Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDR288R)

• DOT Name: Gap junction delta-2 protein (GJD2)
• Synonyms: Connexin-36; Cx36; Gap junction alpha-9 protein
• Gene Name: GJD2
• UniProt ID: CXD2_HUMAN
• PDB ID: 2N6A; 7XKI; 7XKK; 7XKT; 7XL8; 7XNH; 7XNV; 8HKP
• Pfam ID: PF00029
• Sequence:
  MGEWTILERLLEAAVQQHSTMIGRILLTVVVIFRILIVAIVGETVYDDEQTMFVCNTLQP
  GCNQACYDRAFPISHIRYWVFQIIMVCTPSLCFITYSVHQSAKQRERRYSTVFLALDRDP
  PESIGGPGGTGGGGSGGGKREDKKLQNAIVNGVLQNTENTSKETEPDCLEVKELTPHPSG
  LRTASKSKLRRQEGISRFYIIQVVFRNALEIGFLVGQYFLYGFSVPGLYECNRYPCIKEV
  ECYVSRPTEKTVFLVFMFAVSGICVVLNLAELNHLGWRKIKLAVRGAQAKRKSIYEIRNK
  DLPRVSVPNFGRTQSSDSAYV
• Function: One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.
• Tissue Specificity: Highly expressed in neurons.
• KEGG Pathway: Gap junction (hsa04540)
• Reactome Pathway:
  Gap junction assembly (R-HSA-190861)
  Electric Transmission Across Gap Junctions (R-HSA-112303)

Molecular Interaction Atlas (MIA) of This DOT

3 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 Gap junction delta-2 protein (GJD2).	[1]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Gap junction delta-2 protein (GJD2).	[2]
Tetracycline	DMZA017	Approved	Tetracycline decreases the expression of Gap junction delta-2 protein (GJD2).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Gap junction delta-2 protein (GJD2).	[4]

References

• [1] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [2] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [3] Effects of residual levels of tetracycline on the barrier functions of human intestinal epithelial cells. Food Chem Toxicol. 2017 Nov;109(Pt 1):253-263. doi: 10.1016/j.fct.2017.09.004. Epub 2017 Sep 4.
• [4] 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.