Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT67IP7F)

• DOT Name: Keratin, type II cuticular Hb5 (KRT85)
• Synonyms: Hair keratin K2.12; Keratin-85; K85; Type II hair keratin Hb5; Type-II keratin Kb25
• Gene Name: KRT85
• Related Disease:
  Ectodermal dysplasia
  Ectodermal dysplasia 4, hair/nail type
  Pure hair and nail ectodermal dysplasia
• UniProt ID: KRT85_HUMAN
• Pfam ID: PF00038 ; PF16208
• Sequence:
  MSCRSYRISSGCGVTRNFSSCSAVAPKTGNRCCISAAPYRGVSCYRGLTGFGSRSLCNLG
  SCGPRIAVGGFRAGSCGRSFGYRSGGVCGPSPPCITTVSVNESLLTPLNLEIDPNAQCVK
  QEEKEQIKSLNSRFAAFIDKVRFLEQQNKLLETKWQFYQNQRCCESNLEPLFSGYIETLR
  REAECVEADSGRLASELNHVQEVLEGYKKKYEEEVALRATAENEFVVLKKDVDCAYLRKS
  DLEANVEALVEESSFLRRLYEEEIRVLQAHISDTSVIVKMDNSRDLNMDCIIAEIKAQYD
  DVASRSRAEAESWYRSKCEEMKATVIRHGETLRRTKEEINELNRMIQRLTAEIENAKCQR
  AKLEAAVAEAEQQGEAALSDARCKLAELEGALQKAKQDMACLLKEYQEVMNSKLGLDIEI
  ATYRRLLEGEEHRLCEGVGSVNVCVSSSRGGVSCGGLSYSTTPGRQITSGPSAIGGSITV
  VAPDSCAPCQPRSSSFSCGSSRSVRFA
• Tissue Specificity: Synthesis occurs immediately above a small population of matrix cells at the base of the hair bulb and the trichocytes lining the dermal papilla and extends upward through the matrix and ends in the lower part of the cortex of the hair shaft.
• Reactome Pathway:
  Formation of the cornified envelope (R-HSA-6809371)
  Keratinization (R-HSA-6805567)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ectodermal dysplasia	DISLRS4M	Definitive	Genetic Variation	[1]
Ectodermal dysplasia 4, hair/nail type	DISIN0OB	Definitive	Autosomal recessive	[2]
Pure hair and nail ectodermal dysplasia	DIS83WTF	Supportive	Autosomal dominant	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Keratin, type II cuticular Hb5 (KRT85).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Keratin, type II cuticular Hb5 (KRT85).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Keratin, type II cuticular Hb5 (KRT85).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Keratin, type II cuticular Hb5 (KRT85).	[6]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Keratin, type II cuticular Hb5 (KRT85).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Keratin, type II cuticular Hb5 (KRT85).	[9]

References

• [1] Autosomal recessive pure hair and nail ectodermal dysplasia linked to chromosome 12p11.1-q14.3 without KRTHB5 gene mutation.Eur J Dermatol. 2010 Jul-Aug;20(4):443-6. doi: 10.1684/ejd.2010.0962. Epub 2010 Apr 21.
• [2] Mutations in the keratin 85 (KRT85/hHb5) gene underlie pure hair and nail ectodermal dysplasia. J Invest Dermatol. 2010 Mar;130(3):892-5. doi: 10.1038/jid.2009.341. Epub 2009 Oct 29.
• [3] A mutation in the hair matrix and cuticle keratin KRTHB5 gene causes ectodermal dysplasia of hair and nail type. J Med Genet. 2006 Mar;43(3):274-9. doi: 10.1136/jmg.2005.033381.
• [4] 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.
• [5] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [6] Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
• [7] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [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] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.