EC Number   |
General Information |
Reference |
|---|
   2.7.1.171 | evolution |
fructosamine-3-kinases belong to the large superfamily of protein kinase-like (PKL) enzymes. The strained disulfides in the dimeric Arabidosis thalina enzyme function as redox switches to reversibly regulate the activity and dimerization of FN3K. Human FN3K, which contains an equivalent P-loop Cys, is also redox sensitive, whereas ancestral bacterial FN3K homologues, which lack a P-loop Cys, are not. Redox control mediated by the P-loop Cys is an ancient mechanism of FN3K regulation that emerged progressively during FN3K evolution from bacteria to humans. Redox regulation seem to have evolved in FN3K homologues in response to changing cellular redox conditions |
762465 |
| 2.7.1.171 | evolution |
fructosamine-3-kinases belong to the large superfamily of protein kinase-like (PKL) enzymes. The strained disulfides in the dimeric Arabidosis thalina enzyme function as redox switches to reversibly regulate the activity and dimerization of FN3K. Human FN3K, which contains an equivalent P-loop Cys, is also redox sensitive, whereas ancestral bacterial FN3K homologues, which lack a P-loop Cys, are not. Redox control mediated by the P-loop Cys is an ancient mechanism of FN3K regulation that emerged progressively during FN3K evolution from bacteria to humans. Redox regulation seems to have evolved in FN3K homologues in response to changing cellular redox conditions |
762465 |
| 2.7.1.171 | evolution |
the FN3K gene may have arisen by an event of duplication of an ancestral gene, FN3K-related protein (FN3K-RP). The gene encoding FN3K-RP is located next to the one encoding FN3K, and share a 65% sequence homology with FN3K and an identical genome organization. Both FN3K and FN3K-RP phosphorylate psicosamines and ribulosamines, but only the former act on fructosamines |
738073 |
| 2.7.1.171 | malfunction |
FN3K CRISPR knockout alters redox-sensitive cellular metabolites |
762465 |
| 2.7.1.171 | malfunction |
Fn3k-/- mice look healthy and have normal blood glucose and serum fructosamine levels. Their level of haemoglobin-bound fructosamines is approx. 2.5-fold higher than that of control (Fn3k+/+) or Fn3k+/- mice. Other intracellular proteins are also significantly more glycated in Fn3k-/- mice in erythrocytes and in brain, kidney, liver and skeletal muscle, indicating that FN3K removes fructosamines from intracellular proteins in vivo |
707426 |
| 2.7.1.171 | malfunction |
mice deficient in FN3K accumulate protein-bound fructosamines and free fructoselysine, indicating that the deglycation mechanism initiated by FN3K is operative in vivo |
707094 |
| 2.7.1.171 | malfunction |
N-acetyl cysteine treatment partially rescues the effects of FN3K loss on NRF2 driven tumor phenotypes. FN3K deficiency increases NRF2 glycation and impairs its ability to counter ROS stress in liver and lung cancer cells. Pre-treatment with the ROS scavenger and GSH precursor N-acetyl cysteine (NAC) reverses H2O2 and DLS toxicity and restores glutathione balance in FN3K-deficient HepG2 and H3255 cells, respectively. FN3K deficiency leads to increased proteasomal and MG132-sensitive degradation of the glycated NRF2 protein. Glycation also affects NRF2 function in KEAP1 mutant cells, for example gene and protein expression analyses of FN3K deficient and control Huh-1 liver cancer cells (KEAP1N414Y) show loss of NRF2 targets and resultant redox imbalance as indicated by increased glutathione oxidation |
760823 |
| 2.7.1.171 | malfunction |
polymorphisms of the FN3K gene are associated with variations in HbA1c levels and with the onset of type 2 diabetes mellitus (T2DM) and pathogenic mechanisms related to its complications, role of FN3K polymorphisms in the development of microvascular and macrovascular complications of diabetes, overview. The FN3K genotype presenting GG at position -385, TT at position -232, and CC at c.900 A, is associated with less severe microangiopathic and macroangiopathic complications as a whole, compared to all other genotypes |
760800 |
| 2.7.1.171 | malfunction |
removal of the chloroplast signal peptide results in the localization of AtFN3K in different cellular compartments, including nucleus and mitochondria. FN3K CRISPR knockout alters redox-sensitive cellular metabolites |
762465 |
| 2.7.1.171 | malfunction |
significant relationship of FN3K (rs1056534) and (rs3848403) polymorphisms with with endothelial dysfunction and concentration of soluble receptor for advanced glycation end-products (sRAGE) in patients with diabetes, clinical parameters, overview |
739258 |
