{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Fructosamine‐3‐kinase–related protein (FN3KRP) is a highly conserved enzyme that, together with its paralog FN3K, appears to function as a constitutive “housekeeping” protein repair enzyme. Unlike FN3K—which phosphorylates protein‐bound fructosamines—FN3KRP exhibits a distinct substrate specificity, targeting glycated ketosamines such as ribulosamines and psicosamines. By phosphorylating these adducts at the third carbon of the sugar moiety, FN3KRP destabilizes the glycation products, thereby promoting their removal from proteins and reducing the burden of nonenzymatic glycation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " \n This deglycation mechanism is thought to be essential in preventing the accumulation of damaged proteins implicated in diabetes‐related complications and aging.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its role in endogenous protein maintenance, FN3KRP is expressed in a wide variety of human tissues—including erythrocytes—and its steady expression underscores its importance in cellular metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " \n Moreover, genetic studies have linked FN3KRP to longevity and cardiometabolic traits, suggesting that altered activity of this enzyme may contribute to metabolic regulation and serve as a potential marker for glycation-associated pathologies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Intriguingly, FN3KRP also has the capacity to phosphorylate hydrophobic xenobiotics; for instance, it plays a major role in the activation of the prodrug CS‐0777 in human red blood cells (RBCs), where inhibition studies and kinetic analyses indicate that FN3KRP is the principal kinase acting on this substrate."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " \n Although some mechanistic details remain unresolved—including overlapping substrate preferences and potential compensatory deglycation pathways"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}, {"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "—FN3KRP clearly represents an ancient and evolutionarily conserved component of the cellular defense against nonenzymatic glycation.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, FN3KRP functions as a protein deglycation enzyme by selectively phosphorylating specific glycated substrates (primarily ketosamines), thereby destabilizing them and facilitating their removal from proteins. Its ubiquitous expression and genetic associations with metabolic traits underline its significance in maintaining protein homeostasis, as well as its emerging role in xenobiotic metabolism.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "James R Conner, Paul J Beisswenger, Benjamin S Szwergold "}, {"type": "b", "children": [{"type": "t", "text": "Some clues as to the regulation, expression, function, and distribution of fructosamine-3-kinase and fructosamine-3-kinase-related protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann N Y Acad Sci (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1196/annals.1333.095"}], "href": "https://doi.org/10.1196/annals.1333.095"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16037310"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16037310"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "James R Conner, Paul J Beisswenger, Benjamin S Szwergold "}, {"type": "b", "children": [{"type": "t", "text": "The expression of the genes for fructosamine-3-kinase and fructosamine-3-kinase-related protein appears to be constitutive and unaffected by environmental signals."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2004.08.181"}], "href": "https://doi.org/10.1016/j.bbrc.2004.08.181"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15381090"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15381090"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Juliette Fortpied, Rita Gemayel, Vincent Stroobant, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "A mammalian protein homologous to fructosamine-3-kinase is a ketosamine-3-kinase acting on psicosamines and ribulosamines but not on fructosamines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/diabetes.52.12.2888"}], "href": "https://doi.org/10.2337/diabetes.52.12.2888"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14633848"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14633848"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Emile Van Schaftingen, François Collard, Elsa Wiame, et al. 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