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Information on EC 1.14.11.16 - peptide-aspartate beta-dioxygenase and Organism(s) Homo sapiens

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EC Tree
IUBMB Comments
Requires Fe2+. Some vitamin K-dependent coagulation factors, as well as synthetic peptides based on the structure of the first epidermal growth factor domain of human coagulation factor IX or X, can act as acceptors.
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Homo sapiens
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
factor inhibiting hif, aspartyl beta-hydroxylase, aspartyl (asparaginyl) beta-hydroxylase, factor-inhibiting hypoxia-inducible factor, factor inhibiting hypoxia-inducible factor, hif asparaginyl hydroxylase, aspartyl/asparaginyl beta-hydroxylase, aspartate beta-hydroxylase, aspartyl (asparaginyl)-beta-hydroxylase, human aspartyl (asparaginyl) beta-hydroxylase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
asparaginyl hydroxylase factor inhibiting HIF-1
-
aspartate beta-hydroxylase
aspartate-beta-hydroxylase
-
aspartate/asparagine-beta-hydroxylase
-
aspartyl (asparaginyl) beta-hydroxylase
-
-
aspartyl (asparaginyl)-beta-hydroxylase
-
-
aspartyl beta-hydroxylase
aspartyl-(asparaginyl) beta-hydroxylase
-
-
aspartyl-(asparaginyl)-b-hydroxylase
-
-
aspartyl-(asparaginyl)-beta-hydroxylase
-
aspartyl-(asparagyl)-beta-hydroxylase
-
-
aspartyl/asparaginyl beta-hydroxylase
-
aspartylpeptide beta-dioxygenase
-
-
-
-
EGF beta-hydroxylase
-
-
EGFH
-
-
factor inhibiting HIF
-
-
factor inhibiting hypoxia-inducible factor
-
-
factor inhibiting hypoxia-inducible transcription factor (HIF)
factor-inhibiting hypoxia-inducible factor
-
-
HIF asparaginyl hydroxylase
-
-
human aspartyl (asparaginyl) beta-hydroxylase
-
-
hypoxia-inducible factor asparaginyl hydroxylase
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
decarboxylation
-
-
hydroxylation
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
peptide-L-aspartate,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating)
Requires Fe2+. Some vitamin K-dependent coagulation factors, as well as synthetic peptides based on the structure of the first epidermal growth factor domain of human coagulation factor IX or X, can act as acceptors.
CAS REGISTRY NUMBER
COMMENTARY hide
122544-66-5
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ankyrin repeat domain of endogenous Notch receptor L-asparagine + 2-oxoglutarate + O2
ankyrin repeat domain of endogenous Notch receptor 3-hydroxy-L-asparagine + succinate + CO2
show the reaction diagram
-
hydroxylation of highly conserved asparaginyl residues within the ankyrin repeat
-
-
?
ankyrin repeat domain protein
?
show the reaction diagram
-
a maximum of three ankyrin repeats enables ankyrin repeat domain proteins as a substrate
-
-
?
HIF (L-Asn803) + 2-oxoglutarate + O2
HIF (3-hydroxy-L-Asn803) + succinate + CO2
show the reaction diagram
-
accepts HIF-1alpha and HIF-2-alpha as substrate, HIF mutant V802A exhibits 4fold lower substrate activity than native protein, no activity with N803A mutant
-
-
?
HIF-1alpha peptide Asp788-Leu822 (L-Asn803) + 2-oxoglutarate + O2
HIF-1alpha peptide Asp788-Leu822 (3-hydroxy-L-Asn803) + succinate + CO2
show the reaction diagram
much lower activity with peptides lacking residues 819-822, 807-822, and 815-822
-
-
?
HIF-1alpha peptide Asp788-Leu822 (L-asparagine803) + 2-oxoglutarate + O2
?
show the reaction diagram
-
-
-
r
peptide L-asparagine + 2-oxoglutarate + O2
peptide 3-hydroxy-L-asparagine + succinate + CO2
show the reaction diagram
peptide L-aspartate + 2-oxoglutarate + O2
peptide 3-hydroxy-L-aspartate + succinate + CO2
show the reaction diagram
peptide-L-aspartate + 2-oxoglutarate + O2
peptide-3-hydroxy-L-aspartate + succinate + CO2
show the reaction diagram
[factor X first EGF-like domain]-L-aspartate + 2-oxoglutarate + O2
[factor X first EGF-like domain]-3-hydroxy-L-aspartate + succinate + CO2
show the reaction diagram
-
-
-
?
