Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT706ZLF)

• DOT Name: Keratin, type II cytoskeletal 78 (KRT78)
• Synonyms: Cytokeratin-78; CK-78; Keratin-5b; Keratin-78; K78; Type-II keratin Kb40
• Gene Name: KRT78
• UniProt ID: K2C78_HUMAN
• Pfam ID: PF00038 ; PF16208
• Sequence:
  MSLSPCRAQRGFSARSACSARSRGRSRGGFSSRGGFSSRSLNSFGGCLEGSRGSTWGSGG
  RLGVRFGEWSGGPGLSLCPPGGIQEVTINQNLLTPLKIEIDPQFQVVRTQETQEIRTLNN
  QFASFIDKVRFLEQQNKVLETKWHLLQQQGLSGSQQGLEPVFEACLDQLRKQLEQLQGER
  GALDAELKACRDQEEEYKSKYEEEAHRRATLENDFVVLKKDVDGVFLSKMELEGKLEALR
  EYLYFLKHLNEEELGQLQTQASDTSVVLSMDNNRYLDFSSIITEVRARYEEIARSSKAEA
  EALYQTKYQELQVSAQLHGDRMQETKVQISQLHQEIQRLQSQTENLKKQNASLQAAITDA
  EQRGELALKDAQAKVDELEAALRMAKQNLARLLCEYQELTSTKLSLDVEIATYRRLLEGE
  ECRMSGECTSQVTISSVGGSAVMSGGVGGGLGSTCGLGSGKGSPGSCCTSIVTGGSNIIL
  GSGKDPVLDSCSVSGSSAGSSCHTILKKTVESSLKTSITY
• Tissue Specificity: In non-keratinising esophageal and vaginal epithelium, strongly expressed in the basal and parabasal/lower suprabasal cell layers with considerably decreased expression in the mid/upper suprabasal layers (at protein level) . A similar gradient from basal to lower suprabasal layers is seen in the partially keratinised dorsal tongue epithelium, in the scalp and in the plantar epidermis (at protein level) . Extension of expression into the suprabasal compartments is distinctly more pronounced in non-keratinising epithelia than in keratinising epithelia and epidermis (at protein level) . In scalp sections, present in the interfollicular epidermis and infundibulum including the entire outer root sheath of the hair follicles and also in the sebocytes (at protein level) . In sweat glands, expressed in peripheral and luminal cells of the lower duct and in peripheral cells of the middle/upper duct with no expression observed in luminal cells (at protein level) . In embryos at the 14th week of pregnancy, detected in basal and parabasal layers but is absent from the uppermost epidermal layer (at protein level) . Expressed in tongue epithelium .
• Reactome Pathway:
  Formation of the cornified envelope (R-HSA-6809371)
  Keratinization (R-HSA-6805567)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Keratin, type II cytoskeletal 78 (KRT78).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Keratin, type II cytoskeletal 78 (KRT78).	[3]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Keratin, type II cytoskeletal 78 (KRT78).	[4]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Keratin, type II cytoskeletal 78 (KRT78).	[2]

References

• [1] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [2] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [3] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [4] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.