Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTI91X9Z)

DOT Name Keratin, type II cytoskeletal 71 (KRT71)
Synonyms Cytokeratin-71; CK-71; Keratin-71; K71; Type II inner root sheath-specific keratin-K6irs1; Keratin 6 irs; hK6irs; hK6irs1; Type-II keratin Kb34
Gene Name KRT71
Related Disease
Carcinoma ( )
Colorectal carcinoma ( )
Hypotrichosis ( )
Alopecia ( )
Isolated familial wooly hair disorder ( )
Undifferentiated carcinoma ( )
Diphtheria ( )
Hypotrichosis 13 ( )
UniProt ID
K2C71_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00038 ; PF16208
Sequence
MSRQFTCKSGAAAKGGFSGCSAVLSGGSSSSFRAGSKGLSGGFGSRSLYSLGGVRSLNVA
SGSGKSGGYGFGRGRASGFAGSMFGSVALGPVCPTVCPPGGIHQVTVNESLLAPLNVELD
PEIQKVRAQEREQIKALNNKFASFIDKVRFLEQQNQVLETKWELLQQLDLNNCKNNLEPI
LEGYISNLRKQLETLSGDRVRLDSELRNVRDVVEDYKKRYEEEINKRTAAENEFVLLKKD
VDAAYANKVELQAKVESMDQEIKFFRCLFEAEITQIQSHISDMSVILSMDNNRNLDLDSI
IDEVRTQYEEIALKSKAEAEALYQTKFQELQLAAGRHGDDLKNTKNEISELTRLIQRIRS
EIENVKKQASNLETAIADAEQRGDNALKDARAKLDELEGALHQAKEELARMLREYQELMS
LKLALDMEIATYRKLLESEECRMSGEFPSPVSISIISSTSGGSVYGFRPSMVSGGYVANS
SNCISGVCSVRGGEGRSRGSANDYKDTLGKGSSLSAPSKKTSR
Function Plays a central role in hair formation. Essential component of keratin intermediate filaments in the inner root sheath (IRS) of the hair follicle.
Tissue Specificity
Highly expressed in hair follicles from scalp. Specifically expressed in the inner root sheath (IRS) of the hair follicle. Present in the all 3 IRS layers: the cuticle, the Henle and the Huxley layers. Also detected in the pseudopods of 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
Carcinoma DISH9F1N Definitive Biomarker [1]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [2]
Hypotrichosis DISSW933 Strong Biomarker [3]
Alopecia DIS37HU4 moderate Genetic Variation [4]
Isolated familial wooly hair disorder DISTWYN7 Supportive Autosomal dominant [3]
Undifferentiated carcinoma DISIAZST Disputed Biomarker [1]
Diphtheria DISZWM55 Limited Biomarker [5]
Hypotrichosis 13 DISEECSG Limited Autosomal dominant [6]
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⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 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 71 (KRT71). [7]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Keratin, type II cytoskeletal 71 (KRT71). [10]
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2 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Keratin, type II cytoskeletal 71 (KRT71). [8]
Methotrexate DM2TEOL Approved Methotrexate decreases the expression of Keratin, type II cytoskeletal 71 (KRT71). [9]
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References

1 Global gene expression profiling of chemically induced rat mammary gland carcinomas and adenomas.Toxicol Pathol. 2005;33(7):768-75. doi: 10.1080/01926230500437027.
2 A new chalcone derivative, 3-phenyl-1-(2,4,6-tris(methoxymethoxy)phenyl)prop-2-yn-1-one), inhibits phorbol ester-induced metastatic activity of colorectal cancer cells through upregulation of heme oxygenase-1.Eur J Pharmacol. 2018 Dec 15;841:1-9. doi: 10.1016/j.ejphar.2018.10.011. Epub 2018 Oct 12.
3 A missense mutation within the helix initiation motif of the keratin K71 gene underlies autosomal dominant woolly hair/hypotrichosis. J Invest Dermatol. 2012 Oct;132(10):2342-2349. doi: 10.1038/jid.2012.154. Epub 2012 May 17.
4 A second KRT71 allele in curly coated dogs.Anim Genet. 2019 Feb;50(1):97-100. doi: 10.1111/age.12743. Epub 2018 Nov 15.
5 A novel hairless mouse model on an atopic dermatitis-prone genetic background generated by receptor-mediated transgenesis.Transgenic Res. 2008 Dec;17(6):1155-62. doi: 10.1007/s11248-008-9203-6. Epub 2008 Aug 7.
6 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
7 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.
8 Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
9 The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
10 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.