[thioether-linked cyclic peptide hFX-CP101-119]-L-aspartate + 2-oxoglutarate + O2
[thioether-linked cyclic peptide hFX-CP101-119]-3-hydroxy-L-aspartate + succinate + CO2
show the reaction diagram
the enzyme accepts substrates with a noncanonical EGFD disulfide connectivity (i.e. the Cys 1-2, 3-4, 5-6 disulfide pattern). Stable cyclic thioether analogues of the noncanonical EGFD AspH substrates are developed to avoid disulfide shuffling
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
peptide L-asparagine + 2-oxoglutarate + O2
peptide 3-hydroxy-L-asparagine + succinate + CO2
show the reaction diagram
peptide L-aspartate + 2-oxoglutarate + O2
peptide 3-hydroxy-L-aspartate + succinate + CO2
show the reaction diagram
-
hydroxylates epidermal growth factor-like domains in transformation-associated proteins
-
?
peptide-L-aspartate + 2-oxoglutarate + O2
peptide-3-hydroxy-L-aspartate + succinate + CO2
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
the enzyme binds divalent calcium, high-affinity regulatory binding site for Ca2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(1S,2S,4R)-3-oxalobicyclo[2.2.1]hept-5-ene-2-carboxylic acid
-
-
(R)-gossypol
-
-
1-oxalocyclopropane-1-carboxylic acid
-
-
2,2-dimethyl-4-oxopentanedioic acid
-
-
2-(2-methylpropyl)-4-oxopentanedioic acid
-
-
2-(3,3-dimethylbutyl)-4-oxopentanedioic acid
-
-
2-benzyl-4-oxopentanedioic acid
-
-
2-ethyl-4-oxopentanedioic acid
-
-
2-oxalocyclopropane-1-carboxylic acid
-
-
2-oxo-3-(3-phenylpropyl)pentanedioic acid
-
-
2-oxo-3-propylpentanedioic acid
-
-
2-oxo-3-[[4-(trifluoromethoxy)phenyl]methyl]pentanedioic acid
-
-
2-oxo-4-(3-phenylpropyl)pentanedioic acid
-
-
2-oxo-4-propylpentanedioic acid
-
-
2-[(naphthalen-2-yl)methyl]-4-oxopentanedioic acid
-
-
3-((3-phenylpropyl)amino)pyridine-2,4-dicarboxylic acid
-
-
3-((4-(trifluoromethyl)benzyl)amino)pyridine-2,4-dicarboxylic acid
-
-
3-((4-chlorophenethyl)amino)pyridine-2,4-dicarboxylic acid
-
-
3-((4-methoxybenzyl)amino)pyridine-2,4-dicarboxylic acid
-
-
3-((4-phenylbutyl)amino)pyridine-2,4-dicarboxylic acid
-
-
3-((cyclohexylmethyl)amino)pyridine-2,4-dicarboxylic acid
-
-
3-(2-aminoanilino)pyridine-2,4-dicarboxylic acid
-
-
3-(2-carboxyanilino)pyridine-2,4-dicarboxylic acid
-
-
3-(2-fluoroanilino)pyridine-2,4-dicarboxylic acid
-
-
3-(2-methoxyanilino)pyridine-2,4-dicarboxylic acid
-
-
3-(2-methylanilino)pyridine-2,4-dicarboxylic acid
-
-
3-(2-nitroanilino)pyridine-2,4-dicarboxylic acid
-
-
3-(3,3-dimethylbutyl)-2-oxopentanedioic acid
-
-
3-(benzylamino)pyridine-2,4-dicarboxylic acid
-
-
3-(phenethylamino)pyridine-2,4-dicarboxylic acid
-
-
3-anilinopyridine-2,4-dicarboxylic acid
-
-
3-benzyl-2-oxopentanedioic acid
-
-
3-ethyl-2-oxopentanedioic acid
-
-
3-[(3,5-dimethylphenyl)methyl]-2-oxopentanedioic acid
-
-
3-[(4-fluorophenyl)methyl]-2-oxopentanedioic acid
-
-
3-[(4-methoxyphenyl)methyl]-2-oxopentanedioic acid
-
-
3-[2-(methylsulfanyl)anilino]pyridine-2,4-dicarboxylic acid
-
-
5-oxalothiophene-2-carboxylic acid
-
-
ankyrin repeat domain
-
may function as a natural inhibitor and provide an oxygen-dependent interface that modulates hypoxia-induced factor signaling
-
AS-8351
-
-
belinostat
-
bleomycin A2
-
ciclopirox olamine
-
daprodustat
-
-
deferasirox
-
-
deferiprone
-
deferoxamine mesylate
-
desidustat
-
-
dimethyloxalylglycine
-
-
Insulin-like growth factor-1
-
stimulates peptide-aspartate beta-dioxygenase protein expression and directional motility. Ethanol reduces the stimulation without inhibition of the mRNA expression
-
L-mimosine
-
midostaurin
-
mithramycin A
-
molidustat
-
-
navitoclax
-
-
obatoclax
-
-
plicamycin
-
-
pyridine-2,3-dicarboxylic acid
-
pyridine-2,4-dicarboxylic acid
-
pyridine-2,6-dicarboxylic acid
-
rac-3-((1-phenylethyl)amino)pyridine-2,4-dicarboxylic acid
-
-
rac-3-((1-phenylpropyl)amino)pyridine-2,4-dicarboxylic acid
-
-
roxadustat
-
-
TC-E 5002
-
-
vadadustat
-
-
vemurafenib
-
-
venetoclax
-
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ascorbate
required
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0006 - 0.025
2-oxoglutarate
0.1
HIF-1alpha peptide Asp788-Leu822 (L-asparagine803)
pH 7.8, 30°C
-
0.09 - 0.426
O2
0.086
[factor X first EGF-like domain]-L-aspartate
