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Information on EC 1.6.3.5 - renalase and Organism(s) Homo sapiens and UniProt Accession Q5VYX0

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EC Tree
     1 Oxidoreductases
         1.6 Acting on NADH or NADPH
             1.6.3 With oxygen as acceptor
                1.6.3.5 renalase
IUBMB Comments
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.
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Homo sapiens
UNIPROT: Q5VYX0
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The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
renalase, ren-2, ren-1, renalase-1, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
alphaNAD(P)H oxidase/anomerase
-
Ren-1
isoform
Ren-2
isoform
renalase-1
isoform
renalase-2
isoform
alphaNAD(P)H oxidase/anomerase
-
-
renalase-1
-
-
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.
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
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
-
-
-
?
catecholamine + O2
oxidized catecholamine + NH3 + H2O2
show the reaction diagram
-
-
-
?
NAD(P)H + H+ + tetrazolium
NAD(P)+ + formazan
show the reaction diagram
-
-
-
?
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-NADH + H+ + O2
beta-NAD+ + H2O2
show the reaction diagram
-
-
-
-
?
alpha-NADPH + H+ + O2
beta-NADP+ + H2O2
show the reaction diagram
-
-
-
-
?
dopamine + O2
?
show the reaction diagram
-
-
-
-
?
epinephrine + O2
?
show the reaction diagram
-
-
-
-
?
L-DOPA + O2
?
show the reaction diagram
-
-
-
-
?
norepinephrine + O2
?
show the reaction diagram
-
-
-
-
?
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
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
renalase is a protein hormone secreted into the blood by the kidney that is reported to lower blood pressure and slow heart rate
-
-
?
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
-
-
-
?
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
-
-
-
-
?
dopamine + O2
?
show the reaction diagram
-
-
-
-
?
epinephrine + O2
?
show the reaction diagram
-
-
-
-
?
L-DOPA + O2
?
show the reaction diagram
-
-
-
-
?
norepinephrine + O2
?
show the reaction diagram
-
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NADPH
additional information
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
111
MBP-tagged mutant m6Ren1, pH not specified in the publication, temperature not specified in the publication
1447
mutant m5Ren1, pH not specified in the publication, temperature not specified in the publication
152
SUMO-tagged mutant m6Ren1, pH not specified in the publication, temperature not specified in the publication
19.8
MBP-tagged wild-type, pH not specified in the publication, temperature not specified in the publication
289
SUMO-tagged mutant m5Ren1, pH not specified in the publication, temperature not specified in the publication
63
SUMO-tagged wild-type, pH not specified in the publication, temperature not specified in the publication
760
mutant m6Ren1, pH not specified in the publication, temperature not specified in the publication
87.6
wild-type, pH not specified in the publication, temperature not specified in the publication
91
MBP-tagged mutant m5Ren1, pH not specified in the publication, temperature not specified in the publication
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
enzyme is secreted into the blood by the kidney
Manually annotated by BRENDA team
proximal renal tubular epithelial cell
Manually annotated by BRENDA team
little to no renalase is detected by histochemistry in the normal pancreatic head in the absence of abdominal trauma. In chronic pancreatitis, renalase immunoreactivity localizes to peri-acinar spindle-shaped cells in some samples
Manually annotated by BRENDA team
besides kidney, renalase gene expression is detectable in the heart, skeletal muscle, and the small intestine
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug target
high dopamine levels in patients with schizophrenia might be due to low renalase levels. Renalase enzyme levels may play a substantial role in the pathophysiology of schizophrenia. Renalase levels are significantly lower in schizophrenia patients than in the control group, whereas dopamine levels are significantly higher. The epinephrine levels of both groups are similar, while the norepinephrine levels in patients with schizophrenia are significantly lower than those in the control group
physiological function
malfunction
-
dysregulated extracellular renalase signalling promotes tumour growth
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
RNLS_HUMAN
342
0
37847
Swiss-Prot
Secretory Pathway (Reliability: 5)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
3D molecular models for mutants m5Ren1 and m6Ren1. Regions on the surface of the enzyme that are significantly changed include Q3R, C47R, R75S, S217D, and T329Q. Each of these mutations contributes to changes in polarity, charge, and hydrophilicity. Relative to wild-type, m6Ren1 exhibits a greater density of positively-charged residues around the active site
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
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni-Sepharose column chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
expression in Escherichia coli
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
expressed in HEK-293, IMR-32, and Hep-G2 cells and in Mus musculus kidney
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
renalase expression is significantly increased in cancers of the pancreas, bladder and breast and in melanoma
-
the secretion of renalase in both plasma and urine is increased in patients with chronic kidney disease
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Beaupre, B.A.; Carmichael, B.R.; Hoag, M.R.; Shah, D.D.; Moran, G.R.
