Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV1SGF2)

• DOT Name: Keratin-associated protein 2-1 (KRTAP2-1)
• Synonyms: High sulfur keratin-associated protein 2.1; Keratin-associated protein 2.1
• Gene Name: KRTAP2-1
• UniProt ID: KRA21_HUMAN
• Pfam ID: PF01500 ; PF13885
• Sequence:
  MTGSCCGSTFSSLSYGGGCCQPCCCRDPCCCRPVTCQTTVCRPVTCVPRCTRPICEPCRR
  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
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Keratin-associated protein 2-1 (KRTAP2-1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Keratin-associated protein 2-1 (KRTAP2-1).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Keratin-associated protein 2-1 (KRTAP2-1).	[2]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Keratin-associated protein 2-1 (KRTAP2-1).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Keratin-associated protein 2-1 (KRTAP2-1).	[5]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Keratin-associated protein 2-1 (KRTAP2-1).	[6]

References

• [1] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [2] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [3] Curcumin downregulates the inflammatory cytokines CXCL1 and -2 in breast cancer cells via NFkappaB. Carcinogenesis. 2008 Apr;29(4):779-89.
• [4] 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.
• [5] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [6] Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.