Information on EC 1.14.11.16 - peptide-aspartate beta-dioxygenase:

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The expected taxonomic range for this enzyme is: Eutheria


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EC NUMBERCOMMENTARY
1.14.11.16-

RECOMMENDED NAMEGeneOntology No.
peptide-aspartate beta-dioxygenaseGO:0004597

REACTIONREACTION DIAGRAMCOMMENTARYORGANISM UNIPROT ACCESSION NO.LITERATURE
peptide-L-aspartate + 2-oxoglutarate + O2 = peptide-3-hydroxy-L-aspartate + succinate + CO2
show the reaction diagram
----

REACTION TYPEORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
decarboxylationHomo sapiens--699589
hydroxylation----
hydroxylationHomo sapiens--676817, 699589
oxidation----
redox reaction----
reduction----

PATHWAYKEGG LinkMetaCyc Link
No entries in this field

SYSTEMATIC NAMEIUBMB 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.

SYNONYMSORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
AAHHomo sapiens--673915, 673951, 675183
AAHMus musculus--698158
AAHRattus norvegicus--695432
aspartate beta-hydroxylase----
aspartyl (asparaginyl) beta-hydroxylaseHomo sapiens--698201, 725118
aspartyl (asparaginyl)-beta-hydroxylaseHomo sapiens--698195
aspartyl beta-hydroxylaseHomo sapiens--675861, 725118
aspartyl-(asparaginyl) beta-hydroxylaseHomo sapiens--673951
aspartyl-(asparaginyl)-b-hydroxylaseHomo sapiens--675183
aspartyl-(asparaginyl)-beta-hydroxylaseMus musculus--698158
aspartyl-(asparagyl)-beta-hydroxylaseHomo sapiens--673915
aspartyl-asparaginyl-beta-hydroxylaseRattus norvegicus--695432
aspartylpeptide beta-dioxygenase----
EGF beta-hydroxylaseHomo sapiens--657901
EGFHHomo sapiens--657901
factor inhibiting HIFHomo sapiens--687592
factor inhibiting hypoxia-inducible factorHomo sapiens--676817
factor inhibiting hypoxia-inducible transcription factor (HIF)Homo sapiens--657901, 659316, 659445
factor-inhibiting hypoxia-inducible factorHomo sapiens--699589
FIHHomo sapiens--657901, 659316, 659445, 676817, 699589
HAAHHomo sapiens--698201, 725118
HIF asparaginyl hydroxylaseHomo sapiens--687592
human aspartyl (asparaginyl) beta-hydroxylaseHomo sapiens--657901
hypoxia-inducible factor asparaginyl hydroxylaseHomo sapiens--676817

CAS REGISTRY NUMBERCOMMENTARY
122544-66-5-

ORGANISMCOMMENTARYLITERATURESEQUENCE CODESEQUENCE DB SOURCE
Bos taurus-439253, 439255, 439256, 439258, 439259--Manually annotated by BRENDA team
Homo sapiens-439252, 439254, 657901, 659316, 673915, 673951, 675183, 675861, 676817, 684228, 687022, 687592, 698195, 698201, 699589, 725118--Manually annotated by BRENDA team
Homo sapiens-659445Q9NWT6UniprotManually annotated by BRENDA team
Homo sapienshuman osteosarcoma439257--Manually annotated by BRENDA team
Mus musculus-439260, 687592, 698158--Manually annotated by BRENDA team
Mus musculusthree different size transcripts 2.8, 4.5 and 6.6 kb, the bigger ones lead to active proteins after expression439251--Manually annotated by BRENDA team
Rattus norvegicus-439260, 695432--Manually annotated by BRENDA team

GENERAL INFORMATIONORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
malfunctionRattus norvegicus-inhibition by fetal alcohol spectrum disorder, decrease leads to impairment in neuronal migration695432
physiological functionRattus norvegicus-mediates neuronal motility695432
physiological functionMus musculus-stimulates cell migration698158

