Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9HR05S)

• DOT Name: Ketosamine-3-kinase (FN3KRP)
• Synonyms: EC 2.7.1.172; Fructosamine-3-kinase-related protein; FN3K-RP; FN3K-related protein; Protein-psicosamine 3-kinase FN3KRP; EC 2.7.1.-
• Gene Name: FN3KRP
• Related Disease: Obesity
• UniProt ID: KT3K_HUMAN
• EC Number: 2.7.1.-; 2.7.1.172
• Pfam ID: PF03881
• Sequence:
  MEELLRRELGCSSVRATGHSGGGCISQGRSYDTDQGRVFVKVNPKAEARRMFEGEMASLT
  AILKTNTVKVPKPIKVLDAPGGGSVLVMEHMDMRHLSSHAAKLGAQLADLHLDNKKLGEM
  RLKEAGTVGRGGGQEERPFVARFGFDVVTCCGYLPQVNDWQEDWVVFYARQRIQPQMDMV
  EKESGDREALQLWSALQLKIPDLFRDLEIIPALLHGDLWGGNVAEDSSGPVIFDPASFYG
  HSEYELAIAGMFGGFSSSFYSAYHGKIPKAPGFEKRLQLYQLFHYLNHWNHFGSGYRGSS
  LNIMRNLVK
• Function: Ketosamine-3-kinase involved in protein deglycation by mediating phosphorylation of ribuloselysine and psicoselysine on glycated proteins, to generate ribuloselysine-3 phosphate and psicoselysine-3 phosphate, respectively. Ribuloselysine-3 phosphate and psicoselysine-3 phosphate adducts are unstable and decompose under physiological conditions. Not able to phosphorylate fructoselysine.
• Tissue Specificity: Widely expressed; except in skeletal muscle where it is expressed at very low level . Expressed in erythrocytes .
• Reactome Pathway: Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation (R-HSA-163841)
• BioCyc Pathway: MetaCyc:ENSG00000141560-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Obesity	DIS47Y1K	Strong	Biomarker	[1]

10 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 Ketosamine-3-kinase (FN3KRP).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ketosamine-3-kinase (FN3KRP).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ketosamine-3-kinase (FN3KRP).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Ketosamine-3-kinase (FN3KRP).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ketosamine-3-kinase (FN3KRP).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Ketosamine-3-kinase (FN3KRP).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Ketosamine-3-kinase (FN3KRP).	[8]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Ketosamine-3-kinase (FN3KRP).	[9]
Vitamin C	DMXJ7O8	Approved	Vitamin C increases the expression of Ketosamine-3-kinase (FN3KRP).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ketosamine-3-kinase (FN3KRP).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Ketosamine-3-kinase (FN3KRP).	[10]

References

• [1] Mapping adipose and muscle tissue expression quantitative trait loci in African Americans to identify genes for type 2 diabetes and obesity.Hum Genet. 2016 Aug;135(8):869-80. doi: 10.1007/s00439-016-1680-8. Epub 2016 May 19.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] 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.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Synergistic effects of arsenic trioxide combined with ascorbic acid in human osteosarcoma MG-63 cells: a systems biology analysis. Eur Rev Med Pharmacol Sci. 2014;18(24):3877-88.
• [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] 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.
• [11] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.