Details of Drug Off-Target (DOT)

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

• DOT Name: Keratin, type I cytoskeletal 13 (KRT13)
• Synonyms: Cytokeratin-13; CK-13; Keratin-13; K13
• Gene Name: KRT13
• Related Disease:
  Adrenocortical carcinoma, hereditary
  Esophageal adenocarcinoma
  Anal intraepithelial neoplasia
  Cervical cancer
  Cervical carcinoma
  Corneal neovascularization
  Cystic fibrosis
  Epithelial ovarian cancer
  Esophageal squamous cell carcinoma
  Head-neck squamous cell carcinoma
  Malaria
  Metastatic malignant neoplasm
  Neoplasm
  Oral cancer
  Osteoarthritis
  Periodontitis
  Prostate neoplasm
  Rheumatoid arthritis
  Squamous cell carcinoma
  White sponge nevus 2
  Adenocarcinoma
  Breast cancer
  Breast carcinoma
  Metastatic prostate carcinoma
  Plasmodium falciparum malaria
  Prostate cancer
  Prostate carcinoma
  Hereditary mucosal leukokeratosis
  Early-onset parkinsonism-intellectual disability syndrome
  Leukoplakia
• UniProt ID: K1C13_HUMAN
• Pfam ID: PF00038
• Sequence:
  MSLRLQSSSASYGGGFGGGSCQLGGGRGVSTCSTRFVSGGSAGGYGGGVSCGFGGGAGSG
  FGGGYGGGLGGGYGGGLGGGFGGGFAGGFVDFGACDGGLLTGNEKITMQNLNDRLASYLE
  KVRALEEANADLEVKIRDWHLKQSPASPERDYSPYYKTIEELRDKILTATIENNRVILEI
  DNARLAADDFRLKYENELALRQSVEADINGLRRVLDELTLSKTDLEMQIESLNEELAYMK
  KNHEEEMKEFSNQVVGQVNVEMDATPGIDLTRVLAEMREQYEAMAERNRRDAEEWFHTKS
  AELNKEVSTNTAMIQTSKTEITELRRTLQGLEIELQSQLSMKAGLENTVAETECRYALQL
  QQIQGLISSIEAQLSELRSEMECQNQEYKMLLDIKTRLEQEIATYRSLLEGQDAKMIGFP
  SSAGSVSPRSTSVTTTSSASVTTTSNASGRRTSDVRRP
• Function: Type 1 keratin (Probable). Maintains postnatal tongue mucosal cell homeostasis and tissue organization in response to mechanical stress, potentially via regulation of the G1/S phase cyclins CCNE1 and CCNE2.
• Tissue Specificity: Expressed in some epidermal sweat gland ducts (at protein level) and in exocervix, esophagus and placenta.
• 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

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adrenocortical carcinoma, hereditary	DIS4PDHI	Definitive	Biomarker	[1]
Esophageal adenocarcinoma	DISODWFP	Definitive	Biomarker	[1]
Anal intraepithelial neoplasia	DISJ0JW3	Strong	Altered Expression	[2]
Cervical cancer	DISFSHPF	Strong	Biomarker	[3]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[3]
Corneal neovascularization	DISKOGZP	Strong	Altered Expression	[4]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[5]
Epithelial ovarian cancer	DIS56MH2	Strong	Genetic Variation	[6]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[7]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[8]
Malaria	DISQ9Y50	Strong	Genetic Variation	[9]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[10]
Neoplasm	DISZKGEW	Strong	Biomarker	[11]
Oral cancer	DISLD42D	Strong	Altered Expression	[12]
Osteoarthritis	DIS05URM	Strong	Biomarker	[13]
Periodontitis	DISI9JOI	Strong	Biomarker	[13]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[14]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[13]
Squamous cell carcinoma	DISQVIFL	Strong	Genetic Variation	[15]
White sponge nevus 2	DISZ15N5	Strong	Autosomal dominant	[16]
Adenocarcinoma	DIS3IHTY	moderate	Biomarker	[17]
Breast cancer	DIS7DPX1	moderate	Altered Expression	[10]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[10]
Metastatic prostate carcinoma	DISVBEZ9	moderate	Altered Expression	[10]
Plasmodium falciparum malaria	DIS3Q9KF	moderate	Genetic Variation	[18]
Prostate cancer	DISF190Y	moderate	Altered Expression	[10]
Prostate carcinoma	DISMJPLE	moderate	Altered Expression	[10]
Hereditary mucosal leukokeratosis	DISWAC34	Supportive	Autosomal dominant	[19]
Early-onset parkinsonism-intellectual disability syndrome	DIS206QS	Limited	Genetic Variation	[20]
Leukoplakia	DIST3QD3	Limited	Altered Expression	[21]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Keratin, type I cytoskeletal 13 (KRT13) decreases the response to substance of Paclitaxel.	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Keratin, type I cytoskeletal 13 (KRT13).	[22]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Keratin, type I cytoskeletal 13 (KRT13).	[23]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Keratin, type I cytoskeletal 13 (KRT13).	[24]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Keratin, type I cytoskeletal 13 (KRT13).	[25]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Keratin, type I cytoskeletal 13 (KRT13).	[26]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Keratin, type I cytoskeletal 13 (KRT13).	[27]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Keratin, type I cytoskeletal 13 (KRT13).	[28]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Keratin, type I cytoskeletal 13 (KRT13).	[29]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Keratin, type I cytoskeletal 13 (KRT13).	[31]
PD-153035	DM7KJTI	Discontinued in Phase 1	PD-153035 decreases the expression of Keratin, type I cytoskeletal 13 (KRT13).	[26]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Keratin, type I cytoskeletal 13 (KRT13).	[32]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Keratin, type I cytoskeletal 13 (KRT13).	[33]
TTNPB	DMSABD0	Investigative	TTNPB decreases the expression of Keratin, type I cytoskeletal 13 (KRT13).	[34]

