Information on EC 2.7.1.171 - protein-fructosamine 3-kinase

Information on EC 2.7.1.171 - protein-fructosamine 3-kinase:

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EC NUMBER	COMMENTARY
2.7.1.171	-

RECOMMENDED NAME	GeneOntology No.
protein-fructosamine 3-kinase	-

REACTION	REACTION DIAGRAM	COMMENTARY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
ATP + [protein]-N6-D-fructosyl-L-lysine = ADP + [protein]-N6-(3-O-phospho-D-fructosyl)-L-lysine		phosphorylation destablilizes the fructoselysine adduct and leads to its spontaneous decomposition	Homo sapiens	-	708295
ATP + [protein]-N6-D-fructosyl-L-lysine = ADP + [protein]-N6-(3-O-phospho-D-fructosyl)-L-lysine		-	-	-	-

REACTION TYPE	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

PATHWAY	KEGG Link	MetaCyc Link
No entries in this field

SYSTEMATIC NAME

IUBMB Comments

ATP:[protein]-N6-D-fructosyl-L-lysine 3-phosphotransferase

Nonenzymatic glycation is an important factor in the pathogenesis of diabetic complications. Key early intermediates in this process are fructosamines, such as [protein]-N6-D-fructosyl-L-lysine. Fructosamine-3-kinase is part of an ATP-dependent system for removing carbohydrates from nonenzymatically glycated proteins. The phosphorylation destablilizes the [protein]-N6-D-fructosyl-L-lysine adduct and leads to its spontaneous decomposition. cf. EC 2.7.1.172, protein-ribulosamine 3-kinase.

SYNONYMS	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
FL3P	Rattus norvegicus	-	-	707456
FN3K	Gallus gallus	-	-	708981
FN3K	Mus musculus	-	-	707061, 707426, 708294, 708296, 708981
FN3K	Rattus norvegicus, Sus scrofa	-	-	708981
FN3K	Homo sapiens	-	-	707094, 707098, 707420, 708287, 708294, 708295, 708296, 708589, 708979, 710172
fructosamine 3-kinase	Homo sapiens	-	-	707420
fructosamine 3-kinase	Gallus gallus, Mus musculus, Rattus norvegicus, Sus scrofa	-	-	708981
fructosamine-3-kinase	Mus musculus	-	-	707061
fructosamine-3-kinase	Homo sapiens	-	-	707098, 707351, 708979
fructose-3-kinase	Homo sapiens, Mus musculus	-	-	707094
ketosamine 3-kinase 1	Homo sapiens	Q9HA64	-	708296
ketosamine 3-kinase 1	Mus musculus	Q8K274	-	708296

CAS REGISTRY NUMBER	COMMENTARY
No entries in this field

ORGANISM	COMMENTARY	LITERATURE	SEQUENCE CODE	SEQUENCE DB	SOURCE
Gallus gallus	-	708981	-	-
Homo sapiens	-	707094, 707098, 707351, 708295, 708589, 708979	-	-
Homo sapiens	-	707420, 708287, 708294, 708421	Q9H479	SwissProt
Homo sapiens	-	708296	Q9HA64	SwissProt
Homo sapiens	the mean level of FN3K gene expression is significantly lower in cancer than in the corresponding normal colorectal mucosa. No difference between cancer versus normal mucosa is detected in mRNA FN3K levels stratifying for age, sex, tumour stage and histological grading	710172	-	-
Mus musculus	-	707061, 707426, 708294	Q9ER35	SwissProt
Mus musculus	-	707094, 708981	-	-
Mus musculus	-	708296	Q8K274	SwissProt
Rattus norvegicus	-	708981	-	-
Rattus norvegicus	Sprague�Dawley or Fisher 344. Rats carrying the Tsc2 gene (Eker rats) in a Fisher 344 background	707456	-	-
Sus scrofa	-	708981	-	-

GENERAL INFORMATION	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
malfunction	Mus musculus	-	mice deficient in FN3K accumulate protein-bound fructosamines and free fructoselysine, indicating that the deglycation mechanism initiated by FN3K is operative in vivo	707094
malfunction	Mus musculus	-	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
metabolism	Mus musculus	-	despite its ability to reduce the glycation of intracellular islet proteins, fructosamine-3-kinase is neither required for the maintenance of beta-cell survival and function under control conditions nor involved in protection against beta-cell glucotoxicity	707061
physiological function	Mus musculus	-	FN3K serves as a protein repair enzyme and also in the metabolism of endogenously produced free fructose-epsilon-lysine. Repairing lysine residues may be important to restore enzymatic activity, protein�protein interaction or recognition sites for phosphorylation (which often comprise basic residues) or ubiquitinylation	707426
physiological function	Homo sapiens, Mus musculus	-	the physiological function of fructosamine-3-kinase may be to initiate a process leading to the deglycation of fructoselysine and of glycated proteins	708294