SUBSTRATEPRODUCT                      REACTION DIAGRAMORGANISM UNIPROT ACCESSION NO. COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ankyrin repeat domain of endogenous Notch receptor L-asparagine + 2-oxoglutarate + O2ankyrin repeat domain of endogenous Notch receptor 3-hydroxy-L-asparagine + succinate + CO2
show the reaction diagram
Homo sapiens-hydroxylation of highly conserved asparaginyl residues within the ankyrin repeat687592--?
ankyrin repeat domain of endogenous Notch receptor L-asparagine + 2-oxoglutarate + O2ankyrin repeat domain of endogenous Notch receptor 3-hydroxy-L-asparagine + succinate + CO2
show the reaction diagram
Mus musculus-hydroxylation of hyghly conserved asparaginyl residues within the ankyrin repeat687592--?
ankyrin repeat domain protein?
show the reaction diagram
Homo sapiens-a maximum of three ankyrin repeats enables ankyrin repeat domain proteins as a substrate699589--?
HIF (L-Asn803) + 2-oxoglutarate + O2HIF (3-hydroxy-L-Asn803) + succinate + CO2
show the reaction diagram
Homo sapiens-accepts HIF-1alpha and HIF-2-alpha as substrate, HIF mutant V802A exhibits 4fold lower substrate activity than native protein, no activity with N803A mutant659316--?
peptide L-asparagine + 2-oxoglutarate + O2peptide 3-hydroxy-L-asparagine + succinate + CO2
show the reaction diagram
Homo sapiens--439252, 657901, 659316--?
peptide L-asparagine + 2-oxoglutarate + O2peptide 3-hydroxy-L-asparagine + succinate + CO2
show the reaction diagram
Homo sapiensQ9NWT6-659445--?
peptide L-asparagine + 2-oxoglutarate + O2peptide 3-hydroxy-L-asparagine + succinate + CO2
show the reaction diagram
Homo sapiens--673915, 675183, 675861, 676817--?
peptide L-asparagine + 2-oxoglutarate + O2peptide 3-hydroxy-L-asparagine + succinate + CO2
show the reaction diagram
Bos taurus--439253--?
peptide L-asparagine + 2-oxoglutarate + O2peptide 3-hydroxy-L-asparagine + succinate + CO2
show the reaction diagram
Homo sapiens-first epidermal growth factor-like domain of bovine protein S with an asparagine replacing the aspartic acid at position 18439254--?
peptide L-asparagine + 2-oxoglutarate + O2peptide 3-hydroxy-L-asparagine + succinate + CO2
show the reaction diagram
Bos taurus-first epidermal growth factor-like domain of human protein S with an asparagine replacing the aspartic acid at position 18439256, 439258--?
peptide L-asparagine + 2-oxoglutarate + O2peptide 3-hydroxy-L-asparagine + succinate + CO2
show the reaction diagram
Homo sapiens-enzyme catalyzes the erythro-beta-hydroxylation of asparaginyl and aspartyl residues to form the 2S, 3R-product, possible role in the Notch signalling pathway, hydroxylation of Asn803 in hypoxia-inducible transcription factor, converted protein is incapable in interacting with the transcripitonal coactivator p300657901--?
peptide L-asparagine + 2-oxoglutarate + O2peptide 3-hydroxy-L-asparagine + succinate + CO2
show the reaction diagram
Homo sapiens-hydroxylation of Asn803 in hypoxia-inducible transcription factor, converted protein is incapable in interacting with the transcripitonal coactivator p300659316--?
peptide L-asparagine + 2-oxoglutarate + O2peptide 3-hydroxy-L-asparagine + succinate + CO2
show the reaction diagram
Homo sapiensQ9NWT6hydroxylation of Asn803 in hypoxia-inducible transcription factor, converted protein is incapable in interacting with the transcripitonal coactivator p300659445--?
peptide L-aspartate + 2-oxoglutarate + O2peptide 3-hydroxy-L-aspartate + succinate + CO2
show the reaction diagram
Mus musculus--439251-439251?
peptide L-aspartate + 2-oxoglutarate + O2peptide 3-hydroxy-L-aspartate + succinate + CO2
show the reaction diagram
Bos taurus--439253-439253?
peptide L-aspartate + 2-oxoglutarate + O2peptide 3-hydroxy-L-aspartate + succinate + CO2
show the reaction diagram
Homo sapiens-first epidermal growth factor-like domain of bovine protein S as substrate439252-439252?
peptide L-aspartate + 2-oxoglutarate + O2peptide 3-hydroxy-L-aspartate + succinate + CO2
show the reaction diagram
Bos taurus-first epidermal growth factor-like domain of human protein S as substrate439258-439258?
peptide L-aspartate + 2-oxoglutarate + O2peptide 3-hydroxy-L-aspartate + succinate + CO2
show the reaction diagram
Bos taurus-first epidermal growth factor-like domain of human protein S as substrate439259-439259?
peptide L-aspartate + 2-oxoglutarate + O2peptide 3-hydroxy-L-aspartate + succinate + CO2
show the reaction diagram
Mus musculus, Rattus norvegicus-specific erythro-hydroxylation439260-439260?
peptide L-aspartate + 2-oxoglutarate + O2peptide 3-hydroxy-L-aspartate + succinate + CO2
show the reaction diagram
Bos taurus-specific erythro-hydroxylation439259-439259?
peptide L-aspartate + 2-oxoglutarate + O2peptide 3-hydroxy-L-aspartate + succinate + CO2
show the reaction diagram
Mus musculus, Rattus norvegicus-first epidermal growth factor-like domain of human factor IX as substrate439260-439260?
peptide L-aspartate + 2-oxoglutarate + O2peptide 3-hydroxy-L-aspartate + succinate + CO2
show the reaction diagram
Bos taurus-second epidermal growth factor-like domain of bovine protein S439255-439255?
peptide L-aspartate + 2-oxoglutarate + O2peptide 3-hydroxy-L-aspartate + succinate + CO2
show the reaction diagram
Homo sapiens-hydroxylates epidermal growth factor-like domains in transformation-associated proteins439252-439252?
HIF-1alpha peptide Asp788-Leu822 (L-Asn803) + 2-oxoglutarate + O2HIF-1alpha peptide Asp788-Leu822 (3-hydroxy-L-Asn803) + succinate + CO2
show the reaction diagram
Homo sapiensQ9NWT6much lower activity with peptides lacking residues 819-822, 807-822, and 815-822659445--?
additional information?-Mus musculus-overexpression may be associated with malignant transformation439251---
additional information?-Homo sapiens-overexpression may be associated with malignant transformation439252---
additional information?-Homo sapiens-the enzyme hydroxylates epidermal growth factor-like domains in transformation-associated proteins725118---

