Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAXW63A)

• DOT Name: Keratin, type II cytoskeletal 72 (KRT72)
• Synonyms: Cytokeratin-72; CK-72; Keratin-72; K72; Type II inner root sheath-specific keratin-K6irs2; Type-II keratin Kb35
• Gene Name: KRT72
• Related Disease:
  Clear cell renal carcinoma
  Renal cell carcinoma
  Actinic keratosis
  Advanced cancer
  Carcinoma
  Cutaneous squamous cell carcinoma
• UniProt ID: K2C72_HUMAN
• Pfam ID: PF00038 ; PF16208
• Sequence:
  MSRQLTHFPRGERLGFSGCSAVLSGGIGSSSASFRARVKGSASFGSKSLSCLGGSRSLAL
  SAAARRGGGRLGGFVGTAFGSAGLGPKCPSVCPPGGIPQVTVNKSLLAPLNVEMDPEIQR
  VRAQEREQIKALNNKFASFIDKVRFLEQQNQVLETKWNLLQQLDLNNCRKNLEPIYEGYI
  SNLQKQLEMLSGDGVRLDSELRNMQDLVEDYKKRYEVEINRRTAAENEFVVLKKDVDAAY
  MNKVELQAKVDSLTDEIKFFKCLYEGEITQIQSHISDTSIVLSMDNNRDLDLDSIIAEVR
  AQYEEIALKSKAEAETLYQTKIQELQVTAGQHGDDLKLTKAEISELNRLIQRIRSEIGNV
  KKQCADLETAIADAEQRGDCALKDARAKLDELEGALHQAKEELARMLREYQELVSLKLAL
  DMEIATYRKLLESEECRMSGEYPNSVSISVISSTNAGAGGAGFSMGFGASSSYSYKTAAA
  DVKTKGSCGSELKDPLAKTSGSSCATKKASR
• Function: Has a role in hair formation. Specific component of keratin intermediate filaments in the inner root sheath (IRS) of the hair follicle (Probable).
• Tissue Specificity: Highly expressed in hair follicles from scalp and eyebrow. Also expressed in palmoplantar epidermis. Not expressed in face skin despite the presence of fine hairs histologically. In hair, it is specifically present in the inner root sheath (IRS) of the hair follicle. Present in the IRS cuticle, but not in Henle or Huxley layers of the IRS. In the IRS cuticle, its presence is delayed up to the height of the apex of the dermal papilla (at protein level).
• Reactome Pathway:
  Formation of the cornified envelope (R-HSA-6809371)
  Keratinization (R-HSA-6805567)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[1]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[1]
Actinic keratosis	DISR1RC5	Limited	Biomarker	[2]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[3]
Carcinoma	DISH9F1N	Limited	Altered Expression	[3]
Cutaneous squamous cell carcinoma	DIS3LXUG	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Keratin, type II cytoskeletal 72 (KRT72).	[4]

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 72 (KRT72).	[5]

References

• [1] KRT6 interacting with notch1 contributes to progression of renal cell carcinoma, and aliskiren inhibits renal carcinoma cell lines proliferation in vitro.Int J Clin Exp Pathol. 2015 Aug 1;8(8):9182-8. eCollection 2015.
• [2] Molecular profiling of cutaneous squamous cell carcinomas and actinic keratoses from organ transplant recipients.BMC Cancer. 2013 Feb 5;13:58. doi: 10.1186/1471-2407-13-58.
• [3] The expression of keratin 6 is regulated by the activation of the ERK1/2 pathway in arsenite transformed human urothelial cells.Toxicol Appl Pharmacol. 2017 Sep 15;331:41-53. doi: 10.1016/j.taap.2017.05.007. Epub 2017 May 10.
• [4] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [5] 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.