Information on EC 2.7.1.171 - protein-fructosamine 3-kinase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.7.1.171
-
RECOMMENDED NAME
GeneOntology No.
protein-fructosamine 3-kinase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + [protein]-N6-D-fructosyl-L-lysine = ADP + [protein]-N6-(3-O-phospho-D-fructosyl)-L-lysine
show the reaction diagram
SYSTEMATIC NAME
IUBMB Comments
ATP:[protein]-N6-D-fructosyl-L-lysine 3-phosphotransferase
Non-enzymic 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 non-enzymically 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.
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
-
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
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
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
show the reaction diagram
ATP + 1-deoxy-1-morpholin-4-yl-D-psicose
ADP + 1-deoxy-1-morpholin-4-yl-3-O-phosphono-D-psicose
show the reaction diagram
-
-
-
?
ATP + 1-deoxy-1-morpholin-4-yl-D-ribulose
ADP + 1-deoxy-1-morpholin-4-yl-3-O-phosphono-D-ribulose
show the reaction diagram
-
-
-
?
ATP + D-fructose
ADP + O3-phosphono-D-fructose
show the reaction diagram
ATP + N2-(1-deoxy-D-fructosyl)-glycine
ADP + N2-(1-deoxy-O3-phosphono-D-fructosyl)-glycine
show the reaction diagram
ATP + N2-(1-deoxy-D-fructosyl)-glycylglycine
ADP + N2-(1-deoxy-O3-phosphono-D-fructosyl)-glycylglycine
show the reaction diagram
-
-
-
-
?
ATP + N2-(1-deoxy-D-fructosyl)-L-valine
ADP + N2-(1-deoxy-O3-phosphono-D-fructosyl)-L-valine
show the reaction diagram
-
-
-
-
?
ATP + N2-(1-deoxy-D-fructosyl)-valine
ADP + N2-(1-deoxy-O3-phosphono-D-fructosyl)-valine
show the reaction diagram
ATP + N5-D-fructosyl-L-ornithine
ADP + N5-(O3-phosphono-D-fructosyl)-L-ornithine
show the reaction diagram
-
-
-
-
?
ATP + N6-(1-deoxy-D-fructosyl)-L-lysine
ADP + N6-(1-deoxy-O3-phosphono-D-fructosyl)-L-lysine
show the reaction diagram
-
-
-
-
?
ATP + N6-(1-deoxy-D-fructosyl)-lysine
ADP + N6-(1-deoxy-O3-phosphono-D-fructosyl)-lysine
show the reaction diagram
ATP + N6-D-fructosyl-L-lysine
ADP + N6-(O3-phosphono-D-fructosyl)-L-lysine
show the reaction diagram
-
-
-
-
?
ATP + N6-D-psicosyl-L-lysine
ADP + N6-(O3-phosphono-D-psicosyl)-L-lysine
show the reaction diagram
-
-
-
?
ATP + Nalpha-hippuryl-Nepsilon-(1-deoxy-D-fructosyl)lysine
ADP + Nalpha-hippuryl-Nepsilon-(1-deoxy-3-phospho-D-fructosyl)lysine
show the reaction diagram
-
-
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
show the reaction diagram
-
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
-
-
?
ATP + [protein]-N5-D-ribulosyl-L-lysine
ADP + [protein]-N5-(O3-phosphono-D-fructosyl)-L-lysine
show the reaction diagram
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
-
-
?
ATP + [protein]-N6-D-fructosyl-L-lysine
ADP + [protein]-N6-(O3-phosphono-D-fructosyl)-L-lysine
show the reaction diagram
ATP + [protein]-N6-D-psicosyl-L-lysine
ADP + [protein]-N6-(O3-phosphono-D-psicosyl)-L-lysine
show the reaction diagram
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
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + [protein]-N5-D-ribulosyl-L-lysine
ADP + [protein]-N5-(O3-phosphono-D-fructosyl)-L-lysine
show the reaction diagram
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
-
-
?