NATURAL SUBSTRATESNATURAL PRODUCTSREACTION DIAGRAMORGANISM UNIPROT ACCESSION NO.COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
peptide L-asparagine + 2-oxoglutarate + O2peptide 3-hydroxy-L-asparagine + succinate + CO2
show the reaction diagram
Homo sapiens-enzyme catalyzes the erythro-beta-hydroxylation of asparaginyl and aspartyl residues to form the 2S, 3R-product, possible role in the Notch signalling pathway, hydroxylation of Asn803 in hypoxia-inducible transcription factor, converted protein is incapable in interacting with the transcripitonal coactivator p300657901--?
peptide L-asparagine + 2-oxoglutarate + O2peptide 3-hydroxy-L-asparagine + succinate + CO2
show the reaction diagram
Homo sapiens-hydroxylation of Asn803 in hypoxia-inducible transcription factor, converted protein is incapable in interacting with the transcripitonal coactivator p300659316--?
peptide L-asparagine + 2-oxoglutarate + O2peptide 3-hydroxy-L-asparagine + succinate + CO2
show the reaction diagram
Homo sapiensQ9NWT6hydroxylation of Asn803 in hypoxia-inducible transcription factor, converted protein is incapable in interacting with the transcripitonal coactivator p300659445--?
peptide L-aspartate + 2-oxoglutarate + O2peptide 3-hydroxy-L-aspartate + succinate + CO2
show the reaction diagram
Mus musculus--439251-439251?
peptide L-aspartate + 2-oxoglutarate + O2peptide 3-hydroxy-L-aspartate + succinate + CO2
show the reaction diagram
Homo sapiens-hydroxylates epidermal growth factor-like domains in transformation-associated proteins439252-439252?
additional information?-Mus musculus-overexpression may be associated with malignant transformation439251---
additional information?-Homo sapiens-overexpression may be associated with malignant transformation439252---
additional information?-Homo sapiens-the enzyme hydroxylates epidermal growth factor-like domains in transformation-associated proteins725118---

COFACTORORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATUREIMAGE
No entries in this field

METALS and IONS ORGANISM UNIPROT ACCESSION NO.COMMENTARY LITERATURE
Fe2+Bos taurus--439255, 439256, 439258, 439259
Fe2+Mus musculus-0.05 mM increases activity 6-fold439260
Fe2+Rattus norvegicus--439260
Fe2+Homo sapiens-required657901, 659316, 659445

INHIBITORSORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
2,2'-dipyridylMus musculus-at 1 mM 90% inhibition439260 2D-image
ankyrin repeat domainHomo sapiens, Mus musculus-may function as a natural inhibitor and provide an oxygen-dependent interface that modulates hypoxia-induced factor signaling687592-
dimethyloxalylglycineHomo sapiens--676817 2D-image
ethanolRattus norvegicus--695432 2D-image
Insulin-like growth factor-1Homo sapiens-stimulates peptide-aspartate beta-dioxygenase protein expression and directional motility. Ethanol reduces the stimulation without inhibition of the mRNA expression684228-
iodoacetamideBos taurus-at 1 mM less than 5% activity, 2-oxoglutarate and EDTA protects439256 2D-image
additional informationHomo sapiensQ9NWT6several 2-oxoglutarate analogs inhibits enzyme activity659445-
additional informationRattus norvegicus-phosphorylation by GSK-3beta oder degradation by caspase695432-
additional informationHomo sapiens-development of a ScFv anti-HAAH antibody for specific in vivo inhibition of the enzyme by expression of His-tagged light and heavy chain cloned from the hybridoma cells G3/F11 in Escherichia coli strain BL21(DE3)PlysS/pET-16b, partly in inclusion bodies, or of c-myc-tagged ScFv in Escherichia coli strain HB2151/pHEN1, partly cytosolic. Variable regions of the genes of the heavy chain and light chain are connected with a flexible linker using an overlap extension PCR. Nucleotide sequence analysis revealed that the anti-HAAH VH was a member of the VH V gene family and the VL gene belonged to the Vk gene family VI subgroup725118-

ACTIVATING COMPOUNDORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
ascorbateHomo sapiensQ9NWT6required659445 2D-image
additional informationRattus norvegicus-regulated by insulin and insulin-like growth factor695432-