SUBSTRATE	PRODUCT	REACTION DIAGRAM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY/ Substrate	LITERATURE/ Substrate	COMMENTARY/ Product	LITERATURE/ Product	Reversibility r=reversible ir=irreversible ?=not specified
ATP + 1-deoxy-1-morpholin-4-yl-D-fructose	ADP + 1-deoxy-1-morpholin-4-yl-3-O-phosphono-D-fructose		Gallus gallus, Mus musculus	-	-	708981	-	-	?
ATP + 1-deoxy-1-morpholin-4-yl-D-fructose	ADP + 1-deoxy-1-morpholin-4-yl-3-O-phosphono-D-fructose		Homo sapiens	Q9HA64	-	708296	-	-	?
ATP + 1-deoxy-1-morpholin-4-yl-D-fructose	ADP + 1-deoxy-1-morpholin-4-yl-3-O-phosphono-D-fructose		Rattus norvegicus	-	-	708981	-	-	?
ATP + 1-deoxy-1-morpholin-4-yl-D-fructose	ADP + 1-deoxy-1-morpholin-4-yl-3-O-phosphono-D-fructose		Mus musculus	-	-	708294	-	-	?
ATP + 1-deoxy-1-morpholin-4-yl-D-fructose	ADP + 1-deoxy-1-morpholin-4-yl-3-O-phosphono-D-fructose		Homo sapiens	Q9H479	-	707420	-	-	?
ATP + 1-deoxy-1-morpholin-4-yl-D-fructose	ADP + 1-deoxy-1-morpholin-4-yl-3-O-phosphono-D-fructose		Homo sapiens	-	-	708294	-	-	?
ATP + 1-deoxy-1-morpholin-4-yl-D-psicose	ADP + 1-deoxy-1-morpholin-4-yl-3-O-phosphono-D-psicose		Homo sapiens	Q9HA64	-	708296	-	-	?
ATP + 1-deoxy-1-morpholin-4-yl-D-ribulose	ADP + 1-deoxy-1-morpholin-4-yl-3-O-phosphono-D-ribulose		Homo sapiens	Q9HA64	-	708296	-	-	?
ATP + D-fructose	ADP + O3-phosphono-D-fructose		Mus musculus, Homo sapiens	-	-	708294	-	-	?
ATP + D-fructose	ADP + O3-phosphono-D-fructose		Homo sapiens	-	Vmax is 35% of the value for N6-D-fructosyl-L-lysine	708295	-	-	?
ATP + N2-(1-deoxy-D-fructosyl)-glycine	ADP + N2-(1-deoxy-O3-phosphono-D-fructosyl)-glycine		Mus musculus, Homo sapiens	-	-	708294	-	-	?
ATP + N2-(1-deoxy-D-fructosyl)-glycylglycine	ADP + N2-(1-deoxy-O3-phosphono-D-fructosyl)-glycylglycine		Homo sapiens	-	-	708294	-	-	?
ATP + N2-(1-deoxy-D-fructosyl)-L-valine	ADP + N2-(1-deoxy-O3-phosphono-D-fructosyl)-L-valine		Homo sapiens	-	-	708294	-	-	?
ATP + N2-(1-deoxy-D-fructosyl)-valine	ADP + N2-(1-deoxy-O3-phosphono-D-fructosyl)-valine		Mus musculus, Homo sapiens	-	-	708294	-	-	?
ATP + N5-D-fructosyl-L-ornithine	ADP + N5-(O3-phosphono-D-fructosyl)-L-ornithine		Homo sapiens	-	-	708295	-	-	?
ATP + N6-(1-deoxy-D-fructosyl)-L-lysine	ADP + N6-(1-deoxy-O3-phosphono-D-fructosyl)-L-lysine		Homo sapiens	-	-	708294	-	-	?
ATP + N6-(1-deoxy-D-fructosyl)-lysine	ADP + N6-(1-deoxy-O3-phosphono-D-fructosyl)-lysine		Mus musculus, Homo sapiens	-	displays about 10times less affinity than for 1-deoxy-1-morpholin-4-yl-D-fructose	708294	-	-	?
ATP + N6-D-fructosyl-L-lysine	ADP + N6-(O3-phosphono-D-fructosyl)-L-lysine		Homo sapiens	-	-	708295	-	-	?
ATP + N6-D-psicosyl-L-lysine	ADP + N6-(O3-phosphono-D-psicosyl)-L-lysine		Homo sapiens	Q9HA64	-	708296	-	-	?
ATP + Nalpha-hippuryl-Nepsilon-(1-deoxy-D-fructosyl)lysine	ADP + Nalpha-hippuryl-Nepsilon-(1-deoxy-3-phospho-D-fructosyl)lysine		Homo sapiens	-	-	707098	Nalpha-hippuryl-Nepsilon-(3-phosphofructosyl)lysine like other 3-phosphofructosylamines, is not stable. Terminating the enzyme reaction with trichloracetic acid stabilises the analyte	-	?
ATP + [hemoglobin]-N6-D-fructosyl-L-lysine	ADP + [hemoglobin]-N6-(O3-phosphono-D-fructosyl)-L-lysine		Homo sapiens	-	mass-spectrometric identification of the fructosamine residues that are removed from hemoglobin in intact erythrocytes as a result of the action of fructosamine-3-kinase: Lys16, Lys61 and Lys139 in the alpha-chain of hemoglobin, Val1, Lys17, Lys59, Lys66, Lys132, and Lys144 in the beta-chain of hemoglobin. Some (e.g. Lys139 in the alph-chain of hemoglobin) are readily phosphorylated to a maximal extent by fructosamine-3-kinase in vitro whereas others (e.g. Val1 in the beta-chain of hemoglobin) are slowly and only very partially phosphorylated	708979	-	-	?
ATP + [protein]-N5-D-ribulosyl-L-lysine	ADP + [protein]-N5-(O3-phosphono-D-fructosyl)-L-lysine		Homo sapiens	Q9HA64	proteins glycated with allose, ketosamine-3-kinase 2 plays a role in freeing proteins from ribulosamines or psicosamines, which might arise in a several step process, from the reaction of amines with glucose and/or glycolytic intermediates. This role is shared by fructosamine-3-kinase (ketosamine-3-kinase 1), which has, in addition, the unique capacity to phosphorylate fructosamines	708296	-	-	?
ATP + [protein]-N6-D-fructosyl-L-lysine	ADP + [protein]-N6-(O3-phosphono-D-fructosyl)-L-lysine		Homo sapiens	-	-	707094	-	-	?
ATP + [protein]-N6-D-fructosyl-L-lysine	ADP + [protein]-N6-(O3-phosphono-D-fructosyl)-L-lysine		Rattus norvegicus	-	-	707456	fructoselysine 3-phosphate spontaneously decomposes to lysine, phosphate and 3-deoxyglucosone	-	?
ATP + [protein]-N6-D-fructosyl-L-lysine	ADP + [protein]-N6-(O3-phosphono-D-fructosyl)-L-lysine		Mus musculus	-	FN3K serves as a protein repair enzyme and also in the metabolism of endogenously produced free fructose-epsilon-lysine	707426	-	-	?
