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Information on EC 1.3.1.24 - biliverdin reductase
for references in articles please use BRENDA:EC1.3.1.24
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EC Tree 1 Oxidoreductases
1.3 Acting on the CH-CH group of donors
1.3.1 With NAD+ or NADP+ as acceptor
1.3.1.24 biliverdin reductase
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
- 1.3.1.24
- heme
- oxygenase-1
-
monoxide
-
cytoprotective
-
repolarization
-
beat-to-beat
-
rosenthal
-
hyperbilirubinemia
-
palliation
- tetrapyrrole
- tdp
-
torsades
- diagnostics
-
proarrhythmia
- medicine
-
galenic
-
univentricular
- pharmacology
showSynonyms
bvr, biliverdin reductase, bvr-a, blvra, biliverdin reductase a, biliverdin reductase-a, bvr-b, rv2074, biliverdin-ixalpha reductase, biliverdin ixalpha reductase, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
biliverdin IXalpha reductase
biliverdin reductase
biliverdin reductase A
biliverdin reductase B
Biliverdin reductase-A
BLVRA
BLVRB
BV reductase
BVR
BVR-A
BVRA
BVRB
F-BVR
F420H2-dependent biliverdin reductase
reductase, biliverdin
-
-
-
-
Rv2074
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
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
bilirubin + NAD(P)+ = biliverdin + NAD(P)H + H+
-
-
-
-
bilirubin + NAD(P)+ = biliverdin + NAD(P)H + H+
catalysis via hydride transfer from NADH
bilirubin + NAD(P)+ = biliverdin + NAD(P)H + H+
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
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
redox reaction
-
-
-
-
reduction
oxidation
-
-
-
-
reduction
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
BRENDA
MetaCyc
heme degradation I
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SYSTEMATIC NAME
IUBMB Comments
bilirubin:NAD(P)+ oxidoreductase
-
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CAS REGISTRY NUMBER
COMMENTARY
9074-10-6
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
biliverdin IXalpha + NAD(P)H + H+
bilirubin + NAD(P)+
-
Substrates: -
Products: -
Products: -
?
biliverdin IXalpha + NADH + H+
bilirubin IXalpha + NAD+
Substrates: substrate for isoform BVRA
Products: -
Products: -
r
biliverdin IXalpha + NADPH + H+
bilirubin IXalpha + NADP+
Substrates: substrate for isoform BVRA
Products: -
Products: -
r
biliverdin IXbeta + NADH + H+
bilirubin + NAD+
Substrates: -
Products: -
Products: -
r
biliverdin IXbeta + NADH + H+
bilirubin IXbeta + NAD+
Substrates: substrate for isoform BVRB
Products: -
Products: -
r
biliverdin IXbeta + NADPH + H+
bilirubin + NADP+
Substrates: -
Products: -
Products: -
r
biliverdin IXbeta + NADPH + H+
bilirubin IXbeta + NADP+
Substrates: substrate for isoform BVRB
Products: -
Products: -
r
casein + NAD(P)H
?
-
Substrates: BVR functions as an serine/threonine kinase for casein
Products: -
Products: -
?
extracellular signal-regulated kinase 1 + NAD(P)H
?
-
Substrates: -
Products: -
Products: -
?
extracellular signal-regulated kinase 2 + NAD(P)H
?
-
Substrates: -
Products: -
Products: -
?
insulin receptor substrate-1 + NAD(P)H
?
-
Substrates: the serine residues are targets for BVR phosphorylation
Products: -
Products: -
?
insulin-receptor substrate 1 + NAD(P)H
?
-
Substrates: BVR functions as an serine/threonine kinase for insulin-receptor substrate 1
Products: -
Products: -
?
mitogen-activated protein kinase kinase 1 + NAD(P)H
?
-
Substrates: -
Products: -
Products: -
?
myelin basic protein + NAD(P)H
?
-
Substrates: BVR functions as an serine/threonine kinase for myelin basic protein
Products: -
Products: -
?
protein kinase C-betaII + NAD(P)H
?
-
Substrates: BVR functions as an serine/threonine kinase for protein kinase C-betaII
Products: -
Products: -
?
bilirubin + NAD+
biliverdin + NADH + H+
-
Substrates: -
Products: -
Products: -
r
bilirubin + NAD+
biliverdin + NADH + H+
-
Substrates: -
Products: -
Products: -
r
bilirubin + NAD+
biliverdin + NADH + H+
-
Substrates: -
Products: -
Products: -
?
bilirubin + NADP+
biliverdin + NADPH + H+
-
Substrates: -
Products: -
Products: -
r
bilirubin + NADP+
biliverdin + NADPH + H+
-
Substrates: -
Products: -
Products: -
r
bilirubin + NADP+
biliverdin + NADPH + H+
-
Substrates: -
Products: -
Products: -
r
biliverdin + coenzyme F420 + H+
bilirubin + reduced coenzyme F420
-
Substrates: -
Products: -
Products: -
?