pH and temperature not specified in the publication
-
0.0012
[thioether-linked cyclic peptide hFX-CP101-119]-L-aspartate
pH 7.5, 20°C
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.19
2-oxoglutarate
pH 7.5, 20°C
0.23
O2
pH 7.5, 20°C
1.23
[factor X first EGF-like domain]-L-aspartate
pH and temperature not specified in the publication
-
0.2
[thioether-linked cyclic peptide hFX-CP101-119]-L-aspartate
pH 7.5, 20°C
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
320
2-oxoglutarate
pH 7.5, 20°C
0.54
O2
pH 7.5, 20°C
15
[factor X first EGF-like domain]-L-aspartate
pH and temperature not specified in the publication
-
170
[thioether-linked cyclic peptide hFX-CP101-119]-L-aspartate
pH 7.5, 20°C
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0193
(1S,2S,4R)-3-oxalobicyclo[2.2.1]hept-5-ene-2-carboxylic acid
Homo sapiens
pH 7.5, 20°C
-
0.00025
(R)-gossypol
Homo sapiens
pH 7.5, 20°C
-
0.0033
1-oxalocyclopropane-1-carboxylic acid
Homo sapiens
pH 7.5, 20°C
-
0.0003
2,2-dimethyl-4-oxopentanedioic acid
Homo sapiens
pH 7.5, 20°C
-
0.00051
2-(2-methylpropyl)-4-oxopentanedioic acid
Homo sapiens
pH 7.5, 20°C
-
0.0007
2-(3,3-dimethylbutyl)-4-oxopentanedioic acid
Homo sapiens
pH 7.5, 20°C
-
0.00043
2-benzyl-4-oxopentanedioic acid
Homo sapiens
pH 7.5, 20°C
-
0.00061
2-ethyl-4-oxopentanedioic acid
Homo sapiens
pH 7.5, 20°C
-
0.00052
2-oxalocyclopropane-1-carboxylic acid
Homo sapiens
pH 7.5, 20°C
-
0.0068
2-oxo-3-(3-phenylpropyl)pentanedioic acid
Homo sapiens
pH 7.5, 20°C
-
0.0057
2-oxo-3-propylpentanedioic acid
Homo sapiens
pH 7.5, 20°C
-
0.0063
2-oxo-3-[[4-(trifluoromethoxy)phenyl]methyl]pentanedioic acid
Homo sapiens
pH 7.5, 20°C
-
0.00025
2-oxo-4-(3-phenylpropyl)pentanedioic acid
Homo sapiens
pH 7.5, 20°C
-
0.00047
2-oxo-4-propylpentanedioic acid
Homo sapiens
pH 7.5, 20°C
-
0.00017
2-[(naphthalen-2-yl)methyl]-4-oxopentanedioic acid
Homo sapiens
pH 7.5, 20°C
-
0.0109
3-((3-phenylpropyl)amino)pyridine-2,4-dicarboxylic acid
Homo sapiens
pH 7.5, 20°C
-
0.00186
3-((4-(trifluoromethyl)benzyl)amino)pyridine-2,4-dicarboxylic acid
Homo sapiens
pH 7.5, 20°C
-
0.00367
3-((4-chlorophenethyl)amino)pyridine-2,4-dicarboxylic acid
Homo sapiens
pH 7.5, 20°C
-
0.00058
3-((4-methoxybenzyl)amino)pyridine-2,4-dicarboxylic acid
Homo sapiens
pH 7.5, 20°C
-
0.0108
3-((4-phenylbutyl)amino)pyridine-2,4-dicarboxylic acid
Homo sapiens
pH 7.5, 20°C
-
0.0131
3-((cyclohexylmethyl)amino)pyridine-2,4-dicarboxylic acid
Homo sapiens
pH 7.5, 20°C
-
0.00467
3-(2-aminoanilino)pyridine-2,4-dicarboxylic acid
Homo sapiens
pH 7.5, 20°C
-
0.0104
3-(2-carboxyanilino)pyridine-2,4-dicarboxylic acid
Homo sapiens
pH 7.5, 20°C
-
0.0221
3-(2-fluoroanilino)pyridine-2,4-dicarboxylic acid
Homo sapiens
pH 7.5, 20°C
-
0.0138
3-(2-methoxyanilino)pyridine-2,4-dicarboxylic acid
Homo sapiens
pH 7.5, 20°C
-
0.0129
3-(2-methylanilino)pyridine-2,4-dicarboxylic acid
Homo sapiens
pH 7.5, 20°C
-
0.0161
3-(2-nitroanilino)pyridine-2,4-dicarboxylic acid
Homo sapiens
pH 7.5, 20°C
-
0.0482
3-(3,3-dimethylbutyl)-2-oxopentanedioic acid
Homo sapiens
pH 7.5, 20°C
-
0.00395
3-(benzylamino)pyridine-2,4-dicarboxylic acid
Homo sapiens
pH 7.5, 20°C
-
0.00766
3-(phenethylamino)pyridine-2,4-dicarboxylic acid
Homo sapiens
pH 7.5, 20°C
-
0.0388
3-anilinopyridine-2,4-dicarboxylic acid
Homo sapiens
pH 7.5, 20°C
-
0.0016
3-benzyl-2-oxopentanedioic acid
Homo sapiens
pH 7.5, 20°C
-
0.012
3-ethyl-2-oxopentanedioic acid
Homo sapiens
pH 7.5, 20°C
-
0.0047
3-[(3,5-dimethylphenyl)methyl]-2-oxopentanedioic acid
Homo sapiens
pH 7.5, 20°C
-
0.0026
3-[(4-fluorophenyl)methyl]-2-oxopentanedioic acid
Homo sapiens
pH 7.5, 20°C
-
0.0036
3-[(4-methoxyphenyl)methyl]-2-oxopentanedioic acid
Homo sapiens
pH 7.5, 20°C
-
0.0161
3-[2-(methylsulfanyl)anilino]pyridine-2,4-dicarboxylic acid
Homo sapiens
pH 7.5, 20°C
-
0.0129
5-oxalothiophene-2-carboxylic acid
Homo sapiens
pH 7.5, 20°C
-
0.00307
AS-8351
Homo sapiens
pH 7.5, 20°C
-
0.00749
belinostat
Homo sapiens
pH 7.5, 20°C
0.00147
bleomycin A2
Homo sapiens
pH 7.5, 20°C
0.00439
ciclopirox olamine
Homo sapiens
pH 7.5, 20°C
0.00039
Co2+
Homo sapiens
pH 7.5, 20°C
0.0111
daprodustat
Homo sapiens
pH 7.5, 20°C
-
0.00208
deferasirox
Homo sapiens
pH 7.5, 20°C
-
0.00489
deferiprone
Homo sapiens
pH 7.5, 20°C
0.00316
deferoxamine mesylate
Homo sapiens
