Information on EC 2.4.99.20 - 2'-phospho-ADP-ribosyl cyclase/2'-phospho-cyclic-ADP-ribose transferase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.4.99.20
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RECOMMENDED NAME
GeneOntology No.
2'-phospho-ADP-ribosyl cyclase/2'-phospho-cyclic-ADP-ribose transferase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
2'-phospho-cyclic ADP-ribose + nicotinate = nicotinate-adenine dinucleotide phosphate
show the reaction diagram
NADP+ + nicotinate = nicotinate-adenine dinucleotide phosphate + nicotinamide
show the reaction diagram
NADP+ = 2'-phospho-cyclic ADP-ribose + nicotinamide
show the reaction diagram
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Nicotinate and nicotinamide metabolism
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SYSTEMATIC NAME
IUBMB Comments
NADP+:nicotinate ADP-ribosyltransferase
This multiunctional enzyme catalyses both the removal of nicotinamide from NADP+, forming 2'-phospho-cyclic ADP-ribose, and the addition of nicotinate to the cyclic product, forming NAADP+, a calcium messenger that can mobilize intracellular Ca2+ stores and activate Ca2+ influx to regulate a wide range of physiological processes. In addition, the enzyme also catalyses EC 3.2.2.6, ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase.
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
skeletal muscle isoform
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-
Manually annotated by BRENDA team
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SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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generation of CD38(-/-) knockout mice of determine the role of this enzyme
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
2'-phospho-cyclic ADP-ribose + nicotinate
nicotinate-adenine dinucleotide phosphate
show the reaction diagram
NADP+
2'-phospho-cyclic ADP-ribose + nicotinamide
show the reaction diagram
NADP+ + nicotinate
nicotinate-adenine dinucleotide phosphate + nicotinamide
show the reaction diagram
NGDP+
2'-phospho-cyclic GDP-ribose + nicotinamide
show the reaction diagram
additional information
?
-
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
NADP+ + nicotinate
nicotinate-adenine dinucleotide phosphate + nicotinamide
show the reaction diagram
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
nicotinamide
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inhibition of the cyclization reaction and is 30fold more potent at suppressing the base-exchange reaction. Inhibition is not via a competition with the nicotinic acid-binding site
additional information
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the cyclization reaction is insensitive to free Ca2+ concentration in the range 20 nM100 microM. Mg2+ is not inhibitory
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0334
NGDP+
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pH 7.4, temperature not specified in the publication
5
nicotinate
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00027
Cu2+
Oryctolagus cuniculus
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formation of cGDPr, pH 7.4, temperature not specified in the publication
0.0054
NAD+
Oryctolagus cuniculus
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formation of cGDPr, pH 7.4, temperature not specified in the publication
0.0013
NADP+
Oryctolagus cuniculus
-
formation of cGDPr, pH 7.4, temperature not specified in the publication
0.7
nicotinamide
Oryctolagus cuniculus
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cyclization reaction, pH 7.4, temperature not specified in the publication
0.0023
Zn2+
Oryctolagus cuniculus
-
formation of cGDPr, pH 7.4, temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00000013
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37C, pH 7.2, microsome from CD38(+/+) wild-type mouse brain
0.0000002
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37C, pH 7.2, mitochondria from CD38(+/+) wild-type mouse brain
0.0000016
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37C, pH 7.2, plasma membrane from CD38(+/+) wild-type mouse brain
0.4
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37C, pH 7.2, nucleus from CD38(+/+) wild-type mouse brain
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.2
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assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
additional information
very low activity in kidney cortex and skeletal muscles
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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of heavy sarcoplasmic reticulum
Manually annotated by BRENDA team
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0.13 nM/min*mg
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Manually annotated by BRENDA team
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0.2 nM/min*mg
Manually annotated by BRENDA team
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0.4 nM/min*mg
Manually annotated by BRENDA team
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1.6 nM/min*mg
Manually annotated by BRENDA team
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membrane of heavy sarcoplasmic reticulum
Manually annotated by BRENDA team
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
enzyme is a dimer
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complex of isoform CD38 with substrate NMN shows that the nicotinamide moiety is in close contact with Glu146 at 3.27 A and Asp155 at 2.52 A. Residue Asp147 is situated and directed away from the bound substrate
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D147V
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mutation has minimal effects on pH-dependence of the enzyme
D155N
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mutation eliminates the strong pH dependence of the catalyzed reactions
D155Q
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mutation eliminates the strong pH dependence of the catalyzed reactions; mutation preserves the strong pH dependence of the catalyzed reactions
E146A
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mutation eliminates the strong pH dependence of the catalyzed reactions
E146G
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mutation eliminates the strong pH dependence of the catalyzed reactions