Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1GR3IZ)

• DOT Name: Transcription factor Maf (MAF)
• Synonyms: Proto-oncogene c-Maf; V-maf musculoaponeurotic fibrosarcoma oncogene homolog
• Gene Name: MAF
• Related Disease:
  Ayme-Gripp syndrome
  Cataract 21 multiple types
  Malaria
  T-cell lymphoma
  Advanced cancer
  Aicardi-Goutieres syndrome
  Cataract
  Cholestasis
  Coloboma
  Colorectal carcinoma
  Colorectal neoplasm
  Intrahepatic cholestasis
  Neoplasm
  Nephrotic syndrome
  Obesity
  Ulcerative colitis
  Laryngeal squamous cell carcinoma
  Neurofibromatosis type 1
  Cataract - microcornea syndrome
  Cerulean cataract
  Fine-Lubinsky syndrome
  Pulverulent cataract
  Plasma cell myeloma
• UniProt ID: MAF_HUMAN
• Pfam ID: PF03131 ; PF08383
• Sequence:
  MASELAMSNSDLPTSPLAMEYVNDFDLMKFEVKKEPVETDRIISQCGRLIAGGSLSSTPM
  STPCSSVPPSPSFSAPSPGSGSEQKAHLEDYYWMTGYPQQLNPEALGFSPEDAVEALISN
  SHQLQGGFDGYARGAQQLAAAAGAGAGASLGGSGEEMGPAAAVVSAVIAAAAAQSGAGPH
  YHHHHHHAAGHHHHPTAGAPGAAGSAAASAGGAGGAGGGGPASAGGGGGGGGGGGGGGAA
  GAGGALHPHHAAGGLHFDDRFSDEQLVTMSVRELNRQLRGVSKEEVIRLKQKRRTLKNRG
  YAQSCRFKRVQQRHVLESEKNQLLQQVDHLKQEISRLVRERDAYKEKYEKLVSSGFRENG
  SSSDNPSSPEFFM
• Function: Acts as a transcriptional activator or repressor. Involved in embryonic lens fiber cell development. Recruits the transcriptional coactivators CREBBP and/or EP300 to crystallin promoters leading to up-regulation of crystallin gene during lens fiber cell differentiation. Activates the expression of IL4 in T helper 2 (Th2) cells. Increases T-cell susceptibility to apoptosis by interacting with MYB and decreasing BCL2 expression. Together with PAX6, transactivates strongly the glucagon gene promoter through the G1 element. Activates transcription of the CD13 proximal promoter in endothelial cells. Represses transcription of the CD13 promoter in early stages of myelopoiesis by affecting the ETS1 and MYB cooperative interaction. Involved in the initial chondrocyte terminal differentiation and the disappearance of hypertrophic chondrocytes during endochondral bone development. Binds to the sequence 5'-[GT]G[GC]N[GT]NCTCAGNN-3' in the L7 promoter. Binds to the T-MARE (Maf response element) sites of lens-specific alpha- and beta-crystallin gene promoters. Binds element G1 on the glucagon promoter. Binds an AT-rich region adjacent to the TGC motif (atypical Maf response element) in the CD13 proximal promoter in endothelial cells. When overexpressed, represses anti-oxidant response element (ARE)-mediated transcription. Involved either as an oncogene or as a tumor suppressor, depending on the cell context. Binds to the ARE sites of detoxifying enzyme gene promoters.
• Tissue Specificity: Expressed in endothelial cells.
• KEGG Pathway:
  Th1 and Th2 cell differentiation (hsa04658)
  Transcriptio.l misregulation in cancer (hsa05202)
  Inflammatory bowel disease (hsa05321)
• Reactome Pathway: RUNX2 regulates osteoblast differentiation (R-HSA-8940973)

