Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT248IN0)

• DOT Name: Glycoprotein endo-alpha-1,2-mannosidase-like protein (MANEAL)
• Synonyms: EC 3.2.1.-
• Gene Name: MANEAL
• Related Disease: Nervous system disease
• UniProt ID: MANEL_HUMAN
• EC Number: 3.2.1.-
• Pfam ID: PF16317
• Sequence:
  MARRRRRACIALFLVLLFAFGTLMGLRTLKAPDGLPALGPGLELAPFERRPEGAPAPAAR
  APAAPAAPPPPPPPPRTADPGGSPGPAPAEAEPAPVQSLRVYSDLHAFYYSWYGSPRREG
  HYIHWDHVMVPHWDPKISASYPRGRHSPPDDLGSSFYPELGPYSSRDPEVLREHMTQLKE
  AAIGVLVLSWYPPGMADDNGEPSDDLVPAILDTAHQYSIQVAFHIQPYKGRDDITVHDNI
  KYIIDTYGSHGAFYRYKNSMGKSLPLFYIYDSYLTSPEAWAHLLTPNGPHSIRNTPYDGV
  FIALLVEEGHTHDILAAGFDGMYTYFASNGFSFGSSHQNWKAVKNFCDANNLMFIPSVGP
  GYIDTSIRPWNNHNTRNRVNGKYYETALQAALTVRPEIVSITSFNEWHEGTQIEKAIPKK
  TPTRLYLDYLPHQPSLYLELTRRWAEHFIKEKEQWLM

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nervous system disease	DISJ7GGT	Limited	Biomarker	[1]

11 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 Glycoprotein endo-alpha-1,2-mannosidase-like protein (MANEAL).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Glycoprotein endo-alpha-1,2-mannosidase-like protein (MANEAL).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Glycoprotein endo-alpha-1,2-mannosidase-like protein (MANEAL).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Glycoprotein endo-alpha-1,2-mannosidase-like protein (MANEAL).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Glycoprotein endo-alpha-1,2-mannosidase-like protein (MANEAL).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Glycoprotein endo-alpha-1,2-mannosidase-like protein (MANEAL).	[7]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Glycoprotein endo-alpha-1,2-mannosidase-like protein (MANEAL).	[8]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Glycoprotein endo-alpha-1,2-mannosidase-like protein (MANEAL).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Glycoprotein endo-alpha-1,2-mannosidase-like protein (MANEAL).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Glycoprotein endo-alpha-1,2-mannosidase-like protein (MANEAL).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Glycoprotein endo-alpha-1,2-mannosidase-like protein (MANEAL).	[12]

References

• [1] Coexisting variants in OSTM1 and MANEAL cause a complex neurodegenerative disorder with NBIA-like brain abnormalities.Eur J Hum Genet. 2017 Sep;25(9):1092-1095. doi: 10.1038/ejhg.2017.96. Epub 2017 Jun 14.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [7] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [8] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [9] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011 Sep 16;146(6):904-17.
• [12] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.