Details of Drug Off-Target (DOT)

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

• DOT Name: Partitioning defective 6 homolog gamma (PARD6G)
• Synonyms: PAR-6 gamma; PAR6D
• Gene Name: PARD6G
• Related Disease: Neoplasm
• UniProt ID: PAR6G_HUMAN
• Pfam ID: PF00564 ; PF00595
• Sequence:
  MNRSFHKSQTLRFYDCSAVEVKSKFGAEFRRFSLDRHKPGKFEDFYKLVVHTHHISNSDV
  TIGYADVHGDLLPINNDDNFCKAVSSANPLLRVFIQKREEAERGSLGAGSLCRRRRALGA
  LRDEGPRRRAHLDIGLPRDFRPVSSIIDVDLVPETHRRVRLHRHGCEKPLGFYIRDGASV
  RVTPHGLEKVPGIFISRMVPGGLAESTGLLAVNDEVLEVNGIEVAGKTLDQVTDMMIANS
  HNLIVTVKPANQRNNVVRGGRALGSSGPPSDGTAGFVGPPAPRVLQNFHPDEAESDEDND
  VVIEGTLEPARPPQTPGAPAGSLSRVNGAGLAQRLQRDLALDGGLQRLLSSLRADPRHSL
  ALPPGGVEEHGPAVTL
• Function: Adapter protein involved in asymmetrical cell division and cell polarization processes. May play a role in the formation of epithelial tight junctions. The PARD6-PARD3 complex links GTP-bound Rho small GTPases to atypical protein kinase C proteins.
• Tissue Specificity: Widely expressed, with a higher expression in fetal and adult kidney.
• KEGG Pathway:
  Rap1 sig.ling pathway (hsa04015)
  Endocytosis (hsa04144)
  Axon guidance (hsa04360)
  Hippo sig.ling pathway (hsa04390)
  Tight junction (hsa04530)
  Human papillomavirus infection (hsa05165)
• Reactome Pathway: Tight junction interactions (R-HSA-420029)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]

4 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 Partitioning defective 6 homolog gamma (PARD6G).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Partitioning defective 6 homolog gamma (PARD6G).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Partitioning defective 6 homolog gamma (PARD6G).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Partitioning defective 6 homolog gamma (PARD6G).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Partitioning defective 6 homolog gamma (PARD6G).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Partitioning defective 6 homolog gamma (PARD6G).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Partitioning defective 6 homolog gamma (PARD6G).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Partitioning defective 6 homolog gamma (PARD6G).	[9]

References

• [1] Hepatitis B virus DNA integration in tumour tissue of a non-cirrhotic HFE-haemochromatosis patient with hepatocellular carcinoma.J Hepatol. 2013 Jan;58(1):190-3. doi: 10.1016/j.jhep.2012.09.005. Epub 2012 Sep 16.
• [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] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [5] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [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] 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.
• [8] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.