Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT93MMAK)

• DOT Name: Keratin, type II cuticular Hb6 (KRT86)
• Synonyms: Hair keratin K2.11; Keratin-86; K86; Type II hair keratin Hb6; Type-II keratin Kb26
• Gene Name: KRT86
• Related Disease: Monilethrix
• UniProt ID: KRT86_HUMAN
• Pfam ID: PF00038 ; PF16208
• Sequence:
  MTCGSYCGGRAFSCISACGPRPGRCCITAAPYRGISCYRGLTGGFGSHSVCGGFRAGSCG
  RSFGYRSGGVCGPSPPCITTVSVNESLLTPLNLEIDPNAQCVKQEEKEQIKSLNSRFAAF
  IDKVRFLEQQNKLLETKLQFYQNRECCQSNLEPLFEGYIETLRREAECVEADSGRLASEL
  NHVQEVLEGYKKKYEEEVSLRATAENEFVALKKDVDCAYLRKSDLEANVEALIQEIDFLR
  RLYEEEIRVLQSHISDTSVVVKLDNSRDLNMDCIIAEIKAQYDDIVTRSRAEAESWYRSK
  CEEMKATVIRHGETLRRTKEEINELNRMIQRLTAEVENAKCQNSKLEAAVAQSEQQGEAA
  LSDARCKLAELEGALQKAKQDMACLIREYQEVMNSKLGLDIEIATYRRLLEGEEQRLCEG
  VGSVNVCVSSSRGGVVCGDLCASTTAPVVSTRVSSVPSNSNVVVGTTNACAPSARVGVCG
  GSCKRC
• Tissue Specificity: Synthesis begins slightly higher in the hair shaft than HB1 and HB3 and continues much farther up, ending in the keratogeneous zone.
• Reactome Pathway:
  Formation of the cornified envelope (R-HSA-6809371)
  Keratinization (R-HSA-6805567)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Monilethrix	DISF9MNT	Strong	Autosomal dominant	[1]

11 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, type II cuticular Hb6 (KRT86).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Keratin, type II cuticular Hb6 (KRT86).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Keratin, type II cuticular Hb6 (KRT86).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Keratin, type II cuticular Hb6 (KRT86).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Keratin, type II cuticular Hb6 (KRT86).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Keratin, type II cuticular Hb6 (KRT86).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Keratin, type II cuticular Hb6 (KRT86).	[8]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Keratin, type II cuticular Hb6 (KRT86).	[9]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Keratin, type II cuticular Hb6 (KRT86).	[10]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Keratin, type II cuticular Hb6 (KRT86).	[11]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Keratin, type II cuticular Hb6 (KRT86).	[13]

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 affects the methylation of Keratin, type II cuticular Hb6 (KRT86).	[12]

References

• [1] Identification of novel mutations in basic hair keratins hHb1 and hHb6 in monilethrix: implications for protein structure and clinical phenotype. J Invest Dermatol. 1999 Oct;113(4):607-12. doi: 10.1046/j.1523-1747.1999.00722.x.
• [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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Research resource: STR DNA profile and gene expression comparisons of human BG-1 cells and a BG-1/MCF-7 clonal variant. Mol Endocrinol. 2014 Dec;28(12):2072-81.
• [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] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [9] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [10] Dissecting progressive stages of 5-fluorouracil resistance in vitro using RNA expression profiling. Int J Cancer. 2004 Nov 1;112(2):200-12. doi: 10.1002/ijc.20401.
• [11] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [12] 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.
• [13] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.