Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOW7WTS)

• DOT Name: Homeobox protein unc-4 homolog
• Synonyms: Homeobox protein Uncx4.1
• Gene Name: UNCX
• UniProt ID: UNC4_HUMAN
• Pfam ID: PF00046
• Sequence:
  MMDGRLLEHPHAQFGGSLGGVVGFPYPLGHHHVYELAGHQLQSAAAAASVPFSIDGLLGG
  SCAAAASVVNPTPLLPAACGVGGDGQPFKLSDSGDPDKESPGCKRRRTRTNFTGWQLEEL
  EKAFNESHYPDVFMREALALRLDLVESRVQVWFQNRRAKWRKKENTKKGPGRPAHNSHPT
  TCSGEPMDPEEIARKELEKMEKKKRKHEKKLLKSQGRHLHSPGGLSLHSAPSSDSDSGGG
  GLSPEPPEPPPPAAKGPGAHASGAAGTAPAPPGEPPAPGTCDPAFYPSQRSGAGPQPRPG
  RPADKDAASCGPGAAVAAVERGAAGLPKASPFSVESLLSDSPPRRKAASNAAAAAAAGLD
  FAPGLPCAPRTLIGKGHFLLYPITQPLGFLVPQAALKGGAGLEPAPKDAPPAPAVPPAPP
  AQASFGAFSGPGGAPDSAFARRSPDAVASPGAPAPAPAPFRDLASAAATEGGGGDCADAG
  TAGPAPPPPAPSPRPGPRPPSPAEEPATCGVPEPGAAAGPSPPEGEELDMD
• Function: Transcription factor involved in somitogenesis and neurogenesis. Required for the maintenance and differentiation of particular elements of the axial skeleton. May act upstream of PAX9. Plays a role in controlling the development of connections of hypothalamic neurons to pituitary elements, allowing central neurons to reach the peripheral blood circulation and to deliver hormones for control of peripheral functions.

Molecular Interaction Atlas (MIA) of This DOT

3 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 Homeobox protein unc-4 homolog.	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Homeobox protein unc-4 homolog.	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Homeobox protein unc-4 homolog.	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Homeobox protein unc-4 homolog.	[2]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Homeobox protein unc-4 homolog.	[4]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Homeobox protein unc-4 homolog.	[2]
Thalidomide	DM70BU5	Approved	Thalidomide decreases the expression of Homeobox protein unc-4 homolog.	[2]
Phenytoin	DMNOKBV	Approved	Phenytoin decreases the expression of Homeobox protein unc-4 homolog.	[2]
Nilotinib	DM7HXWT	Approved	Nilotinib decreases the expression of Homeobox protein unc-4 homolog.	[2]
Abacavir	DMMN36E	Approved	Abacavir decreases the expression of Homeobox protein unc-4 homolog.	[2]
Polyethylene glycol	DM4I1JP	Approved	Polyethylene glycol decreases the expression of Homeobox protein unc-4 homolog.	[2]
Dabigatran	DMDI6R4	Approved	Dabigatran decreases the expression of Homeobox protein unc-4 homolog.	[2]
Ramelteon	DM7IW9J	Approved	Ramelteon decreases the expression of Homeobox protein unc-4 homolog.	[2]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Homeobox protein unc-4 homolog.	[2]
Hydroxyacetic acid	DMQFBH6	Investigative	Hydroxyacetic acid decreases the expression of Homeobox protein unc-4 homolog.	[2]

References

• [1] 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.
• [2] Exposure-based assessment of chemical teratogenicity using morphogenetic aggregates of human embryonic stem cells. Reprod Toxicol. 2020 Jan;91:74-91. doi: 10.1016/j.reprotox.2019.10.004. Epub 2019 Nov 8.
• [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] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] 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.