Renalase is an alpha-NAD(P)H oxidase/anomerase
J. Am. Chem. Soc.
135
13980-13987
2013
Homo sapiens (Q5VYX0)
Manually annotated by BRENDA team
Beaupre, B.A.; Hoag, M.R.; Carmichael, B.R.; Moran, G.R.
Kinetics and equilibria of the reductive and oxidative half-reactions of human renalase with alpha-NADPH
Biochemistry
52
8929-8937
2013
Homo sapiens (Q5VYX0), Homo sapiens
Manually annotated by BRENDA team
Xu, J.; Li, G.; Wang, P.; Velazquez, H.; Yao, X.; Li, Y.; Wu, Y.; Peixoto, A.; Crowley, S.; Desir, G.V.
Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure
J. Clin. Invest.
115
1275-1280
2005
Rattus norvegicus (Q5U2W9), Homo sapiens (Q5VYX0), Homo sapiens
Manually annotated by BRENDA team
Milani, M.; Ciriello, F.; Baroni, S.; Pandini, V.; Canevari, G.; Bolognesi, M.; Aliverti, A.
FAD-binding site and NADP reactivity in human renalase: a new enzyme involved in blood pressure regulation
J. Mol. Biol.
411
463-473
2011
Homo sapiens (Q5VYX0), Homo sapiens
Manually annotated by BRENDA team
Beaupre, B.A.; Hoag, M.R.; Moran, G.R.
Renalase does not catalyze the oxidation of catecholamines
Arch. Biochem. Biophys.
579
62-66
2015
Homo sapiens
Manually annotated by BRENDA team
Moran, G.R.; Hoag, M.R.
The enzyme Renalase
Arch. Biochem. Biophys.
632
66-76
2017
Pseudomonas savastanoi (Q48MT7), Homo sapiens (Q5VYX0), Pseudomonas savastanoi 1448A (Q48MT7)
Manually annotated by BRENDA team
Severina, I.; Fedchenko, V.; Veselovsky, A.; Medvedev, A.
The history of renalase from amine oxidase to alpha-NAD(P)H-oxidase/anomerase
Biochemistry (Moscow)
10
97-109
2016
Homo sapiens (Q5VYX0)
Manually annotated by BRENDA team
Sonawane, P.J.; Gupta, V.; Sasi, B.K.; Kalyani, A.; Natarajan, B.; Khan, A.A.; Sahu, B.S.; Mahapatra, N.R.
Transcriptional regulation of the novel monoamine oxidase renalase Crucial roles of transcription factors Sp1, STAT3, and ZBP89
Biochemistry
53
6878-6892
2014
Homo sapiens
Manually annotated by BRENDA team
Beaupre, B.A.; Hoag, M.R.; Roman, J.; Foersterling, F.H.; Moran, G.R.
Metabolic function for human renalase oxidation of isomeric forms of beta-NAD(P)H that are inhibitory to primary metabolism
Biochemistry
54
795-806
2015
Homo sapiens
Manually annotated by BRENDA team
Moran, G.R.
The catalytic function of renalase A decade of phantoms
Biochim. Biophys. Acta
1864
177-186
2016
Homo sapiens (Q5VYX0), Homo sapiens
Manually annotated by BRENDA team
Quelhas-Santos, J.; Soares-Silva, I.; Fernandes-Cerqueira, C.; Simoes-Silva, L.; Ferreira, I.; Carvalho, C.; Coentrao, L.; Vaz, R.; Sampaio-Maia, B.; Pestana, M.
