Information on EC 1.3.1.24 - biliverdin reductase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY
1.3.1.24
-
RECOMMENDED NAME
GeneOntology No.
biliverdin reductase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
bilirubin + NAD(P)+ = biliverdin + NAD(P)H + H+
show the reaction diagram
-
-
-
-
bilirubin + NAD(P)+ = biliverdin + NAD(P)H + H+
show the reaction diagram
catalysis via hydride transfer from NADH
-
bilirubin + NAD(P)+ = biliverdin + NAD(P)H + H+
show the reaction diagram
induced fit docking is emplyed to study the substrate binding modes to hBVR-A of biliverdin-IXalpha and four analogues. Substrate binding modes are examined further by performing molecular dynamics (MD) simulations followed by molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations. On the basis of our calculations, the energetically preferred pathway consists of an initial protonation of the pyrrolic nitrogen on the biliverdin substrate followed by hydride transfer to yield the reduction product
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
oxidation
-
-
oxidation
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
reduction
-
-
reduction
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
heme degradation
-
-
heme metabolism
-
-
Porphyrin and chlorophyll metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
bilirubin:NAD(P)+ oxidoreductase
-
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
biliverdin IXalpha reductase
-
-
biliverdin IXalpha reductase
P46844
-
biliverdin reductase
-
-
biliverdin reductase
-
-
biliverdin reductase
P46844
-
biliverdin reductase
-
-
biliverdin reductase A
-
-
biliverdin reductase A
-
-
Biliverdin reductase-A
-
-
BLVRA
-
-
BVR
-
-
-
BVR
-
BVR reduces biliverdin to the antioxidant bilirubin, functions as a kinase and as a transcription factor in the MAPK signalling cascade, as well as in the nuclear transport of haematin
BVR
P46844
-
BVR
-
-
BVR-A
-
isoform
BVR-B
-
isoform
BVRA
-
-
BVRA
P53004
isoform
BVRA
P46844
isoform
BVRB
P30043
isoform, predominant during fetal development
BVRB
-
isoform, predominant during fetal development
hBVR-A
-
-
reductase, biliverdin
-
-
-
-
slr1784
-
gene name
CAS REGISTRY NUMBER
COMMENTARY
9074-10-6
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
cow
-
-
Manually annotated by BRENDA team
expression in 293A cell, increase in level of heme oxigenase 1 mRNA and protein
-
-
Manually annotated by BRENDA team
expression in Nicotiana tabacum
-
-
Manually annotated by BRENDA team
Sprague-Dawley rats
-
-
Manually annotated by BRENDA team
Syncerus sp.
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
using BVR siRNA, blocking generation of bilirubin, reverses the effect of hypoxia on enhancing cell survival and apoptotic protein (Bcl-2, procasepase-9, procasepase-3) expression, preventing nuclear shrinkage, DNA fragmentation and mitochondrial depolarization in starved pulmonary arterial smooth muscle cell, which are recovered by exogenous bilirubin. The inhibitory effect of bilirubin on pulmonary arterial smooth muscle cell apoptosis under hypoxic condition is blocked by the inhibitor of ERK1/2 pathway
metabolism
-
BVR is part of the heme oxygenase protection system, overview
metabolism
-
HIF-1alpha regulates the expression of BVR and other enzymes involved in oxidative stress response in lung macrophages, overview
metabolism
-
the heme oxygenase/biliverdin reductase axis is the main metabolic pathway for heme degradation. Activation during stress results in increased heme degradation and acceleration of biliverdin transformation to bilirubin
metabolism
-
the heme oxygenase/biliverdin reductase axis is the main metabolic pathway for heme degradation. Activation suirng stress results in increased heme degradation and acceleration of biliverdin transformation to bilirubin
physiological function
-
biliverdin reductase converts biliverdin to bilirubin. Additionally, acting as a transcription factor and possessing a capacity of a serine/threonine kinase, it may modulate signaling pathways. BVR exhibits cytoprotection, important role of PKCa/b kinase in BVR-mediated improvement in cell survival
physiological function
-
blockage of BVR protein expression by retroviral siBVR inhibits the HO-2 protein induction but not vice versa
physiological function
-
BV reductase regulates cell growth and apoptosis, its knockdown increases apoptosis. The BVR also phosphorylates the insulin receptor substrate 1, IRS-1, on serine residues preventing its phosphorylation by insulin receptor, which represent a physiological mechanism for increasing glucose uptake. And BVR is a nuclear transporter of ERK1/2 with metabolic regulatory role
physiological function
-
BVR is required for heme degradation. BVR plays a role in bile pigment metabolism, in cell protection, and in signal transduction, detailed overview. BVR reverses the inhibitory effect of biliverdin on PKC enzymes
physiological function
-
coordinated increased expression of biliverdin reductase and heme oxygenase-2 promotes cardiomyocyte survival, a reductase-based peptide counters beta-adrenergic receptor ligand-mediated cardiac dysfunction
physiological function
-
primary spontaneous pneumothorax, PSP, in smokers is associated with lung macrophage oxidative stress. The response to this condition involves HIF-1alpha-mediated induction of HO-1, BVR and H-ferritin. Cigarette smoke is a risk factor of recurrence of the disease, overview
physiological function
-
the significant effect of biliverdin on decrease in extracellular oxidative stress in BVR-deficient cells may be related to direct scavenging of extracellular reactive oxygen and nitrogen species by biliverdin
physiological function
-
BLVRA may be among the most effective physiological reactive oxygen species scavenging systems and may play an important role in regulating cellular senescence
physiological function
-
BVR-A up-regulation and post-translational modifications significantly correlate with beta-secretase protein levels in the brain
physiological function
-
H2O2 markedly induces BLVRA activity in young human diploid fibroblasts, but not in senescent human diploid fibroblasts(HDF). Depletion of BLVRA reduces the H2O2-dependent induction of heme oxygenase-1 (HO-1) in young human diploid fibroblasts, but not in senescent cells. Lentiviral RNAi transfected stable primary HDFs with reduced BLVRA expression show upregulation of the CDK inhibitor family members p16, p53, and p21, followed by cell cycle arrest in G0-G1 phase with high expression of senescence-associated beta-galactosidase
