Details of Drug Off-Target (DOT)

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
• 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]

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]

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]

References

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