Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2V7AP3)

• DOT Name: Keratin, type II cytoskeletal 2 oral (KRT76)
• Synonyms: Cytokeratin-2P; CK-2P; K2P; Keratin-76; K76; Type-II keratin Kb9
• Gene Name: KRT76
• Related Disease:
  Advanced cancer
  Neoplasm
  Skin disease
• UniProt ID: K22O_HUMAN
• Pfam ID: PF00038 ; PF16208
• Sequence:
  MNRQVCKKSFSGRSQGFSGRSAVVSGSSRMSCVARSGGAGGGACGFRSGAGSFGSRSLYN
  LGSNKSISISVAAGSSRAGGFGGGRSSCGFAGGYGGGFGGSYGGGFGGGRGVGSGFGGAG
  GFGGAGGFGGPGVFGGPGSFGGPGGFGPGGFPGGIQEVIVNQSLLQPLNVEIDPQIGQVK
  AQEREQIKTLNNKFASFIDKVRFLEQQNKVLETKWELLQQQTTGSGPSSLEPCFESYISF
  LCKQLDSLLGERGNLEGELKSMQDLVEDFKKKYEDEINKRTAAENEFVGLKKDVDAAFMN
  KVELQAKVDSLTDEVSFLRTLYEMELSQMQSHASDTSVVLSMDNNRCLDLGSIIAEVRAQ
  YEEIAQRSKSEAEALYQTKLGELQTTAGRHGDDLRNTKSEIMELNRMIQRLRAEIENVKK
  QNANLQTAIAEAEQRGEMALKDANAKLQDLQTALQKAKDDLARLLRDYQELMNVKLALDV
  EIATYRKLLEGEECRMSGECQSAVCISVVSNVTSTSGSSGSSRGVFGGVSGSGSGGYKGG
  SSSSSSSGYGVSGGSGSGYGGVSSGSTGGRGSSGSYQSSSSGSRLGGAGSISVSHSGMGS
  SSGSIQTSGGSGYKSGGGGSTSIRFSQTTSSSQHSSTK
• Function: Probably contributes to terminal cornification.
• 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
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Skin disease	DISDW8R6	Strong	Biomarker	[2]

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 2 oral (KRT76).	[3]

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 increases the methylation of Keratin, type II cytoskeletal 2 oral (KRT76).	[4]

References

• [1] Downregulation of keratin 76 expression during oral carcinogenesis of human, hamster and mouse.PLoS One. 2013 Jul 30;8(7):e70688. doi: 10.1371/journal.pone.0070688. Print 2013.
• [2] Keratin 76 is required for tight junction function and maintenance of the skin barrier.PLoS Genet. 2014 Oct 23;10(10):e1004706. doi: 10.1371/journal.pgen.1004706. eCollection 2014 Oct.
• [3] 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.
• [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.