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Information on EC 1.3.1.24 - biliverdin reductase and Organism(s) Homo sapiens and UniProt Accession P30043

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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
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Select one or more organisms in this record: ?
This record set is specific for:
Homo sapiens
UNIPROT: P30043 not found.
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
Synonyms
bvr, biliverdin reductase, bvr-a, blvra, biliverdin reductase a, biliverdin reductase-a, rv2074, bvr-b, biliverdin-ixalpha reductase, biliverdin ixalpha reductase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
biliverdin IXbeta reductase
-
biliverdin reductase B
-
BLVR subtype B
-
biliverdin IXalpha reductase
-
biliverdin reductase
biliverdin reductase A
biliverdin reductase B
-
-
Biliverdin reductase-A
-
biliverdin-IXalpha reductase
-
BLVRA
BLVRB
-
-
BV reductase
-
-
BVR-A
BVR-B
-
isoform
hBVR-A
-
-
reductase, biliverdin
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
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 hide
LITERATURE
redox reaction
-
-
-
-
oxidation
reduction
SYSTEMATIC NAME
IUBMB Comments
bilirubin:NAD(P)+ oxidoreductase
-
CAS REGISTRY NUMBER
COMMENTARY hide
9074-10-6
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
biliverdin + NADH + H+
bilirubin + NAD+
show the reaction diagram
-
-
-
r
biliverdin + NADPH + H+
bilirubin + NADP+
show the reaction diagram
-
-
-
r
biliverdin IXbeta + NADH + H+
bilirubin + NAD+
show the reaction diagram
-
-
-
r
biliverdin IXbeta + NADH + H+
bilirubin IXbeta + NAD+
show the reaction diagram
substrate for isoform BVRB
-
-
r
biliverdin IXbeta + NADPH + H+
bilirubin + NADP+
show the reaction diagram
-
-
-
r
biliverdin IXbeta + NADPH + H+
bilirubin IXbeta + NADP+
show the reaction diagram
substrate for isoform BVRB
-
-
r
insulin receptor substrate 1 + NAD(P)H
?
show the reaction diagram
phosphorylates serine residues in insulin receptor substrate 1
-
-
?
bilirubin + NAD+
biliverdin + NADH + H+
show the reaction diagram
bilirubin + NADP+
biliverdin + NADPH + H+
show the reaction diagram
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 + H+
bilirubin + NAD(P)+
show the reaction diagram
-
-
-
-
?
biliverdin + NADH + H+
bilirubin + NAD+
show the reaction diagram
biliverdin + NADPH + H+
bilirubin + NADP+
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 + NADH + H+
bilirubin IXalpha + NAD+
show the reaction diagram
substrate for isoform BVRA
-
-
r
biliverdin IXalpha + NADPH + H+
bilirubin IXalpha + NADP+
show the reaction diagram
substrate for isoform BVRA
-
-
r
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
-
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
-
-
?
mitogen-activated protein kinase kinase 1 + NAD(P)H
?
show the reaction diagram
-
-
-
-
?
myelin basic protein + NAD(P)H
?
show the reaction diagram
-
BVR functions as an serine/threonine kinase for myelin basic protein
-
-
?
protein kinase C-betaII + NAD(P)H
?
show the reaction diagram
-
BVR functions as an serine/threonine kinase for protein kinase C-betaII
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
biliverdin + NADH + H+
bilirubin + NAD+
show the reaction diagram
-
-
-
r
biliverdin + NADPH + H+
bilirubin + NADP+
show the reaction diagram
-
-
-
r
biliverdin IXbeta + NADH + H+
bilirubin + NAD+
show the reaction diagram
-
-
-
r
biliverdin IXbeta + NADH + H+
bilirubin IXbeta + NAD+
show the reaction diagram
substrate for isoform BVRB
-
-
r
biliverdin IXbeta + NADPH + H+
bilirubin + NADP+
show the reaction diagram
-
-
-
r
biliverdin IXbeta + NADPH + H+
bilirubin IXbeta + NADP+
show the reaction diagram
substrate for isoform BVRB
-
-
r
bilirubin + NAD+
biliverdin + NADH + H+
show the reaction diagram
bilirubin + NADP+
biliverdin + NADPH + H+
show the reaction diagram
bilirubin-IXa + NAD+
biliverdin-IXa + NADH + H+
show the reaction diagram
-
-
-
-
?
