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Information on EC 2.7.1.3 - ketohexokinase and Organism(s) Homo sapiens and UniProt Accession P50053
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2.7.1.3 ketohexokinaseIUBMB Comments
D-Sorbose, D-tagatose and 5-dehydro-D-fructose and a number of other ketoses and their analogues can also act as substrates .
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Word Map
- 2.7.1.3
- fructokinase
-
fructose-induced
-
high-fructose
- fructose-1-phosphate
- triokinase
-
fructolytic
-
fructosuria
-
fructose-metabolizing
- medicine
- analysis
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
ketohexokinase, khk-a, khk-c, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ketohexokinase
ketohexokinase (phosphorylating)
-
-
-
-
KHK
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:D-fructose 1-phosphotransferase
D-Sorbose, D-tagatose and 5-dehydro-D-fructose and a number of other ketoses and their analogues can also act as substrates [4].
CAS REGISTRY NUMBER
COMMENTARY
9030-50-6
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + D-fructose
ADP + D-fructose 1-phosphate
-
role in formation of glycoaldehyde
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + D-fructose
ADP + D-fructose 1-phosphate
-
role in formation of glycoaldehyde
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-ethyl-7-(3-hydroxy-3-methylpyrrolidin-1-yl)-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-6-carbonitrile
-
6-[(3S,4S)-3,4-dihydroxypyrrolidin-1-yl]-2-[(3S)-3-hydroxy-3-methylpyrrolidin-1-yl]-4-(trifluoromethyl)pyridine-3-carbonitrile
nonbasic moderately potent and highly selective ketohexokinase inhibitor
6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-[(3S)-3-hydroxy-3-methylpyrrolidin-1-yl]-4-(trifluoromethyl)pyridine-3-carbonitrile
-
6-[4-(2-hydroxyethyl)piperazin-1-yl]-4-[3-(hydroxymethyl)piperidin-1-yl]-2-(trifluoromethyl)pyridine-3-carbonitrile
-
7-[(3R)-3-hydroxy-3-methylpyrrolidin-1-yl]-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-6-carbonitrile
-
7-[(3S)-3-hydroxy-3-methylpyrrolidin-1-yl]-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-6-carbonitrile
-
[(3R)-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-3-yl]methanol
-
2-(4-aminopiperidin-1-yl)-N8-(cyclopropylmethyl)-N4-(2-methylphenyl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
2-[(3R)-3-aminopiperidin-1-yl]-N8-(cyclopropylmethyl)-N4-[2-(methylsulfanyl)phenyl]pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
2-[(3S)-3-aminopiperidin-1-yl]-N8-(cyclopropylmethyl)-N4-[2-(methylsulfanyl)phenyl]pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
2-[3-(aminomethyl)azetidin-1-yl]-N8-(cyclopropylmethyl)-N4-[2-(methylsulfanyl)phenyl]pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
2-[4-(aminomethyl)piperidin-1-yl]-N8-(cyclopropylmethyl)-N4-(2-methylphenyl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
2-[4-(aminomethyl)piperidin-1-yl]-N8-(cyclopropylmethyl)-N4-[2-(methylsulfanyl)phenyl]pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N4-(2-bromophenyl)-N8-cyclopropyl-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N4-(2-chlorophenyl)-N8-cyclopropyl-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N4-(2-methylphenyl)-2-(piperazin-1-yl)-N8-(1,3-thiazol-2-ylmethyl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N4-(2-methylphenyl)-2-(piperazin-1-yl)-N8-(prop-2-yn-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N4-(2-methylphenyl)-2-(piperazin-1-yl)-N8-(tetrahydrothiophen-2-ylmethyl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N4-(2-methylphenyl)-2-(piperazin-1-yl)-N8-propylpyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N4-cyclohexyl-N8-cyclopropyl-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N4-[2-(methylsulfanyl)phenyl]-2-(piperazin-1-yl)-N8-(1,3-thiazol-2-ylmethyl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N4-[2-(methylsulfanyl)phenyl]-2-(piperazin-1-yl)-N8-(pyridin-2-ylmethyl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N4-[2-(methylsulfanyl)phenyl]-2-(piperazin-1-yl)-N8-(thiophen-2-ylmethyl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N4-[2-(methylsulfanyl)phenyl]-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-(2-cyclopropylethyl)-N4-[2-(methylsulfanyl)phenyl]-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-(2-methoxyethyl)-N4-[2-(methylsulfanyl)phenyl]-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