Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5U1Y8L)

• DOT Name: Keratin, type II cytoskeletal 3 (KRT3)
• Synonyms: 65 kDa cytokeratin; Cytokeratin-3; CK-3; Keratin-3; K3; Type-II keratin Kb3
• Gene Name: KRT3
• Related Disease:
  Anca-associated vasculitis
  Corneal dystrophy, Meesmann, 1
  Corneal neovascularization
  Macular corneal dystrophy
  Polycystic ovarian syndrome
  Keratoconus
  Meesmann corneal dystrophy
• UniProt ID: K2C3_HUMAN
• Pfam ID: PF00038 ; PF16208
• Sequence:
  MSRQASKTSGGGSQGFSGRSAVVSGSSRMSCVAHSGGAGGGAYGFRSGAGGFGSRSLYNL
  GGNKSISISVAAGGSRAGGFGGGRSSCAFAGGYGGGFGSGYGGGFGGGFGGGRGMGGGFG
  GAGGFGGAGGFGGAGGFGGPGGFGGSGGFGGPGSLGSPGGFGPGGFPGGIQEVTINQSLL
  QPLNVEIDPQIGQVKAQEREQIKTLNNKFASFIDKVRFLEQQNKVLETKWNLLQQQGTSS
  ISGTNNLEPLFENHINYLRSYLDNILGERGRLDSELKNMEDLVEDFKKKYEDEINKRTAA
  ENEFVTLKKDVDSAYMNKVELQAKVDALIDEIDFLRTLYDAELSQMQSHISDTSVVLSMD
  NNRSLDLDSIIAEVRAQYEDIAQRSKAEAEALYQTKLGELQTTAGRHGDDLRNTKSEIIE
  LNRMIQRLRAEIEGVKKQNANLQTAIAEAEQHGEMALKDANAKLQELQAALQQAKDDLAR
  LLRDYQELMNVKLALDVEIATYRKLLEGEEYRMSGECPSAVSISVVSSSTTSASAGGYGG
  GYGGGMGGGLGGGFSAGGGSGSGFGRGGGGGIGGGFGGGSSGFSGGSGFGSISGARYGVS
  GGGFSSASNRGGSIKFSQSSQSSQRYSR
• Tissue Specificity: Cornea specific.
• Reactome Pathway:
  Formation of the cornified envelope (R-HSA-6809371)
  Keratinization (R-HSA-6805567)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Anca-associated vasculitis	DISU3CNU	Strong	Genetic Variation	[1]
Corneal dystrophy, Meesmann, 1	DIST4WI6	Strong	Autosomal dominant	[2]
Corneal neovascularization	DISKOGZP	Strong	Altered Expression	[3]
Macular corneal dystrophy	DISOLD0H	Strong	Genetic Variation	[2]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[4]
Keratoconus	DISOONXH	moderate	Biomarker	[5]
Meesmann corneal dystrophy	DISJFWTC	Supportive	Autosomal dominant	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Keratin, type II cytoskeletal 3 (KRT3).	[7]

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 3 (KRT3).	[8]

References

• [1] Corneal epithelial-specific cytokeratin 3 is an autoantigen in Wegener's granulomatosis-associated peripheral ulcerative keratitis.Invest Ophthalmol Vis Sci. 1999 Aug;40(9):2147-51.
• [2] Novel mutations in the helix termination motif of keratin 3 and keratin 12 in 2 Taiwanese families with Meesmann corneal dystrophy. Cornea. 2005 Nov;24(8):928-32. doi: 10.1097/01.ico.0000159732.29930.26.
• [3] The Impact of Limbal Mesenchymal Stromal Cells on Healing of Acute Ocular Surface Wounds Is Improved by Pre-cultivation and Implantation in the Presence of Limbal Epithelial Cells.Cell Transplant. 2019 Sep-Oct;28(9-10):1257-1270. doi: 10.1177/0963689719858577. Epub 2019 Jun 17.
• [4] Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
• [5] Proteome profiling of corneal epithelium and identification of marker proteins for keratoconus, a pilot study.Exp Eye Res. 2006 Feb;82(2):201-9. doi: 10.1016/j.exer.2005.06.009. Epub 2005 Aug 3.
• [6] Mutations in cornea-specific keratin K3 or K12 genes cause Meesmann's corneal dystrophy. Nat Genet. 1997 Jun;16(2):184-7. doi: 10.1038/ng0697-184.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [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.