Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8UQKS6)

• DOT Name: Vesicular integral-membrane protein VIP36 (LMAN2)
• Synonyms: Glycoprotein GP36b; Lectin mannose-binding 2; Vesicular integral-membrane protein 36; VIP36
• Gene Name: LMAN2
• Related Disease:
  Gastric cancer
  Neuroblastoma
  Stomach cancer
• UniProt ID: LMAN2_HUMAN
• Pfam ID: PF03388
• Sequence:
  MAAEGWIWRWGWGRRCLGRPGLLGPGPGPTTPLFLLLLLGSVTADITDGNSEHLKREHSL
  IKPYQGVGSSSMPLWDFQGSTMLTSQYVRLTPDERSKEGSIWNHQPCFLKDWEMHVHFKV
  HGTGKKNLHGDGIALWYTRDRLVPGPVFGSKDNFHGLAIFLDTYPNDETTERVFPYISVM
  VNNGSLSYDHSKDGRWTELAGCTADFRNRDHDTFLAVRYSRGRLTVMTDLEDKNEWKNCI
  DITGVRLPTGYYFGASAGTGDLSDNHDIISMKLFQLMVEHTPDEESIDWTKIEPSVNFLK
  SPKDNVDDPTGNFRSGPLTGWRVFLLLLCALLGIVVCAVVGAVVFQKRQERNKRFY
• Function: Plays a role as an intracellular lectin in the early secretory pathway. Interacts with N-acetyl-D-galactosamine and high-mannose type glycans and may also bind to O-linked glycans. Involved in the transport and sorting of glycoproteins carrying high mannose-type glycans.
• Tissue Specificity: Ubiquitous.
• KEGG Pathway: Protein processing in endoplasmic reticulum (hsa04141)
• Reactome Pathway:
  Cargo concentration in the ER (R-HSA-5694530)
  COPII-mediated vesicle transport (R-HSA-204005)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Limited	Altered Expression	[1]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[2]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[1]

2 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 Vesicular integral-membrane protein VIP36 (LMAN2).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Vesicular integral-membrane protein VIP36 (LMAN2).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Vesicular integral-membrane protein VIP36 (LMAN2).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Vesicular integral-membrane protein VIP36 (LMAN2).	[5]
Selenium	DM25CGV	Approved	Selenium increases the expression of Vesicular integral-membrane protein VIP36 (LMAN2).	[6]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Vesicular integral-membrane protein VIP36 (LMAN2).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Vesicular integral-membrane protein VIP36 (LMAN2).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Vesicular integral-membrane protein VIP36 (LMAN2).	[9]
Manganese	DMKT129	Investigative	Manganese increases the expression of Vesicular integral-membrane protein VIP36 (LMAN2).	[10]

References

• [1] Combining multi-dimensional data to identify a key signature (gene and miRNA) of cisplatin-resistant gastric cancer.J Cell Biochem. 2018 Aug;119(8):6997-7008. doi: 10.1002/jcb.26908. Epub 2018 Apr 25.
• [2] Overexpression of quality control proteins reduces prion conversion in prion-infected cells.J Biol Chem. 2018 Oct 12;293(41):16069-16082. doi: 10.1074/jbc.RA118.002754. Epub 2018 Aug 28.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [7] 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.
• [8] 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.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [10] Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.