pH 7.5, 20°C
0.0163
desidustat
Homo sapiens
pH 7.5, 20°C
-
0.00012
ebselen
Homo sapiens
pH 7.5, 20°C
0.129
GSK-J1
Homo sapiens
pH 7.5, 20°C
0.00007
IOX1
Homo sapiens
pH 7.5, 20°C
0.00424
JIB-04
Homo sapiens
pH 7.5, 20°C
0.00506
L-mimosine
Homo sapiens
pH 7.5, 20°C
0.00943
midostaurin
Homo sapiens
pH 7.5, 20°C
0.0095
mithramycin A
Homo sapiens
pH 7.5, 20°C
0.00465
ML324
Homo sapiens
pH 7.5, 20°C
-
0.00506
Mn2+
Homo sapiens
pH 7.5, 20°C
0.01342
molidustat
Homo sapiens
pH 7.5, 20°C
-
0.00103
navitoclax
Homo sapiens
pH 7.5, 20°C
-
0.00017
Ni2+
Homo sapiens
pH 7.5, 20°C
0.01547
NOFD
Homo sapiens
pH 7.5, 20°C
-
0.0129
obatoclax
Homo sapiens
pH 7.5, 20°C
-
0.00014
PBIT
Homo sapiens
pH 7.5, 20°C
-
0.0132
plicamycin
Homo sapiens
pH 7.5, 20°C
-
0.00051
pyridine-2,3-dicarboxylic acid
Homo sapiens
pH 7.5, 20°C
0.00002 - 0.00003
pyridine-2,4-dicarboxylic acid
0.00548
pyridine-2,6-dicarboxylic acid
Homo sapiens
pH 7.5, 20°C
0.00028
rac-3-((1-phenylethyl)amino)pyridine-2,4-dicarboxylic acid
Homo sapiens
pH 7.5, 20°C
-
0.00122
rac-3-((1-phenylpropyl)amino)pyridine-2,4-dicarboxylic acid
Homo sapiens
pH 7.5, 20°C
-
0.0194
roxadustat
Homo sapiens
pH 7.5, 20°C
-
0.00666
TC-E 5002
Homo sapiens
pH 7.5, 20°C
-
0.00412
tubacin
Homo sapiens
pH 7.5, 20°C
0.00439
vadadustat
Homo sapiens
pH 7.5, 20°C
-
0.00338
vemurafenib
Homo sapiens
pH 7.5, 20°C
-
0.0014
venetoclax
Homo sapiens
pH 7.5, 20°C
-
0.00005
Zn2+
Homo sapiens
pH 7.5, 20°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.6
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
assay at room temperature
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
the enzyme is overexpressed in many malignant neoplasms
Manually annotated by BRENDA team
-
proliferating ducts
Manually annotated by BRENDA team
-
hepatocellular carcinoma
Manually annotated by BRENDA team
-
highly expressed in all cholangiocarcinomas
Manually annotated by BRENDA team
-
highly expressed
Manually annotated by BRENDA team
-
cerebellar neuronal cell
Manually annotated by BRENDA team
the enzyme can be detected from the sera of tumor patients
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug target
metabolism
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
ASPH_HUMAN
758
1
85863
Swiss-Prot
Mitochondrion (Reliability: 5)
HIF1N_HUMAN
349
0
40285
Swiss-Prot
other Location (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
28000
-
SDS-PAGE
56000
-
transfected enzyme, SDS-PAGE
86000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
-
peptide-aspartate beta-dioxygenase can be phosphorylated by glycogen synthase kinase 3beta, and high levels of glycogen synthase kinase 3beta activity result in decrease in peptide-aspartate beta-dioxygenase protein, whereas inhibition of the kinase and/or global caspases increases peptide-aspartate beta-dioxygenase protein. Phosphorylation is higher in ethanol-treated compared with control cells
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystals of N-terminally His6-tagged AspH562-758 are grown by the vapour diffusion method at 20°C in sitting drops, crystal structures of the enzyme, with and without substrate
enzyme in complex with peptides of Notch receptor. Significant conformational changes are required in the ankyrin repeat fold of Notch receptor to enable hydroxylation
-
sitting drop vapor diffusion method at 4°C
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D721A
activity is 20% compared to wild-type activity
E617A
activity is 100% compared to wild-type activity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
gel filtration, above 95% purity
-
His6 affinity chromatography
-
Ni2+-NTA garose affinity chromatography
-
recombinant enzyme
-
recombinant enzymes
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
co-immunization in Mus musculus, thereafter cell fusion of immunized mice splenic lymphocytes with myouse myeloma cells
-
expressed in HEK293T cells and in Escherichia coli
-
expressed in Mus musculus liver cells
-
expressed in Sf9 insect cells as His-tag and GST-fusion protein
expression in Escherichia coli
expression in Escherichia coli BL21
-
expression in Escherichia coli DH5alpha
-
in vitro transcription and translation in the presence of canine pancreas microsomes
-
