Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZJUE4P)

• DOT Name: Transcription factor MafK (MAFK)
• Synonyms: Erythroid transcription factor NF-E2 p18 subunit
• Gene Name: MAFK
• Related Disease:
  Angelman syndrome
  Meningioma
  Acute erythroid leukemia
  Acute leukaemia
  Acute lymphocytic leukaemia
  Adult lymphoma
  Advanced cancer
  Bone osteosarcoma
  Breast neoplasm
  Childhood acute lymphoblastic leukemia
  Chromosomal disorder
  Depression
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Hyperparathyroidism
  Lassa fever
  Lung cancer
  Lymphoma
  Lymphoma, non-Hodgkin, familial
  Malignant soft tissue neoplasm
  Melanoma
  Myelodysplastic syndrome
  Non-hodgkin lymphoma
  Non-small-cell lung cancer
  Osteosarcoma
  Pediatric lymphoma
  Psoriatic arthritis
  Retinoblastoma
  Sarcoma
  Status epilepticus seizure
  Thyroid gland undifferentiated (anaplastic) carcinoma
  Triple negative breast cancer
  Tuberculosis
  Viral hemorrhagic fever
  Arterial tortuosity syndrome
  Breast cancer
  Breast carcinoma
  Neuroendocrine neoplasm
  Familial medullary thyroid carcinoma
  Neuroblastoma
  Non-insulin dependent diabetes
  Plasma cell myeloma
• UniProt ID: MAFK_HUMAN
• Pfam ID: PF03131
• Sequence:
  MTTNPKPNKALKVKKEAGENAPVLSDDELVSMSVRELNQHLRGLTKEEVTRLKQRRRTLK
  NRGYAASCRIKRVTQKEELERQRVELQQEVEKLARENSSMRLELDALRSKYEALQTFART
  VARGPVAPSKVATTSVITIVKSTELSSTSVPFSAAS
• Function: Since they lack a putative transactivation domain, the small Mafs behave as transcriptional repressors when they dimerize among themselves. However, they act as transcriptional activators by dimerizing with other (usually larger) basic-zipper proteins, such as NFE2, NFE2L1/NRF1, NFE2L2/NRF2 and NFE2L3/NRF3, and recruiting them to specific DNA-binding sites. Small Maf proteins heterodimerize with Fos and may act as competitive repressors of the NF-E2 transcription factor.
• Reactome Pathway:
  Heme signaling (R-HSA-9707616)
  Regulation of BACH1 activity (R-HSA-9708530)
  Nuclear events mediated by NFE2L2 (R-HSA-9759194)
  NFE2L2 regulating inflammation associated genes (R-HSA-9818026)
  NFE2L2 regulating anti-oxidant/detoxification enzymes (R-HSA-9818027)
  NFE2L2 regulating tumorigenic genes (R-HSA-9818030)
  NFE2L2 regulating MDR associated enzymes (R-HSA-9818032)
  NFE2L2 regulating ER-stress associated genes (R-HSA-9818035)
  Regulation of NFE2L2 gene expression (R-HSA-9818749)
  Factors involved in megakaryocyte development and platelet production (R-HSA-983231)
  Regulation of HMOX1 expression and activity (R-HSA-9707587)

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Angelman syndrome	DIS4QVXO	Definitive	Biomarker	[1]
Meningioma	DISPT4TG	Definitive	Genetic Variation	[2]
Acute erythroid leukemia	DISZFC1O	Strong	Altered Expression	[3]
Acute leukaemia	DISDQFDI	Strong	Altered Expression	[4]
Acute lymphocytic leukaemia	DISPX75S	Strong	Genetic Variation	[4]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[7]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[8]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Genetic Variation	[4]
Chromosomal disorder	DISM5BB5	Strong	Biomarker	[9]
Depression	DIS3XJ69	Strong	Genetic Variation	[10]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[11]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[11]
Hyperparathyroidism	DIS4FVAT	Strong	Altered Expression	[12]
Lassa fever	DISKFYGZ	Strong	Biomarker	[13]
Lung cancer	DISCM4YA	Strong	Biomarker	[14]
Lymphoma	DISN6V4S	Strong	Biomarker	[5]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Strong	Biomarker	[15]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Genetic Variation	[7]
Melanoma	DIS1RRCY	Strong	Biomarker	[16]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[17]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Biomarker	[15]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[18]
Osteosarcoma	DISLQ7E2	Strong	Genetic Variation	[7]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[5]
Psoriatic arthritis	DISLWTG2	Strong	Biomarker	[19]
Retinoblastoma	DISVPNPB	Strong	Biomarker	[20]
Sarcoma	DISZDG3U	Strong	Genetic Variation	[7]
Status epilepticus seizure	DISY3BIC	Strong	Genetic Variation	[21]
Thyroid gland undifferentiated (anaplastic) carcinoma	DISYBB1W	Strong	Biomarker	[22]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[23]
Tuberculosis	DIS2YIMD	Strong	Genetic Variation	[24]
Viral hemorrhagic fever	DISQEBTU	Strong	Genetic Variation	[25]
Arterial tortuosity syndrome	DISWG36B	moderate	Biomarker	[26]
Breast cancer	DIS7DPX1	moderate	Biomarker	[27]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[27]
Neuroendocrine neoplasm	DISNPLOO	moderate	Altered Expression	[28]
Familial medullary thyroid carcinoma	DIS01PWX	Limited	Biomarker	[29]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[30]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[31]
Plasma cell myeloma	DIS0DFZ0	Limited	Biomarker	[32]

5 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 Transcription factor MafK (MAFK).	[33]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide affects the methylation of Transcription factor MafK (MAFK).	[38]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Transcription factor MafK (MAFK).	[44]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Transcription factor MafK (MAFK).	[45]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Transcription factor MafK (MAFK).	[45]

12 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 Transcription factor MafK (MAFK).	[34]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transcription factor MafK (MAFK).	[35]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Transcription factor MafK (MAFK).	[36]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Transcription factor MafK (MAFK).	[37]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Transcription factor MafK (MAFK).	[39]
Nefazodone	DM4ZS8M	Approved	Nefazodone increases the expression of Transcription factor MafK (MAFK).	[40]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Transcription factor MafK (MAFK).	[41]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Transcription factor MafK (MAFK).	[42]
Disulfiram	DMCL2OK	Phase 2 Trial	Disulfiram increases the expression of Transcription factor MafK (MAFK).	[43]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of Transcription factor MafK (MAFK).	[43]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Transcription factor MafK (MAFK).	[46]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Transcription factor MafK (MAFK).	[47]

References

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