KM VALUE [mM]KM VALUE [mM] MaximumSUBSTRATEORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
0.005-2-oxoglutarateBos taurus--439259 2D-image
0.021-2-oxoglutarateBos taurus-56 kDa protein439258 2D-image
0.022-2-oxoglutarateBos taurus-52 kDa protein439258 2D-image
0.025-2-oxoglutarateHomo sapiensQ9NWT6pH 7.8, 30C659445 2D-image
0.098-2-oxoglutarateBos taurus-at 1 mM Fe2+, H675D mutant439255 2D-image
0.102-2-oxoglutarateBos taurus-at 1 mM Fe2+, wild-type439255 2D-image
0.125-2-oxoglutarateBos taurus-at 1 mM Fe2+, H675E mutant439255 2D-image
0.003-Fe2+Bos taurus--439259-
0.0083-Fe2+Bos taurus-56 kDa protein439258-
0.0096-Fe2+Bos taurus-52 kDa protein439258-
0.013-Fe2+Bos taurus-at 0.6 mM 2-oxoglutarate, wild-type439255-
0.052-Fe2+Bos taurus-at 0.6 mM 2-oxoglutarate, H675E mutant439255-
0.093-Fe2+Bos taurus-at 0.6 mM 2-oxoglutarate, H675D mutant439255-
0.019-first epidermal growth factor-like domainBos taurus-substrate is of human protein S with an asparagine replacing the aspartic acid at position 18, native enzyme439256-
0.024-first epidermal growth factor-like domainBos taurus-substrate is of human protein S with an asparagine replacing the aspartic acid at position 18, recombinant enzyme439256-
0.034-first epidermal growth factor-like domainBos taurus-substrate is of human protein S with an asparagine replacing the aspartic acid at position 18, 52 kDa protein439258-
0.035-first epidermal growth factor-like domainBos taurus-substrate is of human protein S with an asparagine replacing the aspartic acid at position 18, 56 kDa protein439258-
0.067-first epidermal growth factor-like domainBos taurus-substrate is of human protein S, 52 kDa protein439258-
0.075-first epidermal growth factor-like domainBos taurus-substrate is of human protein S, 56 kDa protein439258-
0.1-HIF-1alpha peptide Asp788-Leu822 (L-asparagine803)Homo sapiensQ9NWT6pH 7.8, 30C659445-
0.09-O2Homo sapiensQ9NWT6pH 7.8, 30C659445 2D-image

TURNOVER NUMBER [1/s] TURNOVER NUMBER MAXIMUM[1/s] SUBSTRATEORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
0.0167-first epidermal growth factor-like domainBos taurus-substrate is of human protein S, 56 kDa protein439258-
0.0217-first epidermal growth factor-like domainBos taurus-substrate is of human protein S with an asparagine replacing the aspartic acid at position 18, 56 kDa protein439258-
0.025-first epidermal growth factor-like domainBos taurus-substrate is of human protein S, 52 kDa protein439258-
0.0317-first epidermal growth factor-like domainBos taurus-substrate is of human protein S with an asparagine replacing the aspartic acid at position 18, 52 kDa protein439258-

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

Ki VALUE [mM]Ki VALUE [mM] MaximumINHIBITORORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
No entries in this field

IC50 VALUE [mM]IC50 VALUE [mM] MaximumINHIBITORORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE IMAGE
No entries in this field

SPECIFIC ACTIVITY [µmol/min/mg] SPECIFIC ACTIVITY MAXIMUM ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE
0.59-Bos taurus--439258
14-Bos taurus--439256

pH OPTIMUMpH MAXIMUMORGANISM UNIPROT ACCESSION NO. COMMENTARYLITERATURE
6.8-Bos taurus--439259
7.6-Homo sapiens-assay at699589

pH RANGEpH RANGE MAXIMUMORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
6.57.9Bos taurus-about half-maximal activity at pH 6.5 and 7.9439259

TEMPERATURE OPTIMUMTEMPERATURE OPTIMUM MAXIMUMORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
additional information-Homo sapiens-assay at room temperature699589

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

pI VALUEpI VALUE MAXIMUMORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
No entries in this field

