Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9A8JSO)

• DOT Name: MTOR-associated protein MEAK7 (MEAK7)
• Synonyms: MEAK7; MTOR associated protein, eak-7 homolog; TBC/LysM-associated domain-containing protein 1; TLD domain-containing protein 1
• Gene Name: MEAK7
• Related Disease:
  Eosinophilic esophagitis
  Acute myelogenous leukaemia
• UniProt ID: MEAK7_HUMAN
• PDB ID: 7U4T
• Pfam ID: PF07534
• Sequence:
  MGNSRSRVGRSFCSQFLPEEQAEIDQLFDALSSDKNSPNVSSKSFSLKALQNHVGEALPP
  EMVTRLYDGMRRVDLTGKAKGPSENVSQEQFTASMSHLLKGNSEEKSLMIMKMISATEGP
  VKAREVQKFTEDLVGSVVHVLSHRQELRGWTGKEAPGPNPRVQVLAAQLLSDMKLQDGKR
  LLGPQWLDYDCDRAVIEDWVFRVPHVAIFLSVVICKGFLILCSSLDLTTLVPERQVDQGR
  GFESILDVLSVMYINAQLPREQRHRWCLLFSSELHGHSFSQLCGHITHRGPCVAVLEDHD
  KHVFGGFASCSWEVKPQFQGDNRCFLFSICPSMAVYTHTGYNDHYMYLNHGQQTIPNGLG
  MGGQHNYFGLWVDVDFGKGHSRAKPTCTTYNSPQLSAQENFQFDKMEVWAVGDPSEEQLA
  KGNKSILDADPEAQALLEISGHSRHSEGLREVPDDE
• Function: Activates an alternative mTOR signaling through RPS6KB2 activation and EIF4EBP1 repression to regulate cell proliferation and migration. Recruits MTOR at the lysosome, essential for MTOR signaling at the lysosome.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Eosinophilic esophagitis	DISR8WSB	Strong	Genetic Variation	[1]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of MTOR-associated protein MEAK7 (MEAK7).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of MTOR-associated protein MEAK7 (MEAK7).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of MTOR-associated protein MEAK7 (MEAK7).	[5]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of MTOR-associated protein MEAK7 (MEAK7).	[6]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of MTOR-associated protein MEAK7 (MEAK7).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of MTOR-associated protein MEAK7 (MEAK7).	[9]

1 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 MTOR-associated protein MEAK7 (MEAK7).	[8]

References

• [1] Common variants at 5q22 associate with pediatric eosinophilic esophagitis.Nat Genet. 2010 Apr;42(4):289-91. doi: 10.1038/ng.547. Epub 2010 Mar 7.
• [2] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [5] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [6] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [7] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [8] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.