Inhibitors | Comment | Organism | Structure |
---|---|---|---|
2-MeSADP | competitive inhibition | Homo sapiens | |
2-MeSATP | competitive inhibition | Homo sapiens | |
alpha,beta-metADP | competitive inhibition | Homo sapiens | |
alpha,beta-metADP | mixed inhibition type | Rattus norvegicus | |
alpha,beta-metATP | competitive inhibition | Homo sapiens | |
alpha,beta-metATP | competitive inhibition | Rattus norvegicus | |
alpha-borano-beta,gamma-MetATP | - |
Homo sapiens | |
benzoyl-ATP | - |
Homo sapiens | |
benzoyl-ATP | competitive inhibition | Rattus norvegicus | |
dialADP | noncompetitive inhibition | Homo sapiens | |
dialATP | uncompetitive inhibition | Homo sapiens | |
dialATP | - |
Rattus norvegicus | |
gamma-S-adenosine 5'-(alpha,beta-methylene)triphosphate | competitive inhibition | Homo sapiens | |
heparin | - |
Homo sapiens | |
N-[2-[1-(6,7-dimethoxyquinazolin-4-yl)piperidin-4-yl]ethyl] sulfuric diamide | i.e. SAR 03004 | Homo sapiens | |
PZB08513136A | the most potent thioacetamide derivative | Homo sapiens | |
Reactive blue 2 | - |
Homo sapiens | |
suramin | - |
Homo sapiens | |
thiazolobenzimidazolone | and derivatives | Homo sapiens | |
[TiW11CoO40]8- | i.e. PSB-POM141 | Homo sapiens |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | kinetic analysis | Mus musculus | |
additional information | - |
additional information | kinetic analysis | Homo sapiens | |
additional information | - |
additional information | kinetic analysis | Rattus norvegicus | |
0.0051 | - |
Ap3A | pH and temperature not specified in the publication, membrane enzyme | Homo sapiens | |
0.00817 | - |
ATP | pH and temperature not specified in the publication, soluble enzyme | Homo sapiens | |
0.0205 | - |
Ap4A | pH and temperature not specified in the publication, soluble enzyme | Homo sapiens | |
0.0326 | - |
2',3''-cGAMP | pH and temperature not specified in the publication, soluble enzyme | Homo sapiens | |
0.046 | - |
ATP | pH and temperature not specified in the publication | Mus musculus | |
0.0566 | - |
UTP | pH and temperature not specified in the publication, soluble enzyme | Homo sapiens | |
0.0618 | - |
4-nitrophenyl-5'-thymidine monophosphate | pH and temperature not specified in the publication, serum enzyme | Rattus norvegicus | |
0.0914 | - |
4-nitrophenyl-5'-thymidine monophosphate | pH and temperature not specified in the publication, heart enzyme | Rattus norvegicus | |
0.108 | - |
4-nitrophenyl-5'-thymidine monophosphate | pH and temperature not specified in the publication, Walker 256 tumor cell line | Rattus norvegicus | |
0.114 | - |
cAMP | pH and temperature not specified in the publication, soluble enzyme | Homo sapiens | |
0.12 | - |
3'-phosphoadenosine-5'-phosphosulfate | pH and temperature not specified in the publication, membrane enzyme | Homo sapiens | |
0.188 | - |
4-nitrophenyl-5'-adenosine monophosphate | pH and temperature not specified in the publication, soluble enzyme | Homo sapiens | |
0.21 | - |
4-nitrophenyl-5'-thymidine monophosphate | pH and temperature not specified in the publication, liver enzyme | Mus musculus | |
0.222 | - |
4-nitrophenyl-5'-thymidine monophosphate | pH and temperature not specified in the publication, soluble enzyme | Homo sapiens | |
0.33 | - |
NAD+ | pH and temperature not specified in the publication, membrane enzyme | Homo sapiens | |
1.2 | - |
CTP | pH and temperature not specified in the publication | Mus musculus | |
4.2 | - |
GTP | pH and temperature not specified in the publication | Mus musculus | |
4.3 | - |