physiological function
-
hBVR suppresses Goodpasture antigen-binding protein autophosphorylation in a concentration-dependent manner. The inhibitory effect of hBVR on GPBP kinase activity extended to its ability to phosphorylate its substrate, GPA-derived peptide, TNF-alpha alpha-NF-kappaB-dependent expression of Goodpasture antigen-binding protein is regulated by biliverdin reductase
metabolism
-
it is shown that the rates of sHO-1 (shortened form of heme oxygenase-1) metabolism in the presence and absence of BVR are equal
additional information
-
bilirubin is a superior antioxidant in isolated mitochondria and neutrophils as compared to biliverdin, overview. XO-derived superoxide is decreased in a concentration-dependent fashion by bilirubin whereas biliverdin has no inhibitory effect and even significantly increases the signal pointing towards pro-oxidative effects
additional information
-
bilirubin is an important component of cellular defense mechanisms with cytoprotective features
additional information
-
isoproterenol, ISO, stimulation of BVR levels enhances the stability of heme oxygenase 2, HO-2. Interaction between HO-2 and BVR is a survival factor for cardiomyocytes during ISO stimulation
additional information
-
pharmacodynamics of the heme oxygenase/biliverdin reductase system, overview
additional information
-
the BVR activity and expression is not affected by MAP kinase inhibitors, overview
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
Akt protein + NAD(P)H
?
show the reaction diagram
-
-
-
-
-
?
bilirubin + NAD(P)+
biliverdin + NAD(P)H + H+
show the reaction diagram
-
-
-
-
r
bilirubin + NAD+
biliverdin + NADH + H+
show the reaction diagram
-
-
-
-
r
bilirubin + NAD+
biliverdin + NADH + H+
show the reaction diagram
-
-
-
-
-
bilirubin + NAD+
biliverdin + NADH + H+
show the reaction diagram
-
-
-
-
r
bilirubin + NADP+
biliverdin + NADPH + H+
show the reaction diagram
-
-
-
-
r
bilirubin + NADP+
biliverdin + NADPH + H+
show the reaction diagram
-
-
-
-
?
bilirubin + NADP+
biliverdin + NADPH + H+
show the reaction diagram
-
-
-
-
r
bilirubin + NADP+
biliverdin + NADPH + H+
show the reaction diagram
-
-
-
-
r
bilirubin-IXa + NAD+
biliverdin-IXa + NADH + H+
show the reaction diagram
-
-
-
-
-
bilirubin-IXa + NADP+
biliverdin-IXa + NADPH + H+
show the reaction diagram
-
-
-
-
-
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
-
-
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
-
-
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
-
-
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
-
-
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
-
-
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
-
-
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
-
-
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
Syncerus sp.
-
-
-
-
r
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
specific for biliverdin and IXalpha faster than the biliverdin isomers IXbeta, IXr or IXdelta
-
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
pig spleen: IXalpha-biliverdin: most effective substrate among the 4 biliverdin isomers
-
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
it is proposed that the propionate side chains bridging the C10 position on the tetrapyrrole interact with the positively charged residues on biliverdin reductase A to promote binding and subsequent catalysis
-
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
human enzyme is a leucine zipper-like DNA-binding protein and functions in transcriptional activation of heme oxygenase-1 by oxidative stress
-
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
NADH and NADPH can be replaced by 3-acetyl-NADPH and deamino-NADPH (biliverdin I and biliverdin IX reduction)
-
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
not: IXalpha-biliverdin methylester (pig spleen)
-
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
activity with NADPH is 50 times greater than with NADH
-
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
two and four propionates in the biliverdin structure give a biliverdin with substrate activity but biliverdins carrying methyl, ethyl and one propionate residue in their structure and biliverdins with one propionate and one acetate residue or with two acetate residues are no substrates
-
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
specificity of the different molecular forms
-
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
high but no absolute specificity for natural IXalpha isomeric form
-
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
pig spleen: strictly specific to biliverdin, no other oxidoreductase activities
-
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
study with different biliverdin types
-
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
importance in linear tetrapyrrole metabolism
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
physiologic degradation of heme to bile pigments
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
physiologic degradation of heme to bile pigments
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
physiologic degradation of heme to bile pigments
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
physiologic degradation of heme to bile pigments
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
Syncerus sp.
-
bile pigment formation
-
r
biliverdin + NAD(P)H + H+
bilirubin + NAD(P)+
show the reaction diagram
-
-
-
-
?
biliverdin + NAD(P)H + H+
bilirubin + NAD(P)+
show the reaction diagram
-
-
-
-
?
biliverdin + NAD(P)H + H+
bilirubin + NAD(P)+
show the reaction diagram
-
-
-
-
?
biliverdin + NAD(P)H + H+
bilirubin + NAD(P)+
show the reaction diagram
-
-
-
-
?
biliverdin + NAD(P)H + H+
bilirubin + NAD(P)+
show the reaction diagram
-
-
-
-
?
biliverdin + NAD(P)H + H+
bilirubin + NAD(P)+
show the reaction diagram
-
-
-
-
-
?
biliverdin IXalpha + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
-
-
-
?
biliverdin IXalpha + NAD(P)H + H+
bilirubin + NAD(P)+
show the reaction diagram
-
-
-
-
?
biliverdin IXalpha + NAD(P)H + H+
bilirubin IXalpha + NAD(P)+
show the reaction diagram
-
substrate of BVRA but not of BVRB isoform
-
-
ir
biliverdin IXalpha + NAD(P)H + H+
bilirubin IXalpha + NAD(P)+
show the reaction diagram
P30043, P53004
substrate of BVRA but not of BVRB isoform
-
-
ir
casein + NAD(P)H
?
show the reaction diagram
-
BVR functions as an serine/threonine kinase for casein
-
-
?