-(cyclobutylmethyl)-N4-[2-(methylsulfanyl)phenyl]-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-(cyclopropylmethyl)-2-(1,4-diazepan-1-yl)-N4-(2-methylphenyl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-(cyclopropylmethyl)-2-(4-iminopiperidin-1-yl)-N4-(2-methylphenyl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-(cyclopropylmethyl)-2-(4-methylpiperazin-1-yl)-N4-[2-(methylsulfanyl)phenyl]pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-(cyclopropylmethyl)-2-[4-[(dimethylamino)methyl]piperidin-1-yl]-N4-[2-(methylsulfanyl)phenyl]pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-(cyclopropylmethyl)-N2-methyl-N2-[2-(methylamino)ethyl]-N4-[2-(methylsulfanyl)phenyl]pyrimido[5,4-d]pyrimidine-2,4,8-triamine
-
-
N8-(cyclopropylmethyl)-N4-(2-methylphenyl)-2-(4-methylpiperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-(cyclopropylmethyl)-N4-(2-methylphenyl)-2-(morpholin-4-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-benzyl-N4-(2-methylphenyl)-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-cyclohexyl-N4-(2-methylphenyl)-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-cyclopropyl-2-(piperazin-1-yl)-N4-[2-(propan-2-yl)phenyl]pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-cyclopropyl-2-(piperazin-1-yl)-N4-[2-[(trifluoromethyl)sulfanyl]phenyl]pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-cyclopropyl-N4-(2-cyclopropylphenyl)-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-cyclopropyl-N4-(2-ethoxyphenyl)-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-cyclopropyl-N4-(2-ethylphenyl)-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-cyclopropyl-N4-(2-fluorophenyl)-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-cyclopropyl-N4-(2-methoxyphenyl)-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-cyclopropyl-N4-(2-methylphenyl)-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-cyclopropyl-N4-(3-methylphenyl)-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-cyclopropyl-N4-phenyl-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-cyclopropyl-N4-[2-(ethylsulfanyl)phenyl]-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-cyclopropyl-N4-[2-(methylsulfanyl)phenyl]-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-cyclopropyl-N4-[2-(methylsulfonyl)phenyl]-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-cyclopropyl-N4-[3-(methylsulfanyl)phenyl]-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-cyclopropyl-N4-[4-(methylsulfanyl)phenyl]-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-ethyl-N4-(2-methylphenyl)-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-hexyl-N4-(2-methylphenyl)-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
N8-methyl-N4-(2-methylphenyl)-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
-
-
additional information
-
extracts of Angelica archangelica, Garcinia mangostana, Petroselinum crispum, and Scutellaria baicalensis exhibit ketohexokinase inhibitory activity and block fructose-induced ATP depletion and fructose-induced elevation in triglyerides and uric acid
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00148
2-ethyl-7-(3-hydroxy-3-methylpyrrolidin-1-yl)-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-6-carbonitrile
Homo sapiens
23°C, pH 7.4
0.319
4,6-dimethyl-2-(morpholin-4-yl)pyridine-3-carbonitrile
Homo sapiens
23°C, pH 7.4
0.00039 - 0.00045
6-[(3S,4S)-3,4-dihydroxypyrrolidin-1-yl]-2-[(3S)-3-hydroxy-3-methylpyrrolidin-1-yl]-4-(trifluoromethyl)pyridine-3-carbonitrile
0.00103
6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-[(3S)-3-hydroxy-3-methylpyrrolidin-1-yl]-4-(trifluoromethyl)pyridine-3-carbonitrile
Homo sapiens
23°C, pH 7.4
0.01679
6-[4-(2-hydroxyethyl)piperazin-1-yl]-4-[3-(hydroxymethyl)piperidin-1-yl]-2-(trifluoromethyl)pyridine-3-carbonitrile
Homo sapiens
23°C, pH 7.4
0.02421
7-[(3R)-3-hydroxy-3-methylpyrrolidin-1-yl]-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-6-carbonitrile
Homo sapiens
23°C, pH 7.4
0.00067
7-[(3S)-3-hydroxy-3-methylpyrrolidin-1-yl]-5-(trifluoromethyl)-1H-pyrrolo[3,2-b]pyridine-6-carbonitrile
Homo sapiens
23°C, pH 7.4
0.118
[(3R)-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-3-yl]methanol
Homo sapiens
23°C, pH 7.4
0.0002
2-(4-aminopiperidin-1-yl)-N8-(cyclopropylmethyl)-N4-(2-methylphenyl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.000018
