Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4XK81L)

• DOT Name: General transcription factor IIH subunit 2-like protein (GTF2H2C)
• Synonyms: General transcription factor IIH polypeptide 2-like protein
• Gene Name: GTF2H2C
• UniProt ID: T2H2L_HUMAN
• Pfam ID: PF07975 ; PF04056
• Sequence:
  MDEEPERTKRWEGGYERTWEILKEDESGSLKATIEDILFKAKRKRVFEHHGQVRLGMMRH
  LYVVVDGSRTMEDQDLKPNRLTCTLKLLEYFVEEYFDQNPISQIGIIVTKSKRAEKLTEL
  SGNPRKHITSLKEAVDMTCHGEPSLYNSLSMAMQTLKHMPGHTSREVLIIFSSLTTCDPS
  NIYDLIKTLKAAKIRVSVIGLSAEVRVCTVLARETGGTYHVILDESHYKELLTHHLSPPP
  ASSSSECSLIRMGFPQHTIASLSDQDAKPSFSMAHLDGNTEPGLTLGGYFCPQCRAKYCE
  LPVECKICGLTLVSAPHLARSYHHLFPLDAFQEIPLEEYNGERFCYGCQGELKDQHVYVC
  AVCQNVFCVDCDVFVHDSLHCCPGCIHKIPAPSGV
• Function: Component of the core-TFIIH basal transcription factor involved in nucleotide excision repair (NER) of DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II.
• KEGG Pathway:
  Basal transcription factors (hsa03022)
  Nucleotide excision repair (hsa03420)
  Viral carcinogenesis (hsa05203)

Molecular Interaction Atlas (MIA) of This DOT

4 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 General transcription factor IIH subunit 2-like protein (GTF2H2C).	[1]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of General transcription factor IIH subunit 2-like protein (GTF2H2C).	[2]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of General transcription factor IIH subunit 2-like protein (GTF2H2C).	[4]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of General transcription factor IIH subunit 2-like protein (GTF2H2C).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of General transcription factor IIH subunit 2-like protein (GTF2H2C).	[3]

References

• [1] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [2] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] 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.
• [4] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [5] Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines. PLoS One. 2019 Jul 11;14(7):e0219610. doi: 10.1371/journal.pone.0219610. eCollection 2019.