ATP + [protein]-N6-D-fructosyl-L-lysine	ADP + [protein]-N6-(O3-phosphono-D-fructosyl)-L-lysine		Homo sapiens	Q9H479	fructosamine 3-kinase is involved in an intracellular deglycation pathway in human erythrocytes. Spontaneous conversion of fructosamine 3-phosphates into 3-deoxyglucosone	707420	-	-	?
ATP + [protein]-N6-D-fructosyl-L-lysine	ADP + [protein]-N6-(O3-phosphono-D-fructosyl)-L-lysine		Homo sapiens	-	fructosamine-3-kinase phosphorylates fructosamine residues, leading to their destabilization and their shedding from protein	708979	-	-	?
ATP + [protein]-N6-D-fructosyl-L-lysine	ADP + [protein]-N6-(O3-phosphono-D-fructosyl)-L-lysine		Rattus norvegicus	-	fructoselysine 3-phosphate spontaneously decomposes to lysine, phosphate and 3-deoxyglucosone. This pathway appears to dominate 3-deoxyglucosone production in vivo, making it possible to modulate 3-deoxyglucosone levels by stimulating or inhibiting the reaction	707456	-	-	?
ATP + [protein]-N6-D-fructosyl-L-lysine	ADP + [protein]-N6-(O3-phosphono-D-fructosyl)-L-lysine		Mus musculus	-	mice deficient in FN3K accumulate protein-bound fructosamines and free fructoselysine, indicating that the deglycation mechanism initiated by FN3K is operative in vivo	707094	-	-	?
ATP + [protein]-N6-D-fructosyl-L-lysine	ADP + [protein]-N6-(O3-phosphono-D-fructosyl)-L-lysine		Homo sapiens	-	nonenzymatic glycation is an important factor in the pathogenesis of diabetic complications. Key early intermediates in this process are fructosamines, such as protein-bound fructoselysines. The fructosamine most frequently encountered in nature is fructoselysine. Fructosamine-3-kinase is part of an ATP-dependent system for removing carbohydrates from nonenzymatically glycated proteins and protecting cells from the deleterious effects of nonenzymatic glycation	708295	-	-	?
ATP + [protein]-N6-D-fructosyl-L-lysine	ADP + [protein]-N6-(O3-phosphono-D-fructosyl)-L-lysine		Homo sapiens	Q9H479	protein repair mechanism. Fructosamine 3-kinase phosphorylates with high affinity both low-molecular-mass and protein-bound fructosamines on the third carbon of their deoxyfructose moiety, leading to the formation of fructosamine 3-phosphates. The latter are unstable and spontaneously decompose into inorganic phosphate and 3-deoxyglucosone, with concomitant regeneration of the unglycated amine	707420	-	-	?
ATP + [protein]-N6-D-fructosyl-L-lysine	ADP + [protein]-N6-(O3-phosphono-D-fructosyl)-L-lysine		Homo sapiens	-	repairing glucose-mediated non-enzymatic modification of proteins. The function of fructosamine-3-kinase is seen in catalysing the ATP-dependent phosphorylation of the protein-bound fructosamine (Amadori compound) fructoselysine, which is the first stable intermediate resulting from the Maillard reaction between glucose and lysine, on its 3-hydroxy group to 3-phosphofructosyllysine. The phosphorylation destabilises the fructose-amine linkage leading to a spontaneous decomposition of 3-phosphofructosyllysine to the unmodified lysine residue as well as to 3-deoxyglucosulose and inorganic phosphate	707098	-	-	?
ATP + [protein]-N6-D-fructosyl-L-lysine	ADP + [protein]-N6-(O3-phosphono-D-fructosyl)-L-lysine		Gallus gallus, Mus musculus, Rattus norvegicus	-	specific role of fructosamine 3-kinase to repair protein damage caused by glucose	708981	-	-	?
ATP + [protein]-N6-D-fructosyl-L-lysine	ADP + [protein]-N6-(O3-phosphono-D-fructosyl)-L-lysine		Mus musculus, Homo sapiens	-	the physiological function of fructosamine-3-kinase may be to initiate a process leading to the deglycation of fructoselysine and of glycated proteins	708294	-	-	?
ATP + [protein]-N6-D-fructosyl-L-lysine	ADP + [protein]-N6-(O3-phosphono-D-fructosyl)-L-lysine		Homo sapiens	-	[histone]-N6-D-fructosyl-L-lysine, [hemoglobin]-N6-D-fructosyl-L-lysine. Similar experiments with other glycated proteins, including bovine serum albumin, and lysozyme indicate that fructoselysine residues on glycated proteins are readily phosphorylated by fructosamine 3-kinase, apparently irrespective of the protein. Phosphorylation destablilizes the fructoselysine adduct and leads to its spontaneous decomposition	708295	-	-	?
ATP + [protein]-N6-D-psicosyl-L-lysine	ADP + [protein]-N6-(O3-phosphono-D-psicosyl)-L-lysine		Homo sapiens	Q9HA64	ketosamine-3-kinase 2 plays a role in freeing proteins from ribulosamines or psicosamines, which might arise in a several step process, from the reaction of amines with glucose and/or glycolytic intermediates. This role is shared by fructosamine-3-kinase (ketosamine-3-kinase 1), which has, in addition, the unique capacity to phosphorylate fructosamines	708296	-	-	?
additional information	?	-	Homo sapiens	Q9HA64	FN3K-RP does not phosphorylate fructoselysine, 1-deoxy-1-morpholin-4-yl-D-fructose, or lysozyme glycated with glucose	708296	-	-	-
additional information	?	-	Homo sapiens	-	the kinase is specific for 1-deoxy-1-amino fructose adducts and does not catalyze phosphorylation of other monosaccharides and polyols, such as glucose, galactose, mannose, glucosamine, galactosamine, or myo-inositol	708295	-	-	-