bilirubin-IXa + NADP+
biliverdin-IXa + NADPH + H+
show the reaction diagram
-
-
-
-
?
biliverdin + NADH + H+
bilirubin + NAD+
show the reaction diagram
biliverdin + NADPH + H+
bilirubin + NADP+
show the reaction diagram
biliverdin IXalpha + NAD(P)H + H+
bilirubin + NAD(P)+
show the reaction diagram
-
-
-
-
?
biliverdin IXalpha + NADH + H+
bilirubin IXalpha + NAD+
show the reaction diagram
substrate for isoform BVRA
-
-
r
biliverdin IXalpha + NADPH + H+
bilirubin IXalpha + NADP+
show the reaction diagram
substrate for isoform BVRA
-
-
r
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NADPH
NAD(P)H
NADP+
NADPH
additional information
-
the enzyme shows dual cofactor- and pH-dependency in activity
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Zn2+
-
-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5,5'-dithiobis(2-nitrobenzoate)
-
-
bilirubin
-
inhibits the enzyme in a feedback regulation system, biliverdin inhibits the heme oxygenase activity, overview
Biliverdin
-
Ca2+
-
abolishes autophosphorylation of BVR
GATA1
-
transcription factor GATA1 downregulates BVR expression
-
Mg2+
-
abolishes autophosphorylation of BVR
p-chloromercuribenzoate
-
-
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-reagents
-
-
-
Zn2+
-
inhibitory to autophosphorylation of BVR, can not be overcome with Mn2+
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 hide
LITERATURE
IMAGE
Co-protoporphyrin complex
-
activates
cobalt protoporphyrin
-
activates
Fe-protoporphyrin complex
-
activates
heme
-
upregulates BVR expression
Insulin
-
increases BVR tyrosine autophosphorylation
-
oxidant
-
activates
-
Tumor necrosis factor alpha
-
-
-
Urea
the enzyme is activated at low concentrations of urea
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.107 - 0.319
NADH
0.0011 - 0.059
NADPH
0.0038 - 0.0877
Biliverdin
0.33 - 2
NADH
0.001 - 0.003
NADPH
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.01 - 0.4
NADPH
16.8 - 94.8
Biliverdin
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.7 - 21
NADPH
200 - 4600
Biliverdin
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.028 - 0.147
Biliverdin
0.3 - 1.7
NAD+
0.00035 - 0.0016
NADP+
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
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
-
hypoxia activates hBVR activity
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.7
optimal pH value for NADH as cofactor
8.7
optimal pH value for NADPH as cofactor
6.8
-
with NADH
7.3
-
activity assay
8.5
-
assay at
additional information
-
the enzyme shows dual cofactor- and pH-dependency in activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
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
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
BLVRB_HUMAN
206
0
22119
Swiss-Prot
other Location (Reliability: 4)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
21000
BVRB, SDS-PAGE
33000
-
x * 33000, SDS-PAGE
33500
BVRA, SDS-PAGE
34600
-
1 * 39900 + 1 * 34600, in vitro translated proteins, SDS-PAGE
36000
-
-
37000
-
x * 37000, SDS-PAGE
39900
-
1 * 39900 + 1 * 34600, in vitro translated proteins, SDS-PAGE
41000 - 42000
-
the purified protein resolves into two molecular weight forms of 40700 and 39600, two-dimensional electrophoresis
69000
-
in vitro translated reductase, 12% native polyacryamide gel
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
1 * 21000, BVRB, SDS-PAGE
dimer
monomer
1 * 33500, BVRA, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
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
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
R174A
the mutant exhibits an increased Km value for NADPH compared to the wild type enzyme
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
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
C281A/C292A/C293A
R172A