SOURCE TISSUE ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE SOURCE
adiposeMus musculus--439251Manually annotated by BRENDA team
adrenal glandMus musculus--439251Manually annotated by BRENDA team
adrenal glandHomo sapiens--439254Manually annotated by BRENDA team
bileHomo sapiens-proliferating ducts439252Manually annotated by BRENDA team
brainMus musculus--439251Manually annotated by BRENDA team
breast cancer cellHomo sapiens-highly expressed439254Manually annotated by BRENDA team
carcinoma cell lineHomo sapiens-hepatocellular carcinoma698201Manually annotated by BRENDA team
cerebellumRattus norvegicus-of the fetus695432Manually annotated by BRENDA team
cholangiocarcinoma cellHomo sapiens-highly expressed in all cholangiocarcinomas439254Manually annotated by BRENDA team
colonic carcinoma cellHomo sapiens-highly expressed439254Manually annotated by BRENDA team
deciduaHomo sapiens--673951Manually annotated by BRENDA team
endometrial cell lineHomo sapiens--673951Manually annotated by BRENDA team
G3/F11 cellHomo sapiens--725118Manually annotated by BRENDA team
heartMus musculus--439251Manually annotated by BRENDA team
hepatoma cellHomo sapiens-highly expressed in 4 of 10 hepatocarcinomas, 10-fold activity increase439254Manually annotated by BRENDA team
hepatoma cellHomo sapiens--673915, 675183, 675861Manually annotated by BRENDA team
kidneyMus musculus--439251Manually annotated by BRENDA team
large cell lung cancer cell lineHomo sapiens--698195Manually annotated by BRENDA team
large intestineMus musculus--439251Manually annotated by BRENDA team
liverBos taurus--439258, 439259Manually annotated by BRENDA team
liverMus musculus--439251, 439260Manually annotated by BRENDA team
liverRattus norvegicus--439260Manually annotated by BRENDA team
liverHomo sapiens--439254, 675183, 675861Manually annotated by BRENDA team
lungMus musculus--439251Manually annotated by BRENDA team
lung adenocarcinoma cell lineHomo sapiens--698195Manually annotated by BRENDA team
neuronal cell lineRattus norvegicus-of the fetus695432Manually annotated by BRENDA team
non-small cell lung cancer cell lineHomo sapiens--698195Manually annotated by BRENDA team
ovaryMus musculus--439251Manually annotated by BRENDA team
pancreasMus musculus--439251Manually annotated by BRENDA team
placentaHomo sapiens--673951Manually annotated by BRENDA team
PNET-2 cellHomo sapiens-cerebellar neuronal cell684228Manually annotated by BRENDA team
pupRattus norvegicus--695432Manually annotated by BRENDA team
skeletal muscleMus musculus--439251Manually annotated by BRENDA team
stomachMus musculus--439251Manually annotated by BRENDA team
testisMus musculus--439251Manually annotated by BRENDA team
thymusMus musculus--439251Manually annotated by BRENDA team
trophoblastHomo sapiens--673951Manually annotated by BRENDA team
lung squamous cell carcinoma cell lineHomo sapiens--698195Manually annotated by BRENDA team
additional informationHomo sapiens-the enzyme is overexpressed in a wide variety of human malignancies such as breast, hepatic, biliary, colon, pulmonary, pancreatic, and neural origin725118Manually annotated by BRENDA team

LOCALIZATION ORGANISM UNIPROT ACCESSION NO. COMMENTARY GeneOntology No. LITERATURE SOURCE
cytoplasmHomo sapiens--5737659316Manually annotated by BRENDA team
membraneHomo sapiens-membrane-associated16020725118Manually annotated by BRENDA team
rough endoplasmic reticulumBos taurus--5791439259Manually annotated by BRENDA team
microsomeRattus norvegicus---439260Manually annotated by BRENDA team
additional informationMus musculus-L-cell extract-439260Manually annotated by BRENDA team

PDBSCOPCATHORGANISM
3rcq, downloadSCOP (3rcq)CATH (3rcq)Homo sapiens

MOLECULAR WEIGHT MOLECULAR WEIGHT MAXIMUM ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE
28000-Homo sapiens-SDS-PAGE698201
50700-Bos taurus-sedimentation equilibrium439256
51030-Bos taurus-MALDI-TOF439256
52000-Bos taurus-SDS-PAGE, protein with lower molecular weight439258
56000-Homo sapiens-transfected enzyme, SDS-PAGE439257
56000-Bos taurus-SDS-PAGE, protein with higher molecular weight439258
86000-Homo sapiens--675183
86000-Rattus norvegicus-Western blot, full-length protein695432
110000-Rattus norvegicus-Western blot, post-translational modified protein695432

SUBUNITS ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE
dimerHomo sapiens-homodimer, crystal structure analysis657901
dimerHomo sapiensQ9NWT6homodimer659445
monomerBos taurus-1 * 50700, sedimentation equilibrium439256

POSTTRANSLATIONAL MODIFICATION ORGANISM UNIPROT ACCESSION NO. COMMENTARY LITERATURE
phosphoproteinHomo sapiens-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 cells684228

Crystallization/COMMENTARY ORGANISM UNIPROT ACCESSION NO. LITERATURE
enzyme in complex with peptides of Notch receptor. Significant conformational changes are required in the ankyrin repeat fold of Notch receptor to enable hydroxylationHomo sapiens, Mus musculus-687592

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

TEMPERATURE STABILITYTEMPERATURE STABILITY MAXIMUM ORGANISM UNIPROT ACCESSION NO. COMMENTARYLITERATURE
No entries in this field

GENERAL STABILITYORGANISM 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
4C, 50 mM Tris-HCl pH 7.2, 1 mg/ml bovine serum albumin, at least 8 weeks stableBos taurus-439258

Purification/COMMENTARY ORGANISM UNIPROT ACCESSION NO. LITERATURE
-Bos taurus-439256
partialBos taurus-439259
two enzymes, one 52000 Da, the other 56000 DaBos taurus-439258
gel filtration, above 95% purityHomo sapiens-699589
His6 affinity chromatographyHomo sapiens-676817
Ni2+-NTA garose affinity chromatographyHomo sapiens-698201
recombinant enzymeHomo sapiens-659316
recombinant enzymesHomo sapiensQ9NWT6659445

