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Information on EC 2.4.99.20 - 2'-phospho-ADP-ribosyl cyclase/2'-phospho-cyclic-ADP-ribose transferase and Organism(s) Homo sapiens and UniProt Accession P28907

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IUBMB Comments
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.
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Homo sapiens
UNIPROT: P28907
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The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
adp-ribosyl cyclase 1, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
2'-phospho-cyclic-ADP-ribose transferase
-
ADP-ribosyl cyclase 1
-
PATHWAY SOURCE
PATHWAYS
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.
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
-
-
-
?
NGDP+
2'-phospho-cyclic GDP-ribose + nicotinamide
show the reaction diagram
enzyme cyclizes nicotinamide guanine dinucleotide to produce a fluorescent product, cyclic GDP-ribose, which has a site of cyclization different from cADPR
-
-
?
additional information
?
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5
nicotinate
pH 5, 22°C
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
gene silencing of CD38 does not inhibit NAADP synthesis in intact Jurkat T cells. In vitro, both NAADP formation by base-exchange and degradation to 2-phospho adenosine diphosphoribose are efficiently decreased. Thus in vivo CD38 appears to be a NAADP degrading rather than a NAADP forming enzyme
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
CD38_HUMAN
300
1
34328
Swiss-Prot
other Location (Reliability: 5)
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D147V
mutation has minimal effects on pH-dependence of the enzyme
D155N
mutation eliminates the strong pH dependence of the catalyzed reactions
D155Q
E146A
mutation eliminates the strong pH dependence of the catalyzed reactions
E146G
mutation eliminates the strong pH dependence of the catalyzed reactions
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Lee, H.C.; Graeff, R.M.; Walseth, T.F.
ADP-ribosyl cyclase and CD38. Multi-functional enzymes in Ca+2 signaling
Adv. Exp. Med. Biol.
419
411-419
1997
Homo sapiens (P28907), Aplysia californica (P29241)
Manually annotated by BRENDA team
Moreschi, I.; Bruzzone, S.; Melone, L.; De Flora, A.; Zocchi, E.
NAADP+ synthesis from cADPRP and nicotinic acid by ADP-ribosyl cyclases
Biochem. Biophys. Res. Commun.
345
573-580
2006
Axinella polypoides, Homo sapiens (P28907), Aplysia californica (P29241)
Manually annotated by BRENDA team
Schmid, F.; Bruhn, S.; Weber, K.; Mittruecker, H.W.; Guse, A.H.
CD38: a NAADP degrading enzyme
FEBS Lett.
585
3544-3548
2011
Homo sapiens (P28907), Mus musculus (P56528)
Manually annotated by BRENDA team
Aarhus, R.; Graeff, R.M.; Dickey, D.M.; Walseth, T.F.; Lee, H.C.
ADP-ribosyl cyclase and CD38 catalyze the synthesis of a calcium-mobilizing metabolite from NADP+
J. Biol. Chem.
270
30327-30333
1995
Homo sapiens (P28907), Aplysia californica (P29241)
Manually annotated by BRENDA team
Graeff, R.; Liu, Q.; Kriksunov, I.A.; Hao, Q.; Lee, H.C.
Acidic residues at the active sites of CD38 and ADP-ribosyl cyclase determine nicotinic acid adenine dinucleotide phosphate (NAADP) synthesis and hydrolysis activities
J. Biol. Chem.
281
28951-28957
2006
Homo sapiens (P28907)
Manually annotated by BRENDA team