Elk-1 protein + NAD(P)H
?
show the reaction diagram
-
-
-
-
?
extracellular signal-regulated kinase 1 + NAD(P)H
?
show the reaction diagram
-
-
-
-
?
extracellular signal-regulated kinase 2 + NAD(P)H
?
show the reaction diagram
-
-
-
-
?
insulin receptor substrate 1 + NAD(P)H
?
show the reaction diagram
-
-
-
-
?
insulin receptor substrate 1 + NAD(P)H
?
show the reaction diagram
-
phosphorylates serine residues in insulin receptor substrate 1
-
-
?
insulin receptor substrate 1 + NAD(P)H
?
show the reaction diagram
P30043, P53004
phosphorylates serine residues in insulin receptor substrate 1
-
-
?
insulin receptor substrate-1 + NAD(P)H
?
show the reaction diagram
-
the serine residues are targets for BVR phosphorylation
-
-
?
insulin-receptor substrate 1 + NAD(P)H
?
show the reaction diagram
-
BVR functions as an serine/threonine kinase for insulin-receptor substrate 1
-
-
?
myelin basic protein + NAD(P)H
?
show the reaction diagram
-
BVR functions as an serine/threonine kinase for myelin basic protein
-
-
?
phosphatidylinositol 3-kinase + NAD(P)H
?
show the reaction diagram
-
-
-
-
-
?
protein kinase C-betaII + NAD(P)H
?
show the reaction diagram
-
BVR functions as an serine/threonine kinase for protein kinase C-betaII
-
-
?
mitogen-activated protein kinase kinase 1 + NAD(P)H
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
enzyme advances the role of heme oxidase 1 in cytoprotection and also affords cytoprotection independent of heme degradation
-
-
-
additional information
?
-
-
enzyme diverts tetrapyrrole metabolism toward heme synthesis while also reducing heme levels to de-repress synthesis of 5-aminolevulinic acid
-
-
-
additional information
?
-
-
enzyme may be an essential component of normal physiologic gastrointestinal defense
-
-
-
additional information
?
-
-
enzyme physiologically regenerates bilirubin in a catalytic cycle, providing antioxidant cytoprotection
-
-
-
additional information
?
-
-
role of enzyme in regulation of activating protein 1 and cAMP-regulated genes and in cell signaling
-
-
-
additional information
?
-
P30043, P53004
biliverdin IXalpha is no substrate BVRB isoform
-
-
-
additional information
?
-
-
biliverdin IXalpha is no substrate of BVRB isoform, BVR has also serine/threonine/tyrosine kinase activity
-
-
-
additional information
?
-
P30043, P53004
BVR has also serine/threonine/tyrosine kinase activity
-
-
-
additional information
?
-
-
BVR is a substrate for insulin receptor tyrosine kinase
-
-
-
additional information
?
-
P30043, P53004
BVR is a substrate for insulin receptor tyrosine kinase
-
-
-
additional information
?
-
-
BVR is likely to affect the activation of nuclear factor kappaB both in its capacity as a reductase as well as a kinase
-
-
-
additional information
?
-
-
heme-oxygenase-1-dependent activation of Akt protein is in part mediated by BVR
-
-
-
additional information
?
-
-
BVR is an S/T/Y kinase
-
-
-
additional information
?
-
-
the enzyme shows dual cofactor- and pH-dependency in activity
-
-
-
additional information
?
-
-
hBVR binds to Goodpasture antigen-binding protein and down-regulates its TNF-alpha-stimulated kinase activity
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
bilirubin + NAD(P)+
biliverdin + NAD(P)H + H+
show the reaction diagram
-
-
-
-
r
bilirubin + NAD+
biliverdin + NADH + H+
show the reaction diagram
-
-
-
-
r
bilirubin + NAD+
biliverdin + NADH + H+
show the reaction diagram
-
-
-
-
r
bilirubin + NADP+
biliverdin + NADPH + H+
show the reaction diagram
-
-
-
-
r
bilirubin + NADP+
biliverdin + NADPH + H+
show the reaction diagram
-
-
-
-
r
bilirubin + NADP+
biliverdin + NADPH + H+
show the reaction diagram
-
-
-
-
r
bilirubin-IXa + NAD+
biliverdin-IXa + NADH + H+
show the reaction diagram
-
-
-
-
-
bilirubin-IXa + NADP+
biliverdin-IXa + NADPH + H+
show the reaction diagram
-
-
-
-
-
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
importance in linear tetrapyrrole metabolism
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
physiologic degradation of heme to bile pigments
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
physiologic degradation of heme to bile pigments
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
physiologic degradation of heme to bile pigments
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
-
physiologic degradation of heme to bile pigments
-
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
show the reaction diagram
Syncerus sp.
-
bile pigment formation
-
r
biliverdin IXalpha + NAD(P)H + H+
bilirubin + NAD(P)+
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
enzyme advances the role of heme oxidase 1 in cytoprotection and also affords cytoprotection independent of heme degradation
-
-
-
additional information
?
-
-
enzyme diverts tetrapyrrole metabolism toward heme synthesis while also reducing heme levels to de-repress synthesis of 5-aminolevulinic acid
-
-
-
additional information
?
-
-
enzyme may be an essential component of normal physiologic gastrointestinal defense
-
-
-
additional information
?