biliverdin + coenzyme F420 + H+
bilirubin + reduced coenzyme F420
-
Substrates: -
Products: -
Products: -
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
-
Substrates: -
Products: -
Products: -
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
-
Substrates: specific for biliverdin and IXalpha faster than the biliverdin isomers IXbeta, IXr or IXdelta
Products: -
Products: -
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
-
Substrates: physiologic degradation of heme to bile pigments
Products: -
Products: -
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
-
Substrates: -
Products: -
Products: -
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
-
Substrates: activity with NADPH is 50 times greater than with NADH
Products: -
Products: -
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
-
Substrates: high but no absolute specificity for natural IXalpha isomeric form
Products: -
Products: -
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
-
Substrates: physiologic degradation of heme to bile pigments
Products: -
Products: -
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
-
Substrates: 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
Products: -
Products: -
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
-
Substrates: human enzyme is a leucine zipper-like DNA-binding protein and functions in transcriptional activation of heme oxygenase-1 by oxidative stress
Products: -
Products: -
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
-
Substrates: -
Products: -
Products: -
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
-
Substrates: NADH and NADPH can be replaced by 3-acetyl-NADPH and deamino-NADPH (biliverdin I and biliverdin IX reduction)
Products: -
Products: -
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
-
Substrates: 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
Products: -
Products: -
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
-
Substrates: specificity of the different molecular forms
Products: -
Products: -
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
-
Substrates: study with different biliverdin types
Products: -
Products: -
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
-
Substrates: pig spleen: IXalpha-biliverdin: most effective substrate among the 4 biliverdin isomers
Products: -
Products: -
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
-
Substrates: not: IXalpha-biliverdin methylester (pig spleen)
Products: -
Products: -
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
-
Substrates: pig spleen: strictly specific to biliverdin, no other oxidoreductase activities
Products: -
Products: -
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
-
Substrates: importance in linear tetrapyrrole metabolism
Products: -
Products: -
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
Syncerus sp.
-
Substrates: bile pigment formation
Products: -
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r
biliverdin + NAD(P)H + H+
bilirubin + NAD(P)+
-
Substrates: -
Products: -
Products: -
?
biliverdin + NAD(P)H + H+
bilirubin + NAD(P)+
-
Substrates: -
Products: -
Products: -
?
biliverdin + NAD(P)H + H+
bilirubin + NAD(P)+
-
Substrates: -
Products: -
Products: -
?
biliverdin + NADH + H+
bilirubin + NAD+
Substrates: -
Products: -
Products: -
r
biliverdin + NADH + H+
bilirubin + NAD+
Substrates: -
Products: -
Products: -
r
biliverdin + NADPH + H+
bilirubin + NADP+
Substrates: -
Products: -
Products: -
r
biliverdin + NADPH + H+
bilirubin + NADP+
Substrates: -
Products: -
Products: -
r
biliverdin + NADPH + H+
bilirubin + NADP+
Substrates: -
Products: -
Products: -
r
biliverdin IXalpha + NAD(P)H + H+
bilirubin IXalpha + NAD(P)+
Substrates: substrate of BVRA but not of BVRB isoform
Products: -
Products: -
ir
biliverdin IXalpha + NAD(P)H + H+
bilirubin IXalpha + NAD(P)+
Substrates: substrate of BVRA but not of BVRB isoform
Products: -
Products: -
ir
insulin receptor substrate 1 + NAD(P)H
?
Substrates: phosphorylates serine residues in insulin receptor substrate 1
Products: -
Products: -
?
insulin receptor substrate 1 + NAD(P)H
?
Substrates: phosphorylates serine residues in insulin receptor substrate 1
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme may be an essential component of normal physiologic gastrointestinal defense
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme advances the role of heme oxidase 1 in cytoprotection and also affords cytoprotection independent of heme degradation
Products: -
Products: -
?
additional information
?
-
-
Substrates: role of enzyme in regulation of activating protein 1 and cAMP-regulated genes and in cell signaling
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme physiologically regenerates bilirubin in a catalytic cycle, providing antioxidant cytoprotection
Products: -
Products: -
?
additional information
?
-
Substrates: BVR has also serine/threonine/tyrosine kinase activity
Products: -
Products: -
?
additional information
?
-
Substrates: BVR has also serine/threonine/tyrosine kinase activity
Products: -
Products: -
?
additional information
?
-
Substrates: BVR is a substrate for insulin receptor tyrosine kinase
Products: -
Products: -
?
additional information
?
