Information on EC 1.13.99.1 - inositol oxygenase and Organism(s) Homo sapiens and UniProt Accession Q9UGB7

for references in articles please use BRENDA:EC1.13.99.1
Word Map on EC 1.13.99.1
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Select one or more organisms in this record:
This record set is specific for:
Homo sapiens
UNIPROT: Q9UGB7


The taxonomic range for the selected organisms is: Homo sapiens

The enzyme appears in selected viruses and cellular organisms

top print hide
EC NUMBER
COMMENTARY hide
1.13.99.1
-
top print hide
RECOMMENDED NAME
GeneOntology No.
inositol oxygenase
top print hide
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
myo-Inositol + O2 = D-glucuronate + H2O
show the reaction diagram
the N-terminus is important, through coordination of a set of loops covering the active site, in shielding the active site during catalysis. Role of residue K127 in governing the access o the diiron cluster
-
top print hide
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
-
-
-
-
top print hide
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
UDP-alpha-D-glucuronate biosynthesis (from myo-inositol)
-
-
Ascorbate and aldarate metabolism
-
-
Inositol phosphate metabolism
-
-
top print hide
SYSTEMATIC NAME
IUBMB Comments
myo-Inositol:oxygen oxidoreductase
An iron protein.
top
top print hide
CAS REGISTRY NUMBER
COMMENTARY hide
9029-59-8
-
top print hide
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
top print hide
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
upregulation of MIOX accompanied by mitochondrial fragmentation and depolarization, inhibition of autophagy/mitophagy, and altered expression of mitochondrial dynamic and mitophagic proteins under high-glucose ambience. Additionally, dysfunctional mitochondria accumulate in the cytoplasm. Decreasing the expression of MIOX under high-glucose ambience increases PTEN-induced putative kinase 1 expression and the dependent mitofusin-2-Parkin interaction. Overexpression of MIOX in the cells enhances the effects of high-glucose, whereas MIOX siRNA or D-glucarate, an inhibitor of MIOX, partially reverse these perturbations
metabolism
-
a mechanism links MIOX to impaired mitochondrial quality control during tubular injury in the pathogenesis of diabetic kidney disease
physiological function
metabolism
-
MIOX is the first and rate-limiting enzyme in myo-inositol metabolism pathway
additional information
-
increase in MIOX enzyme activity is in proportion to serum glucose concentrations and may be responsible for the myo-inositol depletion found in the type I diabetes mellitus complications, detailed phenotype analysis of 130 Caucasian patients, overview
top print hide
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
myo-inositol + O2
D-glucuronate + H2O
show the reaction diagram
-
-
-
-
?
myo-inositol + O2
D-glucuronic acid + H2O
show the reaction diagram
top print hide
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
myo-inositol + O2
D-glucuronate + H2O
show the reaction diagram
-
-
-
-
?
myo-inositol + O2
D-glucuronic acid + H2O
show the reaction diagram
top print hide
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Iron
-
diiron cluster
top print hide
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
D-glucarate
-
a MIOX inhibitor
6-(4-hydroxy-3,5-dimethoxyphenyl)-4,8-dihydronaphthalene-1,3,8-triol
-
docking energy level (Kcal/mol): -6.9602
ascochitine
-
docking energy level (Kcal/mol): -9.5382
heritonin
-
docking energy level (Kcal/mol): -10.4072
stigmasterol
-
docking energy level (Kcal/mol): -14.589
taraxasterol
-
docking energy level (Kcal/mol): -14.8894
tretinoin
-
docking energy level (Kcal/mol): -12.1034
top print hide
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3.5 - 5.8
myo-inositol
top print hide
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8
-
assay at
top print hide
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
top print hide
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
plasma MIOX is increased in critically ill patients with acute kidney injury compared with patients without acute kidney injury and is highest in patients with oliguric acute kidney injury
Manually annotated by BRENDA team
-
MIOX is a tubular-specific enzyme
Manually annotated by BRENDA team
-
is expressed at low levels in cell types where diabetic complications occur
Manually annotated by BRENDA team
additional information
-
immunohistochemic analysis
Manually annotated by BRENDA team
top print hide
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
top print hide
PDB
SCOP
CATH
UNIPROT
ORGANISM
Q9UGB7
Homo sapiens;
top print hide
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
33000
-
1 * 33000, deduced from nucleotide sequence, SDS-PAGE
33000
-
SDS-PAGE
top print hide
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 37000, recombinant detagged enzyme, SDS-PAGE
monomer
-
1 * 33000, deduced from nucleotide sequence, SDS-PAGE
top print hide
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
in complex with myo-inosose-1 bound in a terminal mode to the enzyme's diiron cluster site. The N-terminus is important, through coordination of a set of loops covering the active site, in shielding the active site during catalysis. Role of residue K127 in governing the access o the diiron cluster
-
top print hide
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
after storage at 4�C for few weeks, a specific truncation due to degradation is observed, extended storage also causes the accumulation of a small proportion of apparantly dimerized MIOX
-
top print hide
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant MIOX
-
top print hide
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in epithelial cell line LLC-PK1
-
expression in Escherichia coli
-
gene MIOX, kidney-specific expression, recombinant expression of GST-tagged enzyme in HEK-293 cells, cleavage of the GST tag by thrombin
-
gene MIOX, quantitative enzyme expression analysis
-
gene MIOX, quantitative real-time PCR enzyme expression analysis
-
genotyping of MIOX in Caucasian type I diabetes mellitus patients, overview
-
top print hide
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
transcriptional and translational modulation of myo-inositol oxygenase (Miox) by fatty acids, overview
-
treatment of HK-2 cells with palmitate/bovine serum albumin for 24 h induces an increased Miox expression with a concomitant decrease in the membrane-bound precursor form of pre-Srebp1 in the cytoplasmic fraction. No change in the expression of beta-actin or laminB1 is observed. Miox is transcriptionally upregulated by high glucose ambience. A dose-dependent increase in the expression of Miox is observed following insulin treatment. At the same time, a dose-dependent increase in the mSrebp1 is observed. Rapamycin reverses palmitate/bovine serum albumin-induced Miox, Srebp1, and p53 expression and apoptosis in renal tubular cells
-
upregulation of MIOX accompanied by mitochondrial fragmentation and depolarization, inhibition of autophagy/mitophagy, and altered expression of mitochondrial dynamic and mitophagic proteins under high-glucose ambience
-
top print hide
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
-
the kidney-specific protein myo-inositol oxygenase is a potential biomarker of acute kidney injury, AKI
medicine
-
the enzyme is a possible target for treatment of diabetic kidney disease. MIOX enzyme inhibitor D-glucarate might be a potential therapeutic agent for the amelioration of diabetic kidney disease
top
top
top
top
LINKS TO OTHER DATABASES (specific for EC-Number 1.13.99.1)
ExplorEnz
ExPASy
KEGG
MetaCyc
SABIO-RK
NCBI: PubMed, Protein, Nucleotide, Structure, Genome, OMIM
IUBMB Enzyme Nomenclature
PROSITE Database of protein families and domains
InterPro (database of protein families, domains and functional sites)