Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTDG01Y9)

• DOT Name: Ribokinase (RBKS)
• Synonyms: RK; EC 2.7.1.15
• Gene Name: RBKS
• Related Disease:
  Schizophrenia
  Tuberculosis
  Bipolar disorder
• UniProt ID: RBSK_HUMAN
• PDB ID: 2FV7; 5BYC; 5BYD; 5BYE; 5BYF; 5C3Y; 5C3Z; 5C40; 5C41; 6WJZ; 6WK0
• EC Number: 2.7.1.15
• Pfam ID: PF00294
• Sequence:
  MAASGEPQRQWQEEVAAVVVVGSCMTDLVSLTSRLPKTGETIHGHKFFIGFGGKGANQCV
  QAARLGAMTSMVCKVGKDSFGNDYIENLKQNDISTEFTYQTKDAATGTASIIVNNEGQNI
  IVIVAGANLLLNTEDLRAAANVISRAKVMVCQLEITPATSLEALTMARRSGVKTLFNPAP
  AIADLDPQFYTLSDVFCCNESEAEILTGLTVGSAADAGEAALVLLKRGCQVVIITLGAEG
  CVVLSQTEPEPKHIPTEKVKAVDTTGAGDSFVGALAFYLAYYPNLSLEDMLNRSNFIAAV
  SVQAAGTQSSYPYKKDLPLTLF
• Function: Catalyzes the phosphorylation of ribose at O-5 in a reaction requiring ATP and magnesium. The resulting D-ribose-5-phosphate can then be used either for sythesis of nucleotides, histidine, and tryptophan, or as a component of the pentose phosphate pathway.
• KEGG Pathway:
  Pentose phosphate pathway (hsa00030)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Pentose phosphate pathway (R-HSA-71336)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[1]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[2]
Bipolar disorder	DISAM7J2	Limited	Genetic Variation	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Afimoxifene	DMFORDT	Phase 2	Ribokinase (RBKS) decreases the response to substance of Afimoxifene.	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ribokinase (RBKS).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ribokinase (RBKS).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ribokinase (RBKS).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Ribokinase (RBKS).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Ribokinase (RBKS).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Ribokinase (RBKS).	[9]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Ribokinase (RBKS).	[10]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Ribokinase (RBKS).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Ribokinase (RBKS).	[12]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Ribokinase (RBKS).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ribokinase (RBKS).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ribokinase (RBKS).	[15]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of Ribokinase (RBKS).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Ribokinase (RBKS).	[16]

References

• [1] Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.Schizophr Bull. 2019 Jun 18;45(4):824-834. doi: 10.1093/schbul/sby140.
• [2] Ribokinase screened from T7 phage displayed Mycobacterium tuberculosis genomic DNA library had good potential for the serodiagnosis of tuberculosis.Appl Microbiol Biotechnol. 2019 Jul;103(13):5259-5267. doi: 10.1007/s00253-019-09756-5. Epub 2019 May 8.
• [3] Genome-wide association study identifies 30 loci associated with bipolar disorder.Nat Genet. 2019 May;51(5):793-803. doi: 10.1038/s41588-019-0397-8. Epub 2019 May 1.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [8] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [9] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [10] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [11] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [14] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [15] 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.
• [16] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [17] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.
• [18] High-throughput ectopic expression screen for tamoxifen resistance identifies an atypical kinase that blocks autophagy. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2058-63.