2-[(3R)-3-aminopiperidin-1-yl]-N8-(cyclopropylmethyl)-N4-[2-(methylsulfanyl)phenyl]pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.000023
2-[(3S)-3-aminopiperidin-1-yl]-N8-(cyclopropylmethyl)-N4-[2-(methylsulfanyl)phenyl]pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.00003
2-[3-(aminomethyl)azetidin-1-yl]-N8-(cyclopropylmethyl)-N4-[2-(methylsulfanyl)phenyl]pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.00007
2-[4-(aminomethyl)piperidin-1-yl]-N8-(cyclopropylmethyl)-N4-(2-methylphenyl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.00001
2-[4-(aminomethyl)piperidin-1-yl]-N8-(cyclopropylmethyl)-N4-[2-(methylsulfanyl)phenyl]pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.009
N,N'-dicyclopropyl-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.00017
N4-(2-bromophenyl)-N8-cyclopropyl-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.00054
N4-(2-chlorophenyl)-N8-cyclopropyl-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.00006
N4-(2-methylphenyl)-2-(piperazin-1-yl)-N8-(1,3-thiazol-2-ylmethyl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.0017
N4-(2-methylphenyl)-2-(piperazin-1-yl)-N8-(prop-2-yn-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.0003
N4-(2-methylphenyl)-2-(piperazin-1-yl)-N8-(tetrahydrothiophen-2-ylmethyl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.0004
N4-(2-methylphenyl)-2-(piperazin-1-yl)-N8-propylpyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.009
N4-cyclohexyl-N8-cyclopropyl-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.000016
N4-[2-(methylsulfanyl)phenyl]-2-(piperazin-1-yl)-N8-(1,3-thiazol-2-ylmethyl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.0000098
N4-[2-(methylsulfanyl)phenyl]-2-(piperazin-1-yl)-N8-(pyridin-2-ylmethyl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.00003
N4-[2-(methylsulfanyl)phenyl]-2-(piperazin-1-yl)-N8-(thiophen-2-ylmethyl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.0000071
N4-[2-(methylsulfanyl)phenyl]-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.00005
N8-(2-cyclopropylethyl)-N4-[2-(methylsulfanyl)phenyl]-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.000007
N8-(2-methoxyethyl)-N4-[2-(methylsulfanyl)phenyl]-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.000018
N8-(cyclobutylmethyl)-N4-[2-(methylsulfanyl)phenyl]-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.0003
N8-(cyclopropylmethyl)-2-(1,4-diazepan-1-yl)-N4-(2-methylphenyl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.00071
N8-(cyclopropylmethyl)-2-(4-iminopiperidin-1-yl)-N4-(2-methylphenyl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.00011
N8-(cyclopropylmethyl)-2-(4-methylpiperazin-1-yl)-N4-[2-(methylsulfanyl)phenyl]pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.00014
N8-(cyclopropylmethyl)-2-[4-[(dimethylamino)methyl]piperidin-1-yl]-N4-[2-(methylsulfanyl)phenyl]pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.00013
N8-(cyclopropylmethyl)-N2-methyl-N2-[2-(methylamino)ethyl]-N4-[2-(methylsulfanyl)phenyl]pyrimido[5,4-d]pyrimidine-2,4,8-triamine
Homo sapiens
-
pH and temperature not specified in the publication
0.0015
N8-(cyclopropylmethyl)-N4-(2-methylphenyl)-2-(4-methylpiperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.007
N8-(cyclopropylmethyl)-N4-(2-methylphenyl)-2-(morpholin-4-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.0003
N8-benzyl-N4-(2-methylphenyl)-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.0016
N8-cyclohexyl-N4-(2-methylphenyl)-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.005
N8-cyclopropyl-2-(piperazin-1-yl)-N4-[2-(propan-2-yl)phenyl]pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.003
N8-cyclopropyl-2-(piperazin-1-yl)-N4-[2-[(trifluoromethyl)sulfanyl]phenyl]pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.00038
N8-cyclopropyl-N4-(2-cyclopropylphenyl)-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.0002
N8-cyclopropyl-N4-(2-ethoxyphenyl)-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.00013
N8-cyclopropyl-N4-(2-ethylphenyl)-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.0015
N8-cyclopropyl-N4-(2-fluorophenyl)-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.0001
N8-cyclopropyl-N4-(2-methoxyphenyl)-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.00021
N8-cyclopropyl-N4-(2-methylphenyl)-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.0028
N8-cyclopropyl-N4-(3-methylphenyl)-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.0032