N-terminally His6-tagged human AspH315-758 (His6-AspH315-758) is produced in Escherichia coli BL21 (DE3) cells
N-terminally His6-tagged human AspH315-758 (His6-AspH315-758) is produced in Escherichia coli BL21 (DE3) cells using a pET-28a(+) vector
N-terminally His6-tagged human AspH315-758 (His6-AspH315-758) was produced in Escherichia coli BL21 (DE3) cells using a pET-28a(+) vector
the N-terminally His6-tagged AspH315-758 is transformed into Escherichia coli BL21 (DE3) cells
transfected into NIH-3T3 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
downregulation of asparaginyl hydroxylase factor inhibiting (FIH) in hepatocellular carcinoma is associated with more aggressive tumor behavior and a poor prognosis
expression in tumor cells is increased with the development and progression of carcinomas
IGF-1 stimulation increases asparaginyl-beta-hydroxylase protein expression and shifts localization of asparaginyl-beta-hydroxylase from the perinuclear zone to the cell periphery, including podocytes. Subsequently, Notch-1 intracellular domain is translocated to the nucleus, which is critical for Notch-modulated gene expression. Besides glycogen synthase kinase-3beta, inhibition of protein kinase C, protein kinase A, and casein kinase 2, which can potentially phosphorylate asparaginyl-beta-hydroxylase, increases IGF-1 stimulated asparaginyl-beta-hydroxylase protein. Insulin and LiCl independently and additively increase long-term asparaginyl-beta-hydroxylase protein expression
increased expression of aspartate beta-hydroxylase in hepatocellular carcinoma tissues is associated with tumor invasiveness and a worse prognosis. Aspartate beta-hydroxylase overexpression in hepatocellular carcinoma tissues is correlated with decreased copy numbers of displacement loop (D-loop) and NADH dehydrogenase subunit 1 and enhanced D-loop mutation, suggesting the disrupted mitochondrial DNA (mtDNA) stability. The reduced mtDNA copy numbers are associated with aggressive clinicopathological features of hepatocellular carcinoma. The loss of mtDNA integrity induced by enforced expression of Aspartate beta-hydroxylase is accompanied with mitochondrial dysfunction, which is characterized by the aberrant mitochondrial membrane potential, decreased ATP generation and enhanced reactive oxygen species. The enzyme interacts with histone H2A member X. Overexpression of aspartate beta-hydroxylase diminishes the interaction between histone H2A member X and mitochondrial transcription factor A (mtTFA), an important DNA-binding protein for mtDNA replication, which then reduced the binding of mtTFA to D-loop region. Overexpression of aspartate beta-hydroxylase disrupts the mtDNA integrity through H2AX-mtTFA signal, thereby affecting mitochondrial functions in hepatocellular carcinoma
overexpressed in breast cancer and correlates with cancer type, lymph node involvement, and TNM stage. The enzyme levels does not correlate with patient age, invasive carcinoma types, or molecular subtypes
overexpression in malignant neoplasms
-
overexpression in many types of cancer tissues
the enzyme is highly overexpressed in pancreatic cancer. Upregulation of the enzyme confers a malignant phenotype characterized by enhanced cell proliferation, migration, invasion and colony formation in vitro as well as pancreatic cancer tumor growth in vivo. The transforming properties of aspartate beta-hydroxylase depend on enzymatic activity
the enzyme is overexpressed in hepatocellular carcinoma and promotes a malignant phenotype
upregulated on the cell surface of invasive cancer cells
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
-
isolation of human single-chain Fv fragments directed against human aspartyl-asparaginyl beta-hydroxylase. Antibodies show significant binding to recombinant enzyme in ELISA, tumor cell lines, and tumor tissues. They target different domains of the enzyme. A goat-anti-human IgG saporin conjugate can be delivered into tumor cells by antibody 6-22 and elicits cytotoxicity toward the tumor cells in vitro
diagnostics
the enzyme may have utility as a prognostic biomarker in breast cancer
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ince, N.; De la Monte, S.M.; Wands, J.R.
