Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIOJWA4)

• DOT Name: Keratin, type II cytoskeletal 1 (KRT1)
• Synonyms: 67 kDa cytokeratin; Cytokeratin-1; CK-1; Hair alpha protein; Keratin-1; K1; Type-II keratin Kb1
• Gene Name: KRT1
• Related Disease:
  Advanced cancer
  Annular epidermolytic ichthyosis
  Autoimmune disease
  Breast cancer
  Breast carcinoma
  Cataract
  Colon cancer
  Colon carcinoma
  Coronary atherosclerosis
  Crohn disease
  Diffuse nonepidermolytic palmoplantar keratoderma
  Diffuse palmoplantar keratoderma
  Epidermolysis bullosa simplex
  Epidermolytic ichthyosis
  Epstein barr virus infection
  Hereditary spherocytosis type 1
  Ichthyosis hystrix of Curth-Macklin
  Ichthyosis, annular epidermolytic 1
  Inflammatory bowel disease
  Intestinal disorder
  Myocardial infarction
  Neoplasm
  Skin neoplasm
  Stomach cancer
  Systemic lupus erythematosus
  Systemic sclerosis
  Ulcerative colitis
  X-linked reticulate pigmentary disorder
  Nasopharyngeal carcinoma
  Skin cancer
  Squamous cell carcinoma
  Congenital reticular ichthyosiform erythroderma
  Striate palmoplantar keratoderma
  Carcinoma of esophagus
  Esophageal cancer
  Neoplasm of esophagus
  Neural tube defect
  Atopic dermatitis
  Darier disease
  Exfoliative dermatitis
  Glioma
  Ichthyosis hystrix
  Mycosis fungoides
  Neuroblastoma
  Palmoplantar keratosis
  Skin disease
  Superficial epidermolytic ichthyosis
• UniProt ID: K2C1_HUMAN
• PDB ID: 4ZRY; 6E2J; 6UUI
• Pfam ID: PF00038 ; PF16208 ; PF16210
• Sequence:
  MSRQFSSRSGYRSGGGFSSGSAGIINYQRRTTSSSTRRSGGGGGRFSSCGGGGGSFGAGG
  GFGSRSLVNLGGSKSISISVARGGGRGSGFGGGYGGGGFGGGGFGGGGFGGGGIGGGGFG
  GFGSGGGGFGGGGFGGGGYGGGYGPVCPPGGIQEVTINQSLLQPLNVEIDPEIQKVKSRE
  REQIKSLNNQFASFIDKVRFLEQQNQVLQTKWELLQQVDTSTRTHNLEPYFESFINNLRR
  RVDQLKSDQSRLDSELKNMQDMVEDYRNKYEDEINKRTNAENEFVTIKKDVDGAYMTKVD
  LQAKLDNLQQEIDFLTALYQAELSQMQTQISETNVILSMDNNRSLDLDSIIAEVKAQYED
  IAQKSKAEAESLYQSKYEELQITAGRHGDSVRNSKIEISELNRVIQRLRSEIDNVKKQIS
  NLQQSISDAEQRGENALKDAKNKLNDLEDALQQAKEDLARLLRDYQELMNTKLALDLEIA
  TYRTLLEGEESRMSGECAPNVSVSVSTSHTTISGGGSRGGGGGGYGSGGSSYGSGGGSYG
  SGGGGGGGRGSYGSGGSSYGSGGGSYGSGGGGGGHGSYGSGSSSGGYRGGSGGGGGGSSG
  GRGSGGGSSGGSIGGRGSSSGGVKSSGGSSSVKFVSTTYSGVTR
• Function: May regulate the activity of kinases such as PKC and SRC via binding to integrin beta-1 (ITB1) and the receptor of activated protein C kinase 1 (RACK1). In complex with C1QBP is a high affinity receptor for kininogen-1/HMWK.
• Tissue Specificity: The source of this protein is neonatal foreskin. The 67-kDa type II keratins are expressed in terminally differentiating epidermis.
• Reactome Pathway:
  Keratinization (R-HSA-6805567)
  Formation of the cornified envelope (R-HSA-6809371)
  Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Annular epidermolytic ichthyosis	DIS61JO0	Strong	Autosomal dominant	[2]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Cataract	DISUD7SL	Strong	Biomarker	[5]
Colon cancer	DISVC52G	Strong	Biomarker	[6]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[6]
Coronary atherosclerosis	DISKNDYU	Strong	Biomarker	[7]
Crohn disease	DIS2C5Q8	Strong	Altered Expression	[8]
Diffuse nonepidermolytic palmoplantar keratoderma	DISKLJS3	Strong	Autosomal dominant	[2]
Diffuse palmoplantar keratoderma	DIS6O9JS	Strong	Genetic Variation	[9]
Epidermolysis bullosa simplex	DIS2CZ6X	Strong	Genetic Variation	[10]
Epidermolytic ichthyosis	DISJPEP3	Strong	Autosomal dominant	[2]
Epstein barr virus infection	DISOO0WT	Strong	Altered Expression	[11]
Hereditary spherocytosis type 1	DIS34V1Z	Strong	Altered Expression	[12]
Ichthyosis hystrix of Curth-Macklin	DISZE1R9	Strong	Autosomal dominant	[2]
Ichthyosis, annular epidermolytic 1	DIS5TSEI	Strong	Autosomal dominant	[13]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[8]
Intestinal disorder	DISGPMUQ	Strong	Altered Expression	[8]
Myocardial infarction	DIS655KI	Strong	Biomarker	[14]
Neoplasm	DISZKGEW	Strong	Biomarker	[15]
Skin neoplasm	DIS16DDV	Strong	Biomarker	[16]