ATP + [protein]-N6-D-fructosyl-L-lysine
ADP + [protein]-N6-(O3-phosphono-D-fructosyl)-L-lysine
show the reaction diagram
ATP + [protein]-N6-D-psicosyl-L-lysine
ADP + [protein]-N6-(O3-phosphono-D-psicosyl)-L-lysine
show the reaction diagram
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
-
-
?
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1-deoxy-1-morpholin-4-yl-D-fructose
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1-deoxy-1-morpholin-4-yl-D-psicose
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1-deoxy-1-morpholin-4-yl-D-ribulose
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1-deoxy-1-morpholinofructose
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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
3-O-methylsorbitol-lysine
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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
N6-D-psicosyl-L-lysine
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.001 - 0.1
1-deoxy-1-morpholin-4-yl-D-fructose
0.16
1-deoxy-1-morpholin-4-yl-D-psicose
pH 7.8, 30C
0.0026
1-deoxy-1-morpholin-4-yl-D-ribulose
pH 7.8, 30C
50
D-fructose
-
pH 8.0, 37C
0.001 - 0.0022
N2-(1-deoxy-D-fructosyl)-glycine
1.5
N2-(1-deoxy-D-fructosyl)-glycylglycine
-
-
0.8
N2-(1-deoxy-D-fructosyl)-L-valine
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-
0.5
N5-D-fructosyl-L-ornithine
-
pH 8.0, 37C
0.0072
N6-(1-deoxy-D-fructosyl)-L-lysine
0.0074 - 0.0132
N6-(1-deoxy-D-fructosyl)-lysine
0.75
N6-D-fructosyl-L-lysine
-
pH 8.0, 37C
0.14
N6-D-psicosyl-L-lysine
pH 7.8, 30C
0.01
[protein]-N6-D-fructosyl-L-lysine
-
pH 8.0, 37C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
3-O-methylsorbitol-lysine
-
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
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.067
1-deoxy-1-morpholin-4-yl-D-fructose
Homo sapiens
Q9HA64
pH 7.8, 30C
0.69
1-deoxy-1-morpholin-4-yl-D-psicose
Homo sapiens
Q9HA64
pH 7.8, 30C, phosphorylation of lysozyme glycated with allose
0.0036
1-deoxy-1-morpholin-4-yl-D-ribulose
Homo sapiens
Q9HA64
pH 7.8, 30C, phosphorylation of lysozyme glycated with allose
0.72
N6-D-psicosyl-L-lysine
Homo sapiens
Q9HA64
pH 7.8, 30C, phosphorylation of lysozyme glycated with allose
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
2.08
-
pH 8.0, 37C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
-
assay at
8
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
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assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
highest levels of expression in bone marrow, brain, spleen and kidney
Manually annotated by BRENDA team
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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
Manually annotated by BRENDA team
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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
Manually annotated by BRENDA team
expressed at low levels
Manually annotated by BRENDA team
-
highest levels of FN3K expression are found in tissues known to be susceptible to glycation and diabetic complications such as kidney and neurons
Manually annotated by BRENDA team
highest levels of expression in bone marrow, brain, spleen and kidney
Manually annotated by BRENDA team
additional information
no expression is observed in the intestinal mucosa
Manually annotated by BRENDA team
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
partial
recombinant enzyme, partially purified by chromatography on Blue Sepharose
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
human FN3K-RP is transfected in human embryonic kidney cells and expressed
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
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
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mildly glycated casein in a standard diet stimulates 3-deoxyglucosone levels 1020fold in the plasma and approximately 3fold in the kidney compared with a control diet containing identical constituents
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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
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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
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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
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
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convenient assay for the determination of FN3K activity in erythrocytes, which can be performed in routine laboratories
medicine
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inhibition of fructoseamine-3-kinase is a promising new therapeutic target for diabetic complications, as well as other 3-deoxyglucosone-dependent pathologies