Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUCH2JP)

• DOT Name: Fructosamine-3-kinase (FN3K)
• Synonyms: EC 2.7.1.171; Protein-psicosamine 3-kinase FN3K; Protein-ribulosamine 3-kinase FN3K; EC 2.7.1.172
• Gene Name: FN3K
• UniProt ID: FN3K_HUMAN
• EC Number: 2.7.1.171; 2.7.1.172
• Pfam ID: PF03881
• Sequence:
  MEQLLRAELRTATLRAFGGPGAGCISEGRAYDTDAGPVFVKVNRRTQARQMFEGEVASLE
  ALRSTGLVRVPRPMKVIDLPGGGAAFVMEHLKMKSLSSQASKLGEQMADLHLYNQKLREK
  LKEEENTVGRRGEGAEPQYVDKFGFHTVTCCGFIPQVNEWQDDWPTFFARHRLQAQLDLI
  EKDYADREARELWSRLQVKIPDLFCGLEIVPALLHGDLWSGNVAEDDVGPIIYDPASFYG
  HSEFELAIALMFGGFPRSFFTAYHRKIPKAPGFDQRLLLYQLFNYLNHWNHFGREYRSPS
  LGTMRRLLK
• Function: Fructosamine-3-kinase involved in protein deglycation by mediating phosphorylation of fructoselysine residues on glycated proteins, to generate fructoselysine-3 phosphate. Fructoselysine-3 phosphate adducts are unstable and decompose under physiological conditions. Involved in intracellular deglycation in erythrocytes. Involved in the response to oxidative stress by mediating deglycation of NFE2L2/NRF2, glycation impairing NFE2L2/NRF2 function. Also able to phosphorylate psicosamines and ribulosamines.
• Tissue Specificity: Widely expressed . Expressed in erythrocytes .
• Reactome Pathway: Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation (R-HSA-163841)
• BioCyc Pathway: MetaCyc:ENSG00000167363-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Fructosamine-3-kinase (FN3K).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Fructosamine-3-kinase (FN3K).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Fructosamine-3-kinase (FN3K).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Fructosamine-3-kinase (FN3K).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Fructosamine-3-kinase (FN3K).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Fructosamine-3-kinase (FN3K).	[6]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] 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.
• [5] 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.
• [6] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.