Cloned/COMMENTARY ORGANISM UNIPROT ACCESSION NO. LITERATURE
expressed in wild-type Escherichia coli and in Escherichia coli BL21Bos taurus-439256
wild-type and mutant enzymes expressed in Escherichia coliBos taurus-439253
wild-type and mutants expressed in Escherichia coli BL21Bos taurus-439255
-Homo sapiens-687022
co-immunization in Mus musculus, thereafter cell fusion of immunized mice splenic lymphocytes with myouse myeloma cells; expression in Escherichia coli DH5alphaHomo sapiens-698201
expressed in HEK293T cells and in Escherichia coliHomo sapiens-659316
expressed in Mus musculus liver cellsHomo sapiens-675183
expressed in Sf9 insect cells as His-tag and GST-fusion proteinHomo sapiensQ9NWT6659445
expression in Escherichia coli BL21Homo sapiens-699589
in vitro transcription and translation in the presence of canine pancreas microsomesHomo sapiens-439257
transfected into NIH-3T3 cellsHomo sapiens-439252
expression in human CNS neuronal and hepatocellulcar carcinoma cellsRattus norvegicus-695432

EXPRESSION ORGANISM UNIPROT ACCESSION NO. LITERATURE
overexpression in malignant neoplasmsHomo sapiens-698195
about 2fold increase in expression in double transgenic mice with expression of hepatitis Bx and insulin receptor substrate-1 under a liver-specific promoterMus musculus-698158
ethanol-treated culturesRattus norvegicus-695432
increase after inhibition of GSK-3beta or global caspasesRattus norvegicus-695432

ENGINEERINGORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
C637ABos taurus-38% activity of wild-type439253
C644ABos taurus-62% activity of wild-type439253
C656ABos taurus-100% activity of wild-type439253
C681ABos taurus-60% activity of wild-type439253
C696ABos taurus-29% activity of wild-type439253
G659ABos taurus-21% activity of wild-type439255
G669ABos taurus-90% activity of wild-type439255
H667LBos taurus-106% activity of wild-type439255
H671LBos taurus-16% activity of wild-type439255
H675DBos taurus-20% activity of wild-type439255
H675EBos taurus-12% activity of wild-type439255
H686LBos taurus-9% activity of wild-type439255
P678VBos taurus-90% activity of wild-type439255
R682ABos taurus-10% activity of wild-type439255
R684ABos taurus-8% activity of wild-type439255
R684KBos taurus-87% activity of wild-type439255

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

APPLICATIONORGANISM UNIPROT ACCESSION NO.COMMENTARYLITERATURE
analysisHomo sapiens-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 vitro687022
medicineHomo sapiens-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, and phosphorylation of the enzyme is higher in ethanol-treated compared with control cells684228
medicineHomo sapiens-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 vitro687022
medicineHomo sapiens-biomarker to prognosticate non-small cell lung cancer698195