Overexpression of human aspartyl (asparaginyl) beta-hydroxylase is associated with malignant transformation
Cancer Res.
60
1261-1266
2000
Homo sapiens
Manually annotated by BRENDA team
Lavaissiere, L.; Jia, S.; Nishiyama, M.; de la Monte, S.; Stern, A.M.; Wands, J.R.; Friedman, P.A.
Overexpression of human aspartyl(asparaginyl)beta-hydroxylase in hepatocellular carcinoma and cholangiocarcinoma
J. Clin. Invest.
98
1313-1323
1996
Homo sapiens
Manually annotated by BRENDA team
Korioth, F.; Gieffers, C.; Frey, J.
Cloning and characterization of the human gene encoding aspartyl beta-hydroxylase
Gene
150
395-399
1994
Homo sapiens
Manually annotated by BRENDA team
Lancaster, D.E.; McDonough, M.A.; Schofield, C.J.
Factor inhibiting hypoxia-inducible factor (FIH) and other asparaginyl hydroxylases
Biochem. Soc. Trans.
32
943-945
2004
Homo sapiens
Manually annotated by BRENDA team
Linke, S.; Stojkoski, C.; Kewley, R.J.; Booker, G.W.; Whitelaw, M.L.; Peet, D.J.
Substrate requirements of the oxygen-sensing asparaginyl hydroxylase factor-inhibiting hypoxia-inducible factor
J. Biol. Chem.
279
14391-14397
2004
Homo sapiens
Manually annotated by BRENDA team
Koivunen, P.; Hirsilae, M.; Guenzler, V.; Kivirikko, K.I.; Myllyharju, J.
Catalytic properties of the asparaginyl hydroxylase (FIH) in the oxygen sensing pathway are distinct from those of its prolyl 4-hydroxylases
J. Biol. Chem.
279
9899-9904
2004
Homo sapiens (Q9NWT6)
Manually annotated by BRENDA team
Cantarini, M.C.; de la Monte, S.M.; Pang, M.; Tong, M.; DErrico, A.; Trevisani, F.; Wands, J.R.
Aspartyl-asparagyl beta hydroxylase over-expression in human hepatoma is linked to activation of insulin-like growth factor and notch signaling mechanisms
Hepatology
44
446-457
2006
Homo sapiens
Manually annotated by BRENDA team
Gundogan, F.; Elwood, G.; Greco, D.; Rubin, L.P.; Pinar, H.; Carlson, R.I.; Wands, J.R.; de la Monte, S.M.
Role of aspartyl-(asparaginyl) beta-hydroxylase in placental implantation: Relevance to early pregnancy loss
Hum. Pathol.
38
50-59
2007
Homo sapiens
Manually annotated by BRENDA team
de la Monte, S.M.; Tamaki, S.; Cantarini, M.C.; Ince, N.; Wiedmann, M.; Carter, J.J.; Lahousse, S.A.; Califano, S.; Maeda, T.; Ueno, T.; DErrico, A.; Trevisani, F.; Wands, J.R.
Aspartyl-(asparaginyl)-beta-hydroxylase regulates hepatocellular carcinoma invasiveness
J. Hepatol.
44
971-983
2006
Homo sapiens
Manually annotated by BRENDA team
Xian, Z.H.; Zhang, S.H.; Cong, W.M.; Yan, H.X.; Wang, K.; Wu, M.C.
Expression of aspartyl beta-hydroxylase and its clinicopathological significance in hepatocellular carcinoma
Mod. Pathol.
19
280-286
2006
Homo sapiens
Manually annotated by BRENDA team
Cockman, M.E.; Lancaster, D.E.; Stolze, I.P.; Hewitson, K.S.; McDonough, M.A.; Coleman, M.L.; Coles, C.H.; Yu, X.; Hay, R.T.; Ley, S.C.; Pugh, C.W.; Oldham, N.J.; Masson, N.; Schofield, C.J.; Ratcliffe, P.J.
Posttranslational hydroxylation of ankyrin repeats in IkB proteins by the hypoxia-inducible factor (HIF) asparaginyl hydroxylase, factor inhibiting HIF (FIH)
Proc. Natl. Acad. Sci. USA
103
14767-14772
2006
Homo sapiens
Manually annotated by BRENDA team
Carter, J.J.; Tong, M.; Silbermann, E.; Lahousse, S.A.; Ding, F.F.; Longato, L.; Roper, N.; Wands, J.R.; de la Monte, S.M.