-
Substrates: BVR is a substrate for insulin receptor tyrosine kinase
Products: -
Products: -
?
additional information
?
-
-
Substrates: BVR is likely to affect the activation of nuclear factor kappaB both in its capacity as a reductase as well as a kinase
Products: -
Products: -
?
additional information
?
-
Substrates: biliverdin IXalpha is no substrate BVRB isoform
Products: -
Products: -
?
additional information
?
-
Substrates: biliverdin IXalpha is no substrate BVRB isoform
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme shows dual cofactor- and pH-dependency in activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: hBVR binds to Goodpasture antigen-binding protein and down-regulates its TNF-alpha-stimulated kinase activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: protein kinase Cdelta is activated by the enzyme. Protein kinase Cdelta is not a substrate for the enzyme in vitro
Products: -
Products: -
?
additional information
?
-
-
Substrates: heme-oxygenase-1-dependent activation of Akt protein is in part mediated by BVR
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme diverts tetrapyrrole metabolism toward heme synthesis while also reducing heme levels to de-repress synthesis of 5-aminolevulinic acid
Products: -
Products: -
?
additional information
?
-
-
Substrates: biliverdin IXalpha is no substrate of BVRB isoform
Products: -
Products: -
?
additional information
?
-
Substrates: biliverdin IXalpha is no substrate of BVRB isoform
Products: -
Products: -
?
additional information
?
-
-
Substrates: BVR has also serine/threonine/tyrosine kinase activity
Products: -
Products: -
?
additional information
?
-
Substrates: BVR has also serine/threonine/tyrosine kinase activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: BVR is a substrate for insulin receptor tyrosine kinase
Products: -
Products: -
?
additional information
?
-
Substrates: BVR is a substrate for insulin receptor tyrosine kinase
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme shows dual cofactor- and pH-dependency in activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: BVR is an S/T/Y kinase
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme may be an essential component of normal physiologic gastrointestinal defense
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
biliverdin IXalpha + NAD(P)H + H+
bilirubin + NAD(P)+
-
Substrates: -
Products: -
Products: -
?
biliverdin IXalpha + NADH + H+
bilirubin IXalpha + NAD+
Substrates: substrate for isoform BVRA
Products: -
Products: -
r
biliverdin IXalpha + NADPH + H+
bilirubin IXalpha + NADP+
Substrates: substrate for isoform BVRA
Products: -
Products: -
r
biliverdin IXbeta + NADH + H+
bilirubin + NAD+
Substrates: -
Products: -
Products: -
r
biliverdin IXbeta + NADH + H+
bilirubin IXbeta + NAD+
Substrates: substrate for isoform BVRB
Products: -
Products: -
r
biliverdin IXbeta + NADPH + H+
bilirubin + NADP+
Substrates: -
Products: -
Products: -
r
biliverdin IXbeta + NADPH + H+
bilirubin IXbeta + NADP+
Substrates: substrate for isoform BVRB
Products: -
Products: -
r
bilirubin + NAD+
biliverdin + NADH + H+
-
Substrates: -
Products: -
Products: -
r
bilirubin + NAD+
biliverdin + NADH + H+
-
Substrates: -
Products: -
Products: -
r
bilirubin + NADP+
biliverdin + NADPH + H+
-
Substrates: -
Products: -
Products: -
r
bilirubin + NADP+
biliverdin + NADPH + H+
-
Substrates: -
Products: -
Products: -
r
bilirubin + NADP+
biliverdin + NADPH + H+
-
Substrates: -
Products: -
Products: -
r
biliverdin + coenzyme F420 + H+
bilirubin + reduced coenzyme F420
-
Substrates: -
Products: -
Products: -
?
biliverdin + coenzyme F420 + H+
bilirubin + reduced coenzyme F420
-
Substrates: -
Products: -
Products: -
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
-
Substrates: physiologic degradation of heme to bile pigments
Products: -
Products: -
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
-
Substrates: physiologic degradation of heme to bile pigments
Products: -
Products: -
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
-
Substrates: importance in linear tetrapyrrole metabolism
Products: -
Products: -
?
biliverdin + NAD(P)H
bilirubin + NAD(P)+
Syncerus sp.
-
Substrates: bile pigment formation
Products: -
Products: -
r
biliverdin + NADH + H+
bilirubin + NAD+
Substrates: -
Products: -
Products: -
r
biliverdin + NADH + H+
bilirubin + NAD+
Substrates: -
Products: -
Products: -
r
biliverdin + NADPH + H+
bilirubin + NADP+
Substrates: -
Products: -
Products: -
r
biliverdin + NADPH + H+
bilirubin + NADP+
Substrates: -
Products: -
Products: -
r
biliverdin + NADPH + H+
bilirubin + NADP+
Substrates: -
Products: -
Products: -
r
additional information
?
