Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVSSJ33)

• DOT Name: Ensconsin (MAP7)
• Synonyms: Epithelial microtubule-associated protein of 115 kDa; E-MAP-115; Microtubule-associated protein 7; MAP-7
• Gene Name: MAP7
• Related Disease:
  Colonic neoplasm
  Hepatocellular carcinoma
  Schizophrenia
  Nervous system disease
  Kennedy disease
• UniProt ID: MAP7_HUMAN
• PDB ID: 7SGS
• Pfam ID: PF05672
• Sequence:
  MAELGAGGDGHRGGDGAVRSETAPDSYKVQDKKNASSRPASAISGQNNNHSGNKPDPPPV
  LRVDDRQRLARERREEREKQLAAREIVWLEREERARQHYEKHLEERKKRLEEQRQKEERR
  RAAVEEKRRQRLEEDKERHEAVVRRTMERSQKPKQKHNRWSWGGSLHGSPSIHSADPDRR
  SVSTMNLSKYVDPVISKRLSSSSATLLNSPDRARRLQLSPWESSVVNRLLTPTHSFLARS
  KSTAALSGEAASCSPIIMPYKAAHSRNSMDRPKLFVTPPEGSSRRRIIHGTASYKKERER
  ENVLFLTSGTRRAVSPSNPKARQPARSRLWLPSKSLPHLPGTPRPTSSLPPGSVKAAPAQ
  VRPPSPGNIRPVKREVKVEPEKKDPEKEPQKVANEPSLKGRAPLVKVEEATVEERTPAEP
  EVGPAAPAMAPAPASAPAPASAPAPAPVPTPAMVSAPSSTVNASASVKTSAGTTDPEEAT
  RLLAEKRRLAREQREKEERERREQEELERQKREELAQRVAEERTTRREEESRRLEAEQAR
  EKEEQLQRQAEERALREREEAERAQRQKEEEARVREEAERVRQEREKHFQREEQERLERK
  KRLEEIMKRTRRTEATDKKTSDQRNGDIAKGALTGGTEVSALPCTTNAPGNGKPVGSPHV
  VTSHQSKVTVESTPDLEKQPNENGVSVQNENFEEIINLPIGSKPSRLDVTNSESPEIPLN
  PILAFDDEGTLGPLPQVDGVQTQQTAEVI
• Function: Microtubule-stabilizing protein that may play an important role during reorganization of microtubules during polarization and differentiation of epithelial cells. Associates with microtubules in a dynamic manner. May play a role in the formation of intercellular contacts. Colocalization with TRPV4 results in the redistribution of TRPV4 toward the membrane and may link cytoskeletal microfilaments.
• Tissue Specificity: Expressed in the skin and cells of epithelial origin. Predominantly expressed in the suprabasal layers of the normal epidermis and relatively abundant in squamous cell carcinomas but barely detectable in basal cell carcinomas.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[2]
Schizophrenia	DISSRV2N	Strong	Biomarker	[3]
Nervous system disease	DISJ7GGT	Disputed	Biomarker	[4]
Kennedy disease	DISXZVM1	Limited	Biomarker	[5]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Ensconsin (MAP7) affects the response to substance of Methotrexate.	[22]
Etoposide	DMNH3PG	Approved	Ensconsin (MAP7) affects the response to substance of Etoposide.	[22]
Mitomycin	DMH0ZJE	Approved	Ensconsin (MAP7) affects the response to substance of Mitomycin.	[22]

17 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 Ensconsin (MAP7).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Ensconsin (MAP7).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ensconsin (MAP7).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Ensconsin (MAP7).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ensconsin (MAP7).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Ensconsin (MAP7).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Ensconsin (MAP7).	[12]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Ensconsin (MAP7).	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Ensconsin (MAP7).	[14]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Ensconsin (MAP7).	[15]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Ensconsin (MAP7).	[16]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Ensconsin (MAP7).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ensconsin (MAP7).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ensconsin (MAP7).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Ensconsin (MAP7).	[6]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Ensconsin (MAP7).	[21]
Forskolin	DM6ITNG	Investigative	Forskolin increases the expression of Ensconsin (MAP7).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Ensconsin (MAP7).	[19]

References

• [1] The expression ratio of Map7/B2M is prognostic for survival in patients with stage II colon cancer.Int J Oncol. 2008 Sep;33(3):579-84.
• [2] The role of proline rich tyrosine kinase 2 (Pyk2) on cisplatin resistance in hepatocellular carcinoma.PLoS One. 2011;6(11):e27362. doi: 10.1371/journal.pone.0027362. Epub 2011 Nov 9.
• [3] Fine mapping of AHI1 as a schizophrenia susceptibility gene: from association to evolutionary evidence.FASEB J. 2010 Aug;24(8):3066-82. doi: 10.1096/fj.09-152611. Epub 2010 Apr 6.
• [4] MAP7 Regulates Axon Collateral Branch Development in Dorsal Root Ganglion Neurons.J Neurosci. 2017 Feb 8;37(6):1648-1661. doi: 10.1523/JNEUROSCI.3260-16.2017. Epub 2017 Jan 9.
• [5] Septin-dependent remodeling of cortical microtubule drives cell reshaping during epithelial wound healing.J Cell Sci. 2018 Jun 28;131(12):jcs212647. doi: 10.1242/jcs.212647.
• [6] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [7] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [8] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] 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.
• [11] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [12] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [13] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [14] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [15] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [16] Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
• [17] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [18] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [19] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [20] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [21] Identification of genes targeted by the androgen and PKA signaling pathways in prostate cancer cells. Oncogene. 2006 Nov 23;25(55):7311-23.
• [22] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.