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Information on EC 3.2.2.6 - ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase and Organism(s) Mus musculus and UniProt Accession P56528
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3.2.2.6 ADP-ribosyl cyclase/cyclic ADP-ribose hydrolaseIUBMB Comments
This multiunctional enzyme acts on NAD+, catalysing both the synthesis and hydrolysis of cyclic ADP-ribose, 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 2.4.99.20, 2'-phospho-ADP-ribosyl cyclase/2'-phospho-cyclic-ADP-ribose transferase. It is also able to act on beta-nicotinamide D-ribonucleotide. cf. EC 3.2.2.5, NAD+ glycohydrolase.
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Word Map
- 3.2.2.6
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cadpr
-
ryanodine
- aplysia
- inositol
-
naadp
-
ectoenzyme
-
ca2+-mobilizing
- californica
- gdp-ribose
- nadase
- beta-nad+
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urchin
- diphosphoribose
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calcium-mobilizing
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8-br-cadpr
- oxytocin
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ca2+-releasing
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anti-cd38
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trisphosphate
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8-bromo-cadpr
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ca2+-induced
- nad+-glycohydrolase
- ngd+
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ryanodine-sensitive
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cd38-deficient
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cadpr-mediated
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cadpr-induced
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
adp-ribosyl cyclase, adpr cyclase, nad(p)ase, nad(p)-glycohydrolase, bcd38, adp-ribosyl cyclase/cyclic adp-ribose hydrolase, nad(p)+ glycohydrolase, 
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topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CD38
NAD(P) nucleosidase
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-
-
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NAD(P)+ glycohydrolase
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-
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NAD(P)-glycohydrolase
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-
-
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NAD(P)ase
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-
-
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nicotinamide adenine dinucleotide (phosphate) glycohydrolase
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-
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nicotinamide adenine dinucleotide (phosphate) nucleosidase
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-
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nucleosidase, nicotinamide adenine dinucleotide (phosphate)
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-
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triphosphopyridine nucleotidase
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-
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CD38
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-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of N-glycosyl bond
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-
-
-
SYSTEMATIC NAME
IUBMB Comments
NAD+ glycohydrolase (cyclic ADP-ribose-forming)
This multiunctional enzyme acts on NAD+, catalysing both the synthesis and hydrolysis of cyclic ADP-ribose, 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 2.4.99.20, 2'-phospho-ADP-ribosyl cyclase/2'-phospho-cyclic-ADP-ribose transferase. It is also able to act on beta-nicotinamide D-ribonucleotide. cf. EC 3.2.2.5, NAD+ glycohydrolase.
CAS REGISTRY NUMBER
COMMENTARY
9025-46-1
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
NAD+ + H2O
cyclic ADP-ribose + nicotinamide + H+
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the cyclization and hydrolysis of NAD(P)+ occur optimally at physiological pH
-
-
?
NADP+ + nicotinic acid
nicotinic acid adenine dinucleotide phosphate
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this reaction occurs only in acidic pH
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-
?
additional information
?
-
CD38 is a NAD+-dependent, multifunctional ectoenzyme that cannot only generate cyclic ADP-ribose from NAD+ but also hydrolyze cyclic ADP-ribose to ADP-ribose and transport cyclic ADP-ribose into cells
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-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
CD38 is a NAD+-dependent, multifunctional ectoenzyme that cannot only generate cyclic ADP-ribose from NAD+ but also hydrolyze cyclic ADP-ribose to ADP-ribose and transport cyclic ADP-ribose into cells
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-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-[2-azido-2-deoxy-5-O-phosphono-D-threo-pentofuranosyl]-3-carbamoylpyridinium
inhibition of the NADase activity
1-[5-O-[(benzyloxy)(hydroxy)phosphoryl]-2-deoxy-2-fluoro-L-erythro-pentofuranosyl]-3-carbamoylpyridinium
inhibition of the NADase activity
1-[5-O-[butoxy(hydroxy)phosphoryl]-2-deoxy-2-fluoro-D-threo-pentofuranosyl]-3-carbamoylpyridinium
inhibition of the NADase activity
3-carbamoyl-1-[2-chloro-2-deoxy-5-O-phosphono-D-threo-pentofuranosyl]pyridinium