1 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 I cytoskeletal 13 (KRT13).	[30]

References

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• [14] Keratin 13 Is Enriched in Prostate Tubule-Initiating Cells and May Identify Primary Prostate Tumors that Metastasize to the Bone.PLoS One. 2016 Oct 6;11(10):e0163232. doi: 10.1371/journal.pone.0163232. eCollection 2016.
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• [16] Identification of two novel mutations in keratin 13 as the cause of white sponge naevus. Oral Dis. 1999 Oct;5(4):321-4. doi: 10.1111/j.1601-0825.1999.tb00097.x.
• [17] In situ adenocarcinoma and squamous carcinoma of uterine cervix. Pathological and immunohistochemical analysis with cytokeratin 13.Eur J Obstet Gynecol Reprod Biol. 2007 Oct;134(2):249-53. doi: 10.1016/j.ejogrb.2006.07.047. Epub 2006 Sep 1.
• [18] Genetic association between the Pfk13 gene mutation and artemisinin resistance phenotype in Plasmodium falciparum isolates from Yunnan Province, China.Malar J. 2018 Dec 18;17(1):478. doi: 10.1186/s12936-018-2619-4.
• [19] Keratin 13 point mutation underlies the hereditary mucosal epithelial disorder white sponge nevus. Nat Genet. 1995 Dec;11(4):453-5. doi: 10.1038/ng1295-453.
• [20] Clinical features and molecular genetic analysis in a Turkish family with oral white sponge nevus.Med Oral Patol Oral Cir Bucal. 2018 Mar 1;23(2):e144-e150. doi: 10.4317/medoral.21437.
• [21] Association of cytokeratin 17 expression with differentiation in oral squamous cell carcinoma.J Cancer Res Clin Oncol. 2012 Aug;138(8):1299-310. doi: 10.1007/s00432-012-1202-6. Epub 2012 Apr 3.
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• [23] Extremely low copper concentrations affect gene expression profiles of human prostate epithelial cell lines. Chem Biol Interact. 2010 Oct 6;188(1):214-9.
• [24] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [25] Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
• [26] 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.
• [27] 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.
• [28] Simvastatin inactivates beta1-integrin and extracellular signal-related kinase signaling and inhibits cell proliferation in head and neck squamous cell carcinoma cells. Cancer Sci. 2007 Jun;98(6):890-9.
• [29] Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome. Cancer Res. 2006 Jul 15;66(14):7334-40.
• [30] 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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• [32] Activin/nodal signaling switches the terminal fate of human embryonic stem cell-derived trophoblasts. J Biol Chem. 2015 Apr 3;290(14):8834-48.
• [33] 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.
• [34] 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.
• [35] cDNA microarray analysis of isogenic paclitaxel- and doxorubicin-resistant breast tumor cell lines reveals distinct drug-specific genetic signatures of resistance. Breast Cancer Res Treat. 2006 Mar;96(1):17-39. doi: 10.1007/s10549-005-9026-6. Epub 2005 Dec 2.