-
-
enzyme physiologically regenerates bilirubin in a catalytic cycle, providing antioxidant cytoprotection
-
-
-
additional information
?
-
-
role of enzyme in regulation of activating protein 1 and cAMP-regulated genes and in cell signaling
-
-
-
additional information
?
-
-
BVR is an S/T/Y kinase
-
-
-
additional information
?
-
-
the enzyme shows dual cofactor- and pH-dependency in activity
-
-
-
additional information
?
-
-
hBVR binds to Goodpasture antigen-binding protein and down-regulates its TNF-alpha-stimulated kinase activity
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NAD(P)H
-
-
NAD(P)H
P30043
;
NADH
-
-
NADH
-
higher activity with NADH than with NADPH
NADH
-
NADH and NADPH can be replaced by 3-acetyl-NADPH and deamino-NADPH (biliverdin I and biliverdin IX reduction)
NADH
Syncerus sp.
-
absolute requirement
NADH
-
time-course of the NADH-dependent reaction displayes no sigmoidal curve
NADH
-
at pH 6.0-7.0 NADH is the most effective cofactor
NADH
-
used at acidic pH
NADPH
-
-
NADPH
-
higher activity with NADH than with NADPH
NADPH
-
NADH and NADPH can be replaced by 3-acetyl-NADPH and deamino-NADPH (biliverdin I and biliverdin IX reduction)
NADPH
Syncerus sp.
-
-
NADPH
-
time-course of the NADPH-dependent reaction displayes a sigmoidal curve
NADPH
-
at pH 8,5-8.75 NADPH is the most effective cofactor
NADPH
-
used in the basic range
additional information
-
the enzyme shows dual cofactor- and pH-dependency in activity
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Cl-
-
-
Mn2+
-
is required for binding of the ATP analogue and for autophosphorylation
Mn2+
-
acitvates BVR tyrosine kinase activity
Mn2+
-
-
Mn2+
-
required
Zn2+
-
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5,5'-dithiobis(2-nitrobenzoate)
-
pretreatment of the enzyme with NADPH and biliverdins fully protects
5,5'-dithiobis(2-nitrobenzoate)
-
-
5,5'-dithiobis(2-nitrobenzoate)
-
-
5,5'-dithiobis(2-nitrobenzoate)
-
-
Albumin
-
-
-
Arsenobenzoate
-
1 mM, slight
bilirubin
-
inhibits the enzyme in a competitive manner
bilirubin
-
product inhibition
bilirubin
-
product inhibition
bilirubin
-
-
bilirubin
-
inhibits the enzyme in a feedback regulation system, biliverdin inhibits the heme oxygenase activity, overview
Biliverdin
-
-
Biliverdin
-
substrate inhibition
Biliverdin
-
the enzyme is inhibited by the substrate when the concentration exceeds 0.004-0.005 mM
Biliverdin
-
substrate inhibition
Biliverdin
-
-
biliverdin IXalpha
-
with cofactor NADPH, inhibitory above 0.004 mM, with cofactor NADH, inhibitory above 0.018 mM
Ca2+
-
abolishes autophosphorylation of BVR
Dithionitrobenzoate
-
-
FAD
-
-
FMN
-
-
GATA1
-
transcription factor GATA1 downregulates BVR expression
-
HgCl2
-
irreversible inhibition
iodoacetamide
-
-
iodoacetamide
-
1 mM, slight
iodoacetamide
-
pretreatment of the enzyme with NADPH and biliverdins fully protects
iodoacetate
-
-
Iron-hematoporphyrin
-
competitive, acts as biliverdin-bilirubin analog
lipase
-
-
-
Metalloporphyrin complexes
-
-
-
N-ethylmaleimide
-
-
N-ethylmaleimide
-
1.0 mM
N-ethylmaleimide
-
pretreatment of the enzyme with NADPH and biliverdins fully protects
N-ethylmaleimide
-
only one of three thiol residues can be alkylated when a ratio N-ethylmaleimide/mol enzyme SH = 90 is used, at a ratio of 300 two thiol residues are alkylated
NAD+
-
product inhibition
NADH
-
at pH 8.5, competitive to NADPH
NADP+
-
-
NADP+
-
product inhibition
NADPH
-
at pH 7.0, competitive to NADH
p-chloromercuribenzoate
-
0.025 mM
p-chloromercuribenzoate
-
pretreatment of the enzyme with NADPH and biliverdins fully protects
p-chloromercuribenzoate
-
-
p-chloromercuribenzoate
-
-
p-chloromercuribenzoate
-
-
p-hydroxymercuribenzoate
-
-
potato acid phosphatase
-
human bilverdin reductase expressed in E. coli
-
Protein phosphatase 2A
-
human bilverdin reductase expressed in E. coli, okadaic acid attenuates the inhibition
-
SH-reactive agent
-
34000 Da form extremely sensitive to, larger 68000 Da form lacks sensitivity to
-
SH-reagents
-
e.g. 5,5'-dithiobis(2-nitrobenzoic acid), N-ethylmaleimide, pretreatment of the enzyme with NADPH and biliverdins fully protects
-
Trypsin
-
-
-
zinc-protoporphyrin
-
-
Zn2+
-
inhibitory to autophosphorylation of BVR, can not be overcome with Mn2+
Mg2+
-
abolishes autophosphorylation of BVR
additional information
-
since no specific inhibitors for BVR are known, siRNA is used to silence the BVR gene in primary endothelial cells and accordingly suppress its activity
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Albumin
-
-
-
cGMP
-
BVR localizes into the nucleus upon activation by cGMP
Co-protoporphyrin complex
-
activates
cobalt protoporphyrin
-
activates
cytokine
-
induces BVR transcription
-
Fe-protoporphyrin complex
-
activates
Ferredoxin
-
-
-
heme
-
upregulates BVR expression
hyperthermia
-
induces BVR transcription
-
oxidant
-
activates
-
Tumor necrosis factor alpha
-
-
-
Insulin
-
increases BVR tyrosine autophosphorylation
-
additional information
-
Zn-protoporphyrin complex does not activate BVR
-
additional information
-
BVR kinase activity is stimulated in the presence of double-stranded DNA fragments corresponding to HO-1 antioxidant and hypoxia response elements, as well as by haematin
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.001 - 0.002
Biliverdin
-
cosubstrate NADH
0.001
Biliverdin
-
-
0.0013
Biliverdin
-
enzyme has a 6-histidine-tagged amino-terminal fusion
0.003
Biliverdin
-
cosubstrate NADPH, rat liver
0.003
Biliverdin
-
cosubstrate NADPH