NATURAL SUBSTRATES	NATURAL PRODUCTS	REACTION DIAGRAM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY SUBSTRATE	LITERATURE (Substrate)	COMMENTARY PRODUCT	LITERATURE (Product)
ATP + [protein]-N5-D-ribulosyl-L-lysine	ADP + [protein]-N5-(O3-phosphono-D-fructosyl)-L-lysine		Homo sapiens	Q9HA64	proteins glycated with allose, ketosamine-3-kinase 2 plays a role in freeing proteins from ribulosamines or psicosamines, which might arise in a several step process, from the reaction of amines with glucose and/or glycolytic intermediates. This role is shared by fructosamine-3-kinase (ketosamine-3-kinase 1), which has, in addition, the unique capacity to phosphorylate fructosamines	708296	-	-
ATP + [protein]-N6-D-fructosyl-L-lysine	ADP + [protein]-N6-(O3-phosphono-D-fructosyl)-L-lysine		Homo sapiens	-	-	707094	-	-
ATP + [protein]-N6-D-fructosyl-L-lysine	ADP + [protein]-N6-(O3-phosphono-D-fructosyl)-L-lysine		Mus musculus	-	FN3K serves as a protein repair enzyme and also in the metabolism of endogenously produced free fructose-epsilon-lysine	707426	-	-
ATP + [protein]-N6-D-fructosyl-L-lysine	ADP + [protein]-N6-(O3-phosphono-D-fructosyl)-L-lysine		Homo sapiens	Q9H479	fructosamine 3-kinase is involved in an intracellular deglycation pathway in human erythrocytes. Spontaneous conversion of fructosamine 3-phosphates into 3-deoxyglucosone	707420	-	-
ATP + [protein]-N6-D-fructosyl-L-lysine	ADP + [protein]-N6-(O3-phosphono-D-fructosyl)-L-lysine		Homo sapiens	-	fructosamine-3-kinase phosphorylates fructosamine residues, leading to their destabilization and their shedding from protein	708979	-	-
ATP + [protein]-N6-D-fructosyl-L-lysine	ADP + [protein]-N6-(O3-phosphono-D-fructosyl)-L-lysine		Rattus norvegicus	-	fructoselysine 3-phosphate spontaneously decomposes to lysine, phosphate and 3-deoxyglucosone. This pathway appears to dominate 3-deoxyglucosone production in vivo, making it possible to modulate 3-deoxyglucosone levels by stimulating or inhibiting the reaction	707456	-	-
ATP + [protein]-N6-D-fructosyl-L-lysine	ADP + [protein]-N6-(O3-phosphono-D-fructosyl)-L-lysine		Mus musculus	-	mice deficient in FN3K accumulate protein-bound fructosamines and free fructoselysine, indicating that the deglycation mechanism initiated by FN3K is operative in vivo	707094	-	-
ATP + [protein]-N6-D-fructosyl-L-lysine	ADP + [protein]-N6-(O3-phosphono-D-fructosyl)-L-lysine		Homo sapiens	-	nonenzymatic glycation is an important factor in the pathogenesis of diabetic complications. Key early intermediates in this process are fructosamines, such as protein-bound fructoselysines. The fructosamine most frequently encountered in nature is fructoselysine. Fructosamine-3-kinase is part of an ATP-dependent system for removing carbohydrates from nonenzymatically glycated proteins and protecting cells from the deleterious effects of nonenzymatic glycation	708295	-	-
ATP + [protein]-N6-D-fructosyl-L-lysine	ADP + [protein]-N6-(O3-phosphono-D-fructosyl)-L-lysine		Homo sapiens	Q9H479	protein repair mechanism. Fructosamine 3-kinase phosphorylates with high affinity both low-molecular-mass and protein-bound fructosamines on the third carbon of their deoxyfructose moiety, leading to the formation of fructosamine 3-phosphates. The latter are unstable and spontaneously decompose into inorganic phosphate and 3-deoxyglucosone, with concomitant regeneration of the unglycated amine	707420	-	-
ATP + [protein]-N6-D-fructosyl-L-lysine	ADP + [protein]-N6-(O3-phosphono-D-fructosyl)-L-lysine		Homo sapiens	-	repairing glucose-mediated non-enzymatic modification of proteins. The function of fructosamine-3-kinase is seen in catalysing the ATP-dependent phosphorylation of the protein-bound fructosamine (Amadori compound) fructoselysine, which is the first stable intermediate resulting from the Maillard reaction between glucose and lysine, on its 3-hydroxy group to 3-phosphofructosyllysine. The phosphorylation destabilises the fructose-amine linkage leading to a spontaneous decomposition of 3-phosphofructosyllysine to the unmodified lysine residue as well as to 3-deoxyglucosulose and inorganic phosphate	707098	-	-
ATP + [protein]-N6-D-fructosyl-L-lysine	ADP + [protein]-N6-(O3-phosphono-D-fructosyl)-L-lysine		Gallus gallus, Mus musculus, Rattus norvegicus	-	specific role of fructosamine 3-kinase to repair protein damage caused by glucose	708981	-	-
ATP + [protein]-N6-D-fructosyl-L-lysine	ADP + [protein]-N6-(O3-phosphono-D-fructosyl)-L-lysine		Mus musculus, Homo sapiens	-	the physiological function of fructosamine-3-kinase may be to initiate a process leading to the deglycation of fructoselysine and of glycated proteins	708294	-	-
ATP + [protein]-N6-D-psicosyl-L-lysine	ADP + [protein]-N6-(O3-phosphono-D-psicosyl)-L-lysine		Homo sapiens	Q9HA64	ketosamine-3-kinase 2 plays a role in freeing proteins from ribulosamines or psicosamines, which might arise in a several step process, from the reaction of amines with glucose and/or glycolytic intermediates. This role is shared by fructosamine-3-kinase (ketosamine-3-kinase 1), which has, in addition, the unique capacity to phosphorylate fructosamines	708296	-	-