Ethanol impaired neuronal migration is associated with reduced aspartyl-asparaginyl-beta-hydroxylase expression
Acta Neuropathol.
116
303-315
2008
Homo sapiens
Manually annotated by BRENDA team
Yeung, Y.A.; Finney, A.H.; Koyrakh, I.A.; Lebowitz, M.S.; Ghanbari, H.A.; Wands, J.R.; Wittrup, K.D.
Isolation and characterization of human antibodies targeting human aspartyl (asparaginyl) beta-hydroxylase
Hum. Antibodies
16
163-176
2007
Homo sapiens
Manually annotated by BRENDA team
Coleman, M.L.; McDonough, M.A.; Hewitson, K.S.; Coles, C.; Mecinovic, J.; Edelmann, M.; Cook, K.M.; Cockman, M.E.; Lancaster, D.E.; Kessler, B.M.; Oldham, N.J.; Ratcliffe, P.J.; Schofield, C.J.
Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factor
J. Biol. Chem.
282
24027-24038
2007
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Luu, M.; Sabo, E.; de la Monte, S.M.; Greaves, W.; Wang, J.; Tavares, R.; Simao, L.; Wands, J.R.; Resnick, M.B.; Wang, L.
Prognostic value of aspartyl (asparaginyl)-beta-hydroxylase/humbug expression in non-small cell lung carcinoma
Hum. Pathol.
40
639-644
2009
Homo sapiens
Manually annotated by BRENDA team
Xue, T.; Xue, X.P.; Huang, Q.S.; Wei, L.; Sun, K.; Xue, T.
Monoclonal antibodies against human aspartyl (asparaginyl) beta-hydroxylase developed by DNA immunization
Hybridoma
28
251-257
2009
Homo sapiens
Manually annotated by BRENDA team
Hardy, A.P.; Prokes, I.; Kelly, L.; Campbell, I.D.; Schofield, C.J.
Asparaginyl beta-hydroxylation of proteins containing ankyrin repeat domains influences their stability and function
J. Mol. Biol.
392
994-1006
2009
Homo sapiens
Manually annotated by BRENDA team
Yang, H.; Wang, H.; Xue, T.; Xue, X.P.; Huyan, T.; Wang, W.; Song, K.
Single-chain variable fragment antibody against human aspartyl/asparaginyl beta-hydroxylase expressed in recombinant Escherichia coli
Hybridoma
30
69-79
2011
Homo sapiens
Manually annotated by BRENDA team
Lyu, F.; Xue, Q.; Gao, S.
Research progress of aspartyl-(asparaginyl) beta-hydroxylase in tumors
Cancer Res. Clinic
27
280-282
2015
Homo sapiens (Q12797)
-
Manually annotated by BRENDA team
Yang, H.; Li, J.; Tang, R.; Li, J.; Liu, Y.; Ye, L.; Shao, D.; Jin, M.; Huang, Q.; Shi, J.
The aspartyl (asparaginyl) beta-hydroxylase in carcinomas
Front. Biosci.
20
902-909
2015
Homo sapiens (Q12797), Homo sapiens
Manually annotated by BRENDA team
Iwagami, Y.; Huang, C.K.; Olsen, M.J.; Thomas, J.M.; Jang, G.; Kim, M.; Lin, Q.; Carlson, R.I.; Wagner, C.E.; Dong, X.; Wands, J.R.
Aspartate beta-hydroxylase modulates cellular senescence through glycogen synthase kinase 3beta in hepatocellular carcinoma
Hepatology
63
1213-1226
2016
Homo sapiens (Q12797)
Manually annotated by BRENDA team
Huyan, T.; Li, Q.; Ye, L.J.; Yang, H.; Xue, X.P.; Zhang, M.J.; Huang, Q.S.; Yin, D.C.; Shang, P.
Inhibition of human natural killer cell functional activity by human aspartyl alpha-hydroxylase
Int. Immunopharmacol.
23
452-459
2014
Homo sapiens (Q12797)
Manually annotated by BRENDA team
Borgas, D.L.; Gao, J.S.; Tong, M.; Roper, N.; de la Monte, S.M.
Regulation of aspartyl-(asparaginyl)-?-hydroxylase protein expression and function by phosphorylation in hepatocellular carcinoma cells
J. Nat. Sci.
1
e84
2015
Homo sapiens (Q12797)
Manually annotated by BRENDA team
Tang, C.; Hou, Y.; Wang, H.; Wang, K.; Xiang, H.; Wan, X.; Xia, Y.; Li, J.; Wei, W.; Xu, S.; Lei, Z.; Pawlik, T.M.; Wang, H.; Wu, M.; Shen, F.
Aspartate beta-hydroxylase disrupts mitochondrial DNA stability and function in hepatocellular carcinoma
Oncogenesis
6
e362
2017
Homo sapiens (Q12797)
Manually annotated by BRENDA team
Dong, X.; Lin, Q.; Aihara, A.; Li, Y.; Huang, C.K.; Chung, W.; Tang, Q.; Chen, X.; Carlson, R.; Nadolny, C.; Gabriel, G.; Olsen, M.; Wands, J.R.
