General Information of Drug Off-Target (DOT) (ID: OTUVZ1DW)

DOT Name Keratin, type I cytoskeletal 14 (KRT14)
Synonyms Cytokeratin-14; CK-14; Keratin-14; K14
Gene Name KRT14
Related Disease
Ectodermal dysplasia ( )
Epidermolysis bullosa simplex 1A, generalized severe ( )
Invasive breast carcinoma ( )
Neoplasm ( )
Advanced cancer ( )
Alzheimer disease ( )
Atopic dermatitis ( )
Autoimmune disease ( )
Barrett esophagus ( )
Bladder cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Carcinoma ( )
Dermatopathia pigmentosa reticularis ( )
Epidermolysis bullosa ( )
Epidermolysis bullosa simplex 1B, generalized intermediate ( )
Epidermolysis bullosa simplex 1C, localized ( )
Epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive ( )
Esophageal squamous cell carcinoma ( )
Hepatitis B virus infection ( )
Hepatitis C virus infection ( )
Lung cancer ( )
Lung carcinoma ( )
Naegeli-Franceschetti-Jadassohn syndrome ( )
Precancerous condition ( )
Prostate neoplasm ( )
Psoriasis ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Metastatic malignant neoplasm ( )
Nasopharyngeal carcinoma ( )
Palmoplantar keratosis ( )
Squamous cell carcinoma ( )
Epidermolysis bullosa simplex 2F, with mottled pigmentation ( )
Adenocarcinoma ( )
Cervical cancer ( )
Cervical carcinoma ( )
Epidermolysis bullosa simplex ( )
Non-small-cell lung cancer ( )
Non-syndromic ichthyosis ( )
Skin disease ( )
Transitional cell carcinoma ( )
UniProt ID
K1C14_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
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PDB ID
3TNU; 6JFV
Pfam ID
PF00038
Sequence
MTTCSRQFTSSSSMKGSCGIGGGIGGGSSRISSVLAGGSCRAPSTYGGGLSVSSSRFSSG
GACGLGGGYGGGFSSSSSSFGSGFGGGYGGGLGAGLGGGFGGGFAGGDGLLVGSEKVTMQ
NLNDRLASYLDKVRALEEANADLEVKIRDWYQRQRPAEIKDYSPYFKTIEDLRNKILTAT
VDNANVLLQIDNARLAADDFRTKYETELNLRMSVEADINGLRRVLDELTLARADLEMQIE
SLKEELAYLKKNHEEEMNALRGQVGGDVNVEMDAAPGVDLSRILNEMRDQYEKMAEKNRK
DAEEWFFTKTEELNREVATNSELVQSGKSEISELRRTMQNLEIELQSQLSMKASLENSLE
ETKGRYCMQLAQIQEMIGSVEEQLAQLRCEMEQQNQEYKILLDVKTRLEQEIATYRRLLE
GEDAHLSSSQFSSGSQSSRDVTSSSRQIRTKVMDVHDGKVVSTHEQVLRTKN
Function
The nonhelical tail domain is involved in promoting KRT5-KRT14 filaments to self-organize into large bundles and enhances the mechanical properties involved in resilience of keratin intermediate filaments in vitro.
Tissue Specificity
Expressed in the corneal epithelium (at protein level) . Detected in the basal layer, lowered within the more apically located layers specifically in the stratum spinosum, stratum granulosum but is not detected in stratum corneum. Strongly expressed in the outer root sheath of anagen follicles but not in the germinative matrix, inner root sheath or hair . Found in keratinocytes surrounding the club hair during telogen .
