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Information on EC 3.6.1.9 - nucleotide diphosphatase and Organism(s) Mus musculus and UniProt Accession Q9EQG7

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EC Tree
     3 Hydrolases
         3.6 Acting on acid anhydrides
             3.6.1 In phosphorus-containing anhydrides
                3.6.1.9 nucleotide diphosphatase
IUBMB Comments
The enzyme preferentially hydrolyses ATP, but can also hydrolyse other nucleoside 5' triphosphates such as GTP, CTP, TTP and UTP to their corresponding monophosphates. In vitro the enzyme also acts as a nucleotidohydrolase on ADP, NAD+, NADP+, FAD, and CoA.
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This record set is specific for:
Mus musculus
UNIPROT: Q9EQG7
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Word Map
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
Synonyms
npp, cd203c, itpase, inosine triphosphatase, inosine triphosphate pyrophosphatase, maf protein, enpp3, nppase, e-npp, nucleoside triphosphate pyrophosphohydrolase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
nucleotide pyrophosphatase
-
nucleoside triphosphate diphosphatase
-
-
-
-
nucleoside-triphosphate pyrophosphatase
-
-
-
-
nucleotide pyrophosphatase
nucleotide pyrophosphatase/phosphodiesterase 1
-
nucleotide pyrophosphatase/phosphodiesterase NPP1
-
nucleotide pyrophosphatase/phosphodiesterase-1
-
-
nucleotide pyrophosphatase/phosphodiesterase-I
-
-
nucleotide pyrophosphohydrolase
-
-
-
-
nucleotide-sugar pyrophosphatase
-
-
-
-
PC-1
-
-
plasma cell membrane glycoprotein-1
-
-
pyrophosphatase, nucleoside triphosphate
-
-
-
-
additional information
see also EC 3.1.4.1
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of phosphoric ester
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
dinucleotide nucleotidohydrolase
The enzyme preferentially hydrolyses ATP, but can also hydrolyse other nucleoside 5' triphosphates such as GTP, CTP, TTP and UTP to their corresponding monophosphates. In vitro the enzyme also acts as a nucleotidohydrolase on ADP, NAD+, NADP+, FAD, and CoA.
CAS REGISTRY NUMBER
COMMENTARY hide
9032-64-8
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
4-nitrophenyl phosphate + H2O
4-nitrophenol + phosphate
show the reaction diagram
-
-
-
-
?
4-nitrophenyl phosphate dianion + H2O
4-nitrophenol + phosphate
show the reaction diagram
-
-
-
-
?
4-nitrophenyl phosphate monoanion + H2O
4-nitrophenol + phosphate
show the reaction diagram
-
72fold higher activity than with 4-nitrophenyl phosphate dianion
-
-
?
4-nitrophenyl-5'-thymidine monophosphate + H2O
4-nitrophenol + 5'-thymidine monophosphate
show the reaction diagram
artificial substrate
-
-
?
4-nitrophenyl-TMP + H2O
4-nitrophenol + TMP
show the reaction diagram
-
-
-
-
?
ADP + H2O
AMP + phosphate
show the reaction diagram
-
-
-
-
?
ATP + H2O
AMP + diphosphate
show the reaction diagram
bis-4-nitrophenyl phosphate + H2O
4-nitrophenol + phosphate
show the reaction diagram
-
2000fold higher activity than with 4-nitrophenyl phosphate dianion
-
-
?
CTP + H2O
CMP + diphosphate
show the reaction diagram
-
-
-
?
diphosphate + H2O
phosphate
show the reaction diagram
-
-
-
-
?
GTP + H2O
GMP + diphosphate
show the reaction diagram
-
-
-
?
methyl 4-nitrophenyl phosphate + H2O
4-nitrophenol + methyl phosphate
show the reaction diagram
-
200fold higher activity than with 4-nitrophenyl phosphate dianion
-
-
?
NAD+ + H2O
NMN + AMP
show the reaction diagram
-
-
-
?
NADH + H2O
NMNH + AMP
show the reaction diagram
-
-
-
?
p-nitrophenyl 5'-thymidine monophosphate + H2O
4-nitrophenol + TMP
show the reaction diagram
-
1500000fold higher activity than with 4-nitrophenyl phosphate dianion
-
-
?
p-nitrophenyl phenylphosphonate + H2O
p-nitrophenol + phenylphosphonate
show the reaction diagram
-
phosphodiesterase-1 activity
-
?
p-nitrophenyl thymidine 5'-monophosphate + H2O
?
show the reaction diagram
-
-
-
?
p-nitrophenyl-dTMP + H2O
p-nitrophenol + dTMP
show the reaction diagram
-
Ca2+-dependent
-
?