the mutant shows strongly reduced catalytic efficiency compared to the wild type enzyme
R172E
inactive
R172K
inactive
R18Stop
V11A/V12A/V13A/V14A
-
not only fails to activate protein kinase C but also decreases its activity by 22%
Y198F
-
mutant, phosphorylation site
Y98F
the mutant shows about wild type catalytic efficiency
additional information
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
glutathione-Sepharose column chromatography, and Superdex 200 gel filtration
-
Ni-NTA agarose column chromatography
nickel affinity gel chromatography and Sephacryl S-200 gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli
-
expressed in Escherichia coli and HeLa cells
-
expressed in Escherichia coli BL-21 cells
expressed in Escherichia coli BL21(DE3) cells
expressed in Escherichia coli BL21(DE3)-RIL 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
ORGANISM
UNIPROT
LITERATURE
bacterial endotoxin, lipopolysaccharide, initiates an inflammatory response in macrophages coming along with a rapid increase in BVR surface expression
-
BVR expression is unaffected by heat shock
-
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
enzyme expression is up-regulated in breast cancer cells
-
expression is up-regulated in breast, lung, and liver cancers, but not ovarian cancer
hypoxia positively regulates hBVR promoter
-
in HEK-293A cells, hypoxia modestly increases BVR mRNA levels
-
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
-
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
-
overexpression of IkappaB increases hBVR mRNA
-
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
-
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
-
TNF-alpha negatively regulates hBVR promoter
-
up-regulation is found in the hippocampus of subjects with Alzheimer disease in its earliest form
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
biliverdin reductase B is a prostate cancer marker
diagnostics
medicine
additional information
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Singleton, J.W.; Laster, L.
Biliverdin reductase of guinea pig liver
J. Biol. Chem.
240
4780-4789
1965
Cavia porcellus, Homo sapiens
Manually annotated by BRENDA team
Salim, M.; Brown-Kipphut, B.A.; Maines, M.D.
Human biliverdin reductase is autophosphorylated, and phosphorylation is required for bilirubin formation
J. Biol. Chem.
276
10929-10934
2001
Homo sapiens
Manually annotated by BRENDA team
Cunningham, O.; Dunne, A.; Sabido, P.; Lightner, D.; Mantle, T.J.
Studies on the specificity of the tetrapyrrole substrate for human biliverdin-IXalpha reductase and biliverdin-IXbeta reductase. Structure-activity relationships define models for both active sites
J. Biol. Chem.
275
19009-19017
2000
Homo sapiens
Manually annotated by BRENDA team
Ahmad, Z.; Salim, M.; Maines, M.D.
Human biliverdin reductase is a leucine zipper-like DNA-binding protein and functions in transcriptional activation of heme oxygenase-1 by oxidative stress
J. Biol. Chem.
277
9226-9232
2002
Homo sapiens
Manually annotated by BRENDA team
Maines, M.D.; Trakshel, G.M.
Purification and characterization of human biliverdin reductase
Arch. Biochem. Biophys.
300
320-326
1993
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Maines, M.D.; Mayer, R.D.; Erturk, E.; Huang, T.J.; Disantagnese, A.
The oxidoreductase, biliverdin reductase, is induced in human renal carcinoma - pH and cofactor-specific increase in activity
J. Urol.
162
1467-1472
1999
Homo sapiens
Manually annotated by BRENDA team
Colpaert, E.E.; Timmermans, J.P.; Lefebvre, R.A.
Immunohistochemical localization of the antioxidant enzymes biliverdin reductase and heme oxygenase-2 in human and pig gastric fundus
Free Radic. Biol. Med.
32
630-637
2002
Homo sapiens, Sus scrofa
Manually annotated by BRENDA team
Kravets, A.; Hu, Z.; Miralem, T.; Torno, M.D.; Maines, M.D.
