Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9MEIJ1)

DOT Name Keratin, type II cytoskeletal 74 (KRT74)
Synonyms Cytokeratin-74; CK-74; Keratin-5c; K5C; Keratin-74; K74; Type II inner root sheath-specific keratin-K6irs4; Type-II keratin Kb37
Gene Name KRT74
Related Disease
Autosomal dominant wooly hair ( )
Ectodermal dysplasia ( )
Hypotrichosis 2 ( )
Hypotrichosis 3 ( )
Alopecia ( )
Hypotrichosis simplex of the scalp ( )
Isolated familial wooly hair disorder ( )
Pure hair and nail ectodermal dysplasia ( )
UniProt ID
K2C74_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00038 ; PF16208
Sequence
MSRQLNIKSSGDKGNFSVHSAVVPRKAVGSLASYCAAGRGAGAGFGSRSLYSLGGNRRIS
FNVAGGGVRAGGYGFRPGSGYGGGRASGFAGSMFGSVALGPACLSVCPPGGIHQVTVNKS
LLAPLNVELDPEIQKVRAQEREQIKVLNDKFASFIDKVRFLEQQNQVLETKWELLQQLDL
NNCKKNLEPILEGYISNLRKQLETLSGDRVRLDSELRSMRDLVEDYKKRYEVEINRRTTA
ENEFVVLKKDADAAYAVKVELQAKVDSLDKEIKFLKCLYDAEIAQIQTHASETSVILSMD
NNRDLDLDSIIAEVRMHYEEIALKSKAEAEALYQTKIQELQLAASRHGDDLKHTRSEMVE
LNRLIQRIRCEIGNVKKQRASLETAIADAEQRGDNALKDAQAKLDELEGALHQAKEELAR
MLREYQELMSLKLALDMEIATYRKLLEGEECRMSGENPSSVSISVISSSSYSYHHPSSAG
VDLGASAVAGSSGSTQSGQTKTTEARGGDLKDTQGKSTPASIPARKATR
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 Huxley layer, but not in Henle layer or cuticle of the IRS. In the IRS Huxley layer, it is expressed in specialized Huxley cells, termed 'Fluegelzellen, along the area of differentiated Henle cells (at protein level).
Reactome Pathway
Formation of the cornified envelope (R-HSA-6809371 )
Keratinization (R-HSA-6805567 )

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Autosomal dominant wooly hair DISKNN9N Strong Autosomal dominant [1]
Ectodermal dysplasia DISLRS4M Strong Genetic Variation [2]
Hypotrichosis 2 DIS1JN13 Strong GermlineCausalMutation [3]
Hypotrichosis 3 DISYT8C5 Strong Autosomal dominant [3]
Alopecia DIS37HU4 moderate Genetic Variation [3]
Hypotrichosis simplex of the scalp DISE73OD Supportive Autosomal dominant [3]
Isolated familial wooly hair disorder DISTWYN7 Supportive Autosomal dominant [1]
Pure hair and nail ectodermal dysplasia DIS83WTF Supportive Autosomal dominant [2]
------------------------------------------------------------------------------------
⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Keratin, type II cytoskeletal 74 (KRT74). [4]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Keratin, type II cytoskeletal 74 (KRT74). [6]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Keratin, type II cytoskeletal 74 (KRT74). [8]
------------------------------------------------------------------------------------
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 74 (KRT74). [5]
------------------------------------------------------------------------------------
1 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Keratin, type II cytoskeletal 74 (KRT74). [7]
------------------------------------------------------------------------------------

References

1 Autosomal-dominant woolly hair resulting from disruption of keratin 74 (KRT74), a potential determinant of human hair texture. Am J Hum Genet. 2010 Apr 9;86(4):632-8. doi: 10.1016/j.ajhg.2010.02.025. Epub 2010 Mar 25.
2 Autosomal recessive transmission of a rare KRT74 variant causes hair and nail ectodermal dysplasia: allelism with dominant woolly hair/hypotrichosis. PLoS One. 2014 Apr 8;9(4):e93607. doi: 10.1371/journal.pone.0093607. eCollection 2014.
3 Novel mutations in the keratin-74 (KRT74) gene underlie autosomal dominant woolly hair/hypotrichosis in Pakistani families. Hum Genet. 2011 Apr;129(4):419-24. doi: 10.1007/s00439-010-0938-9. Epub 2010 Dec 28.
4 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
5 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.
6 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.
7 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
8 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.