Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFRX5KC)

• DOT Name: Keratin-associated protein 2-2 (KRTAP2-2)
• Synonyms: High sulfur keratin-associated protein 2.2; Keratin-associated protein 2.2
• Gene Name: KRTAP2-2
• UniProt ID: KRA22_HUMAN
• Pfam ID: PF01500
• Sequence:
  MTGSCCGSTFSSLSYGGGCCQPCCCRDPCCCRPVTCQTTVCRPVTCVPRCTRPICEPCRR
  PVCCDPCSLQEGCCRPITCCPSSCTAVVCRPCCWATTCCQPVSVQSPCGQPTPCSTTCRT
  SSC
• 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
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Keratin-associated protein 2-2 (KRTAP2-2).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Keratin-associated protein 2-2 (KRTAP2-2).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Keratin-associated protein 2-2 (KRTAP2-2).	[2]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Keratin-associated protein 2-2 (KRTAP2-2).	[4]

References

• [1] Arsenic exposure from drinking water is associated with decreased gene expression and increased DNA methylation in peripheral blood. Toxicol Appl Pharmacol. 2017 Apr 15;321:57-66. doi: 10.1016/j.taap.2017.02.019. Epub 2017 Feb 24.
• [2] 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.
• [3] 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.
• [4] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.