COFACTOR	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
No entries in this field

METALS and IONS	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

INHIBITORS	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
1-deoxy-1-morpholin-4-yl-D-fructose	Homo sapiens	Q9HA64	-	708296	-
1-deoxy-1-morpholin-4-yl-D-psicose	Homo sapiens	Q9HA64	-	708296	2D-image
1-deoxy-1-morpholin-4-yl-D-ribulose	Homo sapiens	Q9HA64	-	708296	-
1-deoxy-1-morpholinofructose	Homo sapiens	-	substrate and competitive inhibitor of fructosamine 3-kinase, doubles the rate of accumulation of glycated haemoglobin, but markedly decreases the amount of haemoglobin containing alkali-labile phosphate	707420	-
3-O-methylsorbitol-lysine	Rattus norvegicus	-	inhibitors based on sorbitol show competitive inhibition of the fructoseamine-3-kinase reaction but also prevent the formation of 3-deoxyglucosone, because there is no spontaneous decomposition of the product to 3-deoxyglucosone. For compounds blocked at C3, also there is no product formed. The Ki values of these compounds are approx. 0.5 mM. Although high for an in vivo drug, their apparent low toxicity make it possible to use them, at least in animals, to lower 3-deoxyglucosone levels	707456	-
N6-D-psicosyl-L-lysine	Homo sapiens	Q9HA64	-	708296	-

ACTIVATING COMPOUND	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
No entries in this field

KM VALUE [mM]	KM VALUE [mM] Maximum	SUBSTRATE	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
0.001	-	1-deoxy-1-morpholin-4-yl-D-fructose	Homo sapiens	-	pH 7.8, 30�C, erythrocyte enzyme; pH 7.8, 30�C, recombinant enzyme	708294	-
0.001	-	1-deoxy-1-morpholin-4-yl-D-fructose	Mus musculus	-	pH 7.8, 30�C	708294	-
0.01	-	1-deoxy-1-morpholin-4-yl-D-fructose	Homo sapiens	Q9HA64	pH 7.8, 30�C	708296	-
0.1	-	1-deoxy-1-morpholin-4-yl-D-fructose	Homo sapiens	-	37�C, pH not specified in the publication	707420	-
0.16	-	1-deoxy-1-morpholin-4-yl-D-psicose	Homo sapiens	Q9HA64	pH 7.8, 30�C	708296	2D-image
0.0026	-	1-deoxy-1-morpholin-4-yl-D-ribulose	Homo sapiens	Q9HA64	pH 7.8, 30�C	708296	-
50	-	D-fructose	Homo sapiens	-	pH 8.0, 37�C	708295	2D-image
0.001	-	N2-(1-deoxy-D-fructosyl)-glycine	Homo sapiens	-	pH 7.8, 30�C, erythrocyte enzyme	708294	-
0.001	-	N2-(1-deoxy-D-fructosyl)-glycine	Mus musculus	-	pH 7.8, 30�C	708294	-
0.0022	-	N2-(1-deoxy-D-fructosyl)-glycine	Homo sapiens	-	pH 7.8, 30�C, recombinant enzyme	708294	-
1.5	-	N2-(1-deoxy-D-fructosyl)-glycylglycine	Homo sapiens	-	-	708294	-
0.8	-	N2-(1-deoxy-D-fructosyl)-L-valine	Homo sapiens	-	-	708294	-
0.5	-	N5-D-fructosyl-L-ornithine	Homo sapiens	-	pH 8.0, 37�C	708295	-
0.0072	-	N6-(1-deoxy-D-fructosyl)-L-lysine	Homo sapiens	-	-	708294	-
0.0072	-	N6-(1-deoxy-D-fructosyl)-lysine	Homo sapiens	-	pH 7.8, 30�C, recombinant enzyme	708294	-
0.0074	-	N6-(1-deoxy-D-fructosyl)-lysine	Mus musculus	-	pH 7.8, 30�C	708294	-
0.0132	-	N6-(1-deoxy-D-fructosyl)-lysine	Homo sapiens	-	pH 7.8, 30�C, erythrocyte enzyme	708294	-
0.75	-	N6-D-fructosyl-L-lysine	Homo sapiens	-	pH 8.0, 37�C	708295	-
0.14	-	N6-D-psicosyl-L-lysine	Homo sapiens	Q9HA64	pH 7.8, 30�C	708296	-
0.01	-	[protein]-N6-D-fructosyl-L-lysine	Homo sapiens	-	pH 8.0, 37�C	708295	2D-image