KEGG Pathway
Estrogen sig.ling pathway (hsa04915 )
Staphylococcus aureus infection (hsa05150 )
Reactome Pathway
Keratinization (R-HSA-6805567 )
Formation of the cornified envelope (R-HSA-6809371 )
Type I hemidesmosome assembly (R-HSA-446107 )

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Ectodermal dysplasia DISLRS4M Definitive Biomarker [1]
Epidermolysis bullosa simplex 1A, generalized severe DISD362G Definitive Autosomal dominant [2]
Invasive breast carcinoma DISANYTW Definitive Biomarker [3]
Neoplasm DISZKGEW Definitive Altered Expression [4]
Advanced cancer DISAT1Z9 Strong Altered Expression [5]
Alzheimer disease DISF8S70 Strong Biomarker [6]
Atopic dermatitis DISTCP41 Strong Biomarker [7]
Autoimmune disease DISORMTM Strong Biomarker [8]
Barrett esophagus DIS416Y7 Strong Altered Expression [9]
Bladder cancer DISUHNM0 Strong Altered Expression [10]
Breast cancer DIS7DPX1 Strong Altered Expression [11]
Breast carcinoma DIS2UE88 Strong Altered Expression [11]
Breast neoplasm DISNGJLM Strong Biomarker [12]
Carcinoma DISH9F1N Strong Biomarker [13]
Dermatopathia pigmentosa reticularis DISPNU4A Strong Autosomal dominant [14]
Epidermolysis bullosa DISVOTZQ Strong Genetic Variation [15]
Epidermolysis bullosa simplex 1B, generalized intermediate DISI80OT Strong Autosomal dominant [14]
Epidermolysis bullosa simplex 1C, localized DISQCPMC Strong Autosomal dominant [14]
Epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive DIS0EG3S Strong Autosomal recessive [14]
Esophageal squamous cell carcinoma DIS5N2GV Strong Biomarker [16]
Hepatitis B virus infection DISLQ2XY Strong Biomarker [17]
Hepatitis C virus infection DISQ0M8R Strong Genetic Variation [17]
Lung cancer DISCM4YA Strong Biomarker [5]
Lung carcinoma DISTR26C Strong Biomarker [5]
Naegeli-Franceschetti-Jadassohn syndrome DISQERK4 Strong Autosomal dominant [14]
Precancerous condition DISV06FL Strong Altered Expression [18]
Prostate neoplasm DISHDKGQ Strong Altered Expression [19]
Psoriasis DIS59VMN Strong Genetic Variation [20]
Urinary bladder cancer DISDV4T7 Strong Altered Expression [10]
Urinary bladder neoplasm DIS7HACE Strong Altered Expression [10]
Metastatic malignant neoplasm DIS86UK6 moderate Altered Expression [21]
Nasopharyngeal carcinoma DISAOTQ0 moderate Altered Expression [22]
Palmoplantar keratosis DISYQGFB moderate Genetic Variation [23]
Squamous cell carcinoma DISQVIFL moderate Altered Expression [24]
Epidermolysis bullosa simplex 2F, with mottled pigmentation DIS7VDBV Supportive Autosomal dominant [25]
Adenocarcinoma DIS3IHTY Limited Biomarker [26]
Cervical cancer DISFSHPF Limited Genetic Variation [27]
Cervical carcinoma DIST4S00 Limited Biomarker [28]
Epidermolysis bullosa simplex DIS2CZ6X Limited Genetic Variation [29]
Non-small-cell lung cancer DIS5Y6R9 Limited Biomarker [26]
Non-syndromic ichthyosis DISZ9QBQ Limited Genetic Variation [30]
Skin disease DISDW8R6 Limited Genetic Variation [31]
Transitional cell carcinoma DISWVVDR Limited Genetic Variation [24]
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⏷ Show the Full List of 43 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
17 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of Keratin, type I cytoskeletal 14 (KRT14). [32]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Keratin, type I cytoskeletal 14 (KRT14). [33]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Keratin, type I cytoskeletal 14 (KRT14). [34]
Folic acid DMEMBJC Approved Folic acid decreases the expression of Keratin, type I cytoskeletal 14 (KRT14). [35]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of Keratin, type I cytoskeletal 14 (KRT14). [32]
Troglitazone DM3VFPD Approved Troglitazone decreases the expression of Keratin, type I cytoskeletal 14 (KRT14). [36]
Malathion DMXZ84M Approved Malathion increases the expression of Keratin, type I cytoskeletal 14 (KRT14). [37]
Alitretinoin DMME8LH Approved Alitretinoin decreases the expression of Keratin, type I cytoskeletal 14 (KRT14). [32]
Methamphetamine DMPM4SK Approved Methamphetamine increases the expression of Keratin, type I cytoskeletal 14 (KRT14). [38]
Imatinib DM7RJXL Approved Imatinib increases the expression of Keratin, type I cytoskeletal 14 (KRT14). [39]
Bexarotene DMOBIKY Approved Bexarotene decreases the expression of Keratin, type I cytoskeletal 14 (KRT14). [40]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Keratin, type I cytoskeletal 14 (KRT14). [42]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Keratin, type I cytoskeletal 14 (KRT14). [43]
PD-153035 DM7KJTI Discontinued in Phase 1 PD-153035 decreases the expression of Keratin, type I cytoskeletal 14 (KRT14). [36]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Keratin, type I cytoskeletal 14 (KRT14). [44]
chloropicrin DMSGBQA Investigative chloropicrin decreases the expression of Keratin, type I cytoskeletal 14 (KRT14). [45]
all-trans-4-oxo-retinoic acid DMM2R1N Investigative all-trans-4-oxo-retinoic acid decreases the expression of Keratin, type I cytoskeletal 14 (KRT14). [32]
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⏷ Show the Full List of 17 Drug(s)
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 I cytoskeletal 14 (KRT14). [41]
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References

1 KRT14 haploinsufficiency results in increased susceptibility of keratinocytes to TNF-alpha-induced apoptosis and causes Naegeli-Franceschetti-Jadassohn syndrome.J Invest Dermatol. 2008 Jun;128(6):1517-24. doi: 10.1038/sj.jid.5701187. Epub 2007 Nov 29.