0.0032
Biliverdin
-
cosubstrate NADPH, biliverdin reductase C291A
0.0034
Biliverdin
-
cosubstrate NADPH, biliverdin reductase wild-type
0.0049
Biliverdin
-
cosubstrate NADH, biliverdin reductase wild-type
0.005
Biliverdin
-
cosubstrate NADH
0.0052
Biliverdin
-
cosubstrate NADH, biliverdin reductase C291A
0.0069
Biliverdin
-
at pH 7
0.0097
Biliverdin
-
cosubstrate NADH, biliverdin reductase C280A
0.0102
Biliverdin
-
cosubstrate NADPH, biliverdin reductase C280A
0.0004
biliverdin IXalpha
-
cosubstrate NADPH
0.0006
biliverdin IXalpha
-
pH 7.0, 37C, cosubstrate NADPH
0.0015
biliverdin IXalpha
-
cosubstrate NADH
0.0068
biliverdin IXalpha
-
pH 7.0, 37C, cosubstrate NADH
0.023
biliverdin IXalpha
-
-
0.24
NADH
-
-
0.27
NADH
-
-
0.333
NADH
-
in the presence of 0.005 mM biliverdin, biliverdin reductase wild-type
0.394
NADH
-
in the presence of 0.005 mM biliverdin, biliverdin reductase C280A
0.567
NADH
-
in the presence of 0.005 mM biliverdin, biliverdin reductase C291A
1.5 - 2
NADH
-
pig spleen, rat liver
0.0023
NADPH
-
in the presence of 0.005 mM biliverdin, biliverdin reductase C280A
0.0029
NADPH
-
in the presence of 0.005 mM biliverdin, biliverdin reductase wild-type
0.003 - 0.005
NADPH
-
pig spleen
0.003
NADPH
-
-
0.0133
NADPH
-
in the presence of 0.005 mM biliverdin, biliverdin reductase C291A
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.7
NADH
-
without Cl-
5.6
NADH
-
with Cl-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0026
bilirubin
-
0.01 mM NADPH as substrate
0.0098
bilirubin
-
at pH 7
0.0117
bilirubin
-
0.1 mM biliverdin as substrate
0.0019
NAD+
-
at pH 7
0.0454 - 0.583
NADP+
-
at pH 8.7
0.09
NADP+
-
0.1 mM biliverdin as substrate
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0001
-
HeLa cells transfected with BVR-targeted RNAi
0.00035
-
BVR activity in HeLa cells, control
0.00075
-
HeLa cells transfected with pcDNA3-BVR, overexpression of BVR
additional information
-
-
additional information
-
hypoxia activates hBVR activity
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.5
-
cosubstrate NADPH
5.8
-
biliverdin + NADPH
6
-
biliverdin + NADH
6
-
cosubstrate NADH
6.7
-
biliverdin + NADH
6.7
P30043
optimal pH value for NADH as cofactor; optimal pH value for NADH as cofactor
6.7
-
optimal pH value for NADH as cofactor; optimal pH value for NADH as cofactor
6.7
-
with cofactor NADH
6.7
-
assay at
6.8
-
biliverdin + NADPH
6.8
-
with NADH
6.9
-
biliverdin + NADH
7
-
biliverdin + NADH
7
-
biliverdin + NADH
7.3
-
activity assay
8.5
-
biliverdin + NADPH
8.5
-
-
8.5
-
biliverdin + NADPH
8.5
-
assay at
8.7
-
biliverdin + NADPH
8.7
P30043
optimal pH value for NADPH as cofactor; optimal pH value for NADPH as cofactor
8.7
-
optimal pH value for NADPH as cofactor; optimal pH value for NADPH as cofactor
8.7
-
with cofactor NADPH
8.7
-
with NADPH
additional information
-
the enzyme shows dual cofactor- and pH-dependency in activity
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 9
-
biliverdin + NADPH, pH 6: about 50% of activity maximum, pH 9: 27% of activity maximum
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
-
assay at
37
-
assay at
37
-
activity assay
37
-
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30 - 42
-
exposure of male rats to 42C for 20 min does not decrease brain biliverdin activity, the 1.5 kb biliverdin reductase mRNA displayes thermal tolerance too
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
protein detected in the infiltrating monocytes, macrophages, T cells and neutrophils as well as in circulating lymphocytes
Manually annotated by BRENDA team
-
cellular localization reveals age-related pattern of expression of the reductase in selected regions such as cortex, substantia nigra, hippocampus and in the cerebellum
Manually annotated by BRENDA team
-
immuno-chemical localization of biliverdin reductase protein in normal brain correlates well with the presence of HO-1 and HO-2 throughout the forebrain, diencephalon, cerebellum and brainstem regions
Manually annotated by BRENDA team
-
six hours after middle cerebral artery occlusion, increased immunoreactivity for biliverdin reductase is noted in neurons in the peri-ischemic areas, intraischemic cortical layers 3 and 5, as well as in neurons in regions distant from the borders of vascular distribution of the MCA, such as those in substantia nigra, in the Purkinje layer of the cerebellum and in the central nucleus of inferior colliculus
Manually annotated by BRENDA team
-
abundantly expressed
Manually annotated by BRENDA team
-
BVR expression patterns, overview
Manually annotated by BRENDA team
-
co-expression with heme oxygenases HO-1 and HO-2, BVR expression patterns, overview
Manually annotated by BRENDA team
-
mucosal epithelial cells and endothelium of intramural vessels of, all intrinsic nerve cell bodies of both submucous and myenteric plexuses
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
immunocytochemical analysis reveals that biliverdin reductase is localised in proximal tubules of the inner cortex of the rat kidney
Manually annotated by BRENDA team
-
kidney tissue with or without renal carcinoma, the enzyme activity is nearly doubled in the tumor tissue
Manually annotated by BRENDA team
-
abundantly expressed
Manually annotated by BRENDA team
-
abundantly expressed
Manually annotated by BRENDA team
-
lung, increased expression in macrophages of primary spontaneous pneumothorax of smokers compared to non-smokers
Manually annotated by BRENDA team
-
low activity
