Details of Drug Off-Target (DOT)

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

• DOT Name: Cytosolic phospholipase A2 beta (JMJD7-PLA2G4B)
• Synonyms: cPLA2-beta; EC 3.1.1.4; Lysophospholipase A1 group IVB; EC 3.1.1.5; Phospholipase A2 group IVB
• Gene Name: JMJD7-PLA2G4B
• Related Disease: Head-neck squamous cell carcinoma
• UniProt ID: PA24B_HUMAN
• EC Number: 3.1.1.4; 3.1.1.5
• Pfam ID: PF00168 ; PF18695 ; PF01735
• Sequence:
  MAVAEVSRTCLLTVRVLQAHRLPSKDLVTPSDCYVTLWLPTACSHRLQTRTVKNSSSPVW
  NQSFHFRIHRQLKNVMELKVFDQDLVTGDDPVLSVLFDAGTLRAGEFRRESFSLSPQGEG
  RLEVEFRLQSLADRGEWLVSNGVLVARELSCLHVQLEETGDQKSSEHRVQLVVPGSCEGP
  QEASVGTGTFRFHCPACWEQELSIRLQDAPEEQLKAPLSALPSGQVVRLVFPTSQEPLMR
  VELKKEAGLRELAVRLGFGPCAEEQAFLSRRKQVVAAALRQALQLDGDLQEDEIPVVAIM
  ATGGGIRAMTSLYGQLAGLKELGLLDCVSYITGASGSTWALANLYEDPEWSQKDLAGPTE
  LLKTQVTKNKLGVLAPSQLQRYRQELAERARLGYPSCFTNLWALINEALLHDEPHDHKLS
  DQREALSHGQNPLPIYCALNTKGQSLTTFEFGEWCEFSPYEVGFPKYGAFIPSELFGSEF
  FMGQLMKRLPESRICFLEGIWSNLYAANLQDSLYWASEPSQFWDRWVRNQANLDKEQVPL
  LKIEEPPSTAGRIAEFFTDLLTWRPLAQATHNFLRGLHFHKDYFQHPHFSTWKATTLDGL
  PNQLTPSEPHLCLLDVGYLINTSCLPLLQPTRDVDLILSLDYNLHGAFQQLQLLGRFCQE
  QGIPFPPISPSPEEQLQPRECHTFSDPTCPGAPAVLHFPLVSDSFREYSAPGVRRTPEEA
  AAGEVNLSSSDSPYHYTKVTYSQEDVDKLLHLTHYNVCNNQEQLLEALRQAVQRRRQRRP
  H
• Function: Calcium-dependent phospholipase A1 and A2 and lysophospholipase that may play a role in membrane phospholipid remodeling; [Isoform 3]: Calcium-dependent phospholipase A2 and lysophospholipase. Cleaves the ester bond of the fatty acyl group attached to the sn-2 position of phosphatidylethanolamines, producing lysophospholipids that may be used in deacylation-reacylation cycles. Hydrolyzes lysophosphatidylcholines with low efficiency but is inefficient toward phosphatidylcholines; [Isoform 5]: Calcium-dependent phospholipase A1 and A2 and lysophospholipase. Cleaves the ester bond of the fatty acyl group attached to the sn-1 or sn-2 position of diacyl phospholipids (phospholipase A1 and A2 activity, respectively), producing lysophospholipids that may be used in deacylation-reacylation cycles. Can further hydrolyze lysophospholipids enabling complete deacylation. Has no activity toward alkylacyl phospholipids.
• Tissue Specificity: Widely expressed. Expressed at higher level in brain, heart, liver, cerebellum and pancreas.
• 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)
  MAPK sig.ling pathway (hsa04010)
  Ras sig.ling pathway (hsa04014)
  Phospholipase D sig.ling pathway (hsa04072)
  Necroptosis (hsa04217)
  Vascular smooth muscle contraction (hsa04270)
  VEGF sig.ling pathway (hsa04370)
  Platelet activation (hsa04611)
  Fc epsilon RI sig.ling pathway (hsa04664)
  Fc gamma R-mediated phagocytosis (hsa04666)
  Glutamatergic sy.pse (hsa04724)
  Serotonergic sy.pse (hsa04726)
  Long-term depression (hsa04730)
  Inflammatory mediator regulation of TRP channels (hsa04750)
  GnRH sig.ling pathway (hsa04912)
  Ovarian steroidogenesis (hsa04913)
  Oxytocin sig.ling pathway (hsa04921)
  Choline metabolism in cancer (hsa05231)
• Reactome Pathway:
  Acyl chain remodelling of PS (R-HSA-1482801)
  Acyl chain remodelling of PE (R-HSA-1482839)
  Acyl chain remodelling of PG (R-HSA-1482925)
  Hydrolysis of LPC (R-HSA-1483115)
  Synthesis of PA (R-HSA-1483166)
  XBP1(S) activates chaperone genes (R-HSA-381038)
  Acyl chain remodelling of PC (R-HSA-1482788)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Head-neck squamous cell carcinoma	DISF7P24	moderate	Biomarker	[1]

3 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 Cytosolic phospholipase A2 beta (JMJD7-PLA2G4B).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Cytosolic phospholipase A2 beta (JMJD7-PLA2G4B).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Cytosolic phospholipase A2 beta (JMJD7-PLA2G4B).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cytosolic phospholipase A2 beta (JMJD7-PLA2G4B).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Cytosolic phospholipase A2 beta (JMJD7-PLA2G4B).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cytosolic phospholipase A2 beta (JMJD7-PLA2G4B).	[7]

References

• [1] A novel read-through transcript JMJD7-PLA2G4B regulates head and neck squamous cell carcinoma cell proliferation and survival.Oncotarget. 2017 Jan 10;8(2):1972-1982. doi: 10.18632/oncotarget.14081.
• [2] 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.
• [3] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [7] Global gene expression analysis reveals novel transcription factors associated with long-term low-level exposure of EA.hy926 human endothelial cells to bisphenol A. Chem Biol Interact. 2023 Aug 25;381:110571. doi: 10.1016/j.cbi.2023.110571. Epub 2023 May 25.