Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4LA861)

• DOT Name: JmjC domain-containing protein 8 (JMJD8)
• Synonyms: Jumonji domain-containing protein 8
• Gene Name: JMJD8
• Related Disease:
  Colorectal carcinoma
  Neoplasm
• UniProt ID: JMJD8_HUMAN
• Pfam ID: PF13621
• Sequence:
  MAPASRLLALWALAAVALPGSGAEGDGGWRPGGPGAVAEEERCTVERRADLTYAEFVQQY
  AFVRPVILQGLTDNSRFRALCSRDRLLASFGDRVVRLSTANTYSYHKVDLPFQEYVEQLL
  HPQDPTSLGNDTLYFFGDNNFTEWASLFRHYSPPPFGLLGTAPAYSFGIAGAGSGVPFHW
  HGPGYSEVIYGRKRWFLYPPEKTPEFHPNKTTLAWLRDTYPALPPSARPLECTIRAGEVL
  YFPDRWWHATLNLDTSVFISTFLG
• Function: Functions as a positive regulator of TNF-induced NF-kappa-B signaling. Regulates angiogenesis and cellular metabolism through interaction with PKM.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[2]

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 JmjC domain-containing protein 8 (JMJD8).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of JmjC domain-containing protein 8 (JMJD8).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of JmjC domain-containing protein 8 (JMJD8).	[4]

References

• [1] MiR-873-5p suppresses cell proliferation and epithelial-mesenchymal transition via directly targeting Jumonji domain-containing protein 8 through the NF-B pathway in colorectal cancer.J Cell Commun Signal. 2019 Dec;13(4):549-560. doi: 10.1007/s12079-019-00522-w. Epub 2019 May 31.
• [2] JmjC domain-containing protein 8 (JMJD8) represses Ku70/Ku80 expression via attenuating AKT/NF-B/COX-2 signaling.Biochim Biophys Acta Mol Cell Res. 2019 Dec;1866(12):118541. doi: 10.1016/j.bbamcr.2019.118541. Epub 2019 Aug 29.
• [3] 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.
• [4] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [5] 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.