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ayme-Gripp syndrome	DISCRS6K	Definitive	Autosomal dominant	[1]
Cataract 21 multiple types	DISIGLA9	Definitive	Autosomal dominant	[2]
Malaria	DISQ9Y50	Definitive	Biomarker	[3]
T-cell lymphoma	DISSXRTQ	Definitive	Altered Expression	[4]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[5]
Aicardi-Goutieres syndrome	DIS1NH4X	Strong	Genetic Variation	[6]
Cataract	DISUD7SL	Strong	Genetic Variation	[7]
Cholestasis	DISDJJWE	Strong	Altered Expression	[8]
Coloboma	DISP39N5	Strong	Genetic Variation	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[9]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[9]
Intrahepatic cholestasis	DISHITDZ	Strong	Biomarker	[10]
Neoplasm	DISZKGEW	Strong	Biomarker	[11]
Nephrotic syndrome	DISSPSC2	Strong	Biomarker	[12]
Obesity	DIS47Y1K	Strong	Genetic Variation	[13]
Ulcerative colitis	DIS8K27O	Strong	Genetic Variation	[14]
Laryngeal squamous cell carcinoma	DIS9UUVF	moderate	Altered Expression	[15]
Neurofibromatosis type 1	DIS53JH9	moderate	Biomarker	[16]
Cataract - microcornea syndrome	DISL51AQ	Supportive	Autosomal dominant	[17]
Cerulean cataract	DIS5D1OI	Supportive	Autosomal dominant	[18]
Fine-Lubinsky syndrome	DIS02NYV	Supportive	Autosomal recessive	[1]
Pulverulent cataract	DISMJ2AH	Supportive	Autosomal dominant	[2]
Plasma cell myeloma	DIS0DFZ0	Limited	Genetic Variation	[19]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Uric acid	DMA1MKT	Investigative	Transcription factor Maf (MAF) affects the abundance of Uric acid.	[48]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Transcription factor Maf (MAF).	[20]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transcription factor Maf (MAF).	[21]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transcription factor Maf (MAF).	[22]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Transcription factor Maf (MAF).	[23]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transcription factor Maf (MAF).	[24]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Transcription factor Maf (MAF).	[25]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Transcription factor Maf (MAF).	[26]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Transcription factor Maf (MAF).	[27]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Transcription factor Maf (MAF).	[28]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Transcription factor Maf (MAF).	[29]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Transcription factor Maf (MAF).	[30]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Transcription factor Maf (MAF).	[31]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of Transcription factor Maf (MAF).	[32]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Transcription factor Maf (MAF).	[33]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid increases the expression of Transcription factor Maf (MAF).	[34]
Enzalutamide	DMGL19D	Approved	Enzalutamide decreases the expression of Transcription factor Maf (MAF).	[35]
Bexarotene	DMOBIKY	Approved	Bexarotene increases the expression of Transcription factor Maf (MAF).	[36]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Transcription factor Maf (MAF).	[35]
Isoflavone	DM7U58J	Phase 4	Isoflavone decreases the expression of Transcription factor Maf (MAF).	[37]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Transcription factor Maf (MAF).	[38]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Transcription factor Maf (MAF).	[39]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Transcription factor Maf (MAF).	[40]
ACYLINE	DM9GRTK	Phase 2	ACYLINE decreases the expression of Transcription factor Maf (MAF).	[41]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Transcription factor Maf (MAF).	[44]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Transcription factor Maf (MAF).	[45]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Transcription factor Maf (MAF).	[46]
Forskolin	DM6ITNG	Investigative	Forskolin decreases the expression of Transcription factor Maf (MAF).	[46]
Bilirubin	DMI0V4O	Investigative	Bilirubin decreases the expression of Transcription factor Maf (MAF).	[47]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Transcription factor Maf (MAF).	[42]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Transcription factor Maf (MAF).	[43]

References

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• [45] Molecular events in human T cells treated with diesel exhaust particles or formaldehyde that underlie their diminished interferon-gamma and interleukin-10 production. Int Arch Allergy Immunol. 2009;148(3):239-50. doi: 10.1159/000161584. Epub 2008 Oct 10.
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