Details of Drug Off-Target (DOT)

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

• DOT Name: Pancreatic triacylglycerol lipase (PNLIP)
• Synonyms: PL; PTL; Pancreatic lipase; EC 3.1.1.3
• Gene Name: PNLIP
• Related Disease: Pancreatic triacylglycerol lipase deficiency
• UniProt ID: LIPP_HUMAN
• PDB ID: 1GPL; 1LPA; 1LPB; 1N8S
• EC Number: 3.1.1.3
• Pfam ID: PF00151 ; PF01477
• Sequence:
  MLPLWTLSLLLGAVAGKEVCYERLGCFSDDSPWSGITERPLHILPWSPKDVNTRFLLYTN
  ENPNNFQEVAADSSSISGSNFKTNRKTRFIIHGFIDKGEENWLANVCKNLFKVESVNCIC
  VDWKGGSRTGYTQASQNIRIVGAEVAYFVEFLQSAFGYSPSNVHVIGHSLGAHAAGEAGR
  RTNGTIGRITGLDPAEPCFQGTPELVRLDPSDAKFVDVIHTDGAPIVPNLGFGMSQVVGH
  LDFFPNGGVEMPGCKKNILSQIVDIDGIWEGTRDFAACNHLRSYKYYTDSIVNPDGFAGF
  PCASYNVFTANKCFPCPSGGCPQMGHYADRYPGKTNDVGQKFYLDTGDASNFARWRYKVS
  VTLSGKKVTGHILVSLFGNKGNSKQYEIFKGTLKPDSTHSNEFDSDVDVGDLQMVKFIWY
  NNVINPTLPRVGASKIIVETNVGKQFNFCSPETVREEVLLTLTPC
• Function: Plays an important role in fat metabolism. It preferentially splits the esters of long-chain fatty acids at positions 1 and 3, producing mainly 2-monoacylglycerol and free fatty acids, and shows considerably higher activity against insoluble emulsified substrates than against soluble ones.
• KEGG Pathway:
  Glycerolipid metabolism (hsa00561)
  Metabolic pathways (hsa01100)
  Pancreatic secretion (hsa04972)
  Fat digestion and absorption (hsa04975)
  Vitamin digestion and absorption (hsa04977)
• Reactome Pathway:
  Retinoid metabolism and transport (R-HSA-975634)
  Digestion of dietary lipid (R-HSA-192456)
• BioCyc Pathway: MetaCyc:HS10947-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
Pancreatic triacylglycerol lipase deficiency	DISZ8R74	Strong	Autosomal recessive	[1]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Pancreatic triacylglycerol lipase (PNLIP).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Pancreatic triacylglycerol lipase (PNLIP).	[6]

5 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Pancreatic triacylglycerol lipase (PNLIP).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Pancreatic triacylglycerol lipase (PNLIP).	[4]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Pancreatic triacylglycerol lipase (PNLIP).	[4]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Pancreatic triacylglycerol lipase (PNLIP).	[5]
4-Hydroxybenzylalcohol	DMKDZMQ	Patented	4-Hydroxybenzylalcohol decreases the activity of Pancreatic triacylglycerol lipase (PNLIP).	[7]

References

• [1] Identification of a novel mutation in the PNLIP gene in two brothers with congenital pancreatic lipase deficiency. J Lipid Res. 2014 Feb;55(2):307-12. doi: 10.1194/jlr.P041103. Epub 2013 Nov 21.
• [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] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [5] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [6] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [7] p-Hydroxybenzyl alcohol inhibits four obesity-related enzymes in vitro. J Biochem Mol Toxicol. 2018 Dec;32(12):e22223. doi: 10.1002/jbt.22223. Epub 2018 Oct 1.