Aspartate beta-hydroxylase expression promotes a malignant pancreatic cellular phenotype
Oncotarget
6
1231-1248
2015
Homo sapiens (Q12797)
Manually annotated by BRENDA team
Ma, M.; Hua, S.; Li, G.; Wang, S.; Cheng, X.; He, S.; Wu, P.; Chen, X.
Prolyl hydroxylase domain protein 3 and asparaginyl hydroxylase factor inhibiting HIF-1 levels are predictive of tumoral behavior and prognosis in hepatocellular carcinoma
Oncotarget
8
12983-13002
2017
Homo sapiens (Q9NWT6), Homo sapiens
Manually annotated by BRENDA team
Tomimaru, Y.; Mishra, S.; Safran, H.; Charpentier, K.P.; Martin, W.; De Groot, A.S.; Gregory, S.H.; Wands, J.R.
Aspartate-beta-hydroxylase induces epitope-specific T cell responses in hepatocellular carcinoma
Vaccine
33
1256-1266
2015
Homo sapiens (Q12797)
Manually annotated by BRENDA team
Brewitz, L.; Tumber, A.; Zhang, X.; Schofield, C.J.
Small-molecule active pharmaceutical ingredients of approved cancer therapeutics inhibit human aspartate/asparagine-beta-hydroxylase
Bioorg. Med. Chem.
28
115675
2020
Homo sapiens (Q12797)
Manually annotated by BRENDA team
Barboro, P.; Benelli, R.; Tosetti, F.; Costa, D.; Capaia, M.; Astigiano, S.; Vene, R.; Poggi, A.; Ferrari, N.
Aspartate beta-hydroxylase targeting in castration-resistant prostate cancer modulates the NOTCH/HIF1alpha/GSK3beta crosstalk
Carcinogenesis
41
1246-1252
2020
Homo sapiens
Manually annotated by BRENDA team
Brewitz, L.; Nakashima, Y.; Schofield, C.J.
Synthesis of 2-oxoglutarate derivatives and their evaluation as cosubstrates and inhibitors of human aspartate/asparagine-beta-hydroxylase
Chem. Sci.
12
1327-1342
2020
Homo sapiens (Q12797)
Manually annotated by BRENDA team
Brewitz, L.; Tumber, A.; Thalhammer, A.; Salah, E.; Christensen, K.E.; Schofield, C.J.
Synthesis of novel pyridine-carboxylates as small-molecule inhibitors of human aspartate/asparagine-beta-hydroxylase
ChemMedChem
15
1139-1149
2020
Homo sapiens (Q12797)
Manually annotated by BRENDA team
Brewitz, L.; Tumber, A.; Schofield, C.J.
Kinetic parameters of human aspartate/asparagine-beta-hydroxylase suggest that it has a possible function in oxygen sensing
J. Biol. Chem.
295
7826-7838
2020
Homo sapiens (Q12797)
Manually annotated by BRENDA team
Zhou, Y.; Liu, F.; Li, C.; Shi, G.; Xu, X.; Luo, X.; Zhang, Y.; Fu, J.; Zeng, A.; Chen, L.
Construction and characterization of adenovirus vectors encoding aspartate-beta-hydroxylase to preliminary application in immunotherapy of hepatocellular carcinoma
J. Immunol. Res.
2018
9832467
2018
Homo sapiens (Q12797)
Manually annotated by BRENDA team
Zhang, Y.; Gao, Y.; Li, Y.; Zhang, X.; Xie, H.
Characterization of the relationship between the expression of aspartate beta-hydroxylase and the pathological characteristics of breast cancer
Med. Sci. Monit.
26
e926752
2020
Homo sapiens (Q12797)
Manually annotated by BRENDA team
Greve, J.M.; Pinkham, A.M.; Thompson, Z.; Cowan, J.A.
Active site characterization and activity of the human aspartyl (asparaginyl) beta-hydroxylase
Metallomics
13
mfab056
2021
Homo sapiens (Q12797), Homo sapiens
Manually annotated by BRENDA team
Pfeffer, I.; Brewitz, L.; Krojer, T.; Jensen, S.A.; Kochan, G.T.; Kershaw, N.J.; Hewitson, K.S.; McNeill, L.A.; Kramer, H.; Muenzel, M.; Hopkinson, R.J.; Oppermann, U.; Handford, P.A.; McDonough, M.A.; Schofield, C.J.
Aspartate/asparagine-beta-hydroxylase crystal structures reveal an unexpected epidermal growth factor-like domain substrate disulfide pattern
Nat. Commun.
10
4910
2019
Homo sapiens (Q12797)
Manually annotated by BRENDA team
Brewitz, L.; Tumber, A.; Pfeffer, I.; McDonough, M.A.; Schofield, C.J.
Aspartate/asparagine-beta-hydroxylase a high-throughput mass spectrometric assay for discovery of small molecule inhibitors
Sci. Rep.
10
8650
2020
Homo sapiens (Q12797)
Manually annotated by BRENDA team