -!- PATHWAY: Lipid metabolism. {ECO:0000256|ARBA:ARBA00005189}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000256|ARBA:ARBA00004236}.
CC Cytoplasm, cytosol {ECO:0000256|ARBA:ARBA00004514}. Lipid droplet
CC {ECO:0000256|ARBA:ARBA00004502}. Membrane, caveola
CC {ECO:0000256|ARBA:ARBA00004345}.
CC -!- SIMILARITY: Belongs to the 'GDXG' lipolytic enzyme family.
CC {ECO:0000256|ARBA:ARBA00010515}.
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DR RefSeq; XP_028333275.1; XM_028477474.2.
DR AlphaFoldDB; A0A455AB62; -.
DR STRING; 9755.ENSPCTP00005009234; -.
DR KEGG; pcad:102989235; -.
DR InParanoid; A0A455AB62; -.
DR OrthoDB; 2941058at2759; -.
DR UniPathway; UPA00256; -.
DR Proteomes; UP000248484; Chromosome 17.
DR GO; GO:0005901; C:caveola; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005811; C:lipid droplet; IEA:UniProtKB-SubCell.
DR GO; GO:0047372; F:acylglycerol lipase activity; IEA:UniProtKB-EC.
DR GO; GO:0033878; F:hormone-sensitive lipase activity; IEA:UniProtKB-EC.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0019433; P:triglyceride catabolic process; IEA:UniProtKB-UniPathway.
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 3: Inferred from homology;
KW Cell membrane {ECO:0000256|ARBA:ARBA00022475};
KW Cholesterol metabolism {ECO:0000256|ARBA:ARBA00022548};
KW Hydrolase {ECO:0000256|ARBA:ARBA00022801};
KW Lipid degradation {ECO:0000256|ARBA:ARBA00022963};
KW Lipid droplet {ECO:0000256|ARBA:ARBA00022677};
KW Lipid metabolism {ECO:0000256|ARBA:ARBA00023098};
KW Membrane {ECO:0000256|ARBA:ARBA00023136};
KW Phosphoprotein {ECO:0000256|ARBA:ARBA00022553};
KW Reference proteome {ECO:0000313|Proteomes:UP000248484};
KW Steroid metabolism {ECO:0000256|ARBA:ARBA00023221};
KW Sterol metabolism {ECO:0000256|ARBA:ARBA00023166}.
FT DOMAIN 139..446
FT /note="Hormone-sensitive lipase N-terminal"
FT /evidence="ECO:0000259|Pfam:PF06350"
FT DOMAIN 478..626
FT /note="Alpha/beta hydrolase fold-3"
FT /evidence="ECO:0000259|Pfam:PF07859"
FT DOMAIN 778..857
FT /note="Alpha/beta hydrolase fold-3"
FT /evidence="ECO:0000259|Pfam:PF07859"
FT REGION 1..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 100..130
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 712..736
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 712..734
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 556
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU10038"
SQ SEQUENCE 888 AA; 96603 MW; 88A746606CECEBBD CRC64;
MRARGRGQVA GPSGGGRDLT VKGGPRCSEG GTQREVSPRL GGVGARRWYV ARIGPRGGDW
RLELAPAGGI GPGWWNWPRA PDRGKLMESA REMRFPLAAG APGSKKVQEG SKIQRRGRWR
KGKAKASRLS HSMDLHTMTQ SLVTLAEDNM AFFSSQGPGE TARRLSSVFA GVREQALGLE
PTLGRLLSVA HLFDLDTETP ANGYRSLVHT ARCCLLHLLH KSRHVASNRR SIFFRTSHNL
AELEAYLATL TQLRALAYYA QHLLATNQPG RLFFEGDERV TADFLHEYVS LHKGCFYGRC
LGFQFTPAIR PFLQTVSVGL VSFGEHYKRN ETGLSVTASS LFTGGRFAID PELRGAEFER
IVQNLDVHFW KAFWNITEIQ VLSSLANMAS ATVRVSRVLS LPPTAFEMPL TADPKVTVTI
SPPLAHTGPG PVLVRLISYD LREGQDSEEL SSLVRSEGPR SLELRSRPQQ APRSRRLVVH
IHGGGFVAQT SKSHEPYLKS WAQELGAPIL SIDYSLAPEA PFPRALEECF YAYCWAVKHC
ALLGSTGERI CLAGDSAGGN LCFTVSLRAA AYGVRVPDGI MAAYPATMLQ ATASPSRLLS
LMDPLLPLSM LSKCVNAYAG GVTEDHSDSD QKALGVMGLV QRDTALLFRD LRLGASSWLN
SFLELSGHKS HSNSVPVAEP MRCSVSETAL AQPEGPLGMD SLKGLTLHDL SLRGSSETPD
TPELSLSAGA RGHSTPSAVN FLLRPEDTSE ESEAGDELST KDRVQGVCAA FPEGFHPRRS
SHGAKRMTLY SSPIVKNPFM SPLLAPDSML QTLPPVHIVA CALDPMLDDS VMFARRLRSL
SQPVTLRVVE DLPHGFLGLA ALCRETRQAA ALCVERIRLI LNPPGPPV
//