TURNOVER NUMBER [1/s]	TURNOVER NUMBER MAXIMUM[1/s]	SUBSTRATE	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
No entries in this field

kcat/KM VALUE [1/mMs^-1]	kcat/KM VALUE [1/mMs^-1] Maximum	SUBSTRATE	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
No entries in this field

Ki VALUE [mM]	Ki VALUE [mM] Maximum	INHIBITOR	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
additional information	-	3-O-methylsorbitol-lysine	Rattus norvegicus	-	inhibitors based on sorbitol show competitive inhibition of the fructoseamine-3-kinase reaction but also prevent the formation of 3-deoxyglucosone, because there is no spontaneous decomposition of the product to 3-deoxyglucosone. For compounds blocked at C3, also there is no product formed. The Ki values of these compounds are approx. 0.5 mM. Although high for an in vivo drug, their apparent low toxicity make it possible to use them, at least in animals, to lower 3-deoxyglucosone levels	707456	-

IC50 VALUE [mM]	IC50 VALUE [mM] Maximum	INHIBITOR	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	IMAGE
0.067	-	1-deoxy-1-morpholin-4-yl-D-fructose	Homo sapiens	Q9HA64	pH 7.8, 30�C	708296	-
0.69	-	1-deoxy-1-morpholin-4-yl-D-psicose	Homo sapiens	Q9HA64	pH 7.8, 30�C, phosphorylation of lysozyme glycated with allose	708296	2D-image
0.0036	-	1-deoxy-1-morpholin-4-yl-D-ribulose	Homo sapiens	Q9HA64	pH 7.8, 30�C, phosphorylation of lysozyme glycated with allose	708296	-
0.72	-	N6-D-psicosyl-L-lysine	Homo sapiens	Q9HA64	pH 7.8, 30�C, phosphorylation of lysozyme glycated with allose	708296	-

SPECIFIC ACTIVITY [µmol/min/mg]	SPECIFIC ACTIVITY MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
2.08	-	Homo sapiens	-	pH 8.0, 37�C	708295

pH OPTIMUM	pH MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
7.5	-	Homo sapiens	-	assay at	707098
7.8	-	Homo sapiens, Mus musculus	-	assay at	708294
7.8	-	Gallus gallus, Mus musculus, Rattus norvegicus	-	asay at	708981
8	-	Homo sapiens	-	assay at	708295

pH RANGE	pH RANGE MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

TEMPERATURE OPTIMUM	TEMPERATURE OPTIMUM MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
30	-	Homo sapiens, Mus musculus	-	assay at	708294
30	-	Gallus gallus, Mus musculus	-	assay at	708981
37	-	Homo sapiens	-	assay at	707098, 708295

TEMPERATURE RANGE	TEMPERATURE MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

pI VALUE	pI VALUE MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

SOURCE TISSUE	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE	SOURCE
blood plasma	Rattus norvegicus	-	-	707456
bone marrow	Mus musculus	Q8K274	highest levels of expression in bone marrow, brain, spleen and kidney	708296
brain	Mus musculus	Q8K274	highest levels of expression in bone marrow, brain, spleen and kidney	708296
brain	Gallus gallus, Mus musculus, Rattus norvegicus	-	-	708981
colon	Homo sapiens	-	fructosamine-3-kinase is a functionally active enzyme in human colon tissue, without significant differences between normal mucosa and cancer. The mean level of fructosamine-3-kinase mRNA is significantly lower in cancer than in the corresponding normal colorectal mucosa. The colorectal tumors located on the left side show lower levels of both enzymatic activity and mRNA fructosamine-3-kinase than tumors located in the right side of colon	708589
erythrocyte	Homo sapiens	-	the human erythrocyte FN3K activity, which is stable with time in a single individual, is highly variable from person to person. This variability, which is linked to single nucleotide polymorphisms that are present in the FN3K gene, affects the glycation level of at least one specific site in haemoglobin	707094
erythrocyte	Homo sapiens	-	the mean erythrocyte FN3K activity does not differ between normoglycaemic subjects and type 1 diabetic patients, but there is a wide interindividual variability in both groups (from about 1 to 4 mU/g haemoglobin). This variability is stable with time and associated with two single nucleotide polymorphisms in the promoter region and exon 6 of the FN3K gene. There is no significant correlation between FN3K activity and the levels of HbA1c, total glycated haemoglobin and haemoglobin fructoselysine residues, either in the normoglycaemic or diabetic group. The glycation level of Lys144 (in beta-chain of hemoglobin) is about twice as high in normoglycaemic subjects with the lowest FN3K activities as compared to those with the highest FN3K activities	708287
erythrocyte	Homo sapiens	-	-	707098, 707420, 708294, 708295, 708979
erythrocyte	Gallus gallus	-	; low activity	708981
erythrocyte	Mus musculus	-	-	708294, 708981
erythrocyte	Rattus norvegicus	-	-	708981
erythrocyte	Sus scrofa	-	low activity	708981
fibroblast	Homo sapiens	-	cultured fibroblasts treated with conditions mimicking the hormonal and biochemical profile of the diabetic state show no changes in fructosamine-3-kinase expression relative to untreated cells. FN3K acts as protein repair enzyme and is expressed constitutively in human cells independently of some of the variables altered in the diabetic state	707351
heart	Gallus gallus	-	-	708981
heart	Mus musculus	-	-	708296, 708981
heart	Rattus norvegicus	-	-	708981
kidney	Homo sapiens	-	highest levels of FN3K expression are found in tissues known to be susceptible to glycation and diabetic complications such as kidney and neurons	707351
kidney	Homo sapiens	-	the enzyme is present in all tissues, with the highest level of expression in the kidney	708295
kidney	Mus musculus	Q8K274	highest levels of expression in bone marrow, brain, spleen and kidney	708296
kidney	Gallus gallus, Mus musculus, Rattus norvegicus	-	-	708981
neuron	Homo sapiens	-	highest levels of FN3K expression are found in tissues known to be susceptible to glycation and diabetic complications such as kidney and neurons	707351
skeletal muscle	Mus musculus	Q8K274	expressed at low levels	708296
skeletal muscle	Gallus gallus, Mus musculus, Rattus norvegicus	-	-	708981
spleen	Mus musculus	Q8K274	highest levels of expression in bone marrow, brain, spleen and kidney	708296
liver	Mus musculus	Q8K274	expressed at low levels	708296
additional information	Mus musculus	Q8K274	no expression is observed in the intestinal mucosa	708296

