Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2U776E)

• DOT Name: Thyroid transcription factor 1-associated protein 26 (CCDC59)
• Synonyms: TTF-1-associated protein 26; Coiled-coil domain-containing protein 59; TTF-1-associated protein BR2
• Gene Name: CCDC59
• Related Disease: Hypospadias
• UniProt ID: TAP26_HUMAN
• Pfam ID: PF08524
• Sequence:
  MAPVRRSAKWRPGGIEARGEGVSTVGYRNKNVRQKTWRPNHPQAFVGSVREGQGFAFRRK
  LKIQQSYKKLLRKEKKAQTSLESQFTDRYPDNLKHLYLAEEERHRKQARKVDHPLSEQVH
  QPLLEEQCSIDEPLFEDQCSFDQPQPEEQCIKTVNSFTIPKKNKKKTSNQKAQEEYEQIQ
  AKRAAKKQEFERRKQEREEAQRQYKKKKMEVFKILNKKTKKGQPNLNVQMEYLLQKIQEK
  C
• Function: Component of the transcription complexes of the pulmonary surfactant-associated protein-B (SFTPB) and -C (SFTPC). Enhances homeobox protein Nkx-2.1-activated SFTPB and SFTPC promoter activities.
• Tissue Specificity: Ubiquitously expressed. In lung, expression is restricted to the alveolar epithelial cells.
• Reactome Pathway: Surfactant metabolism (R-HSA-5683826)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hypospadias	DIS48CCP	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Thyroid transcription factor 1-associated protein 26 (CCDC59).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Thyroid transcription factor 1-associated protein 26 (CCDC59).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Thyroid transcription factor 1-associated protein 26 (CCDC59).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Thyroid transcription factor 1-associated protein 26 (CCDC59).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Thyroid transcription factor 1-associated protein 26 (CCDC59).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Thyroid transcription factor 1-associated protein 26 (CCDC59).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Thyroid transcription factor 1-associated protein 26 (CCDC59).	[8]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Thyroid transcription factor 1-associated protein 26 (CCDC59).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Thyroid transcription factor 1-associated protein 26 (CCDC59).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Thyroid transcription factor 1-associated protein 26 (CCDC59).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Thyroid transcription factor 1-associated protein 26 (CCDC59).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Thyroid transcription factor 1-associated protein 26 (CCDC59).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Thyroid transcription factor 1-associated protein 26 (CCDC59).	[15]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Thyroid transcription factor 1-associated protein 26 (CCDC59).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Thyroid transcription factor 1-associated protein 26 (CCDC59).	[10]

References

• [1] Genome-wide association analyses identify variants in developmental genes associated with hypospadias.Nat Genet. 2014 Sep;46(9):957-63. doi: 10.1038/ng.3063. Epub 2014 Aug 10.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] 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.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [7] 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.
• [8] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [9] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [10] 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.
• [11] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [14] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.