Manually annotated by BRENDA team
-
shows increased BVR level
Manually annotated by BRENDA team
-
increased activity of BVR, but only in the presence of NADH
Manually annotated by BRENDA team
-
pulmonary arterial smooth muscle cell
Manually annotated by BRENDA team
-
inflamed lesions, increased in rats with clinical autoimmune encephalomyelitis, also present in both white and gray matter
Manually annotated by BRENDA team
-
abundantly expressed
Manually annotated by BRENDA team
-
sparingly expressed
Manually annotated by BRENDA team
-
sparingly expressed
Manually annotated by BRENDA team
Syncerus sp.
-
-
Manually annotated by BRENDA team
additional information
-
the BVR activity progressively increases after birth and reaches adult levels by postpartum day 28
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
in normoxic cells, hBVR is located primarily in the cytoplasm, with some protein also being seen in the nucleus
Manually annotated by BRENDA team
-
role for the enzyme in intracellular traffic of protein kinase C betaII and its membrane translocation
Manually annotated by BRENDA team
-
in the nucleus, BVR is a leucine zipper-like DNA binding protein and can act as a transcription factor for activator protein 1-regulated genes
Manually annotated by BRENDA team
-
only kinase-competent BVR translocates to the nucleus
Manually annotated by BRENDA team
-
hBVR is detected in the nucleus at 1, 2, and 4 h after hypoxia, at which times its kinase and reductase activities are increased
Manually annotated by BRENDA team
-
external plasma membrane
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
21000
P30043
BVRB, SDS-PAGE
689373
21000
-
BVRB, SDS-PAGE
689373
30100
-
SDS-PAGE
437793
30400 - 31400
-
various forms, two dimensional PAGE
437791
32000
-
gel filtration; kidney, gel filtration
437804
33000
-
SDS-PAGE
437824
33500
P30043
BVRA, SDS-PAGE
689373
33500
-
BVRA, SDS-PAGE
689373
34000 - 36000
-
liver
437789
34000
-
gel filtration
437788
34000
-
major form 1, SDS-PAGE
437794
34000
-
form 1 in liver, kidney and spleen, SDS-PAGE
437795
34000
-
-
437819
34000
-
converted to a larger 68000 Da form when rats are treated with SH-reactive agents
676353
36000
-
SDS-PAGE
437804
36000
-
-
701357
38000
-
the HY2 gene encodes a soluble protein precursor with a putative N-terminal plastid transit peptide, this protein is phytochromobilin synthase, a ferredoxin-dependent biliverdin reductase, SDS-PAGE
437767
41000 - 42000
-
the purified protein resolves into two molecular weight forms of 40700 and 39600, two-dimensional electrophoresis
437821
46000
-
form 2 in liver, SDS-PAGE; liver (form 2), SDS-PAGE
437795
46000
-
form 2 in liver, SDS-PAGE
437795
54000
-
liver (form 2), HPLC
437797
56000
-
minor form 2, SDS-PAGE
437794
60000
-
expression of rat biliverdin reductase as a gluthatione-S-transferase protein, SDS-PAGE
437820
68000
-
major form 1 from liver is converted into a second major form by a NAD+ -dependent peroximal dehydrogenase, SDS-PAGE
437794
68000
-
liver (form 3), HPLC
437797
68000
-
-
676353
69000
-
in vitro translated reductase, 12% native polyacryamide gel
437812
70000
-
gel filtration
437807
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 68000, SDS-PAGE
dimer
-
2 * 34000, liver (form I), minor dimeric form, SDS-PAGE
dimer
-
1 * 39900 + 1 * 34600, in vitro translated proteins, SDS-PAGE
dimer
-
hBVR in dimeric form binds to DNA
monomer
-
1 * 34000, multiple forms, SDS-PAGE
monomer
-
1 * 34000, multiple forms, SDS-PAGE
monomer
-
1 * 36000, kidney, SDS-PAGE
monomer
-
1 * 21000, BVRB, SDS-PAGE
monomer
P30043
1 * 21000, BVRB, SDS-PAGE
monomer
-
1 * 33500, BVRA, SDS-PAGE
monomer
P30043
1 * 33500, BVRA, SDS-PAGE
additional information
-
enzyme binds to truncated soluble human heme oxygenase-1, binding site overlaps with binding site of P450 reductase
additional information
-
general acid in catalysis is Y97
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
-
atorvastatin significantly increases tyrosine phosphorylation
phosphoprotein
-
-
phosphoprotein
-
in Escherichia coli expressed human biliverdin reductase is autophoshorylated and the phosphorylation is required for its activity, the enzyme is a renaturable phosphoprotein and the autophosphorylation is most prominent at pH 8.7, the enzyme is autophosphorylated on serine/threonine residues
phosphoprotein
-
a significant reduction in the phosphorylation of serine, threonine and tyrosine residues of biliverdin reductase-A is found which is paralleled by a marked reduction in its reductase activity
phosphoprotein
-
-
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
apo enzyme and in complex with NADH
-
BVR-NADH complex, NH2-terminal domain in dinucleotide binding
-
crystals of the biliverdin reductase obtained by sitting-drop vapour-diffusion method, enzyme diffraction data collected to 1.6 A, crystals belong to the orthorhombic space group P212121 with unit-cell parameters a=58.89, b=70.41, c=87.76 A
-
an X-ray diffraction experiment using a native BVR crystal is performed on the BL38B1 beamline. The crystal belongs to the orthorhombic space group P2-1-2-1-2-1, with unit-cell parameters a = 58.8, b = 88.4, c = 132.6 A. A complete data set is collected to a resolution of 2.34 A
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
-
0.1 M potassium phosphate buffer, most stable
437789
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45
-
10 min, no loss of activity
437789
55
-
10 min, complete loss of activity
437789
56
-