Biliverdin reductase, a novel regulator for induction of activating transcription factor-2 and heme oxygenase-1
J. Biol. Chem.
279
19916-19923
2004
Homo sapiens
Manually annotated by BRENDA team
Miralem, T.; Hu, Z.; Torno, M.D.; Lelli, K.M.; Maines, M.D.
siRNA-mediated gene silencing of human biliverdin reductase, but not that of heme oxygenase-1, attenuates arsenite-mediated induction of the oxygenase and increases apoptosis in 293A kidney cells
J. Biol. Chem.
280
17084-17092
2005
Homo sapiens
Manually annotated by BRENDA team
Baranano, D.E.; Rao, M.; Ferris, C.D.; Snyder, S.H.
Biliverdin reductase: a major physiologic cytoprotectant
Proc. Natl. Acad. Sci. USA
99
16093-16098
2002
Homo sapiens
Manually annotated by BRENDA team
Lerner-Marmarosh, N.; Shen, J.; Torno, M.D.; Kravets, A.; Hu, Z.; Maines, M.D.
Human biliverdin reductase: A member of the insulin receptor substrate family with serine/threonine/tyrosine kinase activity
Proc. Natl. Acad. Sci. USA
102
7109-7114
2005
Homo sapiens
Manually annotated by BRENDA team
Maines, M.D.; Miralem, T.; Lerner-Marmarosh, N.; Shen, J.; Gibbs, P.E.
Human biliverdin reductase - a previously unknown activator of protein kinase C beta II
J. Biol. Chem.
282
8110-8122
2007
Homo sapiens
Manually annotated by BRENDA team
Maines, M.D.
New insights into biliverdin reductase functions: linking heme metabolism to cell signaling
Physiology
20
382-389
2005
Arabidopsis sp., Canis lupus familiaris, Cavia porcellus, Gallus gallus, Cyanidium caldarium, Homo sapiens, Mus musculus, Pan troglodytes, Rattus norvegicus, Sus scrofa, Takifugu rubripes, Xenopus sp.
Manually annotated by BRENDA team
Maines, M.D.
Biliverdin reductase: PKC interaction at the cross-talk of MAPK and PI3K signaling pathways
Antioxid. Redox Signal.
9
2187-2195
2007
Homo sapiens
Manually annotated by BRENDA team
Tudor, C.; Lerner-Marmarosh, N.; Engelborghs, Y.; Gibbs, P.E.; Maines, M.D.
Biliverdin reductase is a transporter of haem into the nucleus and is essential for regulation of HO-1 gene expression by haematin
Biochem. J.
413
405-416
2008
Homo sapiens
Manually annotated by BRENDA team
Lerner-Marmarosh, N.; Miralem, T.; Gibbs, P.E.; Maines, M.D.
Regulation of TNF-alpha-activated PKC-zeta signaling by the human biliverdin reductase: identification of activating and inhibitory domains of the reductase
FASEB J.
21
3949-3962
2007
Homo sapiens
Manually annotated by BRENDA team
Gibbs, P.E.; Maines, M.D.
Biliverdin inhibits activation of NF-kappaB: reversal of inhibition by human biliverdin reductase
Int. J. Cancer
121
2567-2574
2007
Homo sapiens
Manually annotated by BRENDA team
Wu, B.; Liu, X.; Shen, J.
Old biliverdin reductase: links to insulin resistance and may be a novel therapeutic target
Med. Hypotheses
71
73-76
2008
Homo sapiens
Manually annotated by BRENDA team
Florczyk, U.M.; Jozkowicz, A.; Dulak, J.
Biliverdin reductase: new features of an old enzyme and its potential therapeutic significance
Pharmacol. Rep.
60
38-48
2008
Rattus norvegicus, Rattus norvegicus (P46844), Homo sapiens (P30043), Homo sapiens (P53004)
Manually annotated by BRENDA team
Lerner-Marmarosh, N.; Miralem, T.; Gibbs, P.E.; Maines, M.D.