N8-cyclopropyl-N4-phenyl-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.009
N8-cyclopropyl-N4-[2-(ethylsulfanyl)phenyl]-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.000012
N8-cyclopropyl-N4-[2-(methylsulfanyl)phenyl]-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.009
N8-cyclopropyl-N4-[2-(methylsulfonyl)phenyl]-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.002
N8-cyclopropyl-N4-[3-(methylsulfanyl)phenyl]-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.009
N8-cyclopropyl-N4-[4-(methylsulfanyl)phenyl]-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.0023
N8-ethyl-N4-(2-methylphenyl)-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.0004
N8-hexyl-N4-(2-methylphenyl)-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.0004
N8-methyl-N4-(2-methylphenyl)-2-(piperazin-1-yl)pyrimido[5,4-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.00039
6-[(3S,4S)-3,4-dihydroxypyrrolidin-1-yl]-2-[(3S)-3-hydroxy-3-methylpyrrolidin-1-yl]-4-(trifluoromethyl)pyridine-3-carbonitrile
Homo sapiens
23°C, pH 7.4, splice variant KHK-A
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
expressed at significantly higher level in glioma tissues than in non-tumor brain
expressed at significantly higher level in glioma tissues than in non-tumor brain
represent the most prevalent cancer of the kidney. The mean ketohexokinase activity in the renal cell carcinoma tissue samples is approximately 1.4fold lower than that in their normal kidney tissue. Ketohexokinase activity is approximately 1.5fold lower in pT3 renal cell carcinoma tissue than that in pT1 renal cell carcinoma tissue. The enzyme activity of tumor in histological grade 3 is 1.8fold lower than for grade 1 tumor(reaction mixture activity assay: acid-treated supernatant (100 microl) containing 10 mM MgCl2, 50 mM TrisHCl, pH 7.4, 10 mM ATP, 50 mM N-acetyl-D-glucosamine, 10 mM D[UL-14C]fructose and water, at 37°C). The expression level of ketohexokinase mRNA is reduced two- to eightfold in nearly all the clear cell renal cell carcinoma tissue samples compared with normal kidney, except for one renal cell carcinoma sample.
-
relatively low expression of ketohexokinase.The expression profile for ketohexokinase in human is derived from from Unigene by adding the number of EST clones obtained from normal tissues
-
relatively low expression of ketohexokinase.The expression profile for ketohexokinase in human is derived from from Unigene by adding the number of EST clones obtained from normal tissues
-
relatively high expression of ketohexokinase.The expression profile for ketohexokinase in human is derived from from Unigene by adding the number of EST clones obtained from normal tissues
-
relatively low expression of ketohexokinase.The expression profile for ketohexokinase in human is derived from from Unigene by adding the number of EST clones obtained from normal tissues
-
relatively low expression of ketohexokinase.The expression profile for ketohexokinase in human is derived from from Unigene by adding the number of EST clones obtained from normal tissues
-
relatively low expression of ketohexokinase.The expression profile for ketohexokinase in human is derived from from Unigene by adding the number of EST clones obtained from normal tissues
additional information
-
relatively high expression of ketohexokinase.The expression profile for ketohexokinase in human is derived from from Unigene by adding the number of EST clones obtained from normal tissues
-
relatively low expression of ketohexokinase.The expression profile for ketohexokinase in human is derived from from Unigene by adding the number of EST clones obtained from normal tissues
-
high expression of ketohexokinase.The expression profile for ketohexokinase in human is derived from from Unigene by adding the number of EST clones obtained from normal tissues
-
high expression of ketohexokinase.The expression profile for ketohexokinase in human is derived from from Unigene by adding the number of EST clones obtained from normal tissues
-
relatively low expression of ketohexokinase.The expression profile for ketohexokinase in human is derived from from Unigene by adding the number of EST clones obtained from normal tissues
additional information
peripheral isoform (isoform C is a hepatic isoform)
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug target