-
-
Substrates: enzyme may be an essential component of normal physiologic gastrointestinal defense
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme advances the role of heme oxidase 1 in cytoprotection and also affords cytoprotection independent of heme degradation
Products: -
Products: -
?
additional information
?
-
-
Substrates: role of enzyme in regulation of activating protein 1 and cAMP-regulated genes and in cell signaling
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme physiologically regenerates bilirubin in a catalytic cycle, providing antioxidant cytoprotection
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme shows dual cofactor- and pH-dependency in activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: hBVR binds to Goodpasture antigen-binding protein and down-regulates its TNF-alpha-stimulated kinase activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme diverts tetrapyrrole metabolism toward heme synthesis while also reducing heme levels to de-repress synthesis of 5-aminolevulinic acid
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme shows dual cofactor- and pH-dependency in activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: BVR is an S/T/Y kinase
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme may be an essential component of normal physiologic gastrointestinal defense
Products: -
Products: -
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NADH
-
-
NADH
-
NADH and NADPH can be replaced by 3-acetyl-NADPH and deamino-NADPH (biliverdin I and biliverdin IX reduction)
NADPH
-
-
NADPH
-
NADH and NADPH can be replaced by 3-acetyl-NADPH and deamino-NADPH (biliverdin I and biliverdin IX reduction)
additional information
-
the enzyme shows dual cofactor- and pH-dependency in activity
-
additional information
-
the enzyme shows dual cofactor- and pH-dependency in activity
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mn2+
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
biliverdin IXalpha
-
with cofactor NADPH, inhibitory above 0.004 mM, with cofactor NADH, inhibitory above 0.018 mM
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
-
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
-
5,5'-dithiobis(2-nitrobenzoate)
-
pretreatment of the enzyme with NADPH and biliverdins fully protects
bilirubin
-
inhibits the enzyme in a feedback regulation system, biliverdin inhibits the heme oxygenase activity, overview
Biliverdin
-
the enzyme is inhibited by the substrate when the concentration exceeds 0.004-0.005 mM
iodoacetamide
-
pretreatment of the enzyme with NADPH and biliverdins fully protects
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
p-chloromercuribenzoate
-
pretreatment of the enzyme with NADPH and biliverdins fully protects
SH-reagents
-
e.g. 5,5'-dithiobis(2-nitrobenzoic acid), N-ethylmaleimide, pretreatment of the enzyme with NADPH and biliverdins fully protects
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
-
additional information
the enzyme is directly activated by insulin receptor kinase
-
additional information
-
the enzyme is directly activated by insulin receptor kinase
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0018
Biliverdin
wild type enzyme, at pH 5.8, temperature not specified in the publication
0.0019
Biliverdin
mutant enzyme S184A, at pH 5.8, temperature not specified in the publication
0.0033
Biliverdin
mutant enzyme R188A, at pH 5.8, temperature not specified in the publication
0.0034
Biliverdin
mutant enzyme T169A, at pH 5.8, temperature not specified in the publication
0.0038
Biliverdin
mutant enzyme Y98F, at pH 8.9, temperature not specified in the publication
0.004
Biliverdin
mutant enzyme Y102F, at pH 5.8, temperature not specified in the publication
0.0046
Biliverdin
wild type enzyme, at pH 8.9, temperature not specified in the publication
0.0048
Biliverdin
mutant enzyme K237A, at pH 5.8, temperature not specified in the publication
0.0051
Biliverdin
mutant enzyme R246A, at pH 5.8, temperature not specified in the publication
0.0069
Biliverdin
mutant enzyme R185A, at pH 5.8, temperature not specified in the publication
0.0117
Biliverdin
mutant enzyme Y97F, at pH 8.9, temperature not specified in the publication
0.0126
Biliverdin
mutant enzyme R185K, at pH 5.8, temperature not specified in the publication
0.0207
Biliverdin
wild type enzyme, at pH 8.9, temperature not specified in the publication
0.0244
Biliverdin
mutant enzyme R171A, at pH 8.9, temperature not specified in the publication
0.0457
Biliverdin
mutant enzyme R171E, at pH 8.9, temperature not specified in the publication
0.0877
Biliverdin
mutant enzyme R172A, at pH 8.9, temperature not specified in the publication
0.1633
Biliverdin
mutant enzyme R171K, at pH 8.9, temperature not specified in the publication
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
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
0.0133
NADPH
-
in the presence of 0.005 mM biliverdin, biliverdin reductase C291A
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.7
Biliverdin
mutant enzyme R185A, at pH 5.8, temperature not specified in the publication
0.7
Biliverdin
mutant enzyme R171E, at pH 8.9, temperature not specified in the publication
0.9
Biliverdin
mutant enzyme R185K, at pH 5.8, temperature not specified in the publication
2 - 3.7
Biliverdin
mutant enzyme K237A, at pH 5.8, temperature not specified in the publication
2.7
Biliverdin
mutant enzyme Y102F, at pH 5.8, temperature not specified in the publication
6
Biliverdin
mutant enzyme R171A, at pH 8.9, temperature not specified in the publication
7.1
Biliverdin