Human biliverdin reductase is an ERK activator; hBVR is an ERK nuclear transporter and is required for MAPK signaling
Proc. Natl. Acad. Sci. USA
105
6870-6875
2008
Homo sapiens
Manually annotated by BRENDA team
Wegiel, B.; Baty, C.J.; Gallo, D.; Csizmadia, E.; Scott, J.R.; Akhavan, A.; Chin, B.Y.; Kaczmarek, E.; Alam, J.; Bach, F.H.; Zuckerbraun, B.S.; Otterbein, L.E.
Cell surface biliverdin reductase mediates biliverdin-induced anti-inflammatory effects via phosphatidylinositol 3-kinase and Akt
J. Biol. Chem.
284
21369-21378
2009
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Maghzal, G.J.; Leck, M.C.; Collinson, E.; Li, C.; Stocker, R.
Limited role for the bilirubin-biliverdin redox amplification cycle in the cellular antioxidant protection by biliverdin reductase
J. Biol. Chem.
284
29251-29259
2009
Homo sapiens
Manually annotated by BRENDA team
Gafvels, M.; Holmstroem, P.; Somell, A.; Sjoevall, F.; Svensson, J.O.; Stahle, L.; Broome, U.; Stal, P.
A novel mutation in the biliverdin reductase-A gene combined with liver cirrhosis results in hyperbiliverdinaemia (green jaundice)
Liver Int.
29
1116-1124
2009
Homo sapiens
Manually annotated by BRENDA team
Perez, M.J.; Castano, B.; Jimenez, S.; Serrano, M.A.; Gonzalez-Buitrago, J.M.; Marin, J.J.
Role of vitamin C transporters and biliverdin reductase in the dual pro-oxidant and anti-oxidant effect of biliary compounds on the placental-fetal unit in cholestasis during pregnancy
Toxicol. Appl. Pharmacol.
232
327-336
2008
Rattus norvegicus, Homo sapiens (P53004), Homo sapiens
Manually annotated by BRENDA team
Kapitulnik, J.; Maines, M.D.
Pleiotropic functions of biliverdin reductase: cellular signaling and generation of cytoprotective and cytotoxic bilirubin
Trends Pharmacol. Sci.
30
129-137
2009
Homo sapiens
Manually annotated by BRENDA team
Florczyk, U.; Golda, S.; Zieba, A.; Cisowski, J.; Jozkowicz, A.; Dulak, J.
Overexpression of biliverdin reductase enhances resistance to chemotherapeutics
Cancer Lett.
300
40-47
2010
Homo sapiens (P53004)
Manually annotated by BRENDA team
Mancuso, C.; Barone, E.
The heme oxygenase/biliverdin reductase pathway in drug research and development
Curr. Drug Metab.
10
579-594
2009
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Maines, M.D.
Potential application of biliverdin reductase and its fragments to modulate insulin/IGF-1/MAPK/PI3-K signaling pathways in therapeutic settings
Curr. Drug Targets
11
1586-1594
2010
Homo sapiens
Manually annotated by BRENDA team
Ding, B.; Gibbs, P.E.; Brookes, P.S.; Maines, M.D.
The 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
FASEB J.
25
301-313
2010
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Jansen, T.; Hortmann, M.; Oelze, M.; Opitz, B.; Steven, S.; Schell, R.; Knorr, M.; Karbach, S.; Schuhmacher, S.; Wenzel, P.; Muenzel, T.; Daiber, A.
Conversion of biliverdin to bilirubin by biliverdin reductase contributes to endothelial cell protection by heme oxygenase-1-evidence for direct and indirect antioxidant actions of bilirubin
J. Mol. Cell. Cardiol.
49
186-195
2010
Homo sapiens
Manually annotated by BRENDA team
Goven, D.; Boutten, A.; Lecon-Malas, V.; Marchal-Somme, J.; Soler, P.; Boczkowski, J.; Bonay, M.