Plasma and urine renalase levels and activity during the recovery of renal function in kidney transplant recipients
Exp. Biol. Med. (Maywood)
239
502-508
2014
Homo sapiens
Manually annotated by BRENDA team
Fedchenko, V.I.; Buneeva, O.A.; Kopylov, A.T.; Veselovsky, A.V.; Zgoda, V.G.; Medvedev, A.E.
Human urinary renalase lacks the N-terminal signal peptide crucial for accommodation of its FAD cofactor
Int. J. Biol. Macromol.
78
347-353
2015
Homo sapiens (Q5VYX0), Homo sapiens
Manually annotated by BRENDA team
Wang, Y.; Safirstein, R.; Velazquez, H.; Guo, X.J.; Hollander, L.; Chang, J.; Chen, T.M.; Mu, J.J.; Desir, G.V.
Extracellular renalase protects cells and organs by outside-in signalling
J. Cell. Mol. Med.
21
1260-1265
2017
Homo sapiens
Manually annotated by BRENDA team
Fedchenko, V.; Kopylov, A.; Kozlova, N.; Buneeva, O.; Kaloshin, A.; Zgoda, V.; Medvedev, A.
Renalase secreted by human kidney HEK293T cells lacks its n-terminal peptide implications for putative mechanisms of renalase action
Kidney Blood Press. Res.
41
593-603
2016
Homo sapiens
Manually annotated by BRENDA team
Li, X.; Huang, R.; Xie, Z.; Lin, M.; Liang, Z.; Yang, Y.; Jiang, W.
Renalase, a new secretory enzyme Its role in hypertensive-ischemic cardiovascular diseases
Med. Sci. Monit.
20
688-692
2014
Homo sapiens
Manually annotated by BRENDA team
Wu, Y.; Wang, L.; Deng, D.; Zhang, Q.; Liu, W.
Renalase protects against renal fibrosis by inhibiting the activation of the ERK signaling pathways
Int. J. Mol. Sci.
18
855
2017
Rattus norvegicus (Q5U2W9), Homo sapiens (Q5VYX0), Homo sapiens
Manually annotated by BRENDA team
Kolodecik, T.R.; Reed, A.M.; Date, K.; Shugrue, C.A.; Patel, V.; Chung, S.L.; Desir, G.V.; Gorelick, F.S.
The serum protein renalase reduces injury in experimental pancreatitis
J. Biol. Chem.
292
21047-21059
2017
Mus musculus (A7RDN6), Homo sapiens (Q5VYX0)
Manually annotated by BRENDA team
Catak, Z.; Kocdemir, E.; Ugur, K.; Yardim, M.; Sahin, I.; Kaya, H.; Aydin, S.
A novel biomarker renalase and its relationship with its substrates in schizophrenia
J. Med. Biochem.
38
299-305
2019
Homo sapiens (Q5VYX0), Homo sapiens
Manually annotated by BRENDA team
Morrison, C.; Paskaleva, E.; Rios, M.; Beusse, T.; Blair, E.; Lin, L.; Hu, J.; Gorby, A.; Dodds, D.; Armiger, W.; Dordick, J.; Koffas, M.
Improved soluble expression and use of recombinant human renalase
PLoS ONE
15
e0242109
2020
Homo sapiens (Q5VYX0), Homo sapiens
Manually annotated by BRENDA team
Gao, Y.; Wang, M.; Guo, X.; Hu, J.; Chen, T.M.; Finn, S.M.B.; Lacy, J.; Kunstman, J.W.; Cha, C.H.; Bellin, M.D.; Robert, M.E.; Desir, G.V.; Gorelick, F.S.
Renalase is a novel tissue and serological biomarker in pancreatic ductal adenocarcinoma
PLoS ONE
16
e0250539
2021
Homo sapiens (Q5VYX0)
Manually annotated by BRENDA team