Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4Y7T9L)

• DOT Name: Methionine adenosyltransferase 2 subunit beta (MAT2B)
• Synonyms: Methionine adenosyltransferase II beta; MAT II beta; Putative dTDP-4-keto-6-deoxy-D-glucose 4-reductase
• Gene Name: MAT2B
• UniProt ID: MAT2B_HUMAN
• PDB ID: 2YDX; 2YDY; 4KTT; 4KTV; 4NDN
• Pfam ID: PF04321
• Sequence:
  MVGREKELSIHFVPGSCRLVEEEVNIPNRRVLVTGATGLLGRAVHKEFQQNNWHAVGCGF
  RRARPKFEQVNLLDSNAVHHIIHDFQPHVIVHCAAERRPDVVENQPDAASQLNVDASGNL
  AKEAAAVGAFLIYISSDYVFDGTNPPYREEDIPAPLNLYGKTKLDGEKAVLENNLGAAVL
  RIPILYGEVEKLEESAVTVMFDKVQFSNKSANMDHWQQRFPTHVKDVATVCRQLAEKRML
  DPSIKGTFHWSGNEQMTKYEMACAIADAFNLPSSHLRPITDSPVLGAQRPRNAQLDCSKL
  ETLGIGQRTPFRIGIKESLWPFLIDKRWRQTVFH
• Function: Regulatory subunit of S-adenosylmethionine synthetase 2, an enzyme that catalyzes the formation of S-adenosylmethionine from methionine and ATP. Regulates MAT2A catalytic activity by changing its kinetic properties, increasing its affinity for L-methionine. Can bind NADP (in vitro).
• Tissue Specificity: Widely expressed.
• KEGG Pathway:
  Cysteine and methionine metabolism (hsa00270)
  Metabolic pathways (hsa01100)
  Biosynthesis of amino acids (hsa01230)
  Biosynthesis of cofactors (hsa01240)
• Reactome Pathway:
  Ub-specific processing proteases (R-HSA-5689880)
  Methylation (R-HSA-156581)
• BioCyc Pathway: MetaCyc:HS00531-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

9 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 Methionine adenosyltransferase 2 subunit beta (MAT2B).	[1]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Methionine adenosyltransferase 2 subunit beta (MAT2B).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Methionine adenosyltransferase 2 subunit beta (MAT2B).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Methionine adenosyltransferase 2 subunit beta (MAT2B).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Methionine adenosyltransferase 2 subunit beta (MAT2B).	[5]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Methionine adenosyltransferase 2 subunit beta (MAT2B).	[6]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Methionine adenosyltransferase 2 subunit beta (MAT2B).	[7]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Methionine adenosyltransferase 2 subunit beta (MAT2B).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Methionine adenosyltransferase 2 subunit beta (MAT2B).	[9]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [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] Interplay between cellular methyl metabolism and adaptive efflux during oncogenic transformation from chronic arsenic exposure in human cells. J Biol Chem. 2008 Jul 11;283(28):19342-50.
• [6] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [7] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [8] Methionine adenosyltransferase 2B, HuR, and sirtuin 1 protein cross-talk impacts on the effect of resveratrol on apoptosis and growth in liver cancer cells. J Biol Chem. 2013 Aug 9;288(32):23161-70.
• [9] 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.