Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE97BCI)

• DOT Name: Keratin-associated protein 2-3 (KRTAP2-3)
• Synonyms: High sulfur keratin-associated protein 2.4; Keratin-associated protein 2.3
• Gene Name: KRTAP2-3
• UniProt ID: KRA23_HUMAN
• Pfam ID: PF01500 ; PF13885
• Sequence:
  MTGSCCGSTLSSLSYGGGCCQPCCCRDPCCCRPVTCQTTVCRPVTCVPRCTRPICEPCRR
  PVCCDPCSLQEGCCRPITCCPSSCTAVVCRPCCWATTCCQPVSVQSPCCRPPCGQPTPCS
  TTCRTSSC
• Function: In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.
• Reactome Pathway: Keratinization (R-HSA-6805567)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Keratin-associated protein 2-3 (KRTAP2-3).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Keratin-associated protein 2-3 (KRTAP2-3).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Keratin-associated protein 2-3 (KRTAP2-3).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Keratin-associated protein 2-3 (KRTAP2-3).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Keratin-associated protein 2-3 (KRTAP2-3).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Keratin-associated protein 2-3 (KRTAP2-3).	[5]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Keratin-associated protein 2-3 (KRTAP2-3).	[6]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Keratin-associated protein 2-3 (KRTAP2-3).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Keratin-associated protein 2-3 (KRTAP2-3).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Keratin-associated protein 2-3 (KRTAP2-3).	[5]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Keratin-associated protein 2-3 (KRTAP2-3).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Keratin-associated protein 2-3 (KRTAP2-3).	[11]

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] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Comparative Analysis of Transcriptomic Changes including mRNA and microRNA Expression Induced by the Xenoestrogens Zearalenone and Bisphenol A in Human Ovarian Cells. Toxins (Basel). 2023 Feb 9;15(2):140. doi: 10.3390/toxins15020140.
• [6] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [7] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [8] 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.
• [9] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [10] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [11] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.