UDP-alpha-D-galactose + H2O
UMP + alpha-D-galactose-1-phosphate
show the reaction diagram
UDP-N-acetyl-alpha-D-glucosamine + H2O
UMP + N-acetyl-alpha-D-glucosaminyl-1-phosphate
show the reaction diagram
-
-
-
?
UTP + H2O
UMP + diphosphate
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
ATP + H2O
AMP + diphosphate
show the reaction diagram
CTP + H2O
CMP + diphosphate
show the reaction diagram
-
-
-
?
GTP + H2O
GMP + diphosphate
show the reaction diagram
-
-
-
?
NAD+ + H2O
NMN + AMP
show the reaction diagram
-
-
-
?
NADH + H2O
NMNH + AMP
show the reaction diagram
-
-
-
?
UDP-alpha-D-galactose + H2O
UMP + alpha-D-galactose-1-phosphate
show the reaction diagram
UDP-N-acetyl-alpha-D-glucosamine + H2O
UMP + N-acetyl-alpha-D-glucosaminyl-1-phosphate
show the reaction diagram
-
-
-
?
UTP + H2O
UMP + diphosphate
show the reaction diagram
-
-
-
?
additional information
?
-
-
functional enzyme is required in carminerin-deficiency to suppress the resulting pathological endochondral ossifications
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
CaCl2
2-5 mM restores activity of EDTA-inhibited enzyme
MgCl2
2-5 mM partially restores activity of EDTA-inhibited enzyme
ZnCl2
2-5 mM restores activity of EDTA-inhibited enzyme
Ca2+
-
2fold activation at 10 mM
Mg2+
-
2fold activation at 10 mM
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
EDTA
activity can be restored by addition of 2-5 mM ZnCl2 or CaCl2, but only partially by 2-5 mM MgCl2
EDTA
-
strong inhibition at 1 mM, partially reversed by Mg2+, complete reactivation at 10 mM Ca2+
EGTA
-
strong inhibition at 1 mM, partially reversed by Mg2+, complete reactivation at 10 mM Ca2+
UDP-galactose
-
competitive inhibition, Ki: 29 mM
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.21
4-nitrophenyl-5'-thymidine monophosphate
pH and temperature not specified in the publication, liver enzyme
0.046
ATP
pH and temperature not specified in the publication
1.2
CTP
pH and temperature not specified in the publication
4.2
GTP
pH and temperature not specified in the publication
0.11
p-nitrophenyl 5'-thymidine monophosphate
-
25°C, pH 8.0
21
p-nitrophenyl deoxyTMP
-
-
4.3
UTP
pH and temperature not specified in the publication
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
16
ATP
pH and temperature not specified in the publication
8.7
CTP
pH and temperature not specified in the publication
820
GTP
pH and temperature not specified in the publication
200
UTP
pH and temperature not specified in the publication
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
347.8
ATP
pH and temperature not specified in the publication
7.25
CTP
pH and temperature not specified in the publication
195.2
GTP
pH and temperature not specified in the publication
46.5
UTP
pH and temperature not specified in the publication
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
29
UDP-galactose
-
competitive inhibition
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
deficient in carminerin, encoded by Cst10. Functional enzyme is required in carminerin-deficiency to suppress the resulting pathological endochondral ossifications
Manually annotated by BRENDA team
-
enzyme knockout osteoblast cell
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) is a metalloenzyme that belongs to the NPP family, which comprises seven subtypes (NPP1-7)
physiological function
the enzyme is involved in various biological processes including bone mineralization, soft tissue calcification, insulin receptor signalling, cancer cell proliferation and immune modulation
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
ENPP5_MOUSE
477
0
54387
Swiss-Prot
-
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
120000
-
2 * 120000, reducing SDS-PAGE
125000
-
gel filtration
130000
-
gel filtration, SDS-PAGE
240000
-
non-reducing SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
-
2 * 120000, reducing SDS-PAGE
homodimer
NPP1 is a homodimeric type II transmembrane glycoprotein characterized by an N-terminal transmembrane domain, two somatomedin-B-like domains, a catalytic domain and a C-terminal nuclease-like domain
monomer
-
1 * 130000, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
mutations D358N and H362Q still allow a weak labeling, whereas mutation His517, Asp200, Asp405 and His406 completely abolish autophosphorylation in presence of ATP
glycoprotein
phosphoprotein
-
autophosphorylation
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
in absence of ligands and in complex with vanadate or AMP. Comparison of bimetallo active site with Escherichia coli alkaline phosphatase
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D200N
mutation abolishes formation of the nucleotidylated intermediate
D358N
mutant enzyme can still form nucleotidylated catalytic intermediates but is hampered in the second step of catalysis
F239A
mutation halves activity, decreased ability to trap the catalytic intermediate
F239Q
decreased activity and level of covalent intermediate of the mutant may be accounted for by a decreased binding of the substrate
H362Q
mutant enzyme can still form nucleotidylated catalytic intermediates but is hampered in the second step of catalysis
H406Q
mutation abolishes formation of the nucleotidylated intermediate
K237A
mutation halves activity
T238S
mutant enzyme can still form nucleotidylated catalytic intermediates but is hampered in the second step of catalysis
DELTA804-905
mutation results in complete loss of activity, protein remains entirely intracellular
H242L
60% decrease in enzymic acitivity
H242L/V246A
60% decrease in enzymic acitivity
K173Q
polymorphisms of NPP1 is associated with the aetiology of insulin resistance, does not affect the dimerization or catalytic activity of NPP1 and does not endow NPP1 with an affinity for the insulin receptor
V246A
40% decrease in enzymic acitivity
additional information
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
slight loss of activity if repeated freezed and thawed
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
to homogeneity, chromatography techniques
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
mutants expressed in COS-1 cells
expressed in COS-1 cells
-
expression in Cos-7 and mouse Ltk- cells
-
wild-type enzyme NPP1 and NPP1-DELTA804-905 is expressed in COS cells as fusions with enhanced green fluorescent protein
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Belli, S.I.; Goding, J.W.
