Details of Drug Off-Target (DOT)

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

• DOT Name: Keratin, type II cytoskeletal 73 (KRT73)
• Synonyms: Cytokeratin-73; CK-73; Keratin-73; K73; Type II inner root sheath-specific keratin-K6irs3; Type-II keratin Kb36
• Gene Name: KRT73
• Related Disease:
  Creutzfeldt Jacob disease
  Inherited Creutzfeldt-Jakob disease
• UniProt ID: K2C73_HUMAN
• Pfam ID: PF00038 ; PF16208
• Sequence:
  MSRQFTYKSGAAAKGGFSGCSAVLSGGSSSSYRAGGKGLSGGFSSRSLYSLGGARSISFN
  VASGSGWAGGYGFGRGRASGFAGSMFGSVALGSVCPSLCPPGGIHQVTINKSLLAPLNVE
  LDPEIQKVRAQEREQIKVLNNKFASFIDKVRFLEQQNQVLETKWELLQQLDLNNCKNNLE
  PILEGYISNLRKQLETLSGDRVRLDSELRSVREVVEDYKKRYEEEINKRTTAENEFVVLK
  KDVDAAYTSKVELQAKVDALDGEIKFFKCLYEGETAQIQSHISDTSIILSMDNNRNLDLD
  SIIAEVRAQYEEIARKSKAEAEALYQTKFQELQLAAGRHGDDLKHTKNEISELTRLIQRL
  RSEIESVKKQCANLETAIADAEQRGDCALKDARAKLDELEGALQQAKEELARMLREYQEL
  LSVKLSLDIEIATYRKLLEGEECRMSGEYTNSVSISVINSSMAGMAGTGAGFGFSNAGTY
  GYWPSSVSGGYSMLPGGCVTGSGNCSPRGEARTRLGSASEFRDSQGKTLALSSPTKKTMR
• 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. 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, it is expressed between the lowermost bulb region of the cuticle and the region where Henle cells undergo abrupt terminal differentiation. Detected up to the uppermost cortex region where cuticle cells terminally differentiate (at protein level).
• Reactome Pathway:
  Formation of the cornified envelope (R-HSA-6809371)
  Keratinization (R-HSA-6805567)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Creutzfeldt Jacob disease	DISCB6RX	Strong	Biomarker	[1]
Inherited Creutzfeldt-Jakob disease	DIS3TXG8	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Keratin, type II cytoskeletal 73 (KRT73).	[2]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Keratin, type II cytoskeletal 73 (KRT73).	[5]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Keratin, type II cytoskeletal 73 (KRT73).	[7]

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 73 (KRT73).	[3]

2 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 73 (KRT73).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Keratin, type II cytoskeletal 73 (KRT73).	[6]

References

• [1] Snord 3A: a molecular marker and modulator of prion disease progression.PLoS One. 2013;8(1):e54433. doi: 10.1371/journal.pone.0054433. Epub 2013 Jan 21.
• [2] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [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.
• [5] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [6] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [7] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.