ketohexokinase may be a therapeutic target. Complete knockout of all ketohexokinase isoforms prevents fructose-induced disease. In contrast, selective knockout of the ubiquitous, low-activity KHK-A isoform exacerbates fructose-induced disease, possibly by increasing flux through the KHK-C isoform expressed in key metabolic tissues, like liver
malfunction
functionally, knockdown of ketohexokinase can significantly inhibit cell proliferation and migration of glioma cells in fructose medium
metabolism
metabolism
fructose increases de novo lipogenesis through the efficient and uninhibited action of ketohexokinase and aldolase B, which yields substrates for fatty-acid synthesis. Chronic fructose consumption further enhances the capacity for hepatic fructose metabolism via activation of several key transcription factors (i.e. SREBP1c and ChREBP), which augment expression of lipogenic enzymes, increasing lipogenesis, further compounding hypertriglyceridemia, and hepatic steatosis. Hepatic insulin resistance develops from diacylglycerol-PKCe mediated impairment of insulin signaling and possibly additional mechanisms
metabolism
increased fructose consumption and its subsequent metabolism are implicated in hepatic steatosis, dyslipidemia, obesity, and insulin resistance
metabolism
ketohexokinase overexpression is significantly correlated with tumor malignancy and poor survival of glioma patients
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). KHK_HUMAN
298
0
32523
Swiss-Prot
Secretory Pathway (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
32730
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
at 20°C, 10 mg/ml protein pH 7.5 in 10 mM HEPES, vapour-diffusion method applied in hanging- and sitting-drop variants, protein desalted and with Centricon-10 concentrated, precipitants: 2-propanol and MPD, space group: P212121 or P21212 with a: 93.4, b: 121.5 and c: 108.4 A
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
G40R
-
both ketohexokinase-A and ketohexokinase-C become inactive and largely unsoluble
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
55
-
30 min ketohexokinase-A little loss in activity, ketohexokinase-C completely inactivated
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
development of a three-dimensional chemical-feature-based QSAR pharmacophore model by using Discovery Studio v2.5 to identify inhibitors, and screening of chemical databases for validated pharmacophore hypothesis. Hit compounds show good hydrogen bonding interactions with the keyamino acids such as Arg108, Asp258, Gly41, Gly255, Asn42 and water molecules W12, W27, respectively
medicine
medicine
-
compared with normal hepatocytes, hepatocellular carcinoma cells markedly reduce the rate of fructose metabolism and the level of reactive oxygen species, as a result of a c-Myc-dependent and heterogeneous nuclear ribonucleoprotein H1- and H2-mediated switch from expression of the high-activity fructokinase KHK-C to the low-activity KHK-A isoform. KHK-A acts as a protein kinase, phosphorylating and activating phosphoribosyl pyrophosphate synthetase PRPS1. c-Myc, hnRNPH1/2 and KHK-A expression levels and PRPS1 Thr225 phosphorylation levels correlate with each other in hepatocellular carcinoma specimens and are associated with poor prognosis for hepatocellular carcinoma
medicine
-
mutually exclusive splicing of adjacent exons 3A and 3C in ketohexokinase precursor RNA results in expression of ketohexokinase isoform KHK-A or KHK-C. KHK-A but not KHK-C interacts with phosphoribosyl diphosphate synthetase PRPS1. KHK-A functions as a protein kinase and directly phosphorylates PRPS1 at T225. This phosphorylation blocks the binding of the allosteric inhibitor ADP to PRPS1, thereby abrogating the feedback inhibition by ADP and leading to elevated de novo nucleic acid synthesis by constitutively activating PRPS1 in hepytocellular carcinoma cells
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Bais, R.; James, H.M.; Rofe, A.M.; Conyers, A.J.
The purification and properties of human liver ketohexokinase. A role for ketohexokinase and fructose-bisphosphate aldolase in the metabolic production of oxalate from xylitol
Biochem. J.
230
53-60
1985
Homo sapiens
Hayward, B.E.; Warner, J.P.; Dunlop, N.; Fantes, J.; Intody, S.; Leek, J.; Markham, A.F.; Bonthron, D.T.
Molecular genetics of the human glucokinase regulator-fructokinase (GCKR-ketohexokinase) region of chromosome 2p23
Biochem. Soc. Trans.
