Details of Drug Off-Target (DOT)

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

• DOT Name: Hepatocyte nuclear factor 3-beta (FOXA2)
• Synonyms: HNF-3-beta; HNF-3B; Forkhead box protein A2; Transcription factor 3B; TCF-3B
• Gene Name: FOXA2
• Related Disease:
  Adenocarcinoma
  Prostate adenocarcinoma
  Alzheimer disease
  Autoimmune disease
  Bladder cancer
  Cervical cancer
  Cervical carcinoma
  Colon cancer
  Endometrial carcinoma
  Familial hyperinsulinism
  Glioma
  Hepatocellular carcinoma
  Hyperinsulinemia
  Hypopituitarism
  Liver cancer
  Lung adenocarcinoma
  Matthew-Wood syndrome
  Metastatic malignant neoplasm
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Pancreatic cancer
  Parkinson disease
  Prostate neoplasm
  Pulmonary disease
  Urinary bladder cancer
  Urinary bladder neoplasm
  Carcinoma
  Colon carcinoma
  Combined pituitary hormone deficiencies, genetic form
  Gastric cancer
  Malignant uterine tumour
  Obesity
  Prostate cancer
  Prostate carcinoma
  Stomach cancer
  Asthma
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Endometrial cancer
  Hepatitis C virus infection
  Hyperinsulinemic hypoglycemia
  Lung cancer
  Lung carcinoma
  Melanoma
  Non-insulin dependent diabetes
  Panhypopituitarism
• UniProt ID: FOXA2_HUMAN
• PDB ID: 5X07; 7YZE; 7YZF
• Pfam ID: PF00250 ; PF08430 ; PF09354
• Sequence:
  MLGAVKMEGHEPSDWSSYYAEPEGYSSVSNMNAGLGMNGMNTYMSMSAAAMGSGSGNMSA
  GSMNMSSYVGAGMSPSLAGMSPGAGAMAGMGGSAGAAGVAGMGPHLSPSLSPLGGQAAGA
  MGGLAPYANMNSMSPMYGQAGLSRARDPKTYRRSYTHAKPPYSYISLITMAIQQSPNKML
  TLSEIYQWIMDLFPFYRQNQQRWQNSIRHSLSFNDCFLKVPRSPDKPGKGSFWTLHPDSG
  NMFENGCYLRRQKRFKCEKQLALKEAAGAAGSGKKAAAGAQASQAQLGEAAGPASETPAG
  TESPHSSASPCQEHKRGGLGELKGTPAAALSPPEPAPSPGQQQQAAAHLLGPPHHPGLPP
  EAHLKPEHHYAFNHPFSINNLMSSEQQHHHSHHHHQPHKMDLKAYEQVMHYPGYGSPMPG
  SLAMGPVTNKTGLDASPLAADTSYYQGVYSRPIMNSS
• Function: Transcription factor that is involved in embryonic development, establishment of tissue-specific gene expression and regulation of gene expression in differentiated tissues. Is thought to act as a 'pioneer' factor opening the compacted chromatin for other proteins through interactions with nucleosomal core histones and thereby replacing linker histones at target enhancer and/or promoter sites. Binds DNA with the consensus sequence 5'-[AC]A[AT]T[AG]TT[GT][AG][CT]T[CT]-3'. In embryonic development is required for notochord formation. Involved in the development of multiple endoderm-derived organ systems such as the liver, pancreas and lungs; FOXA1 and FOXA2 seem to have at least in part redundant roles. Originally described as a transcription activator for a number of liver genes such as AFP, albumin, tyrosine aminotransferase, PEPCK, etc. Interacts with the cis-acting regulatory regions of these genes. Involved in glucose homeostasis; regulates the expression of genes important for glucose sensing in pancreatic beta-cells and glucose homeostasis. Involved in regulation of fat metabolism. Binds to fibrinogen beta promoter and is involved in IL6-induced fibrinogen beta transcriptional activation.
• KEGG Pathway:
  Longevity regulating pathway - multiple species (hsa04213)
  Maturity onset diabetes of the young (hsa04950)
• Reactome Pathway:
  Formation of axial mesoderm (R-HSA-9796292)
  Formation of definitive endoderm (R-HSA-9823730)
  Regulation of gene expression in beta cells (R-HSA-210745)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Definitive	Altered Expression	[1]
Prostate adenocarcinoma	DISBZYU8	Definitive	Altered Expression	[1]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[2]
Autoimmune disease	DISORMTM	Strong	Altered Expression	[3]
Bladder cancer	DISUHNM0	Strong	Biomarker	[4]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[5]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[5]
Colon cancer	DISVC52G	Strong	Altered Expression	[6]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[7]
Familial hyperinsulinism	DISHQKQE	Strong	Biomarker	[8]
Glioma	DIS5RPEH	Strong	Biomarker	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[10]
Hyperinsulinemia	DISIDWT6	Strong	Genetic Variation	[11]
Hypopituitarism	DIS1QT3G	Strong	Genetic Variation	[8]
Liver cancer	DISDE4BI	Strong	Biomarker	[10]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[12]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[13]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[14]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[15]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[16]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[16]
Pancreatic cancer	DISJC981	Strong	Biomarker	[13]
Parkinson disease	DISQVHKL	Strong	Altered Expression	[17]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[18]
Pulmonary disease	DIS6060I	Strong	Biomarker	[19]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[4]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[4]
Carcinoma	DISH9F1N	moderate	Altered Expression	[20]
Colon carcinoma	DISJYKUO	moderate	Altered Expression	[6]
Combined pituitary hormone deficiencies, genetic form	DISW6YL6	Moderate	Autosomal dominant	[21]
Gastric cancer	DISXGOUK	moderate	Biomarker	[22]
Malignant uterine tumour	DIS3QDT8	moderate	Biomarker	[20]
Obesity	DIS47Y1K	moderate	Altered Expression	[23]
Prostate cancer	DISF190Y	moderate	Biomarker	[24]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[24]
Stomach cancer	DISKIJSX	moderate	Biomarker	[22]
Asthma	DISW9QNS	Limited	Altered Expression	[25]
Breast cancer	DIS7DPX1	Limited	Altered Expression	[26]
Breast carcinoma	DIS2UE88	Limited	Altered Expression	[26]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[27]
Endometrial cancer	DISW0LMR	Limited	Biomarker	[7]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[28]
Hyperinsulinemic hypoglycemia	DIS3KP5D	Limited	Biomarker	[29]
Lung cancer	DISCM4YA	Limited	Biomarker	[30]
Lung carcinoma	DISTR26C	Limited	Biomarker	[30]
Melanoma	DIS1RRCY	Limited	Biomarker	[31]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Altered Expression	[32]
Panhypopituitarism	DISAKJ4T	Limited	Biomarker	[33]