wild type enzyme, at pH 5.8, temperature not specified in the publication
11
Biliverdin
mutant enzyme R246A, at pH 5.8, temperature not specified in the publication
11.3
Biliverdin
mutant enzyme S184A, at pH 5.8, temperature not specified in the publication
13.1
Biliverdin
mutant enzyme T169A, at pH 5.8, temperature not specified in the publication
13.4
Biliverdin
mutant enzyme R188A, at pH 5.8, temperature not specified in the publication
13.6
Biliverdin
mutant enzyme Y97F, at pH 8.9, temperature not specified in the publication
14.7
Biliverdin
mutant enzyme R171K, at pH 8.9, temperature not specified in the publication
16.8
Biliverdin
mutant enzyme Y98F, at pH 8.9, temperature not specified in the publication
17.9
Biliverdin
mutant enzyme R172A, at pH 8.9, temperature not specified in the publication
69.3
Biliverdin
wild type enzyme, at pH 8.9, temperature not specified in the publication
94.8
Biliverdin
wild type enzyme, at pH 8.9, temperature not specified in the publication
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
20
Biliverdin
mutant enzyme R171E, at pH 8.9, temperature not specified in the publication
70
Biliverdin
mutant enzyme R185K, at pH 5.8, temperature not specified in the publication
100
Biliverdin
mutant enzyme R185A, at pH 5.8, temperature not specified in the publication
100
Biliverdin
mutant enzyme R171K, at pH 8.9, temperature not specified in the publication
200
Biliverdin
mutant enzyme R172A, at pH 8.9, temperature not specified in the publication
200
Biliverdin
mutant enzyme R171A, at pH 8.9, temperature not specified in the publication
700
Biliverdin
mutant enzyme Y102F, at pH 5.8, temperature not specified in the publication
1200
Biliverdin
mutant enzyme Y97F, at pH 8.9, temperature not specified in the publication
2200
Biliverdin
mutant enzyme R246A, at pH 5.8, temperature not specified in the publication
3900
Biliverdin
wild type enzyme, at pH 5.8, temperature not specified in the publication
3900
Biliverdin
mutant enzyme T169A, at pH 5.8, temperature not specified in the publication
4100
Biliverdin
mutant enzyme R188A, at pH 5.8, temperature not specified in the publication
4400
Biliverdin
mutant enzyme Y98F, at pH 8.9, temperature not specified in the publication
4600
Biliverdin
wild type enzyme, at pH 8.9, temperature not specified in the publication
4900
Biliverdin
mutant enzyme K237A, at pH 5.8, temperature not specified in the publication
5900
Biliverdin
mutant enzyme S184A, at pH 5.8, temperature not specified in the publication
15100
Biliverdin
wild type enzyme, at pH 8.9, temperature not specified in the publication
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.7
6.8
8.5
8.7
additional information
additional information
-
the enzyme shows dual cofactor- and pH-dependency in activity
additional information
-
the enzyme shows dual cofactor- and pH-dependency in activity
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 9
-
biliverdin + NADPH, pH 6: about 50% of activity maximum, pH 9: 27% of activity maximum
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30 - 42
-
exposure of male rats to 42°C for 20 min does not decrease brain biliverdin activity, the 1.5 kb biliverdin reductase mRNA displayes thermal tolerance too
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
437787, 437809, 437811, 437812, 437821, 437823, 655660, 656281, 657191, 666747, 674899, 676353, 684503, 685007, 686637, 687142, 688803
-
-
brenda
-
-
-
brenda
expression in 293A cell, increase in level of heme oxigenase 1 mRNA and protein
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
fusion protein Tat-biliverdin reductase A (Tat-BLVRA) is effiently transduced into HT-22 cells
brenda
-
increased activity of BVR, but only in the presence of NADH
brenda
-
inflamed lesions, increased in rats with clinical autoimmune encephalomyelitis, also present in both white and gray matter
brenda
additional information
-
the BVR activity progressively increases after birth and reaches adult levels by postpartum day 28
brenda
-
protein detected in the infiltrating monocytes, macrophages, T cells and neutrophils as well as in circulating lymphocytes
brenda
-
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
brenda
-
cellular localization reveals age-related pattern of expression of the reductase in selected regions such as cortex, substantia nigra, hippocampus and in the cerebellum
brenda
-
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
brenda
-
co-expression with heme oxygenases HO-1 and HO-2, BVR expression patterns, overview
brenda
-
mucosal epithelial cells and endothelium of intramural vessels of, all intrinsic nerve cell bodies of both submucous and myenteric plexuses
brenda
mucosal epithelial cells and endothelium of intramural vessels
brenda
-
mucosal epithelial cells and endothelium of intramural vessels of, all intrinsic nerve cell bodies of both submucous and myenteric plexuses
brenda
-
kidney tissue with or without renal carcinoma, the enzyme activity is nearly doubled in the tumor tissue
brenda
-
immunocytochemical analysis reveals that biliverdin reductase is localised in proximal tubules of the inner cortex of the rat kidney
brenda
-
-
brenda
-
increased expression in macrophages of primary spontaneous pneumothorax of smokers compared to non-smokers
brenda
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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
brenda
-
role for the enzyme in intracellular traffic of protein kinase C betaII and its membrane translocation
brenda
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
brenda
-
hBVR is detected in the nucleus at 1, 2, and 4 h after hypoxia, at which times its kinase and reductase activities are increased