25
140-145
1997
Homo sapiens
Kozak, M.; Hayward, B.; Borek, D.; Bonthron, D.T.; Jaskolski, M.
Expression, purification and preliminary crystallographic studies of human ketohexokinase
Acta Crystallogr. Sect. D
57
586-588
2001
Homo sapiens
Asipu, A.; Hayward, B.E.; O'Reilly, J.; Bonthron, D.T.
Properties of normal and mutant recombinant human ketohexokinases and implications for the pathogenesis of essential fructosuria
Diabetes
52
2426-2432
2003
Homo sapiens
Funari, V.A.; Herrera, V.L.; Freeman, D.; Tolan, D.R.
Genes required for fructose metabolism are expressed in Purkinje cells in the cerebellum
Brain Res. Mol. Brain Res.
142
115-122
2005
Homo sapiens, Mus musculus
Hwa, J.S.; Kim, H.J.; Goo, B.M.; Park, H.J.; Kim, C.W.; Chung, K.H.; Park, H.C.; Chang, S.H.; Kim, Y.W.; Kim, D.R.; Cho, G.J.; Choi, W.S.; Kang, K.R.
The expression of ketohexokinase is diminished in human clear cell type of renal cell carcinoma
Proteomics
6
1077-1084
2006
Homo sapiens (P50053), Homo sapiens
Trinh, C.H.; Asipu, A.; Bonthron, D.T.; Phillips, S.E.
Structures of alternatively spliced isoforms of human ketohexokinase
Acta Crystallogr. Sect. D
65
201-211
2009
Homo sapiens (P50053), Homo sapiens
Maryanoff, B.; ONeill, J.; McComsey, D.; Yabut, S.; Luci, D.; Jordan Jr., A.; Masucci, J.; Jones, W.; Abad, M.; Gibbs, A.; Petrounia, I.
Inhibitors of ketohexokinase: Discovery of pyrimidinopyrimidines with specific substitution that complements the ATP-binding site
ACS Med. Chem. Lett.
2
538-543
2011
Homo sapiens
Kavitha, R.; Karunagaran, S.; Chandrabose, S.S.; Lee, K.W.; Meganathan, C.
Pharmacophore modeling, virtual screening, molecular docking studies and density functional theory approaches to identify novel ketohexokinase (KHK) inhibitors
BioSystems
138
39-52
2015
Homo sapiens (P50053)
Li, X.; Qian, X.; Lu, Z.
Fructokinase A acts as a protein kinase to promote nucleotide synthesis
Cell Cycle
15
2689-2690
2016
Homo sapiens
Li, X.; Qian, X.; Peng, L.X.; Jiang, Y.; Hawke, D.H.; Zheng, Y.; Xia, Y.; Lee, J.H.; Cote, G.; Wang, H.; Wang, L.; Qian, C.N.; Lu, Z.
A splicing switch from ketohexokinase-C to ketohexokinase-A drives hepatocellular carcinomaformation
Nat. Cell Biol.
18
561-571
2016
Homo sapiens
Le, M.; Lanaspa, M.; Cicerchi, C.; Rana, J.; Scholten, J.; Hunter, B.; Rivard, C.; Randolph, R.; Johnson, R.
Bioactivity-guided identification of botanical inhibitors of ketohexokinase
PLoS ONE
11
e0157458
2016
Homo sapiens
Gao, W.; Li, N.; Li, Z.; Xu, J.; Su, C.
Ketohexokinase is involved in fructose utilization and promotes tumor progression in glioma
Biochem. Biophys. Res. Commun.
503
1298-1306
2018
Homo sapiens (P50053), Homo sapiens
Huard, K.; Ahn, K.; Amor, P.; Beebe, D.A.; Borzilleri, K.A.; Chrunyk, B.A.; Coffey, S.B.; Cong, Y.; Conn, E.L.; Culp, J.S.; Dowling, M.S.; Gorgoglione, M.F.; Gutierrez, J.A.; Knafels, J.D.; Lachapelle, E.A.; Pandit, J.; Parris, K.D.; Perez, S.; Pfefferkorn, J.A.; Price, D.A.; Raymer, B.; Ross, T.T.; Shavnya, A.
Discovery of fragment-derived small molecules for in vivo inhibition of ketohexokinase (KHK)
J. Med. Chem.
60
7835-7849
2017
Homo sapiens (P50053), Homo sapiens, Rattus norvegicus (Q02974)
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