Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSVRD3Q)

• DOT Name: Keratin, type I cytoskeletal 10 (KRT10)
• Synonyms: Cytokeratin-10; CK-10; Keratin-10; K10
• Gene Name: KRT10
• Related Disease:
  Carcinoma of esophagus
  Epithelial ovarian cancer
  Esophageal cancer
  Neoplasm of esophagus
  Ovarian cancer
  Ovarian neoplasm
  Parkinson disease
  Annular epidermolytic ichthyosis
  Atopic dermatitis
  Carcinoma of liver and intrahepatic biliary tract
  Congenital reticular ichthyosiform erythroderma
  Dermatitis
  Epidermolytic ichthyosis
  Epilepsy
  Gastroenteritis
  Hepatocellular carcinoma
  Ichthyosis vulgaris
  Ichthyosis, annular epidermolytic 1
  Influenza
  Keratinopathic ichthyosis
  Leber hereditary optic neuropathy
  Liver cancer
  Lyme disease
  Neoplasm
  Pachyonychia congenita
  Psoriasis
  Skin disease
  Teratoma
  Vascular purpura
  Vulvar intraepithelial neoplasia
  Bloom syndrome
  Skin cancer
  Skin neoplasm
  Squamous cell carcinoma
  Autosomal recessive epidermolytic ichthyosis
  Pancreatic ductal carcinoma
  Patent ductus arteriosus
  Autoimmune disease
  Contact dermatitis
  Epidermolysis bullosa simplex
  Exfoliative dermatitis
  Non-syndromic ichthyosis
  Oral mucosa leukoplakia
• UniProt ID: K1C10_HUMAN
• PDB ID: 3ASW; 4F1Z; 4ZRY; 6E2J; 6EC0; 6UUI
• Pfam ID: PF00038
• Sequence:
  MSVRYSSSKHYSSSRSGGGGGGGGCGGGGGVSSLRISSSKGSLGGGFSSGGFSGGSFSRG
  SSGGGCFGGSSGGYGGLGGFGGGSFRGSYGSSSFGGSYGGIFGGGSFGGGSFGGGSFGGG
  GFGGGGFGGGFGGGFGGDGGLLSGNEKVTMQNLNDRLASYLDKVRALEESNYELEGKIKE
  WYEKHGNSHQGEPRDYSKYYKTIDDLKNQILNLTTDNANILLQIDNARLAADDFRLKYEN
  EVALRQSVEADINGLRRVLDELTLTKADLEMQIESLTEELAYLKKNHEEEMKDLRNVSTG
  DVNVEMNAAPGVDLTQLLNNMRSQYEQLAEQNRKDAEAWFNEKSKELTTEIDNNIEQISS
  YKSEITELRRNVQALEIELQSQLALKQSLEASLAETEGRYCVQLSQIQAQISALEEQLQQ
  IRAETECQNTEYQQLLDIKIRLENEIQTYRSLLEGEGSSGGGGRGGGSFGGGYGGGSSGG
  GSSGGGHGGGHGGSSGGGYGGGSSGGGSSGGGYGGGSSSGGHGGSSSGGYGGGSSGGGGG
  GYGGGSSGGGSSSGGGYGGGSSSGGHKSSSSGSVGESSSKGPRY
• Function: Plays a role in the establishment of the epidermal barrier on plantar skin. Involved in the maintenance of cell layer development and keratin filament bundles in suprabasal cells of the epithelium; (Microbial infection) Acts as a mediator of S.aureus adherence to desquamated nasal epithelial cells via clfB, and hence may play a role in nasal colonization; (Microbial infection) Binds S.pneumoniae PsrP, mediating adherence of the bacteria to lung cell lines. Reduction of levels of KRT10 keratin decrease adherence, overexpression increases adherence. Neither protein has to be glycosylated for the interaction to occur.
• Tissue Specificity: Seen in all suprabasal cell layers including stratum corneum. Expressed on the surface of lung cell lines . Localized on the surface of desquamated nasal epithelial cells (at protein level) .
• 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

