Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTK6VQ1B)

• DOT Name: DNA-binding protein RFX2 (RFX2)
• Synonyms: Regulatory factor X 2
• Gene Name: RFX2
• Related Disease:
  Candidiasis
  Advanced cancer
  Cerebral palsy
  Neoplasm
• UniProt ID: RFX2_HUMAN
• Pfam ID: PF04589 ; PF02257
• Sequence:
  MQNSEGGADSPASVALRPSAAAPPVPASPQRVLVQAASSNPKGAQMQPISLPRVQQVPQQ
  VQPVQHVYPAQVQYVEGGDAVYTNGAIRTAYTYNPEPQMYAPSSTASYFEAPGGAQVTVA
  ASSPPAVPSHSMVGITMDVGGSPIVSSAGAYLIHGGMDSTRHSLAHTSRSSPATLEMAIE
  NLQKSEGITSHKSGLLNSHLQWLLDNYETAEGVSLPRSSLYNHYLRHCQEHKLDPVNAAS
  FGKLIRSVFMGLRTRRLGTRGNSKYHYYGIRLKPDSPLNRLQEDTQYMAMRQQPMHQKPR
  YRPAQKTDSLGDSGSHSGLHSTPEQTMAVQSQHHQQYIDVSHVFPEFPAPDLGSFLLQDG
  VTLHDVKALQLVYRRHCEATVDVVMNLQFHYIEKLWLSFWNSKASSSDGPTSLPASDEDP
  EGAVLPKDKLISLCQCDPILRWMRSCDHILYQALVEILIPDVLRPVPSTLTQAIRNFAKS
  LEGWLTNAMSDFPQQVIQTKVGVVSAFAQTLRRYTSLNHLAQAARAVLQNTSQINQMLSD
  LNRVDFANVQEQASWVCQCEESVVQRLEQDFKLTLQQQSSLDQWASWLDSVVTQVLKQHA
  GSPSFPKAARQFLLKWSFYSSMVIRDLTLRSAASFGSFHLIRLLYDEYMFYLVEHRVAEA
  TGETPIAVMGEFNDLASLSLTLLDKDDMGDEQRGSEAGPDARSLGEPLVKRERSDPNHSL
  QGI
• Function: Transcription factor that acts as a key regulator of spermatogenesis. Acts by regulating expression of genes required for the haploid phase during spermiogenesis, such as genes required for cilium assembly and function. Recognizes and binds the X-box, a regulatory motif with DNA sequence 5'-GTNRCC(0-3N)RGYAAC-3' present on promoters. Probably activates transcription of the testis-specific histone gene H1-6.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Candidiasis	DISIRYMU	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[2]
Cerebral palsy	DIS82ODL	Limited	Autosomal dominant	[3]
Neoplasm	DISZKGEW	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of DNA-binding protein RFX2 (RFX2).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of DNA-binding protein RFX2 (RFX2).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of DNA-binding protein RFX2 (RFX2).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of DNA-binding protein RFX2 (RFX2).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of DNA-binding protein RFX2 (RFX2).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of DNA-binding protein RFX2 (RFX2).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of DNA-binding protein RFX2 (RFX2).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of DNA-binding protein RFX2 (RFX2).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the phosphorylation of DNA-binding protein RFX2 (RFX2).	[10]

References

• [1] Candida albicans RFX2 encodes a DNA binding protein involved in DNA damage responses, morphogenesis, and virulence.Eukaryot Cell. 2009 Apr;8(4):627-39. doi: 10.1128/EC.00246-08. Epub 2009 Feb 27.
• [2] Genome-wide transcript profiling reveals novel breast cancer-associated intronic sense RNAs.PLoS One. 2015 Mar 23;10(3):e0120296. doi: 10.1371/journal.pone.0120296. eCollection 2015.
• [3] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [4] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [5] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Phosphoproteomics reveals resveratrol-dependent inhibition of Akt/mTORC1/S6K1 signaling. J Proteome Res. 2014 Dec 5;13(12):5734-42. doi: 10.1021/pr500714a. Epub 2014 Oct 29.
• [11] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [12] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.