Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDGDQ75)

DOT Name Keratin, type I cytoskeletal 19 (KRT19)
Synonyms Cytokeratin-19; CK-19; Keratin-19; K19
Gene Name KRT19
UniProt ID
K1C19_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00038
Sequence
MTSYSYRQSSATSSFGGLGGGSVRFGPGVAFRAPSIHGGSGGRGVSVSSARFVSSSSSGA
YGGGYGGVLTASDGLLAGNEKLTMQNLNDRLASYLDKVRALEAANGELEVKIRDWYQKQG
PGPSRDYSHYYTTIQDLRDKILGATIENSRIVLQIDNARLAADDFRTKFETEQALRMSVE
ADINGLRRVLDELTLARTDLEMQIEGLKEELAYLKKNHEEEISTLRGQVGGQVSVEVDSA
PGTDLAKILSDMRSQYEVMAEQNRKDAEAWFTSRTEELNREVAGHTEQLQMSRSEVTDLR
RTLQGLEIELQSQLSMKAALEDTLAETEARFGAQLAHIQALISGIEAQLGDVRADSERQN
QEYQRLMDIKSRLEQEIATYRSLLEGQEDHYNNLSASKVL
Function Involved in the organization of myofibers. Together with KRT8, helps to link the contractile apparatus to dystrophin at the costameres of striated muscle.
Tissue Specificity
Expressed in a defined zone of basal keratinocytes in the deep outer root sheath of hair follicles. Also observed in sweat gland and mammary gland ductal and secretory cells, bile ducts, gastrointestinal tract, bladder urothelium, oral epithelia, esophagus, ectocervical epithelium (at protein level). Expressed in epidermal basal cells, in nipple epidermis and a defined region of the hair follicle. Also seen in a subset of vascular wall cells in both the veins and artery of human umbilical cord, and in umbilical cord vascular smooth muscle. Observed in muscle fibers accumulating in the costameres of myoplasm at the sarcolemma in structures that contain dystrophin and spectrin.
KEGG Pathway
Estrogen sig.ling pathway (hsa04915 )
Staphylococcus aureus infection (hsa05150 )
Reactome Pathway
Formation of the cornified envelope (R-HSA-6809371 )
Keratinization (R-HSA-6805567 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Topotecan DMP6G8T Approved Keratin, type I cytoskeletal 19 (KRT19) affects the response to substance of Topotecan. [36]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Keratin, type I cytoskeletal 19 (KRT19). [1]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Keratin, type I cytoskeletal 19 (KRT19). [24]
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38 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Keratin, type I cytoskeletal 19 (KRT19). [2]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Keratin, type I cytoskeletal 19 (KRT19). [3]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Keratin, type I cytoskeletal 19 (KRT19). [4]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Keratin, type I cytoskeletal 19 (KRT19). [5]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Keratin, type I cytoskeletal 19 (KRT19). [6]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Keratin, type I cytoskeletal 19 (KRT19). [7]
Quercetin DM3NC4M Approved Quercetin increases the expression of Keratin, type I cytoskeletal 19 (KRT19). [8]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Keratin, type I cytoskeletal 19 (KRT19). [9]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the expression of Keratin, type I cytoskeletal 19 (KRT19). [10]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Keratin, type I cytoskeletal 19 (KRT19). [11]
Triclosan DMZUR4N Approved Triclosan increases the expression of Keratin, type I cytoskeletal 19 (KRT19). [12]
Selenium DM25CGV Approved Selenium increases the expression of Keratin, type I cytoskeletal 19 (KRT19). [13]
Isotretinoin DM4QTBN Approved Isotretinoin increases the expression of Keratin, type I cytoskeletal 19 (KRT19). [3]
Hydroquinone DM6AVR4 Approved Hydroquinone decreases the expression of Keratin, type I cytoskeletal 19 (KRT19). [14]
Cytarabine DMZD5QR Approved Cytarabine decreases the expression of Keratin, type I cytoskeletal 19 (KRT19). [15]
Etoposide DMNH3PG Approved Etoposide increases the expression of Keratin, type I cytoskeletal 19 (KRT19). [16]
Azacitidine DMTA5OE Approved Azacitidine increases the expression of Keratin, type I cytoskeletal 19 (KRT19). [17]
Cidofovir DMA13GD Approved Cidofovir increases the expression of Keratin, type I cytoskeletal 19 (KRT19). [18]
Ifosfamide DMCT3I8 Approved Ifosfamide increases the expression of Keratin, type I cytoskeletal 19 (KRT19). [18]
Alitretinoin DMME8LH Approved Alitretinoin increases the expression of Keratin, type I cytoskeletal 19 (KRT19). [3]
Enzalutamide DMGL19D Approved Enzalutamide affects the expression of Keratin, type I cytoskeletal 19 (KRT19). [19]
Beta-carotene DM0RXBT Approved Beta-carotene increases the expression of Keratin, type I cytoskeletal 19 (KRT19). [20]
Vitamin A DMJ2AH4 Approved Vitamin A increases the expression of Keratin, type I cytoskeletal 19 (KRT19). [20]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Keratin, type I cytoskeletal 19 (KRT19). [21]
Coprexa DMA0WEK Phase 3 Coprexa decreases the expression of Keratin, type I cytoskeletal 19 (KRT19). [22]
Genistein DM0JETC Phase 2/3 Genistein increases the expression of Keratin, type I cytoskeletal 19 (KRT19). [23]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Keratin, type I cytoskeletal 19 (KRT19). [25]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Keratin, type I cytoskeletal 19 (KRT19). [26]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN decreases the expression of Keratin, type I cytoskeletal 19 (KRT19). [27]
SB-431542 DM0YOXQ Preclinical SB-431542 increases the expression of Keratin, type I cytoskeletal 19 (KRT19). [28]
EMODIN DMAEDQG Terminated EMODIN decreases the expression of Keratin, type I cytoskeletal 19 (KRT19). [29]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Keratin, type I cytoskeletal 19 (KRT19). [30]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Keratin, type I cytoskeletal 19 (KRT19). [31]
chloropicrin DMSGBQA Investigative chloropicrin decreases the expression of Keratin, type I cytoskeletal 19 (KRT19). [32]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde increases the expression of Keratin, type I cytoskeletal 19 (KRT19). [33]
Lithium chloride DMHYLQ2 Investigative Lithium chloride increases the expression of Keratin, type I cytoskeletal 19 (KRT19). [34]
all-trans-4-oxo-retinoic acid DMM2R1N Investigative all-trans-4-oxo-retinoic acid increases the expression of Keratin, type I cytoskeletal 19 (KRT19). [3]
NADA DM3ORGM Investigative NADA increases the expression of Keratin, type I cytoskeletal 19 (KRT19). [35]
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⏷ Show the Full List of 38 Drug(s)

