Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGA0EQN)

• DOT Name: Keratin, type I cytoskeletal 16 (KRT16)
• Synonyms: Cytokeratin-16; CK-16; Keratin-16; K16
• Gene Name: KRT16
• Related Disease:
  Myocardial infarction
  Neoplasm of esophagus
  Psoriasis
  Adenocarcinoma
  Advanced cancer
  Anal intraepithelial neoplasia
  Atopic dermatitis
  Carcinoma of esophagus
  Diabetic kidney disease
  Diffuse nonepidermolytic palmoplantar keratoderma
  Esophageal cancer
  Focal palmoplantar keratoderma
  Head-neck squamous cell carcinoma
  Her2-receptor negative breast cancer
  High blood pressure
  Hyperinsulinemia
  Insulinoma
  Lung adenocarcinoma
  Matthew-Wood syndrome
  Melanoma
  Non-small-cell lung cancer
  Oral mucosa leukoplakia
  Pachyonychia congenita 1
  Palmoplantar keratoderma, nonepidermolytic, focal 1
  Polycystic ovarian syndrome
  Prostate cancer
  Prostate carcinoma
  Skin disease
  Squamous cell carcinoma
  Type-1/2 diabetes
  Isolated focal non-epidermolytic palmoplantar keratoderma
  Pachyonychia congenita
  Actinic keratosis
  Complex regional pain syndrome
  Cutaneous squamous cell carcinoma
  Darier disease
  Diffuse palmoplantar keratoderma
  Esophageal squamous cell carcinoma
  Non-syndromic ichthyosis
  Rheumatoid arthritis
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: K1C16_HUMAN
• Pfam ID: PF00038
• Sequence:
  MTTCSRQFTSSSSMKGSCGIGGGIGGGSSRISSVLAGGSCRAPSTYGGGLSVSSRFSSGG
  ACGLGGGYGGGFSSSSSFGSGFGGGYGGGLGAGFGGGLGAGFGGGFAGGDGLLVGSEKVT
  MQNLNDRLASYLDKVRALEEANADLEVKIRDWYQRQRPSEIKDYSPYFKTIEDLRNKIIA
  ATIENAQPILQIDNARLAADDFRTKYEHELALRQTVEADVNGLRRVLDELTLARTDLEMQ
  IEGLKEELAYLRKNHEEEMLALRGQTGGDVNVEMDAAPGVDLSRILNEMRDQYEQMAEKN
  RRDAETWFLSKTEELNKEVASNSELVQSSRSEVTELRRVLQGLEIELQSQLSMKASLENS
  LEETKGRYCMQLSQIQGLIGSVEEQLAQLRCEMEQQSQEYQILLDVKTRLEQEIATYRRL
  LEGEDAHLSSQQASGQSYSSREVFTSSSSSSSRQTRPILKEQSSSSFSQGQSS
• Function: Epidermis-specific type I keratin that plays a key role in skin. Acts as a regulator of innate immunity in response to skin barrier breach: required for some inflammatory checkpoint for the skin barrier maintenance.
• Tissue Specificity: Expressed in the corneal epithelium (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

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Myocardial infarction	DIS655KI	Definitive	Genetic Variation	[1]
Neoplasm of esophagus	DISOLKAQ	Definitive	Genetic Variation	[2]
Psoriasis	DIS59VMN	Definitive	Biomarker	[3]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Anal intraepithelial neoplasia	DISJ0JW3	Strong	Genetic Variation	[6]
Atopic dermatitis	DISTCP41	Strong	Genetic Variation	[7]
Carcinoma of esophagus	DISS6G4D	Strong	Genetic Variation	[2]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[8]
Diffuse nonepidermolytic palmoplantar keratoderma	DISKLJS3	Strong	Genetic Variation	[9]
Esophageal cancer	DISGB2VN	Strong	Genetic Variation	[2]
Focal palmoplantar keratoderma	DISGLKBI	Strong	Genetic Variation	[10]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Altered Expression	[11]
Her2-receptor negative breast cancer	DISS605N	Strong	Altered Expression	[12]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[13]
Hyperinsulinemia	DISIDWT6	Strong	Altered Expression	[14]
Insulinoma	DISIU1JS	Strong	Altered Expression	[14]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[15]
Matthew-Wood syndrome	DISA7HR7	Strong	Altered Expression	[16]
Melanoma	DIS1RRCY	Strong	Biomarker	[17]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[4]
Oral mucosa leukoplakia	DISJTL5X	Strong	Biomarker	[18]
Pachyonychia congenita 1	DISO2ZM9	Strong	Autosomal dominant	[19]
Palmoplantar keratoderma, nonepidermolytic, focal 1	DISNOMYP	Strong	Autosomal dominant	[19]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[20]
Prostate cancer	DISF190Y	Strong	Altered Expression	[21]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[21]
Skin disease	DISDW8R6	Strong	Altered Expression	[22]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[23]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[24]
Isolated focal non-epidermolytic palmoplantar keratoderma	DISR6U95	Supportive	Autosomal dominant	[25]
Pachyonychia congenita	DISW8VPN	Supportive	Autosomal dominant	[26]
Actinic keratosis	DISR1RC5	Limited	Altered Expression	[27]
Complex regional pain syndrome	DIS625IE	Limited	Biomarker	[28]
Cutaneous squamous cell carcinoma	DIS3LXUG	Limited	Biomarker	[29]
Darier disease	DIS4WI7S	Limited	Biomarker	[18]
Diffuse palmoplantar keratoderma	DIS6O9JS	Limited	Genetic Variation	[9]
Esophageal squamous cell carcinoma	DIS5N2GV	Limited	Biomarker	[30]
Non-syndromic ichthyosis	DISZ9QBQ	Limited	Altered Expression	[31]
Rheumatoid arthritis	DISTSB4J	Limited	Altered Expression	[32]
Urinary bladder cancer	DISDV4T7	Limited	Biomarker	[33]
Urinary bladder neoplasm	DIS7HACE	Limited	Biomarker	[33]

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 16 (KRT16).	[34]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Keratin, type I cytoskeletal 16 (KRT16).	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Keratin, type I cytoskeletal 16 (KRT16).	[35]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Keratin, type I cytoskeletal 16 (KRT16).	[36]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Keratin, type I cytoskeletal 16 (KRT16).	[37]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Keratin, type I cytoskeletal 16 (KRT16).	[38]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Keratin, type I cytoskeletal 16 (KRT16).	[39]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Keratin, type I cytoskeletal 16 (KRT16).	[40]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Keratin, type I cytoskeletal 16 (KRT16).	[41]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Keratin, type I cytoskeletal 16 (KRT16).	[42]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Keratin, type I cytoskeletal 16 (KRT16).	[43]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Keratin, type I cytoskeletal 16 (KRT16).	[44]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Keratin, type I cytoskeletal 16 (KRT16).	[45]
Tofacitinib	DMBS370	Approved	Tofacitinib decreases the expression of Keratin, type I cytoskeletal 16 (KRT16).	[46]
Calcipotriol	DM03CP7	Approved	Calcipotriol decreases the expression of Keratin, type I cytoskeletal 16 (KRT16).	[47]
Apilimod dimesylate	DM4N2O0	Phase 2	Apilimod dimesylate decreases the expression of Keratin, type I cytoskeletal 16 (KRT16).	[49]
PD-153035	DM7KJTI	Discontinued in Phase 1	PD-153035 decreases the expression of Keratin, type I cytoskeletal 16 (KRT16).	[45]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Keratin, type I cytoskeletal 16 (KRT16).	[51]

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 16 (KRT16).	[48]

References

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