Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMSLE39)

• DOT Name: Nicotinamide riboside kinase 2 (NMRK2)
• Synonyms: NRK 2; NmR-K 2; EC 2.7.1.22; Integrin beta-1-binding protein 3; Muscle integrin-binding protein; MIBP; Nicotinic acid riboside kinase 2; EC 2.7.1.173; Ribosylnicotinamide kinase 2; RNK 2; Ribosylnicotinic acid kinase 2
• Gene Name: NMRK2
• UniProt ID: NRK2_HUMAN
• EC Number: 2.7.1.173; 2.7.1.22
• Pfam ID: PF13238
• Sequence:
  MKLIVGIGGMTNGGKTTLTNSLLRALPNCCVIHQDDFFKPQDQIAVGEDGFKQWDVLESL
  DMEAMLDTVQAWLSSPQKFARAHGVSVQPEASDTHILLLEGFLLYSYKPLVDLYSRRYFL
  TVPYEECKWRRSTRNYTVPDPPGLFDGHVWPMYQKYRQEMEANGVEVVYLDGMKSREELF
  REVLEDIQNSLLNRSQESAPSPARPARTQGPGRGCGHRTARPAASQQDSM
• Function: Catalyzes the phosphorylation of nicotinamide riboside (NR) and nicotinic acid riboside (NaR) to form nicotinamide mononucleotide (NMN) and nicotinic acid mononucleotide (NaMN). Reduces laminin matrix deposition and cell adhesion to laminin, but not to fibronectin. Involved in the regulation of PXN at the protein level and of PXN tyrosine phosphorylation. May play a role in the regulation of terminal myogenesis.
• Tissue Specificity: Predominantly expressed in skeletal muscle and, at a much lower level, in the heart (at protein level). No expression in brain, kidney, liver, lung, pancreas nor placenta.
• KEGG Pathway:
  Nicoti.te and nicoti.mide metabolism (hsa00760)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Nicotinate metabolism (R-HSA-196807)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Nicotinamide riboside kinase 2 (NMRK2).	[1]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nicotinamide riboside kinase 2 (NMRK2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Nicotinamide riboside kinase 2 (NMRK2).	[4]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Nicotinamide riboside kinase 2 (NMRK2).	[5]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Nicotinamide riboside kinase 2 (NMRK2).	[6]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the expression of Nicotinamide riboside kinase 2 (NMRK2).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Nicotinamide riboside kinase 2 (NMRK2).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Nicotinamide riboside kinase 2 (NMRK2).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Nicotinamide riboside kinase 2 (NMRK2).	[2]

References

• [1] 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.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [7] Peroxisome proliferator activated receptor gamma (PPAR-gama) ligand pioglitazone regulated gene networks in term human primary trophoblast cells. Reprod Toxicol. 2018 Oct;81:99-107.
• [8] 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.
• [9] 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.