LOCALIZATION	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	GeneOntology No.	LITERATURE	SOURCE
No entries in this field

PDB	SCOP	CATH	ORGANISM
No entries in this field

MOLECULAR WEIGHT	MOLECULAR WEIGHT MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

SUBUNITS	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
?	Mus musculus	-	x * 35032, calculated from sequence	707061
?	Homo sapiens	-	x * 35000, SDS-PAGE	707420
?	Homo sapiens	-	x * 35000, SDS-PAGE; x * 35032, calculated from sequence; x * 35171, calculated from sequence	708294
?	Mus musculus	-	x * 35000, SDS-PAGE; x * 35032, calculated from sequence	708294
?	Homo sapiens	-	x * 35000, calculated from sequence	708295

POSTTRANSLATIONAL MODIFICATION	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

Crystallization/COMMENTARY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
No entries in this field

pH STABILITY	pH STABILITY MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

TEMPERATURE STABILITY	TEMPERATURE STABILITY MAXIMUM	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

GENERAL STABILITY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
No entries in this field

ORGANIC SOLVENT	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
No entries in this field

OXIDATION STABILITY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
No entries in this field

STORAGE STABILITY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
No entries in this field

Purification/COMMENTARY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
partial	Gallus gallus	-	708981
-	Homo sapiens	-	707094, 707420, 708294, 708295
recombinant enzyme, partially purified by chromatography on Blue Sepharose	Homo sapiens	Q9HA64	708296
-	Mus musculus	-	708294
partial	Mus musculus, Rattus norvegicus	-	708981

Cloned/COMMENTARY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
expression in Escherichia coli	Homo sapiens	-	707420, 708294
human FN3K-RP is transfected in human embryonic kidney cells and expressed	Homo sapiens	Q9HA64	708296
expression in Escherichia coli	Mus musculus	-	708294

EXPRESSION	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
the down-regulation of FN3K gene expression in cancer tissue compared with normal mucosa is a characteristic only of the left-sided tumours of the colon	Homo sapiens	-	710172
no regulation of the expression of fructose-3-kinase is observed in human fibroblasts treated with conditions mimicking the hormonal and biochemical profile of the diabetic state	Homo sapiens	-	707094
highest levels of FN3K expression are found in tissues known to be susceptible to glycation and diabetic complications such as kidney and neurons. Cultured fibroblasts treated with conditions mimicking the hormonal and biochemical profile of the diabetic state show no changes in fructosamine-3-kinase expression relative to untreated cells. FN3K acts as protein repair enzyme and is expressed constitutively in human cells independently of some of the variables altered in the diabetic state	Homo sapiens	-	707351
mildly glycated casein in a standard diet stimulates 3-deoxyglucosone levels 10�20fold in the plasma and approximately 3fold in the kidney compared with a control diet containing identical constituents	Rattus norvegicus	-	707456
rats are starved for 2 days or rendered diabetic with streptozotocin and analyzed 5 days later. No detectable change in the activity of fructosamine 3-kinase is observed in liver, heart, kidney, and brain	Rattus norvegicus	-	708981

ENGINEERING	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
additional information	Homo sapiens	-	diabetic subjects with the CC variant of SNP rs1056534 (G900C), which is associated with a higher FN3K activity, have lower HbA1c levels compared with other genotypes	707094
additional information	Homo sapiens	-	the G900C (rs1056534) single nucleotide polymorphism of the FN3K gene is associated with the enzyme activity, with the level of HbA and the onset of the disease, but not with either of the diabetic microvascular complications	708421

Renatured/COMMENTARY	ORGANISM	UNIPROT ACCESSION NO.	LITERATURE
No entries in this field

APPLICATION	ORGANISM	UNIPROT ACCESSION NO.	COMMENTARY	LITERATURE
analysis	Homo sapiens	-	convenient assay for the determination of FN3K activity in erythrocytes, which can be performed in routine laboratories	707098
medicine	Rattus norvegicus	-	inhibition of fructoseamine-3-kinase is a promising new therapeutic target for diabetic complications, as well as other 3-deoxyglucosone-dependent pathologies	707456

DISEASE	TITLE OF PUBLICATION	LINK TO PUBMED
Adenoma	-	PubMed
Colorectal Neoplasms	-	PubMed
Diabetes Mellitus	-	PubMed
Diabetes Mellitus, Type 2	-	PubMed
Diabetic Nephropathies	-	PubMed
Neoplasms	-	PubMed
protein-fructosamine 3-kinase deficiency	-	PubMed