Stomach cancer	DISKIJSX	Strong	Biomarker	[11]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[3]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[3]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[8]
X-linked reticulate pigmentary disorder	DIS0RB5A	Strong	Altered Expression	[17]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Altered Expression	[18]
Skin cancer	DISTM18U	moderate	Biomarker	[19]
Squamous cell carcinoma	DISQVIFL	moderate	Altered Expression	[20]
Congenital reticular ichthyosiform erythroderma	DISYAB1Q	Supportive	Autosomal dominant	[21]
Striate palmoplantar keratoderma	DISLGEYP	Supportive	Autosomal dominant	[22]
Carcinoma of esophagus	DISS6G4D	Disputed	Genetic Variation	[23]
Esophageal cancer	DISGB2VN	Disputed	Genetic Variation	[23]
Neoplasm of esophagus	DISOLKAQ	Disputed	Genetic Variation	[23]
Neural tube defect	DIS5J95E	Disputed	Biomarker	[24]
Atopic dermatitis	DISTCP41	Limited	Altered Expression	[25]
Darier disease	DIS4WI7S	Limited	Altered Expression	[25]
Exfoliative dermatitis	DISQEWIW	Limited	Genetic Variation	[26]
Glioma	DIS5RPEH	Limited	Genetic Variation	[27]
Ichthyosis hystrix	DISD08MT	Limited	Genetic Variation	[28]
Mycosis fungoides	DIS62RB8	Limited	Altered Expression	[25]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[29]
Palmoplantar keratosis	DISYQGFB	Limited	Genetic Variation	[30]
Skin disease	DISDW8R6	Limited	Genetic Variation	[3]
Superficial epidermolytic ichthyosis	DISWX6O4	Limited	Genetic Variation	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Keratin, type II cytoskeletal 1 (KRT1).	[32]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Keratin, type II cytoskeletal 1 (KRT1).	[33]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Keratin, type II cytoskeletal 1 (KRT1).	[34]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Keratin, type II cytoskeletal 1 (KRT1).	[35]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Keratin, type II cytoskeletal 1 (KRT1).	[36]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Keratin, type II cytoskeletal 1 (KRT1).	[37]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Keratin, type II cytoskeletal 1 (KRT1).	[38]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Keratin, type II cytoskeletal 1 (KRT1).	[39]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Keratin, type II cytoskeletal 1 (KRT1).	[33]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Keratin, type II cytoskeletal 1 (KRT1).	[40]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Keratin, type II cytoskeletal 1 (KRT1).	[41]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Keratin, type II cytoskeletal 1 (KRT1).	[33]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Keratin, type II cytoskeletal 1 (KRT1).	[42]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Keratin, type II cytoskeletal 1 (KRT1).	[43]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Keratin, type II cytoskeletal 1 (KRT1).	[44]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Keratin, type II cytoskeletal 1 (KRT1).	[43]
PD-153035	DM7KJTI	Discontinued in Phase 1	PD-153035 decreases the expression of Keratin, type II cytoskeletal 1 (KRT1).	[40]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Keratin, type II cytoskeletal 1 (KRT1).	[45]
SB 203580	DMAET6F	Terminated	SB 203580 decreases the expression of Keratin, type II cytoskeletal 1 (KRT1).	[46]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Keratin, type II cytoskeletal 1 (KRT1).	[47]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone decreases the expression of Keratin, type II cytoskeletal 1 (KRT1).	[48]
U0126	DM31OGF	Investigative	U0126 increases the expression of Keratin, type II cytoskeletal 1 (KRT1).	[49]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid decreases the expression of Keratin, type II cytoskeletal 1 (KRT1).	[33]
PD98059	DMZC90M	Investigative	PD98059 increases the expression of Keratin, type II cytoskeletal 1 (KRT1).	[46]
Tyrphostin Ag-1478	DM87ZIH	Investigative	Tyrphostin Ag-1478 increases the expression of Keratin, type II cytoskeletal 1 (KRT1).	[50]

References

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