Information on EC 1.6.3.5 - renalase

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

EC NUMBER
COMMENTARY hide
1.6.3.5
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RECOMMENDED NAME
GeneOntology No.
renalase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
1,2-dihydro-beta-NAD(P) + H+ + O2 = beta-NAD(P)+ + H2O2
show the reaction diagram
(1)
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1,6-dihydro-beta-NAD(P) + H+ + O2 = beta-NAD(P)+ + H2O2
show the reaction diagram
(2)
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SYSTEMATIC NAME
IUBMB Comments
dihydro-NAD(P):oxygen oxidoreductase (H2O2-forming)
Requires FAD. Renalase, previously thought to be a hormone, is a flavoprotein secreted into the blood by the kidney that oxidizes the 1,2-dihydro- and 1,6-dihydro- isomeric forms of beta-NAD(P)H back to beta-NAD(P)+. These isomeric forms, generated by nonspecific reduction of beta-NAD(P)+ or by tautomerization of beta-NAD(P)H, are potent inhibitors of primary metabolism dehydrogenases and pose a threat to normal respiration.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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dysregulated extracellular renalase signalling promotes tumour growth
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1,2-dihydro-beta-NADH + H+ + O2
beta-NAD+ + H2O2
show the reaction diagram
1,2-dihydro-beta-NADPH + H+ + O2
beta-NADP+ + H2O2
show the reaction diagram
1,6-dihydro-beta-NADH + H+ + O2
beta-NAD+ + H2O2
show the reaction diagram
1,6-dihydro-beta-NADPH + H+ + O2
beta-NADP+ + H2O2
show the reaction diagram
2-dihydronicotinamide adenine dinucleotide phosphate + O2
?
show the reaction diagram
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?
2-dihydronicotinamide riboside + O2
?
show the reaction diagram
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-
-
?
6-dihydronicotinamide adenine dinucleotide phosphate + O2
?
show the reaction diagram
-
-
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?
6-dihydronicotinamide riboside + O2
?
show the reaction diagram
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-
-
?
alpha-NAD(P)H + H+ + O2
beta-NAD(P)+ + H2O2
show the reaction diagram
alpha-NADH + H+ + O2
beta-NAD+ + H2O2
show the reaction diagram
alpha-NADPH + H+ + O2
beta-NADP+ + H2O2
show the reaction diagram
catecholamine + O2
oxidized catecholamine + H2O2
show the reaction diagram
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-
-
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?
catecholamine + O2
oxidized catecholamine + NH3 + H2O2
show the reaction diagram
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?
dopamine + O2
?
show the reaction diagram
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?
epinephrine + O2
?
show the reaction diagram
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?
L-DOPA + O2
?
show the reaction diagram
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?
NAD(P)H + H+ + tetrazolium
NAD(P)+ formazan
show the reaction diagram
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?
nephrine + O2
?
show the reaction diagram
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?
Norepinephrine + O2
?
show the reaction diagram
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?
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
1,2-dihydro-beta-NADH + H+ + O2
beta-NAD+ + H2O2
show the reaction diagram
1,2-dihydro-beta-NADPH + H+ + O2
beta-NADP+ + H2O2
show the reaction diagram
1,6-dihydro-beta-NADH + H+ + O2
beta-NAD+ + H2O2
show the reaction diagram
1,6-dihydro-beta-NADPH + H+ + O2
beta-NADP+ + H2O2
show the reaction diagram
alpha-NAD(P)H + H+ + O2
beta-NAD(P)+ + H2O2
show the reaction diagram
Q5VYX0
renalase is a protein hormone secreted into the blood by the kidney that is reported to lower blood pressure and slow heart rate
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?
alpha-NADH + H+ + O2
beta-NAD+ + H2O2
show the reaction diagram
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?
alpha-NADPH + H+ + O2
beta-NADP+ + H2O2
show the reaction diagram
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-
-
-
?
catecholamine + O2
oxidized catecholamine + H2O2
show the reaction diagram
-
-
-
-
?
dopamine + O2
?
show the reaction diagram
-
-
-
-
?
epinephrine + O2
?
show the reaction diagram
-
-
-
-
?
L-DOPA + O2
?
show the reaction diagram
-
-
-
-
?
nephrine + O2
?
show the reaction diagram
-
-
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?
Norepinephrine + O2
?
show the reaction diagram
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?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NADPH
additional information
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a recognizable NADP-binding site is absent in the protein structure, enzyme shows poor affinity for, and poor reactivity towards, NADH and NADPH with Kd values of ca 2 mM
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
substantial expression in granulosa
Manually annotated by BRENDA team
substantial expression in oocytes
Manually annotated by BRENDA team
substantial expression in interstitial and luteal cells of ovary. Expression increases in testes and ovaries as mice develop and is further enhanced in the ovaries of pregnant mice
Manually annotated by BRENDA team
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besides kidney, renalase gene expression is detectable in the heart, skeletal muscle, and the small intestine
Manually annotated by BRENDA team
substantial expression spermatogenic cells of testis. Expression increases in testes and ovaries as mice develop
Manually annotated by BRENDA team
additional information
renalase is predominantly expressed in reproductive/steroidogenic systems, with particularly substantial expression in oocytes, granulosa, interstitial and luteal cells of ovary, spermatogenic cells of testis, and cortex of adrenal gland
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
Pseudomonas savastanoi pv. phaseolicola (strain 1448A / Race 6)
Pseudomonas savastanoi pv. phaseolicola (strain 1448A / Race 6)
Pseudomonas savastanoi pv. phaseolicola (strain 1448A / Race 6)
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
to 2.5 A resolution. Renalase adopts the p-hydroxybenzoate hydroxylase fold topology, comprising a Rossmann-fold-based flavin adenine dinucleotide-binding domain and a putative substrate-binding domain, the latter of which contains a five-stranded anti-parallel beta-sheet. A large cavity, facing the flavin ring, presumably represents the active site. The renalase active site is fully solvent exposed and lacks an aromatic cage for binding the substrate amino group
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80°C, stable in PBS buffer (10 mM Na2HPO4, 2 mM KH2PO4, 2.7 mM KCl, 137 mM NaCl, pH 7.4), can be stored indefinitely
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Ni-Sepharose column chromatography
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
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expressed in HEK-293, IMR-32, and Hep-G2 cells and in Mus musculus kidney
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N-terminally His-tagged renalase isoform 1 is expressed in Escherichia coli. Heterologous expression of renalase in Escherichia coli results in significant inclusion body accumulation at all temperatures tested
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
gonadotropin-releasing hormone antagonist, cetrorelix, represses renalase expression in mice ovaries and testes
knockout of leptin, an effector and modulator of steroid hormones and reproduction, causes a dramatic increase of renalase expression in mice testes
renalase expression is significantly increased in cancers of the pancreas, bladder and breast and in melanoma
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the secretion of renalase in both plasma and urine is increased in patients with chronic kidney disease
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
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