brenda
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
brenda
eNOS-generated NO, in part, translocates the enzyme into the nucleus, where BLVRA inhibits toll-like receptor 4 (TLR4) expression
brenda
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug target
the enzyme (BVR-A) is a potential therapeutic target to prevent brain insulin resistance in Alzheimer disease
malfunction
metabolism
physiological function
additional information
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
malfunction
the loss of biliverdin reductase A results in the reduction of mitochondria number, decreased expression of markers of mitochondrial biogenesis, uncoupling, oxidation, and fusion, which paralleles reduced mitochondrial oxygen consumption. Biliverdin reductase A KO cells exhibit increased levels of ROS generation and decreased levels of superoxide dismutase mRNA expression
malfunction
impairment of biliverdin reductase-A (BVR-A) is an early event leading to brain insulin resistance in Alzheimer disease. Cells lacking the enzyme (BVR-A) develop insulin resistance if treated with insulin and can be recovered from insulin resistance only if treated with a BVR-A-mimetic peptide
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
metabolism
-
HIF-1alpha regulates the expression of BVR and other enzymes involved in oxidative stress response in lung macrophages, overview
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
metabolism
isoform BVRA interacts with components in both the PI3-kinase/Akt and the IRK/IRS/PI3-kinase/MAPK pathyway
metabolism
the enzyme is a coactivator of Akt1 and a key mediator of the Akt1/glycogen synthase kinase 3 pathway
metabolism
critical role for biliverdin reductase A in protecting against lipid accumulation and oxidative stress in hepatocytes which may serve as a future therapeutic target for non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH)
metabolism
key enzymes of the hemoglobin degradation cascade. Biliverdin reductase is probably also involved in protecting choroid plexus epithelial cells and the blood-cerebrospinal fluid barrier from the negative effects of subarachnoid hemorrhage
metabolism
the enzyme catalyzes the reduction of heme-derived biliverdin into bilirubin, which is a powerful endogenous free radical scavenger
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
-
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
-
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
-
blockage of BVR protein expression by retroviral siBVR inhibits the HO-2 protein induction but not vice versa
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
-
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
-
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
-
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
-
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
-
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
physiological function
-
TNF-alpha alpha-NF-kappaB-dependent expression of Goodpasture antigen-binding protein is regulated by biliverdin reductase
physiological function
-
BVR-A up-regulation and post-translational modifications significantly correlate with beta-secretase protein levels in the brain
physiological function
the enzyme protects against glucose intolerance and diabetes by affecting the pancreatic islet. Isoform BVRA enhances protein kinase CbetaII localization at the cellular membrane and also modulates protein kinase Cdelta and protein kinase Czeta
physiological function
-
the cytoprotective role of the enzyme may be permissive for cancer/tumor growth. The enzyme plays a role in transporting kinases to the membrane and nucleus and can also transport heme within the cell. The enzyme suppresses the activity of Goodpasture antigen-binding protein and hence limits the exposure of the epitope of Goodpasture antigen, thus limiting autoimmunity
physiological function
the enzyme mediates interleukin-10 expression in macrophages
physiological function
the enzyme exerts a protective role in oxidative stress-induced hippocampal neuronal cell damage by regulating the apoptosis and MAPK signaling
physiological function
a biliverdin reductase-A (BLVRA)-dependent mechanism regulates inflammatory responses and splenocyte death after germinal matrix hemorrhage (GMH)
physiological function
the enzyme is involved in the pathogenesis of neurodegenerative, metabolic, cardiovascular and immune-inflammatory diseases as well as in cancer
physiological function
the enzyme regulates the molecular mechanism underlying cancer development
additional information
the BVR activity and expression is not affected by MAP kinase inhibitors, overview
additional information
-
pharmacodynamics of the heme oxygenase/biliverdin reductase system, overview
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
-
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
Show AA Sequence and Transmembrane Helices (310 entries)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
21000
32000
33000
33500
34000
36000
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
41000 - 42000
-
the purified protein resolves into two molecular weight forms of 40700 and 39600, two-dimensional electrophoresis
46000
60000
-
expression of rat biliverdin reductase as a gluthatione-S-transferase protein, SDS-PAGE
68000
34000
-
converted to a larger 68000 Da form when rats are treated with SH-reactive agents
68000
-
major form 1 from liver is converted into a second major form by a NAD+ -dependent peroximal dehydrogenase, SDS-PAGE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