3 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 Hepatocyte nuclear factor 3-beta (FOXA2).	[34]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Hepatocyte nuclear factor 3-beta (FOXA2).	[44]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Hepatocyte nuclear factor 3-beta (FOXA2).	[46]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Hepatocyte nuclear factor 3-beta (FOXA2).	[35]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Hepatocyte nuclear factor 3-beta (FOXA2).	[36]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Hepatocyte nuclear factor 3-beta (FOXA2).	[37]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Hepatocyte nuclear factor 3-beta (FOXA2).	[38]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Hepatocyte nuclear factor 3-beta (FOXA2).	[39]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Hepatocyte nuclear factor 3-beta (FOXA2).	[40]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Hepatocyte nuclear factor 3-beta (FOXA2).	[41]
Estriol	DMOEM2I	Approved	Estriol increases the expression of Hepatocyte nuclear factor 3-beta (FOXA2).	[38]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Hepatocyte nuclear factor 3-beta (FOXA2).	[42]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Hepatocyte nuclear factor 3-beta (FOXA2).	[43]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Hepatocyte nuclear factor 3-beta (FOXA2).	[45]
Baicalin	DMY1TLZ	Terminated	Baicalin decreases the expression of Hepatocyte nuclear factor 3-beta (FOXA2).	[47]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Hepatocyte nuclear factor 3-beta (FOXA2).	[48]

References

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