Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on curation of immunofluorescence data
Combined Automated Annotation using Multiple IEA Methods
Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation
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This pathway covers irreversible post-translational modifications including gamma-carboxylation, hypusinylation, and hydroxylation - FN3K's deglycation activity does not fit this category of irreversible modifications.
"After translation, many newly formed proteins undergo further covalent modifications that alter their functional properties and that are essentially irreversible under physiological conditions in the body. These modifications include the vitamin K-dependent attachment of carboxyl groups to glutamate residues and the conversion of a lysine residue in eIF5A to hypusine"
FN3K phosphorylates ketosamines
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FN3K phosphorylates ketosamines on the third carbon of the sugar moiety, creating unstable intermediates that decompose (deglycation).
"Ketosamine-3-kinase (FN3K) and ketosamine-3-kinase-related protein (FN3KRP) can phosphorylate protein-bound or free ketosamines on the third carbon of the sugar moiety and the resultant, unstable ketosamine 3-phosphates decompose under physiological conditions (a process called deglycation)."
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FN3K and FN3KRP both phosphorylate psicosamines and ribulosamines, but only FN3K can phosphorylate fructosamines.
"Both enzymes can 3-phosphorylate psicosamines (PsiAm) and ribulosamines (RibAm), but only FN3K can 3-phosphorylate fructosamines (FruAm) as well"
Identification, cloning, and heterologous expression of a mammalian fructosamine-3-kinase.
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Discovery paper identifying and cloning FN3K from erythrocytes, purified as 35,000 Mr protein.
"The enzyme responsible for this conversion was purified approximately 2,500-fold by chromatography on Blue Sepharose, Q Sepharose, and Sephacryl S-200 and shown to copurify with a 35,000-M(r) protein."
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Enzyme phosphorylates DMF, fructoselysine, fructoseglycine, and fructose in order of decreasing affinity.
"They were shown to catalyze the phosphorylation of DMF, fructoselysine, fructoseglycine, and fructose in order of decreasing affinity."
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NMR analysis showed phosphate bound to third carbon of 1-deoxyfructose moiety.
"Nuclear magnetic resonance analysis of phosphorylated DMF and phosphorylated fructoseglycine showed that the phosphate was bound to the third carbon of the 1-deoxyfructose moiety."
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Phosphorylated glycated lysozyme but not unmodified lysozyme.
"They also phosphorylated glycated lysozyme, though not unmodified lysozyme."
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Proposed function is to initiate deglycation of fructoselysine and glycated proteins.
"The physiological function of fructosamine-3-kinase may be to initiate a process leading to the deglycation of fructoselysine and of glycated proteins."
Human fructosamine-3-kinase: purification, sequencing, substrate specificity, and evidence of activity in vivo.
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Characterized human FN3K as a 35-kDa monomer expressed in all mammalian tissues.
"The protein thus identified is a 35-kDa monomer that appears to be expressed in all mammalian tissues."
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FL3P phosphorylation destabilizes FL adduct and leads to spontaneous decomposition, reversing nonenzymatic glycation.
"This phosphorylation destabilizes the FL adduct and leads to its spontaneous decomposition, thereby reversing the nonenzymatic glycation process at an early stage."
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High affinity of FN3K for FL and wide distribution suggest function is deglycation of nonenzymatically glycated proteins.
"The lability of FL3P, the high affinity of FN3K for FL, and the wide distribution of FN3K suggest that the function of this enzyme is deglycation of nonenzymatically glycated proteins."
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Deglycation system mediated by FN3K may protect cells from deleterious effects of nonenzymatic glycation.
"a deglycation system mediated by FN3K may be an important factor in protecting cells from the deleterious effects of nonenzymatic glycation."
Fructosamine 3-kinase is involved in an intracellular deglycation pathway in human erythrocytes.
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In vivo evidence of FN3K activity in erythrocytes with formation of phosphorylated hemoglobin intermediate.
"incubation of human erythrocytes with 200 mM glucose not only caused the progressive formation of glycated haemoglobin, but also increased the level of an anionic form of haemoglobin containing alkali-labile phosphate, to approx. 5% of total haemoglobin."
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DMF (FN3K inhibitor) doubled accumulation of glycated hemoglobin but decreased phosphorylated form - proving FN3K involvement.
"1-Deoxy-1-morpholinofructose (DMF), a substrate and competitive inhibitor of fructosamine 3-kinase, doubled the rate of accumulation of glycated haemoglobin, but markedly decreased the amount of haemoglobin containing alkali-labile phosphate."
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Removal of DMF caused decrease in glycated hemoglobin and transient increase in FN3P-Hb, demonstrating active deglycation cycle.
"Returning erythrocytes incubated with 200 mM glucose and DMF to a low-glucose medium devoid of DMF caused a decrease in the amount of glycated haemoglobin, a transient increase in FN3P-Hb and a net decrease in the sum (glycated haemoglobin+FN3P-Hb)."
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Second step is spontaneous decomposition of fructosamine 3-phosphate to free amine, 3-deoxyglucosone, and Pi.
"The second step of this 'deglycation' process is most likely a spontaneous decomposition of the fructosamine 3-phosphate residues to a free amine, 3-deoxyglucosone and P(i)."
Analysis of proteomic changes induced upon cellular differentiation of the human intestinal cell line Caco-2.
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High-throughput proteomics study comparing proliferating and differentiated Caco-2 cells.
"The proteome of proliferating Caco-2 cells was compared with that of fully differentiated cells."
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Two-dimensional gel analysis identified 53 differentially regulated proteins during differentiation.
"Two-dimensional gel analysis yielded 53 proteins that were differently regulated during the differentiation process."
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Study provides expression correlation data but no mechanistic link to differentiation.
"Thus, the proteomic approach in combination with a literature-based pathway analysis yielded valuable information about the differentiation process of Caco-2 cells on the molecular level"
Deep research on FN3K from Perplexity
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FN3K exhibits highly specific substrate recognition with preference for fructose-lysine residues and 10-100x higher affinity for epsilon-lysine vs N-terminal modifications.
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Structural studies show bulky aromatic residues (His288, Trp219, Phe252, Tyr296) create the specialized substrate-binding pocket.
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FN3K activity is redox-regulated via P-loop cysteine C24 forming disulfide-linked dimers in oxidized state.
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Multi-compartmental localization to cytosol, mitochondria, and nucleus supported by multi-omics studies.