Induction of heme oxygenase-1, biliverdin reductase and H-ferritin in lung macrophage in smokers with primary spontaneous pneumothorax: role of HIF-1alpha
PLoS ONE
5
e10886
2010
Homo sapiens
Manually annotated by BRENDA team
Barone, E.; Di Domenico, F.; Cenini, G.; Sultana, R.; Cini, C.; Preziosi, P.; Perluigi, M.; Mancuso, C.; Butterfield, D.A.
Biliverdin reductase--a protein levels and activity in the brains of subjects with Alzheimer disease and mild cognitive impairment
Biochim. Biophys. Acta
1812
480-487
2011
Homo sapiens
Manually annotated by BRENDA team
Reed, J.R.; Huber, W.J.; Backes, W.L.
Human heme oxygenase-1 efficiently catabolizes heme in the absence of biliverdin reductase
Drug Metab. Dispos.
38
2060-2066
2010
Homo sapiens
Manually annotated by BRENDA team
Kim, S.Y.; Kang, H.T.; Choi, H.R.; Park, S.C.
Biliverdin reductase A in the prevention of cellular senescence against oxidative stress
Exp. Mol. Med.
43
15-23
2011
Homo sapiens
Manually annotated by BRENDA team
Gibbs, P.E.; Miralem, T.; Maines, M.D.
Characterization of the human biliverdin reductase gene structure and regulatory elements: promoter activity is enhanced by hypoxia and suppressed by TNF-alpha-activated NF-kappaB
FASEB J.
24
3239-3254
2010
Homo sapiens
Manually annotated by BRENDA team
Miralem, T.; Lerner-Marmarosh, N.; Gibbs, P.E.; Tudor, C.; Hagen, F.K.; Maines, M.D.
The human biliverdin reductase-based peptide fragments and biliverdin regulate protein kinase C? activity: the peptides are inhibitors or substrate for the protein kinase C
J. Biol. Chem.
287
24698-24712
2012
Homo sapiens
Manually annotated by BRENDA team
Fu, G.; Liu, H.; Doerksen, R.J.
Molecular modeling to provide insight into the substrate binding and catalytic mechanism of human biliverdin-IXalpha reductase
J. Phys. Chem. B
116
9580-9594
2012
Homo sapiens
Manually annotated by BRENDA team
Franklin, E.; Mantle, T.; Dunne, A.
Activation of human biliverdin-IXalpha reductase by urea: generation of kinetically distinct forms during the unfolding pathway
Biochim. Biophys. Acta
1834
2573-2578
2013
Homo sapiens (P53004)
Manually annotated by BRENDA team
Huan, L.; Bao, C.; Chen, D.; Li, Y.; Lian, J.; Ding, J.; Huang, S.; Liang, L.; He, X.
MicroRNA-127-5p targets the biliverdin reductase B/nuclear factor-kappaB pathway to suppress cell growth in hepatocellular carcinoma cells
Cancer Sci.
107
258-266
2016
Homo sapiens
Manually annotated by BRENDA team
Lee, S.J.; Kang, H.K.; Eum, W.S.; Park, J.; Choi, S.Y.; Kwon, H.Y.
Tat-biliverdin reductase A protects INS-1 cells from human islet amyloid polypeptide-induced cytotoxicity by alleviating oxidative stress and ER stress
Cell Biol. Int.
41
514-524
2017
Homo sapiens (P53004), Homo sapiens
Manually annotated by BRENDA team
Chu, W.T.; Nesbitt, N.M.; Gnatenko, D.V.; Li, Z.; Zhang, B.; Seeliger, M.A.; Browne, S.; Mantle, T.J.; Bahou, W.F.; Wang, J.
Enzymatic activity and thermodynamic stability of biliverdin IXbeta reductase are maintained by an active site serine
Chemistry
23
1891-1900
2017
Homo sapiens (P30043), Homo sapiens
Manually annotated by BRENDA team
Zhang, M.; Song, S.; Yi, Z.; Zhao, X.; Fu, L.; Wang, L.; Ma, C.; Mao, M.; Xing, Y.; Zhu, D.
