Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOPGRF5)

• DOT Name: Malectin (MLEC)
• Gene Name: MLEC
• Related Disease:
  Cardiac failure
  Cerebral palsy
  Congestive heart failure
  Neoplasm
• UniProt ID: MLEC_HUMAN
• PDB ID: 6S7T
• Pfam ID: PF11721
• Sequence:
  MLGAWAVEGTAVALLRLLLLLLPPAIRGPGLGVAGVAGAAGAGLPESVIWAVNAGGEAHV
  DVHGIHFRKDPLEGRVGRASDYGMKLPILRSNPEDQILYQTERYNEETFGYEVPIKEEGD
  YVLVLKFAEVYFAQSQQKVFDVRLNGHVVVKDLDIFDRVGHSTAHDEIIPMSIRKGKLSV
  QGEVSTFTGKLYIEFVKGYYDNPKVCALYIMAGTVDDVPKLQPHPGLEKKEEEEEEEEYD
  EGSNLKKQTNKNRVQSGPRTPNPYASDNSSLMFPILVAFGVFIPTLFCLCRL
• Function: Carbohydrate-binding protein with a strong ligand preference for Glc2-N-glycan. May play a role in the early steps of protein N-glycosylation.
• Reactome Pathway:
  Neutrophil degranulation (R-HSA-6798695)
  N-glycan trimming in the ER and Calnexin/Calreticulin cycle (R-HSA-532668)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiac failure	DISDC067	Strong	Genetic Variation	[1]
Cerebral palsy	DIS82ODL	Strong	Genetic Variation	[2]
Congestive heart failure	DIS32MEA	Strong	Genetic Variation	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Malectin (MLEC) affects the response to substance of Paclitaxel.	[20]

16 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 Malectin (MLEC).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Malectin (MLEC).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Malectin (MLEC).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Malectin (MLEC).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Malectin (MLEC).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Malectin (MLEC).	[9]
Marinol	DM70IK5	Approved	Marinol increases the expression of Malectin (MLEC).	[11]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Malectin (MLEC).	[12]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Malectin (MLEC).	[13]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Malectin (MLEC).	[14]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Malectin (MLEC).	[12]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Malectin (MLEC).	[15]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Malectin (MLEC).	[16]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Malectin (MLEC).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Malectin (MLEC).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Malectin (MLEC).	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Malectin (MLEC).	[10]

References

• [1] A systematic review of large scale and heterogeneous gene array data in heart failure.J Mol Cell Cardiol. 2005 Mar;38(3):425-32. doi: 10.1016/j.yjmcc.2004.12.016.
• [2] Malectin gene polymorphisms promote cerebral palsy via M2-like macrophage polarization.Clin Genet. 2018 Apr;93(4):794-799. doi: 10.1111/cge.13149. Epub 2018 Jan 25.
• [3] Antiproliferative activity of ((6)-arene)ruthenacarborane sandwich complexes against HCT116 and MCF7 cell lines.Dalton Trans. 2017 Sep 28;46(36):12067-12080. doi: 10.1039/c7dt02027a. Epub 2017 Aug 11.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] 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.
• [10] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [11] Delta9-tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and modulates gene transcription. Mol Hum Reprod. 2006 May;12(5):321-33. doi: 10.1093/molehr/gal036. Epub 2006 Apr 5.
• [12] 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.
• [13] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [14] 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.
• [15] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [17] Activin/nodal signaling switches the terminal fate of human embryonic stem cell-derived trophoblasts. J Biol Chem. 2015 Apr 3;290(14):8834-48.
• [18] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [19] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [20] 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.