DISEASETITLE OF PUBLICATIONLINK TO PUBMED
Abortion, Missed[Expression of aspartyl-(asparaginyl) beta-hydroxylase in villi in patients with missed abortion]. PubMed
Bile Duct NeoplasmsDetection of human aspartyl (asparaginyl) beta-hydroxylase and homeobox B7 mRNA in brush cytology specimens from patients with bile duct cancer. PubMed
Breast NeoplasmsCytoplasmic location of factor-inhibiting hypoxia-inducible factor is associated with an enhanced hypoxic response and a shorter survival in invasive breast cancer. PubMed
Breast NeoplasmsThe key hypoxia regulated gene CAIX is upregulated in basal-like breast tumours and is associated with resistance to chemotherapy. PubMed
CADASILGlial Vascular Degeneration in CADASIL. PubMed
CarcinomaAspartyl-(asparaginyl)-beta-hydroxylase regulates hepatocellular carcinoma invasiveness. PubMed
CarcinomaDNA methylation analysis of the HIF-1? prolyl hydroxylase domain genes PHD1, PHD2, PHD3 and the factor inhibiting HIF gene FIH in invasive breast carcinomas. PubMed
CarcinomaFactor-inhibiting hypoxia-inducible factor expression in patients with high-risk locally advanced renal cell carcinoma and its relationship with tumor progression. PubMed
CarcinomaHuman aspartyl (asparaginyl) beta-hydroxylase monoclonal antibodies: potential biomarkers for pancreatic carcinoma. PubMed
CarcinomaPrognostic value of aspartyl (asparaginyl)-beta-hydroxylase/humbug expression in non-small cell lung carcinoma. PubMed
CarcinomaPrognostic value of humbug gene overexpression in stage II colon cancer. PubMed
Carcinoma, HepatocellularAspartyl-(asparaginyl)-beta-hydroxylase regulates hepatocellular carcinoma invasiveness. PubMed
Carcinoma, HepatocellularAspartyl-asparagyl beta hydroxylase over-expression in human hepatoma is linked to activation of insulin-like growth factor and notch signaling mechanisms. PubMed
Carcinoma, HepatocellularExpression of aspartyl beta-hydroxylase and its clinicopathological significance in hepatocellular carcinoma. PubMed
Carcinoma, HepatocellularMonoclonal antibodies against human aspartyl (asparaginyl) beta-hydroxylase developed by DNA immunization. PubMed
Carcinoma, HepatocellularOverexpression of aspartyl-(asparaginyl)-beta-hydroxylase in hepatocellular carcinoma is associated with worse surgical outcome. PubMed
Carcinoma, HepatocellularPrognostic value of humbug gene overexpression in stage II colon cancer. PubMed
Carcinoma, Renal CellFactor-inhibiting hypoxia-inducible factor expression in patients with high-risk locally advanced renal cell carcinoma and its relationship with tumor progression. PubMed
CholangiocarcinomaAntisense oligodeoxynucleotides directed against aspartyl (asparaginyl) beta-hydroxylase suppress migration of cholangiocarcinoma cells. PubMed
CholangiocarcinomaClinicopathological correlates of aspartyl (asparaginyl) beta-hydroxylase over-expression in cholangiocarcinoma. PubMed
CholangiocarcinomaPrognostic value of humbug gene overexpression in stage II colon cancer. PubMed
GlioblastomaThe Role of Factor Inhibiting HIF (FIH-1) in Inhibiting HIF-1 Transcriptional Activity in Glioblastoma Multiforme. PubMed
Kidney NeoplasmsFactor inhibiting HIF (FIH-1) promotes renal cancer cell survival by protecting cells from HIF-1?-mediated apoptosis. PubMed
Myocardial InfarctionDouble knockdown of prolyl hydroxylase and factor-inhibiting hypoxia-inducible factor with nonviral minicircle gene therapy enhances stem cell mobilization and angiogenesis after myocardial infarction. PubMed
Neoplasm MetastasisExpression of aspartyl beta-hydroxylase and its clinicopathological significance in hepatocellular carcinoma. PubMed
NeoplasmsA hypoxic niche regulates glioblastoma stem cells through hypoxia inducible factor 2 alpha. PubMed
NeoplasmsAntisense oligonucleotides selectively regulate aspartyl beta-hydroxylase and its truncated protein isoform in vitro but distribute poorly into A549 tumors in vivo. PubMed
NeoplasmsAspartyl-asparagyl beta hydroxylase over-expression in human hepatoma is linked to activation of insulin-like growth factor and notch signaling mechanisms. PubMed
NeoplasmsClinicopathological correlates of aspartyl (asparaginyl) beta-hydroxylase over-expression in cholangiocarcinoma. PubMed
NeoplasmsDetection of human aspartyl (asparaginyl) beta-hydroxylase and homeobox B7 mRNA in brush cytology specimens from patients with bile duct cancer. PubMed
NeoplasmsExpression of aspartyl beta-hydroxylase and its clinicopathological significance in hepatocellular carcinoma. PubMed
NeoplasmsFactor-inhibiting hypoxia-inducible factor expression in patients with high-risk locally advanced renal cell carcinoma and its relationship with tumor progression. PubMed
NeoplasmsIsolation and characterization of human antibodies targeting human aspartyl (asparaginyl) beta-hydroxylase. PubMed
NeoplasmsRegulation of IL-1?-induced NF-?B by hydroxylases links key hypoxic and inflammatory signaling pathways. PubMed
NeoplasmsRole of the aspartyl-asparaginyl-beta-hydroxylase gene in neuroblastoma cell motility. PubMed
NeoplasmsThe key hypoxia regulated gene CAIX is upregulated in basal-like breast tumours and is associated with resistance to chemotherapy. PubMed
NeoplasmsTranscriptional activity and Sp 1/3 transcription factor binding to the P1 promoter sequences of the human AbetaH-J-J locus. PubMed
Neoplasms[Expression of human aspartyl beta-hydroxylase and preparation of its monoclonal antibody]. PubMed
NeuroblastomaDifferential growth factor regulation of aspartyl-(asparaginyl)-beta-hydroxylase family genes in SH-Sy5y human neuroblastoma cells. PubMed
NeuroblastomaRole of the aspartyl-asparaginyl-beta-hydroxylase gene in neuroblastoma cell motility. PubMed