Human biliverdin reductase promotes EMT through the ERK1/2 signal pathway in breast cancer
Eur. J. Pharmacol.
788
45-53
2016
Homo sapiens
Manually annotated by BRENDA team
Miralem, T.; Lerner-Marmarosh, N.; Gibbs, P.E.; Jenkins, J.L.; Heimiller, C.; Maines, M.D.
Interaction of human biliverdin reductase with Akt/protein kinase B and phosphatidylinositol-dependent kinase 1 regulates glycogen synthase kinase 3 activity: a novel mechanism of Akt activation
FASEB J.
30
2926-2944
2016
Homo sapiens (P53004), Homo sapiens
Manually annotated by BRENDA team
Gibbs, P.E.; Miralem, T.; Maines, M.D.
Biliverdin reductase: a target for cancer therapy?
Front. Pharmacol.
6
119
2015
Homo sapiens
Manually annotated by BRENDA team
Spencer, A.L.; Bagai, I.; Becker, D.F.; Zuiderweg, E.R.; Ragsdale, S.W.
Protein/protein interactions in the mammalian heme degradation pathway: heme oxygenase-2, cytochrome P450 reductase, and biliverdin reductase
J. Biol. Chem.
289
29836-29858
2014
Homo sapiens
Manually annotated by BRENDA team
Pallua, J.D.; Schaefer, G.; Seifarth, C.; Becker, M.; Meding, S.; Rauser, S.; Walch, A.; Handler, M.; Netzer, M.; Popovscaia, M.; Osl, M.; Baumgartner, C.; Lindner, H.; Kremser, L.; Sarg, B.; Bartsch, G.; Huck, C.W.; Bonn, G.K.; Klocker, H.
MALDI-MS tissue imaging identification of biliverdin reductase B overexpression in prostate cancer
J. Proteomics
91
500-514
2013
Homo sapiens (P30043)
Manually annotated by BRENDA team
Takao, H.; Hirabayashi, K.; Nishigaya, Y.; Kouriki, H.; Nakaniwa, T.; Hagiwara, Y.; Harada, J.; Sato, H.; Yamazaki, T.; Sakakibara, Y.; Suiko, M.; Asada, Y.; Takahashi, Y.; Yamamoto, K.; Fukuyama, K.; Sugishima, M.; Wada, K.
A substrate-bound structure of cyanobacterial biliverdin reductase identifies stacked substrates as critical for activity
Nat. Commun.
8
14397
2017
Rattus norvegicus (P06762), Homo sapiens (P53004), Synechocystis sp. PCC 6803 (P72782)
Manually annotated by BRENDA team
Subhanova, I.; Muchova, L.; Lenicek, M.; Vreman, H.J.; Luksan, O.; Kubickova, K.; Kreidlova, M.; Zima, T.; Vitek, L.; Urbanek, P.
Expression of biliverdin reductase A in peripheral blood leukocytes is associated with treatment response in HCV-infected patients
PLoS ONE
8
e57555
2013
Homo sapiens (P53004), Homo sapiens
Manually annotated by BRENDA team
O'Brien, L.; Hosick, P.A.; John, K.; Stec, D.E.; Hinds, T.D.
Biliverdin reductase isozymes in metabolism
Trends Endocrinol. Metab.
26
212-220
2015
Homo sapiens (P30043), Homo sapiens (P53004)
Manually annotated by BRENDA team
Mancuso, C.
Biliverdin reductase as a target in drug research and development Facts and hypotheses
Free Radic. Biol. Med.
172
521-529
2021
Homo sapiens (P53004), Homo sapiens
Manually annotated by BRENDA team
Zhang, M.; Xin, W.; Yi, Z.; Li, Y.; Liu, Y.; Zhang, H.; Chen, H.; Chen, X.; Tan, S.; Zhu, D.
Human biliverdin reductase regulates the molecular mechanism underlying cancer development
J. Cell. Biochem.
119
1337-1345
2018
Homo sapiens (P53004), Homo sapiens
Manually annotated by BRENDA team