43 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma of esophagus	DISS6G4D	Definitive	Biomarker	[1]
Epithelial ovarian cancer	DIS56MH2	Definitive	Altered Expression	[2]
Esophageal cancer	DISGB2VN	Definitive	Biomarker	[1]
Neoplasm of esophagus	DISOLKAQ	Definitive	Biomarker	[1]
Ovarian cancer	DISZJHAP	Definitive	Altered Expression	[2]
Ovarian neoplasm	DISEAFTY	Definitive	Altered Expression	[2]
Parkinson disease	DISQVHKL	Definitive	Biomarker	[3]
Annular epidermolytic ichthyosis	DIS61JO0	Strong	Autosomal dominant	[4]
Atopic dermatitis	DISTCP41	Strong	Altered Expression	[5]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[6]
Congenital reticular ichthyosiform erythroderma	DISYAB1Q	Strong	Autosomal dominant	[4]
Dermatitis	DISY5SZC	Strong	Altered Expression	[7]
Epidermolytic ichthyosis	DISJPEP3	Strong	Autosomal dominant	[4]
Epilepsy	DISBB28L	Strong	Biomarker	[8]
Gastroenteritis	DISXQCG5	Strong	Genetic Variation	[8]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[6]
Ichthyosis vulgaris	DISTRF9L	Strong	Biomarker	[9]
Ichthyosis, annular epidermolytic 1	DIS5TSEI	Strong	Autosomal dominant	[10]
Influenza	DIS3PNU3	Strong	Biomarker	[11]
Keratinopathic ichthyosis	DIS5N46O	Strong	Genetic Variation	[12]
Leber hereditary optic neuropathy	DIS7Y2EE	Strong	Genetic Variation	[13]
Liver cancer	DISDE4BI	Strong	Biomarker	[6]
Lyme disease	DISO70G5	Strong	Biomarker	[14]
Neoplasm	DISZKGEW	Strong	Biomarker	[15]
Pachyonychia congenita	DISW8VPN	Strong	Biomarker	[16]
Psoriasis	DIS59VMN	Strong	Biomarker	[17]
Skin disease	DISDW8R6	Strong	Genetic Variation	[18]
Teratoma	DIS6ICY4	Strong	Altered Expression	[19]
Vascular purpura	DIS6ZZMF	Strong	Biomarker	[20]
Vulvar intraepithelial neoplasia	DISA474V	Strong	Altered Expression	[21]
Bloom syndrome	DISKXQ7J	moderate	Biomarker	[22]
Skin cancer	DISTM18U	moderate	Biomarker	[23]
Skin neoplasm	DIS16DDV	moderate	Biomarker	[23]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[24]
Autosomal recessive epidermolytic ichthyosis	DISEPMLG	Supportive	Autosomal recessive	[25]
Pancreatic ductal carcinoma	DIS26F9Q	Disputed	Biomarker	[26]
Patent ductus arteriosus	DIS9P8YS	Disputed	Biomarker	[26]
Autoimmune disease	DISORMTM	Limited	Biomarker	[27]
Contact dermatitis	DISQ3AU0	Limited	Biomarker	[28]
Epidermolysis bullosa simplex	DIS2CZ6X	Limited	Genetic Variation	[29]
Exfoliative dermatitis	DISQEWIW	Limited	Biomarker	[30]
Non-syndromic ichthyosis	DISZ9QBQ	Limited	Genetic Variation	[13]
Oral mucosa leukoplakia	DISJTL5X	Limited	Biomarker	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Keratin, type I cytoskeletal 10 (KRT10).	[32]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Keratin, type I cytoskeletal 10 (KRT10).	[33]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Keratin, type I cytoskeletal 10 (KRT10).	[34]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Keratin, type I cytoskeletal 10 (KRT10).	[35]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Keratin, type I cytoskeletal 10 (KRT10).	[36]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Keratin, type I cytoskeletal 10 (KRT10).	[37]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Keratin, type I cytoskeletal 10 (KRT10).	[38]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Keratin, type I cytoskeletal 10 (KRT10).	[39]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Keratin, type I cytoskeletal 10 (KRT10).	[40]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Keratin, type I cytoskeletal 10 (KRT10).	[41]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Keratin, type I cytoskeletal 10 (KRT10).	[41]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Keratin, type I cytoskeletal 10 (KRT10).	[42]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Keratin, type I cytoskeletal 10 (KRT10).	[34]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Keratin, type I cytoskeletal 10 (KRT10).	[34]
Calcipotriol	DM03CP7	Approved	Calcipotriol decreases the expression of Keratin, type I cytoskeletal 10 (KRT10).	[43]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Keratin, type I cytoskeletal 10 (KRT10).	[45]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Keratin, type I cytoskeletal 10 (KRT10).	[46]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Keratin, type I cytoskeletal 10 (KRT10).	[47]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Keratin, type I cytoskeletal 10 (KRT10).	[48]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone decreases the expression of Keratin, type I cytoskeletal 10 (KRT10).	[49]
U0126	DM31OGF	Investigative	U0126 increases the expression of Keratin, type I cytoskeletal 10 (KRT10).	[50]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid decreases the expression of Keratin, type I cytoskeletal 10 (KRT10).	[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 10 (KRT10).	[44]

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