Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY7GXA6)

• DOT Name: Group XIIB secretory phospholipase A2-like protein (PLA2G12B)
• Synonyms: Group XIII secretory phospholipase A2-like protein; GXIII sPLA2-like; sPLA2-GXIIB; GXIIB
• Gene Name: PLA2G12B
• UniProt ID: PG12B_HUMAN
• Pfam ID: PF06951
• Sequence:
  MKLASGFLVLWLSLGGGLAQSDTSPDTEESYSDWGLRHLRGSFESVNSYFDSFLELLGGK
  NGVCQYRCRYGKAPMPRPGYKPQEPNGCGSYFLGLKVPESMDLGIPAMTKCCNQLDVCYD
  TCGANKYRCDAKFRWCLHSICSDLKRSLGFVSKVEAACDSLVDTVFNTVWTLGCRPFMNS
  QRAACICAEEEKEEL
• Function: Not known; does not seem to have catalytic activity.
• Tissue Specificity: Strong expression in liver, small intestine and kidney.
• KEGG Pathway:
  Glycerophospholipid metabolism (hsa00564)
  Ether lipid metabolism (hsa00565)
  Arachidonic acid metabolism (hsa00590)
  Linoleic acid metabolism (hsa00591)
  alpha-Linolenic acid metabolism (hsa00592)
  Metabolic pathways (hsa01100)
  Ras sig.ling pathway (hsa04014)
  Vascular smooth muscle contraction (hsa04270)
  Pancreatic secretion (hsa04972)
  Fat digestion and absorption (hsa04975)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Group XIIB secretory phospholipase A2-like protein (PLA2G12B).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Group XIIB secretory phospholipase A2-like protein (PLA2G12B).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Group XIIB secretory phospholipase A2-like protein (PLA2G12B).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Group XIIB secretory phospholipase A2-like protein (PLA2G12B).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Group XIIB secretory phospholipase A2-like protein (PLA2G12B).	[5]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Group XIIB secretory phospholipase A2-like protein (PLA2G12B).	[6]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Group XIIB secretory phospholipase A2-like protein (PLA2G12B).	[7]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Group XIIB secretory phospholipase A2-like protein (PLA2G12B).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Group XIIB secretory phospholipase A2-like protein (PLA2G12B).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Group XIIB secretory phospholipase A2-like protein (PLA2G12B).	[10]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [7] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [8] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [9] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [10] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.