monomer
additional information
additional information
-
enzyme binds to truncated soluble human heme oxygenase-1, binding site overlaps with binding site of P450 reductase
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
phosphoprotein
-
atorvastatin significantly increases tyrosine phosphorylation
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
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
apo-, NADP+-bound and biliverdin-NADP+ complex forms of the enzyme, hanging drop vapor diffusion method, using 15% (w/v) PEG 4,000, 50 mM Tris-HCl (pH 7.25), 0.2 M sodium acetate and 0.2 mM Cymal-2
hanging drop vapor diffusion method, using 27% (w/v) PEG 3350, 0.2M MgCl2 and 0.1 M BisTris at pH 5.5
-
apo-, NADP+-bound and biliverdin-NADP+ complex forms of the enzyme, hanging drop vapor diffusion method, using 15% (w/v) PEG 4,000, 50mM Tris-HCl (pH 7.25), 0.2M sodium acetate and 0.2mM Cymal-2
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
-
apo-, NADP+-bound and biliverdin-NADP+ complex forms of the enzyme, hanging drop vapor diffusion method, using 15% (w/v) PEG 4,000, 50mM Tris-HCl (pH 7.25), 0.2M sodium acetate and 0.2mM Cymal-2
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C281A/C292A/C293A
G17A
H132A
the mutant exhibits an increased Km value for NADPH compared to the wild type enzyme
R124A
the mutant exhibits an increased Km value for NADPH compared to the wild type enzyme
R172A
the mutant shows strongly reduced catalytic efficiency compared to the wild type enzyme
R174A
the mutant exhibits an increased Km value for NADPH compared to the wild type enzyme
R18Stop
R35A
the mutant exhibits a strongly increased Km value for NADPH compared to the wild type enzyme
R35S
the mutant exhibits a strongly increased Km value for NADPH compared to the wild type enzyme
R39A
the mutant exhibits a reduced Km value for NADPH compared to the wild type enzyme
R78A
the mutant exhibits an increased Km value for NADPH compared to the wild type enzyme
S111A
the mutant shows strongly reduced activity compared to the wild type enzyme
S111L
the mutant shows strongly reduced activity compared to the wild type enzyme
V11A/V12A/V13A/V14A
-
not only fails to activate protein kinase C but also decreases its activity by 22%
W116A
the mutant exhibits a reduced Km value for NADPH compared to the wild type enzyme
W116F
the mutant exhibits a reduced Km value for NADPH compared to the wild type enzyme
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.
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
R171A
the mutant shows strongly reduced catalytic efficiency compared to the wild type enzyme
R171E
the mutant shows strongly reduced catalytic efficiency compared to the wild type enzyme
R171K
the mutant shows strongly reduced catalytic efficiency compared to the wild type enzyme
Y97F
K237A
the mutant shows increased catalytic efficiency compared to the wild type enzyme
R185A
the mutant shows reduced catalytic efficiency compared to the wild type enzyme
R185K
the mutant shows strongly reduced catalytic efficiency compared to the wild type enzyme
R188A
the mutant shows increased catalytic efficiency compared to the wild type enzyme
R246A
the mutant shows reduced catalytic efficiency compared to the wild type enzyme
S184A
the mutant shows increased catalytic efficiency compared to the wild type enzyme
Y102F
the mutant shows reduced catalytic efficiency compared to the wild type enzyme
additional information
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
Y97F
the mutant shows strongly reduced catalytic efficiency compared to the wild type enzyme
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 mutations of serine residues in the kinase domain of the enzyme inhibits phosphotransferase activity
additional information
-
point mutation of residues that in BVR interact with the adenine nucleotide, all inactivate the enzyme, S149 essential for acitvity
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
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
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
loss of activity in solutions with protein concentration below 0.030-0.035 mg/ml
-
repeated freeze-thawing: little loss of activity , no significant loss of activity, partially purified enzyme
repeated freeze-thawing: little loss of activity , no significant loss of activity, partially purified enzyme
-
repeated freeze-thawing: little loss of activity , no significant loss of activity, partially purified enzyme
-
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 8 weeks, 1-10 mg protein per ml, 5-25% loss of activity, partially purified enzyme
-
-20C, several months -25C, 1 month: no loss of activity, 2 months: 50% loss of activity
-20C, several months -25C, 1 month: no loss of activity, 2 months: 50% loss of activity
-
-20C, several months -25C, 1 month: no loss of activity, 2 months: 50% loss of activity
-
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni-NTA resin column chromatography, HisTrap column chromatography and Superdex 75 gel filtration
-
nickel affinity gel chromatography and Sephacryl S-200 gel filtration
protein extracts of transgenic Arabidopsis thaliana plants are prepared
purification of biliverdin reductase expressed in Escherichia coli and from rat tissue
-
nickel affinity gel chromatography and Sephacryl S-200 gel filtration
nickel affinity gel chromatography and Sephacryl S-200 gel filtration
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
biliverdin reductase cDNA cloned into pUC18, used for expression and purification
-
expressed in Escherichia coli
expressed in Escherichia coli BL21(DE3) cells