5 min, complete loss of activity
437808
60
-
1 h, 15-30% loss of activity
437803
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
repeated freeze-thawing: little loss of activity , no significant loss of activity, partially purified enzyme
-
loss of activity in solutions with protein concentration below 0.030-0.035 mg/ml
-
NADPH stabilizes
-
repeated freeze-thawing: little loss of activity , no significant loss of activity, partially purified enzyme
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, 8 weeks, 1-10 mg protein per ml, 5-25% loss of activity, partially purified enzyme
-
0C, 8 weeks, 1-10 mg protein per ml, 15-25% loss of activity
-
-20C, several months -25C, 1 month: no loss of activity, 2 months: 50% loss of activity
-
0-4C, 5 days
-
-20C, 50 mM potassium phosphate, pH 7.0, stable for at least eight months
-
-20C, several months -25C, 1 month: no loss of activity, 2 months: 50% loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
affinitiy chromatography
-
protein extracts of transgenic Arabidopsis thaliana plants are prepared
-
purification of biliverdin reductase expressed in Escherichia coli and from rat tissue
-
using affinity purification
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli
-
expressed in Escherichia coli and HeLa cells
-
expressed in HEK-293 cells
-
expressed in HEK293A and MCF-7 cells
-
expression in HEK-293A cells
-
human biliverdin reductase expressed in Escherichia coli
-
into pcDNA3 and expressed in 293A cells pcDNA3, into pGEX4-T2 and expressed in Escherichia coli
-
into the pGEM-T easy vector, subcloned into the vectors pcDNA3 and pESC-LEU
-
into the vector pcDNA3.1
-
into vector pcDNA3, transformed into Escherichia coli DH5alpha, pGEX-4T2/human BVR vector
-
recombinant BVR is used
-
reversible overexpression of BVR in mouse fibroblasts, doxycycline-dependent overexpression of BVR in NIH 3T3 BVR-Tet-On cells confers protection against cytotoxic drugs cisplatin and doxorubicin
-
expression in H9C2 cell
-
into the vector pcDNA3.1
-
biliverdin reductase cDNA cloned into pUC18, used for expression and purification
-
expression in SH-SY5Y cells
-
kidney form of the enzyme cloned into the expression vector pGEX-KG
-
recombinant biliverdin reductase expressed in Escherichia coli
-
the expression of rat kidney biliverdin reductase is targeted by translational fusion of the chloroplast transit peptide sequence of the soybean small subunit of ribulose bisphosphate carboxylase gene to the enzyme cDNA, with this method transgenic Arabidopsis plants are cloned which express constitutive biliverdin reductase and display aberrant photomorphogenesis throughout their life-cycle
-
using the vector pBIB-KAN a plant transformation vector, containing the CAB3 promoter, a chloroplast targeting sequence and the BVR gene, is constructed, using pMON672 leads to a similar construct containing the MERI5 promoter
-
expressed in Escherichia coli
-
overexpressed in Escherichia coli as a His-tagged fusion protein
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
atorvastatin significantly increases BVR-A protein levels, phosphorylation and activity only in parietal cortex
-
BVR expression is unaffected by heat shock
-
bacterial endotoxin, lipopolysaccharide, initiates an inflammatory response in macrophages coming along with a rapid increase in BVR surface expression
-
in HepG2 and JAr cells taurocholic acid and ursodeoxycholic acid up-regulate biliverdin-IX reductase
-
BVR is induced by lipopolysaccharides and bromobenzene at a post-transcriptional level
-
doxycycline dose-dependently induces BVR gene expression at the level of mRNA as well as a protein, and BVR activity in genetically modified NIH 3T3 fibroblasts
-
in HEK-293A cells, hypoxia modestly increases BVR mRNA levels
-
induction of BVR and HO-2 is mediated by the cAMP-PKA pathway and isoproterenol, overview. The beta-adrenergic antagonist propranolol only slightly induces BVR expression in HEK-293A cells
-
oxidative stress induces HO-1, BVR and H-ferritin in lung macrophages, this is involved in development of primary spontaneous pneumothorax disease, overview. HIF-1alpha siRNA transfection completely abrogated the increased HO-1, BVR and H-ferritin mRNA levels
-
hypoxia positively regulates hBVR promoter
-
increased expression in macrophages of primary spontaneous pneumothorax of smokers compared to non-smokers
-
overexpression of IkappaB increases hBVR mRNA
-
TNF-alpha negatively regulates hBVR promoter
-
up-regulation is found in the hippocampus of subjects with Alzheimer disease in its earliest form
-
treatment of cultured TALH or IMCD-3 cells with BVR siRNA, 50 or 100 nM, results in an 80% decrease in the level of BVR protein
-
bacterial endotoxin, lipopolysaccharide, initiates an inflammatory response in macrophages coming along with a rapid increase in BVR surface expression
-
in fetal liver and maternal liver and placenta ursodeoxycholic acid up-regulates biliverdin-IX reductase
-
induction of BVR and HO-2 is mediated by the cAMP-PKA pathway and isoproterenol, overview
-
about 56% of the BVR expression in total lung tissue is increased by hypoxia
-
up-regulated in levels of protein and mRNA by hypoxia in pulmonary arterial smooth muscle cell
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C281A/C292A/C293A
-
mutant is defective for protein-protein-dependent interaction and haematin binding
C281A/C292A/C293A
-