2 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.
3 Quantitative, in situ analysis of mRNAs and proteins with subcellular resolution.Sci Rep. 2017 Nov 28;7(1):16459. doi: 10.1038/s41598-017-16492-1.
4 ALDH1-positive intratumoral stromal cells indicate differentiated epithelial-like phenotype and good prognosis in prostate cancer.Transl Res. 2019 Jan;203:49-56. doi: 10.1016/j.trsl.2018.08.007. Epub 2018 Sep 12.
5 Keratin 14-high subpopulation mediates lung cancer metastasis potentially through Gkn1 upregulation.Oncogene. 2019 Sep;38(36):6354-6369. doi: 10.1038/s41388-019-0889-0. Epub 2019 Jul 18.
6 Buccal cell cytokeratin 14 identifies mild cognitive impairment and Alzheimer' s disease in the AIBL study of aging.Curr Alzheimer Res. 2015;12(3):233-41. doi: 10.2174/1567205012666150302154650.
7 IL-33-Induced Atopic Dermatitis-Like Inflammation in Mice Is Mediated by Group 2 Innate Lymphoid Cells in Concert with Basophils.J Invest Dermatol. 2019 Oct;139(10):2185-2194.e3. doi: 10.1016/j.jid.2019.04.016. Epub 2019 May 21.
8 The use of mouse models to better understand mechanisms of autoimmunity and tolerance.J Autoimmun. 2010 Nov;35(3):192-8. doi: 10.1016/j.jaut.2010.06.007. Epub 2010 Jul 23.
9 MicroRNA-143 and -205 expression in neosquamous esophageal epithelium following Argon plasma ablation of Barrett's esophagus.J Gastrointest Surg. 2009 May;13(5):846-53. doi: 10.1007/s11605-009-0799-5. Epub 2009 Feb 4.
10 Differential expression of cytokeratin 14 and 18 in bladder cancer tumorigenesis.Exp Biol Med (Maywood). 2018 Feb;243(4):344-349. doi: 10.1177/1535370218754493. Epub 2018 Jan 19.
11 Reporters to mark and eliminate basal or luminal epithelial cells in culture and in vivo.PLoS Biol. 2018 Jun 20;16(6):e2004049. doi: 10.1371/journal.pbio.2004049. eCollection 2018 Jun.
12 Combined deletion of Pten and p53 in mammary epithelium accelerates triple-negative breast cancer with dependency on eEF2K.EMBO Mol Med. 2014 Dec;6(12):1542-60. doi: 10.15252/emmm.201404402.
13 Prognostic stratification of muscle invasive urothelial carcinomas using limited immunohistochemical panel of Gata3 and cytokeratins 5/6, 14 and 20.Ann Diagn Pathol. 2019 Dec;43:151397. doi: 10.1016/j.anndiagpath.2019.08.001. Epub 2019 Aug 3.
14 The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
15 Revertant mosaicism in junctional epidermolysis bullosa due to multiple correcting second-site mutations in LAMB3.J Clin Invest. 2007 May;117(5):1240-8. doi: 10.1172/JCI30465.
16 Fascin and CK4 as biomarkers for esophageal squamous cell carcinoma.Anticancer Res. 2011 Mar;31(3):945-52.
17 Activation-induced cytidine deaminase is dispensable for virus-mediated liver and skin tumor development in mouse models.Int Immunol. 2014 Jul;26(7):397-406. doi: 10.1093/intimm/dxu040. Epub 2014 Feb 25.
18 Constitutive expression of human keratin 14 gene in mouse lung induces premalignant lesions and squamous differentiation.Carcinogenesis. 2008 Dec;29(12):2377-84. doi: 10.1093/carcin/bgn190. Epub 2008 Aug 12.
19 In vivo functional studies of tumor-specific retrogene NanogP8 in transgenic animals.Cell Cycle. 2013 Aug 1;12(15):2395-408. doi: 10.4161/cc.25402. Epub 2013 Jun 26.