REF. AUTHORS TITLE JOURNAL VOL. PAGES YEAR ORGANISM (UNIPROT ACCESSION NO.)LINK TO PUBMEDSOURCE
439251Dinchuk, J.E.; Henderson, N.L.; Burn, T.C.; Huber, R.; Ho, S.P.; Link, J.; O'Neil, K.T.; Focht, R.J.; Scully, M.S.; Hollis, J.M.; Hollis, G.F.; Friedman, P.A.Aspartyl beta-hydroxylase (Asph) and an evolutionarily conserved isoform of Asph missing the catalytic domain share exons with junctinJ. Biol. Chem.27539543-395542000Mus musculus PubMed
439252Ince, N.; De la Monte, S.M.; Wands, J.R.Overexpression of human aspartyl (asparaginyl) beta-hydroxylase is associated with malignant transformationCancer Res.601261-12662000Homo sapiens PubMed
439253McGinnis, K.; Ku, G.M.; Fu, J.; Stern, A.M.; Friedman, P.A.The five cysteine residues located in the active site region of bovine aspartyl (asparaginyl) beta-hydroxylase are not essential for catalysisBiochim. Biophys. Acta1387454-4561998Bos taurus PubMed
439254Lavaissiere, 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 cholangiocarcinomaJ. Clin. Invest.981313-13231996Homo sapiens PubMed
439255McGinnis, K.; Ku, G.M.; VanDusen, W.J.; Fu, J.; Garsky, V.; Stern, A.M.; Friedman, P.A.Site-directed mutagenesis of residues in a conserved region of bovine aspartyl (asparaginyl) beta-hydroxylase: Evidence that histidine 675 has a role in binding Fe2+Biochemistry353957-39621996Bos taurus PubMed
439256Jia, S.; McGinnis, K.; VanDusen, W.J.; Burke, C.J.; Kuo, A.; Griffin, P.R.; Sardana, M.K.; Elliston, K.O.; Stern, A.M.; Friedman, P.A.A fully active catalytic domain of bovine aspartyl (asparaginyl) beta-hydroxylase expressed in Escherichia coli: characterization and evidence for the identification of an active-site region in vertebrate alpha-ketoglutarate-dependent dioxygenasesProc. Natl. Acad. Sci. USA917227-72311994Bos taurus PubMed
439257Korioth, F.; Gieffers, C.; Frey, J.Cloning and characterization of the human gene encoding aspartyl beta-hydroxylaseGene150395-3991994Homo sapiens PubMed
439258Wang, Q.; VanDusen, W.J.; Petrosky, C.J.; Garsky, V.M.; Stern, A.M.; Friedman, P.A.Bovine liver aspartyl beta-hydroxylase. Purification and characterizationJ. Biol. Chem.26614004-140101991Bos taurus PubMed
439259Gronke, R.S.; Welsch, D.J.; VanDusen, W.J.; Garsky, V.M.; Sardana, M.K.; Stern, A.M.; Friedman, P.A.Partial purification and characterization of bovine liver aspartyl beta-hydroxylaseJ. Biol. Chem.2658558-85651990Bos taurus PubMed
439260Gronke, R.S.; VanDusen, W.J.; Garsky, V.M.; Jacobs, J.W.; Sardana, M.K.; Stern, A.M.; Friedman, P.A.Aspartyl beta-hydroxylase: in vitro hydroxylation of a synthetic peptide based on the structure of the first growth factor-like domain of human factor IXProc. Natl. Acad. Sci. USA863609-36131989Mus musculus, Rattus norvegicus PubMed
657901Lancaster, D.E.; McDonough, M.A.; Schofield, C.J.Factor inhibiting hypoxia-inducible factor (FIH) and other asparaginyl hydroxylasesBiochem. Soc. Trans.32943-9452004Homo sapiens PubMed
659316Linke, 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 factorJ. Biol. Chem.27914391-143972004Homo sapiens PubMed
659445Koivunen, 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-hydroxylasesJ. Biol. Chem.2799899-99042004Homo sapiens, Homo sapiens (Q9NWT6) PubMed
673915Cantarini, 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 mechanismsHepatology44446-4572006Homo sapiens PubMed
673951Gundogan, 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 lossHum. Pathol.3850-592007Homo sapiens PubMed
675183de 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 invasivenessJ. Hepatol.44971-9832006Homo sapiens PubMed
675861Xian, 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 carcinomaMod. Pathol.19280-2862006Homo sapiens PubMed
676817Cockman, 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. USA10314767-147722006Homo sapiens PubMed
684228Carter, 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 expressionActa Neuropathol.116303-3152008Homo sapiens PubMed
687022Yeung, 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-hydroxylaseHum. Antibodies16163-1762007Homo sapiens PubMed
687592Coleman, 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 factorJ. Biol. Chem.28224027-240382007Homo sapiens, Mus musculus PubMed
695432de la Monte, S.M.; Tong, M.; Carlson, R.I.; Carter, J.J.; Longato, L.; Silbermann, E.; Wands, J.R.Ethanol inhibition of aspartyl-asparaginyl-beta-hydroxylase in fetal alcohol spectrum disorder: potential link to the impairments in central nervous system neuronal migrationAlcohol43225-2402009Rattus norvegicus PubMed
698158Longato, L.; de la Monte, S.; Kuzushita, N.; Horimoto, M.; Rogers, A.B.; Slagle, B.L.; Wands, J.R.Overexpression of insulin receptor substrate-1 and hepatitis Bx genes causes premalignant alterations in the liverHepatology491935-19432009Mus musculus PubMed
698195Luu, 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 carcinomaHum. Pathol.40639-6442009Homo sapiens PubMed
698201Xue, T.; Xue, X.P.; Huang, Q.S.; Wei, L.; Sun, K.; Xue, T.Monoclonal antibodies against human aspartyl (asparaginyl) beta-hydroxylase developed by DNA immunizationHybridoma28251-2572009Homo sapiens PubMed
699589Hardy, 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 functionJ. Mol. Biol.392994-10062009Homo sapiens PubMed
725118Yang, 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 coliHybridoma3069-792011Homo sapiens PubMed

LINKS TO OTHER DATABASES (specific for EC-Number 1.14.11.16)
ExplorEnz
ExPASy
KEGG
MetaCyc
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)