References

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12 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
13 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
14 Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
15 Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
16 Cell death mechanisms of the anti-cancer drug etoposide on human cardiomyocytes isolated from pluripotent stem cells. Arch Toxicol. 2018 Apr;92(4):1507-1524.
17 The effect of DNA methylation inhibitor 5-Aza-2'-deoxycytidine on human endometrial stromal cells. Hum Reprod. 2010 Nov;25(11):2859-69.
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19 NOTCH signaling is activated in and contributes to resistance in enzalutamide-resistant prostate cancer cells. J Biol Chem. 2019 May 24;294(21):8543-8554. doi: 10.1074/jbc.RA118.006983. Epub 2019 Apr 2.
20 Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells. Arch Biochem Biophys. 2006 Nov 1;455(1):48-60.
21 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.
22 Copper deprivation enhances the chemosensitivity of pancreatic cancer to rapamycin by mTORC1/2 inhibition. Chem Biol Interact. 2023 Sep 1;382:110546. doi: 10.1016/j.cbi.2023.110546. Epub 2023 Jun 7.
23 Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
24 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.
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27 Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
28 Activin/nodal signaling switches the terminal fate of human embryonic stem cell-derived trophoblasts. J Biol Chem. 2015 Apr 3;290(14):8834-48.
29 Gene expression alteration during redox-dependent enhancement of arsenic cytotoxicity by emodin in HeLa cells. Cell Res. 2005 Jul;15(7):511-22.
30 Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.
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35 N-arachidonoyl dopamine inhibits epithelial-mesenchymal transition of breast cancer cells through ERK signaling and decreasing the cellular cholesterol. J Biochem Mol Toxicol. 2021 Apr;35(4):e22693. doi: 10.1002/jbt.22693. Epub 2021 Jan 4.
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