20 IL-37 ameliorates the inflammatory process in psoriasis by suppressing proinflammatory cytokine production.J Immunol. 2014 Feb 15;192(4):1815-23. doi: 10.4049/jimmunol.1300047. Epub 2014 Jan 22.
21 Polyclonal breast cancer metastases arise from collective dissemination of keratin 14-expressing tumor cell clusters.Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):E854-63. doi: 10.1073/pnas.1508541113. Epub 2016 Feb 1.
22 Regulation of DNA Damage Signaling and Cell Death Responses by Epstein-Barr Virus Latent Membrane Protein 1 (LMP1) and LMP2A in Nasopharyngeal Carcinoma Cells.J Virol. 2015 Aug;89(15):7612-24. doi: 10.1128/JVI.00958-15. Epub 2015 May 13.
23 Novel keratin 14 gene mutations in patients from Hungary with epidermolysis bullosa simplex.Exp Dermatol. 2004 Mar;13(3):185-91. doi: 10.1111/j.0906-6705.2004.0120.x.
24 FOXA1 and CK14 as markers of luminal and basal subtypes in histologic variants of bladder cancer and their associated conventional urothelial carcinoma.Virchows Arch. 2017 Sep;471(3):337-345. doi: 10.1007/s00428-017-2190-3. Epub 2017 Jul 18.
25 Epidermolysis bullosa simplex with mottled pigmentation resulting from a recurrent mutation in KRT14. J Invest Dermatol. 2006 Jul;126(7):1654-7. doi: 10.1038/sj.jid.5700296. Epub 2006 Apr 6.
26 The diagnostic value of cytokeratin 5/6, 14, 17, and 18 expression in human non-small cell lung cancer.Oncology. 2011;80(5-6):333-40. doi: 10.1159/000329098. Epub 2011 Jul 26.
27 Indole-3-carbinol prevents cervical cancer in human papilloma virus type 16 (HPV16) transgenic mice.Cancer Res. 1999 Aug 15;59(16):3991-7.
28 Epithelial oestrogen receptor is dispensable for the development of oestrogen-induced cervical neoplastic diseases.J Pathol. 2018 Jun;245(2):147-152. doi: 10.1002/path.5069. Epub 2018 Apr 3.
29 Biallelic KRT5 mutations in autosomal recessive epidermolysis bullosa simplex, including a complete human keratin 5 "knock-out".Matrix Biol. 2019 Oct;83:48-59. doi: 10.1016/j.matbio.2019.07.002. Epub 2019 Jul 11.
30 Disease-linked connexin26 S17F promotes volar skin abnormalities and mild wound healing defects in mice.Cell Death Dis. 2017 Jun 1;8(6):e2845. doi: 10.1038/cddis.2017.234.
31 A novel de novo mutation p.Ala428Asp in KRT5 gene as a cause of localized epidermolysis bullosa simplex.Exp Dermatol. 2019 Oct;28(10):1131-1134. doi: 10.1111/exd.13788. Epub 2019 May 20.
32 Retinoic acid and its 4-oxo metabolites are functionally active in human skin cells in vitro. J Invest Dermatol. 2005 Jul;125(1):143-53.
33 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
34 Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
35 Impact of extracellular folate levels on global gene expression. Mol Pharmacol. 2001 Dec;60(6):1288-95. doi: 10.1124/mol.60.6.1288.
36 Activation of PPAR and inhibition of cell proliferation reduces key proteins associated with the basal subtype of bladder cancer in As3+-transformed UROtsa cells. PLoS One. 2020 Aug 21;15(8):e0237976. doi: 10.1371/journal.pone.0237976. eCollection 2020.
37 Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
38 Methamphetamine alters the normal progression by inducing cell cycle arrest in astrocytes. PLoS One. 2014 Oct 7;9(10):e109603.
39 Oral lichenoid eruption secondary to imatinib (Glivec). J Dermatolog Treat. 2004 Jul;15(4):253-5. doi: 10.1080/09546630410015556.
40 Retinoic acid receptor- and retinoid X receptor-selective retinoids activate signaling pathways that converge on AP-1 and inhibit squamous differentiation in human bronchial epithelial cells. Cell Growth Differ. 1996 Aug;7(8):997-1004.
41 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.
42 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
43 Selective inhibition of BET bromodomains. Nature. 2010 Dec 23;468(7327):1067-73.
44 Low dose of bisphenol a modulates ovarian cancer gene expression profile and promotes epithelial to mesenchymal transition via canonical Wnt pathway. Toxicol Sci. 2018 Aug 1;164(2):527-538.
45 Molecular targets of chloropicrin in human airway epithelial cells. Toxicol In Vitro. 2017 Aug;42:247-254.