Biochemical characterization of human PC-1, an enzyme possessing alkaline phosphodiesterase I and nucleotide pyrophosphatase activities
Eur. J. Biochem.
226
433-443
1994
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Abney, E.R.; Evans, W.H.; Parkhouse, R.M.E.
Location of nucleotide pyrophosphatase and alkaline phosphodiesterase activities on the lymphocyte surface membrane
Biochem. J.
159
293-299
1976
Mus musculus
Manually annotated by BRENDA team
Evans, W.H.; Hood, D.; Gurd, J.W.
Purification and properties of a mouse liver plasma-membrane glycoprotein hydrolysing nucleotide pyrophosphate and phosphodiester bonds
Biochem. J.
135
819-826
1973
Mus musculus
Manually annotated by BRENDA team
Gijsbers, R.; Ceulemans, H.; Bollen, M.
Functional characterization of the non-catalytic ectodomains of the nucleotide pyrophosphatase/phosphodiesterase NPP1
Biochem. J.
371
321-330
2003
Mus musculus (P06802)
Manually annotated by BRENDA team
Gijsbers, R.; Ceulemans, H.; Stalmans, W.; Bollen, M.
Structural and catalytic similarities between nucleotide pyrophosphatases/phosphodiesterases and alkaline phosphatases
J. Biol. Chem.
276
1361-1368
2001
Mus musculus (Q9EQG7)
Manually annotated by BRENDA team
Vaingankar, S.M.; Fitzpatrick, T.A.; Johnson, K.; Goding, J.W.; Maurice, M.; Terkeltaub, R.
Subcellular targeting and function of osteoblast nucleotide pyrophosphatase phosphodiesterase 1
Am. J. Physiol.
286
C1177-C1187
2004
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Cimpean, A.; Stefan, C.; Gijsbers, R.; Stalmans, W.; Bollen, M.
Substrate-specifying determinants of the nucleotide pyrophosphatases/phosphodiesterases NPP1 and NPP2
Biochem. J.
381
71-77
2004
Mus musculus (P06802)
Manually annotated by BRENDA team
Zalatan, J.G.; Fenn, T.D.; Brunger, A.T.; Herschlag, D.
Structural and functional comparisons of nucleotide pyrophosphatase/phosphodiesterase and alkaline phosphatase: implications for mechanism and evolution
Biochemistry
45
9788-9803
2006
Mus musculus
Manually annotated by BRENDA team
Yamada, T.; Kawano, H.; Koshizuka, Y.; Fukuda, T.; Yoshimura, K.; Kamekura, S.; Saito, T.; Ikeda, T.; Kawasaki, Y.; Azuma, Y.; Ikegawa, S.; Hoshi, K.; Chung, U.I.; Nakamura, K.; Kato, S.; Kawaguchi, H.
Carminerin contributes to chondrocyte calcification during endochondral ossification
Nat. Med.
12
665-670
2006
Mus musculus
Manually annotated by BRENDA team
Simao, A.M.; Yadav, M.C.; Narisawa, S.; Bolean, M.; Pizauro, J.M.; Hoylaerts, M.F.; Ciancaglini, P.; Millan, J.L.
Proteoliposomes harboring alkaline phosphatase and nucleotide pyrophosphatase as matrix vesicle biomimetics
J. Biol. Chem.
285
7598-7609
2010
Mus musculus
Manually annotated by BRENDA team
Lee, S.Y.; Mueller, C.E.
Nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) and its inhibitors
MedChemComm
8
823-840
2017
Mus musculus (P06802), Homo sapiens (P22413), Homo sapiens, Rattus norvegicus (Q924C3)
Manually annotated by BRENDA team