Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEFJ2DS)

• DOT Name: PITH domain-containing protein 1 (PITHD1)
• Gene Name: PITHD1
• UniProt ID: PITH1_HUMAN
• Pfam ID: PF06201
• Sequence:
  MSHGHSHGGGGCRCAAEREEPPEQRGLAYGLYLRIDLERLQCLNESREGSGRGVFKPWEE
  RTDRSKFVESDADEELLFNIPFTGNVKLKGIIIMGEDDDSHPSEMRLYKNIPQMSFDDTE
  REPDQTFSLNRDLTGELEYATKISRFSNVYHLSIHISKNFGADTTKVFYIGLRGEWTELR
  RHEVTICNYEASANPADHRVHQVTPQTHFIS
• Function: Promotes megakaryocyte differentiation by up-regulating RUNX1 expression. Regulates RUNX1 expression by activating the proximal promoter of the RUNX1 gene and by enhancing the translation activity of an internal ribosome entry site (IRES) element in the RUNX1 gene.
• Tissue Specificity: Down-regulated in primary acute myeloid leukemia (AML) patients.

Molecular Interaction Atlas (MIA) of This DOT

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 PITH domain-containing protein 1 (PITHD1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of PITH domain-containing protein 1 (PITHD1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of PITH domain-containing protein 1 (PITHD1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of PITH domain-containing protein 1 (PITHD1).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of PITH domain-containing protein 1 (PITHD1).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of PITH domain-containing protein 1 (PITHD1).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of PITH domain-containing protein 1 (PITHD1).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of PITH domain-containing protein 1 (PITHD1).	[9]

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 PITH domain-containing protein 1 (PITHD1).	[5]

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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [9] 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.