REF.	AUTHORS	TITLE	JOURNAL	VOL.	PAGES	YEAR	ORGANISM (UNIPROT ACCESSION NO.)	LINK TO PUBMED	SOURCE
707061	Pascal, S.M.; Veiga-da-Cunha, M.; Gilon, P.; van Schaftingen, E.; Jonas, J.C.	Effects of fructosamine-3-kinase deficiency on function and survival of mouse pancreatic islets after prolonged culture in high glucose or ribose concentrations	Am. J. Physiol. Endocrinol. Metab.	298	E586-596	2009	Mus musculus, Mus musculus (Q9ER35)	PubMed
707094	van Schaftingen, E.; Collard, F.; Wiame, E.; Veiga-da-Cunha, M.	Enzymatic repair of Amadori products	Amino Acids	42	1143-1150	2012	Homo sapiens, Mus musculus	PubMed
707098	Krause, R.; Oehme, A.; Wolf, K.; Henle, T.	A convenient HPLC assay for the determination of fructosamine-3-kinase activity in erythrocytes	Anal. Bioanal. Chem.	386	2019-2025	2006	Homo sapiens	PubMed
707351	Conner, J.R.; Beisswenger, P.J.; Szwergold, B.S.	The expression of the genes for fructosamine-3-kinase and fructosamine-3-kinase-related protein appears to be constitutive and unaffected by environmental signals	Biochem. Biophys. Res. Commun.	323	932-936	2004	Homo sapiens	PubMed
707420	Delpierre, G.; Collard, F.; Fortpied, J.; van Schaftingen, E.	Fructosamine 3-kinase is involved in an intracellular deglycation pathway in human erythrocytes	Biochem. J.	365	801-808	2002	Homo sapiens, Homo sapiens (Q9H479)	PubMed
707426	Veiga da-Cunha, M.; Jacquemin, P.; Delpierre, G.; Godfraind, C.; Theate, I.; Vertommen, D.; Clotman, F.; Lemaigre, F.; Devuyst, O.; van Schaftingen, E.	Increased protein glycation in fructosamine 3-kinase-deficient mice	Biochem. J.	399	257-264	2006	Mus musculus (Q9ER35)	PubMed
707456	Brown, T.R.; Su, B.; Brown, K.A.; Schwartz, M.A.; Tobia, A.M.; Kappler, F.	Modulation of in vivo 3-deoxyglucosone levels	Biochem. Soc. Trans.	31	1433-1437	2003	Rattus norvegicus	PubMed
708287	Delpierre, G.; Veiga-da-Cunha, M.; Vertommen, D.; Buysschaert, M.;, Van Schaftingen E.	Variability in erythrocyte fructosamine 3-kinase activity in humans correlates with polymorphisms in the FN3K gene and impacts on haemoglobin glycation at specific sites	Diabetes Metab.	32	31-39	2005	Homo sapiens, Homo sapiens (Q9H479)	PubMed
708294	Delpierre, G.; Rider, M.H.; Collard, F.; Stroobant, V.; Vanstapel, F.; Santos, H.; van Schaftingen, E.	Identification, cloning, and heterologous expression of a mammalian fructosamine-3-kinase	Diabetes	49	1627-1634	2000	Homo sapiens, Homo sapiens (Q9H479), Mus musculus, Mus musculus (Q9ER35)	PubMed
708295	Szwergold, B.S.; Howell, S.; Beisswenger, P.J.	Human fructosamine-3-kinase: purification, sequencing, substrate specificity, and evidence of activity in vivo	Diabetes	50	2139-2147	2001	Homo sapiens	PubMed
708296	Collard, F.; Delpierre, G.; Stroobant, V.; Matthijs, G.; van Schaftingen, E.	A mammalian protein homologous to fructosamine-3-kinase is a ketosamine-3-kinase acting on psicosamines and ribulosamines but not on fructosamines	Diabetes	52	2888-2895	2004	Homo sapiens, Homo sapiens (Q9HA64), Mus musculus, Mus musculus (Q8K274)	PubMed
708421	Mohas, M.; Kisfali, P.; Baricza, E.; Merei, A.; Maasz, A.; Cseh, J.; Mikolas, E.; Szijarto, I.A.; Melegh, B.; Wittmann, I.	A polymorphism within the fructosamine-3-kinase gene is associated with HbA1c levels and the onset of type 2 diabetes mellitus	Exp. Clin. Endocrinol. Diabetes	118	209-212	2009	Homo sapiens, Homo sapiens (Q9H479)	PubMed
708589	Notarnicola, M.; Caruso, M.G.; Tutino, V.; Guerra, V.; Frisullo, S.; Altomare, D.F.; Misciagna, G.	Reduced fructosamine-3-kinase activity and its mRNA in human distal colorectal carcinoma	Genes Nutr.	5	257-262	2010	Homo sapiens	PubMed
708979	Delpierrre, G.; Vertommen. D.; Communi, D.; Rider, M.H.; van Schaftingen, E.	Identification of fructosamine residues deglycated by fructosamine-3-kinase in human hemoglobin	J. Biol. Chem.	279	27613-27620	2004	Homo sapiens	PubMed
708981	Delplanque, J.; Delpierre, G.; Opperdoes, F.R.; van Schaftingen, E.	Tissue distribution and evolution of fructosamine 3-kinase and fructosamine 3-kinase-related protein	J. Biol. Chem.	279	46606-46613	2004	Gallus gallus, Mus musculus, Rattus norvegicus, Sus scrofa	PubMed
710172	Caruso, M.G.; Notarnicola, M.; Altomare, D.F.; Misciagna, G.	Gene expression of fructosamine 3 kinase in patients with colorectal cancer	Oncology	73	72-75	2008	Homo sapiens	PubMed

LINKS TO OTHER DATABASES (specific for EC-Number 2.7.1.171)

NCBI: PubMed, Protein, Nucleotide, Structure, Genome, OMIM

IUBMB Enzyme Nomenclature

PROSITE Database of protein families and domains

SYSTERS

Protein Mutant Database

InterPro (database of protein families, domains and functional sites)

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