C-terminal fragment 272-296 in which cysteine residues are replaced by alanine do not interact with Goodpasture antigen-binding protein whereas wild-type C-terminal fragment 276-296 does
G17A
-
does not effectively bind ATP, hence kinase-dead, is not as effective as the wild-type in potentiating protein kinase C activity
R18Stop
-
heterozygous nonsense mutation predicted to truncate the protein N-terminally to the active site tyrosine 97, discovered in nucleotide 52 of exon I of the DNA isolated from a hyperbiliverdinaemic patient
R18Stop
-
a naturally occuring mutation of BVR leading to a severely truncated enzyme, liver cirrhosis and death
V11A/V12A/V13A/V14A
-
not only fails to activate protein kinase C but also decreases its activity by 22%
Y198F
-
mutant, phosphorylation site
E47A
-
mutant, does affect the edge of the beta2 strand of substrate and cofactor binding in the pocket, which likely influences the strength of their interaction with BVR
E97A
-
mutant, data strongly support this site as important for conversion of biliverdin to bilirubin and for transmission of signaling by BVR
C280A
-
although modification of either of the two cysteines located near the C-terminus significantly reduces activity with both cofactors, these mutations do not inactivate the enzyme, mutation of both C-terminal cysteines causes inactivation of the enzyme, comparison of Km values suggests that Cys 280 principally functions in substrate binding
C291A
-
although modification of either of the two cysteines located near the C-terminus significantly reduces activity with both cofactors, these mutations do not inactivate the enzyme, mutation of both C-terminal cysteines causes inactivation of the enzyme, comparison of Km values suggests that Cys 291 is predominantly involved in cofactor binding.
Y97F
-
50% of activity compared to wild type
G17A
-
mutant is defective for ATP binding
additional information
-
cells transfected with small interfering RNA directed to enzyme gene display a fourfold increase in apoptotic cells when treated with 0.01 mM sodium arsenite
additional information
-
point mutation of residues that in BVR interact with the adenine nucleotide, all inactivate the enzyme, S149 essential for acitvity
additional information
-
point mutations of serine residues in the kinase domain of the enzyme inhibits phosphotransferase activity
additional information
-
inhibition of isoproterenol-induced expression of BVR using siBVR
additional information
-
since no specific inhibitors for BVR are known, siRNA is used to silence the BVR gene in primary endothelial cells and accordingly suppress its activity
C73A
-
the modification of the amino-proximal cysteine, which is flanked by a tyrosine residue, completely inactivates the enzyme with NADH at pH 6.75 and NADPH at pH 8.7
additional information
-
expression of enzyme in Nicotiana tabacum, expression in dark-grown plants leads to reduced accumulation of protochlorophyllide and transcripts for the two committed enzymes for 5-aminolevulinic acid synthesis, enzyme dependent inhibition of chlorophyll biosynthesis in light-grown plants depends mainly on misregulated tetrapyrrole metabolism
additional information
-
changing C73 to alanine inactivates the enzyme, as it is involved in substrate/cofactor binding
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
data gathered to date have identified the potential utility of hBVR in modulating cell signaling and the wide range of functions that are regulated by protein kinases that include growth, differentiation, gene transcription and metabolism, regulation of glucose uptake, induction of HO-1, and cytokine and Toll-like receptor signaling are potential target candidates for hBVR-based therapeutic strategies
medicine
-
hyperbiliverdinaemia, green jaundice, with green plasma and urine may be caused by a genetic defect in the BVR-A gene in conjunction with decompensated liver cirrosis
medicine
-
finding that BVR and HO-2 levels, myocyte apoptosis, and contractile function of the heart can be modulated by small human BVR-based peptides offers a promising therapeutic approach for treatment of cardiac dysfunctions
medicine
-
therapeutic potential of human BVR and human HVR-based peptides by affecting the MAPK signaling pathways, overview
additional information
-
interacts with the insulin receptor kinase domain, key factor in the MAPK pathway and the PI3K pathway as well as regulating PKC isoforms that link the two pathways, plays a role in the mechanism of insulin resistance
additional information
-
potential function in propagation of signals relayed through protein kinase C, binds to protein kinase C betaII, increases its phosphorylation, and is a substrate for the kinase, increases PMA-dependent c-fos activation and protein kinase C translocation to the membrane
additional information
-
potential role in the insulin signaling pathway, BVR is both a substrate for insulin receptor tyrosine kinase activity and a kinase for serine phosphorylation of insulin receptor substrate 1
medicine
-
BVR may represent a novel strategy for the treatment of multiple sclerosis and other oxidative stress-mediated diseases, treatment with BVR ameliorates both clinical and pathological signs of autoimmune encephalomyelitis more efficiently than treatments with traditional antioxidant enzymes
additional information
-
regulates oxidative response and HO-1 expression
additional information
-
BVR regualtes cellular levels of biliverdin, a potent gene regulator and determinant factor for dorsal axis development in Xenopus larva