inhibition of the NADase activity
3-carbamoyl-1-[2-deoxy-2-fluoro-5-O-phosphono-D-threo-pentofuranosyl]pyridinium
inhibition of the NADase activity
3-carbamoyl-1-[2-deoxy-2-fluoro-5-O-phosphono-L-threo-pentofuranosyl]pyridinium
inhibition of the NADase activity
3-carbamoyl-1-[2-deoxy-2-fluoro-5-O-thiophosphono-L-erythro-pentofuranosyl]pyridinium
inhibition of the NADase activity
3-carbamoyl-1-[2-deoxy-2-fluoro-5-O-[(hexyloxy)(hydroxy)phosphoryl]-D-threo-pentofuranosyl]pyridinium
inhibition of the NADase activity
3-carbamoyl-1-[2-deoxy-2-fluoro-5-O-[hydroxy(2-phenylethoxy)phosphoryl]-L-erythro-pentofuranosyl]pyridinium
inhibition of the NADase activity
3-carbamoyl-1-[2-deoxy-2-fluoro-D-threo-pentofuranosyl]pyridinium
inhibition of the NADase activity
3-carbamoyl-1-[2-deoxy-5-O-(diethoxyphosphoryl)-2-fluoro-D-threo-pentofuranosyl]pyridinium
inhibition of the NADase activity
3-carbamoyl-1-[2-deoxy-5-O-[(ethenyloxy)(propoxy)phosphoryl]-2-fluoro-D-threo-pentofuranosyl]pyridinium
inhibition of the NADase activity
3-carbamoyl-1-[3-deoxy-3-fluoro-5-O-phosphono-L-threo-pentofuranosyl]pyridinium
inhibition of the NADase activity
arabinosyl-2'-fluoro-2'-deoxynicotinamide mononucleotide
inhibition of the NADase activity
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
malfunction
-
CD38 knockout mice manifest multiple defects relating to Ca2+ signaling, including that of insulin secretion, hormonal signaling in pancreatic acinar cells, migration of dendritic cell precursors, bone resorption, airway responsiveness, alpha-adrenoceptor signaling in aorta, cardiac hypertrophy, susceptibility to bacterial infection, as well as social behavior in mice through modulation of oxytocin secretion
additional information
structure-function relationship anaysis, overview. Covalent intermediates are formed with the catalytic residue, Glu226
malfunction
ablation of the CD38 gene in mice causes multiple physiological defects, including impaired oxytocin release, that result in altered social behavior
malfunction
CD38 reductions lead to microglial apoptosis. inhibition of CD38/cADPR-dependent signaling by CD38 silencing or 8-bromo-cADPR, a ryanodine receptor antagonist, produced significant ATP release from BV2 microglia. Cx43 small interfering RNA and Cx43 hemichannel blocker 18-alpha-glycyrrhetinic acid completely prevented the CD38 silencing or 8-bromo-cADPR-induced ATP release. Prevention of the ATP release might also be due to P2X7 receptor antagonists. Key role of ATP release in the microglial apoptosis induced by decreased CD38/cADPR-dependent signaling, overview
physiological function
CD38 is an ectoenzyme that consumes NAD+ to produce cyclic ADP-ribose, a potent agonist of ryanodine receptors. Basal CD38/cyclic ADP-ribose-dependent signaling plays a key role in ATP release, which mediates basal survival of microglia, overview
physiological function
the enzyme is a signaling enzyme responsible for catalyzing the synthesis of cyclic ADP ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate, both are universal Ca2+ messenger molecules
physiological function
in cultured macrophages, lipopolysaccharide LPS can upregulate CD38 expression in time- and dose-dependent manner. Knocking down or blockade of CD38 in macrophages inhibits LPS-induced macrophage M1 polarization accompanied by diminished NF-kappaB signaling activation. In a mouse model with LPS-induced acute kidney injury, blocking CD38 with quercetin significantly relieves kidney dysfunction, kidney pathological changes as well as inflammatory cell accumulation
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). CD38_MOUSE
304
1
34408
Swiss-Prot
other Location (Reliability: 5)
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
enzyme in complex with inhibitors, hanging drop vapor diffusion method, mixing of 10 mg/ml protein in 20 mM HEPES with 5 mm ligands, with reservoir solution containing 0.1 M sodium acetate, pH 4.0, 0.2 M ammonium acetate, 3% 2-propanol, and 15% PEG 10000, X-ray diffraction structure determination and analysis, molecular replacement
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
in cultured macrophages, lipopolysaccharide LPS can upregulate CD38 expression in time- and dose-dependent manner
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Lee, H.C.
Cyclic ADP-ribose and NAADP: fraternal twin messengers for calcium signaling
Sci. China Life Sci.
54
699-711
2011
Mus musculus
Kwong, A.; Chen, Z.; Zhang, H.; Leung, F.; Lam, C.; Ting, K.; Zhang, L.; Hao, Q.; Zhang, L.; Lee, H.
Catalysis-based inhibitors of the calcium signaling function of CD38
Biochemistry
51
555-564
2012
Homo sapiens (P28907), Mus musculus (P56528), Rattus norvegicus
Ma, Y.; Cao, W.; Wang, L.; Jiang, J.; Nie, H.; Wang, B.; Wei, X.; Ying, W.
Basal CD38/cyclic ADP-ribose-dependent signaling mediates ATP release and survival of microglia by modulating connexin 43 hemichannels
Glia
62
943-955
2014
Mus musculus (P56528)
Shu, B.; Feng, Y.; Gui, Y.; Lu, Q.; Wei, W.; Xue, X.; Sun, X.; He, W.; Yang, J.; Dai, C.
Blockade of CD38 diminishes lipopolysaccharide-induced macrophage classical activation and acute kidney injury involving NF-kappaB signaling suppression
Cell. Signal.
42
249-258
2018
Mus musculus (P56528), Mus musculus
EXTERNAL LINKS (specific for EC-Number 3.2.2.6)
Transporter Classification Database (TCDB): 8.A.23.1.11
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