Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMMVJ8A)

DOT Name Hormone-sensitive lipase (LIPE)
Synonyms HSL; EC 3.1.1.79; Monoacylglycerol lipase LIPE; EC 3.1.1.23; Retinyl ester hydrolase; REH
Gene Name LIPE
Related Disease
LIPE-related familial partial lipodystrophy ( )
UniProt ID
LIPS_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
3.1.1.23; 3.1.1.79
Pfam ID
PF07859 ; PF06350
Sequence
MEPGSKSVSRSDWQPEPHQRPITPLEPGPEKTPIAQPESKTLQGSNTQQKPASNQRPLTQ
QETPAQHDAESQKEPRAQQKSASQEEFLAPQKPAPQQSPYIQRVLLTQQEAASQQGPGLG
KESITQQEPALRQRHVAQPGPGPGEPPPAQQEAESTPAAQAKPGAKREPSAPTESTSQET
PEQSDKQTTPVQGAKSKQGSLTELGFLTKLQELSIQRSALEWKALSEWVTDSESESDVGS
SSDTDSPATMGGMVAQGVKLGFKGKSGYKVMSGYSGTSPHEKTSARNHRHYQDTASRLIH
NMDLRTMTQSLVTLAEDNIAFFSSQGPGETAQRLSGVFAGVREQALGLEPALGRLLGVAH
LFDLDPETPANGYRSLVHTARCCLAHLLHKSRYVASNRRSIFFRTSHNLAELEAYLAALT
QLRALVYYAQRLLVTNRPGVLFFEGDEGLTADFLREYVTLHKGCFYGRCLGFQFTPAIRP
FLQTISIGLVSFGEHYKRNETGLSVAASSLFTSGRFAIDPELRGAEFERITQNLDVHFWK
AFWNITEMEVLSSLANMASATVRVSRLLSLPPEAFEMPLTADPTLTVTISPPLAHTGPGP
VLVRLISYDLREGQDSEELSSLIKSNGQRSLELWPRPQQAPRSRSLIVHFHGGGFVAQTS
RSHEPYLKSWAQELGAPIISIDYSLAPEAPFPRALEECFFAYCWAIKHCALLGSTGERIC
LAGDSAGGNLCFTVALRAAAYGVRVPDGIMAAYPATMLQPAASPSRLLSLMDPLLPLSVL
SKCVSAYAGAKTEDHSNSDQKALGMMGLVRRDTALLLRDFRLGASSWLNSFLELSGRKSQ
KMSEPIAEPMRRSVSEAALAQPQGPLGTDSLKNLTLRDLSLRGNSETSSDTPEMSLSAET
LSPSTPSDVNFLLPPEDAGEEAEAKNELSPMDRGLGVRAAFPEGFHPRRSSQGATQMPLY
SSPIVKNPFMSPLLAPDSMLKSLPPVHIVACALDPMLDDSVMLARRLRNLGQPVTLRVVE
DLPHGFLTLAALCRETRQAAELCVERIRLVLTPPAGAGPSGETGAAGVDGGCGGRH
Function
Lipase with broad substrate specificity, catalyzing the hydrolysis of triacylglycerols (TAGs), diacylglycerols (DAGs), monoacylglycerols (MAGs), cholesteryl esters and retinyl esters. Shows a preferential hydrolysis of DAGs over TAGs and MAGs and preferentially hydrolyzes the fatty acid (FA) esters at the sn-3 position of the glycerol backbone in DAGs. Preferentially hydrolyzes FA esters at the sn-1 and sn-2 positions of the glycerol backbone in TAGs. Catalyzes the hydrolysis of 2-arachidonoylglycerol, an endocannabinoid and of 2-acetyl monoalkylglycerol ether, the penultimate precursor of the pathway for de novo synthesis of platelet-activating factor. In adipose tissue and heart, it primarily hydrolyzes stored triglycerides to free fatty acids, while in steroidogenic tissues, it principally converts cholesteryl esters to free cholesterol for steroid hormone production.
Tissue Specificity Testis.
KEGG Pathway
cAMP sig.ling pathway (hsa04024 )
AMPK sig.ling pathway (hsa04152 )
Apelin sig.ling pathway (hsa04371 )
Thermogenesis (hsa04714 )
Insulin sig.ling pathway (hsa04910 )
Regulation of lipolysis in adipocytes (hsa04923 )
Aldosterone synthesis and secretion (hsa04925 )
Reactome Pathway
Triglyceride catabolism (R-HSA-163560 )
BioCyc Pathway
MetaCyc:HS01328-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
LIPE-related familial partial lipodystrophy DISCQBMN Strong Autosomal recessive [1]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
14 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Hormone-sensitive lipase (LIPE). [2]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Hormone-sensitive lipase (LIPE). [3]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Hormone-sensitive lipase (LIPE). [4]
Dexamethasone DMMWZET Approved Dexamethasone increases the expression of Hormone-sensitive lipase (LIPE). [5]
Rosiglitazone DMILWZR Approved Rosiglitazone increases the expression of Hormone-sensitive lipase (LIPE). [6]
Zidovudine DM4KI7O Approved Zidovudine affects the expression of Hormone-sensitive lipase (LIPE). [7]
Adenosine triphosphate DM79F6G Approved Adenosine triphosphate increases the activity of Hormone-sensitive lipase (LIPE). [8]
Epinephrine DM3KJBC Approved Epinephrine increases the activity of Hormone-sensitive lipase (LIPE). [8]
Vitamin B3 DMQVRZH Approved Vitamin B3 decreases the expression of Hormone-sensitive lipase (LIPE). [9]
CS-038 DM67P0F Phase 3 CS-038 increases the expression of Hormone-sensitive lipase (LIPE). [6]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Hormone-sensitive lipase (LIPE). [10]
PMID28870136-Compound-48 DMPIM9L Patented PMID28870136-Compound-48 increases the activity of Hormone-sensitive lipase (LIPE). [8]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Hormone-sensitive lipase (LIPE). [11]
[3H]cAMP DMZRQU7 Investigative [3H]cAMP increases the activity of Hormone-sensitive lipase (LIPE). [8]
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⏷ Show the Full List of 14 Drug(s)

References

1 Targeted disruption of hormone-sensitive lipase results in male sterility and adipocyte hypertrophy, but not in obesity. Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):787-92. doi: 10.1073/pnas.97.2.787.
2 Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
3 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
4 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
5 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
6 In Vitro and In Vivo Characterizations of Chiglitazar, a Newly Identified PPAR Pan-Agonist. PPAR Res. 2012;2012:546548. doi: 10.1155/2012/546548. Epub 2012 Oct 22.
7 Adipocyte differentiation, mitochondrial gene expression and fat distribution: differences between zidovudine and tenofovir after 6 months. Antivir Ther. 2009;14(8):1089-100. doi: 10.3851/IMP1457.
8 Hormone-sensitive lipase in human adipose tissue, isolated adipocytes, and cultured adipocytes. Pediatr Res. 1982 Dec;16(12):982-8. doi: 10.1203/00006450-198212000-00002.
9 Effects of extended-release niacin on lipid profile and adipocyte biology in patients with impaired glucose tolerance. Atherosclerosis. 2009 Jul;205(1):207-13. doi: 10.1016/j.atherosclerosis.2008.11.026. Epub 2008 Dec 3.
10 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
11 Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.