into pcDNA3 and expressed in 293A cells pcDNA3, into pGEX4-T2 and expressed in Escherichia coli
-
into the vector pcDNA3.1
into vector pcDNA3, transformed into Escherichia coli DH5alpha, pGEX-4T2/human BVR vector
-
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
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
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
about 56% of the BVR expression in total lung tissue is increased by hypoxia
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atorvastatin significantly increases BVR-A protein levels, phosphorylation and activity only in parietal cortex
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bacterial endotoxin, lipopolysaccharide, initiates an inflammatory response in macrophages coming along with a rapid increase in BVR surface expression
BVR is induced by lipopolysaccharides and bromobenzene at a post-transcriptional level
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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
expression is up-regulated in breast, lung, and liver cancers, but not ovarian cancer
in fetal liver and maternal liver and placenta ursodeoxycholic acid up-regulates biliverdin-IX reductase
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in HepG2 and JAr cells taurocholic acid and ursodeoxycholic acid up-regulate biliverdin-IX reductase
increased expression in macrophages of primary spontaneous pneumothorax of smokers compared to non-smokers
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increased levels of heme oxygenase-1 and biliverdin reductase protein in the choroid plexus over the entire period following subarachnoid hemorrhage induction
induction of BVR and HO-2 is mediated by the cAMP-PKA pathway and isoproterenol, overview
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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
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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
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patients with chronic hepatitis C virus infection show significantly upregulated enzyme expression in peripheral blood leukocytes
the transcript and protein levels are increased in human tumors and the infiltrating T-cells, monocytes and circulating lymphocytes, as well as the circulating and infiltrating macrophages
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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
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up-regulated in levels of protein and mRNA by hypoxia in pulmonary arterial smooth muscle cell
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up-regulation is found in the hippocampus of subjects with Alzheimer disease in its earliest form
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bacterial endotoxin, lipopolysaccharide, initiates an inflammatory response in macrophages coming along with a rapid increase in BVR surface expression
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bacterial endotoxin, lipopolysaccharide, initiates an inflammatory response in macrophages coming along with a rapid increase in BVR surface expression
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
medicine
pharmacology
additional information
diagnostics
peripheral biomarker for the early diagnosis of Alzheimer's disease
diagnostics
antiapoptotic effect of the enzyme in cancers portens strategies for developing novel biomarkers and effective treatment ways for cancer patients
medicine
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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
medicine
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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
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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
-
therapeutic potential of human BVR and human HVR-based peptides by affecting the MAPK signaling pathways, overview
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
Tat-mediated transduction of biliverdin reductase A may provide a potential tool to ameliorate beta-cell deficit in pancreas with type 2 diabetes mellitus
pharmacology
critical role for biliverdin reductase A in protecting against lipid accumulation and oxidative stress in hepatocytes which may serve as a future therapeutic target for non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH)
pharmacology
transduced fusion protein Tat-biliverdin reductase A (Tat-BLVRA) markedly inhibits cell death, DNA fragmentation, and generation of ROS. Transduced Tat-BLVRA inhibits the apoptosis and mitogen activated protein kinase (MAPK) signaling pathway and it passes through the blood-brain barrier (BBB) and significantly prevents hippocampal cell death in an ischemic model. Tat-BLVRA provides a possibility as a therapeutic molecule for ischemia
additional information
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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
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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
additional information
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BVR regualtes cellular levels of biliverdin, a potent gene regulator and determinant factor for dorsal axis development in Xenopus larva
additional information
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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
EXTERNAL LINKS (specific for EC-Number 1.3.1.24)
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Release 2026.1 (March 2026)
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