UTP | pH and temperature not specified in the publication | Mus musculus |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
membrane | NPP1 is a homodimeric type II transmembrane glycoprotein with an N-terminal transmembrane domain | Mus musculus | 16020 | - |
membrane | NPP1 is a homodimeric type II transmembrane glycoprotein with an N-terminal transmembrane domain | Homo sapiens | 16020 | - |
membrane | NPP1 is a homodimeric type II transmembrane glycoprotein with an N-terminal transmembrane domain | Rattus norvegicus | 16020 | - |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
2',3''-cGAMP + H2O | Homo sapiens | - |
? | - |
? | |
ATP + H2O | Mus musculus | - |
AMP + diphosphate | - |
? | |
ATP + H2O | Homo sapiens | - |
AMP + diphosphate | - |
? | |
ATP + H2O | Rattus norvegicus | - |
AMP + diphosphate | - |
? | |
CTP + H2O | Mus musculus | - |
CMP + diphosphate | - |
? | |
CTP + H2O | Homo sapiens | - |
CMP + diphosphate | - |
? | |
CTP + H2O | Rattus norvegicus | - |
CMP + diphosphate | - |
? | |
GTP + H2O | Mus musculus | - |
GMP + diphosphate | - |
? | |
GTP + H2O | Homo sapiens | - |
GMP + diphosphate | - |
? | |
GTP + H2O | Rattus norvegicus | - |
GMP + diphosphate | - |
? | |
UTP + H2O | Mus musculus | - |
UMP + diphosphate | - |
? | |
UTP + H2O | Homo sapiens | - |
UMP + diphosphate | - |
? | |
UTP + H2O | Rattus norvegicus | - |
UMP + diphosphate | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P22413 | - |
- |
Mus musculus | P06802 | - |
- |
Rattus norvegicus | Q924C3 | - |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
glycoprotein | NPP1 is a homodimeric type II transmembrane glycoprotein | Mus musculus |
glycoprotein | NPP1 is a homodimeric type II transmembrane glycoprotein | Homo sapiens |
glycoprotein | NPP1 is a homodimeric type II transmembrane glycoprotein | Rattus norvegicus |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
astrocytoma cell | - |
Homo sapiens | - |
brain | - |
Mus musculus | - |
brain | - |
Homo sapiens | - |
brain | - |
Rattus norvegicus | - |
chondrocyte | increased expression of NPP1 in chondrocytes | Homo sapiens | - |
liver | - |
Mus musculus | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
2',3''-cGAMP + H2O | - |
Homo sapiens | ? | - |
? | |
3'-phosphoadenosine-5'-phosphosulfate + H2O | - |
Homo sapiens | ? | - |
? | |
4-nitrophenyl phenyl phosphate + H2O | - |
Homo sapiens | 4-nitrophenol + phenyl phosphate | - |
? | |
4-nitrophenyl-5'-adenosine monophosphate + H2O | artificial substrate | Homo sapiens | 4-nitrophenol + 5'-adenosine monophosphate | - |
? | |
4-nitrophenyl-5'-thymidine monophosphate + H2O | artificial substrate | Mus musculus | 4-nitrophenol + 5'-thymidine monophosphate | - |
? | |
4-nitrophenyl-5'-thymidine monophosphate + H2O | artificial substrate | Homo sapiens | 4-nitrophenol + 5'-thymidine monophosphate | - |
? | |
4-nitrophenyl-5'-thymidine monophosphate + H2O | artificial substrate | Rattus norvegicus | 4-nitrophenol + 5'-thymidine monophosphate | - |
? | |
Ap3A + H2O | - |
Homo sapiens | ? | - |
? | |
Ap4A + H2O | - |
Homo sapiens | ? | - |
? | |
ATP + H2O | - |
Mus musculus | AMP + diphosphate | - |
? | |
ATP + H2O | - |
Homo sapiens | AMP + diphosphate | - |
? | |
ATP + H2O | - |
Rattus norvegicus | AMP + diphosphate | - |
? | |
bis(4-nitrophenyl) phosphate + H2O | - |
Homo sapiens | ? | - |
? | |
cAMP + H2O | - |
Homo sapiens | ? | - |
? | |
CTP + H2O | - |
Mus musculus | CMP + diphosphate | - |
? | |
CTP + H2O | - |
Homo sapiens | CMP + diphosphate | - |
? | |
CTP + H2O | - |
Rattus norvegicus | CMP + diphosphate | - |
? | |
GTP + H2O | - |
Mus musculus | GMP + diphosphate | - |
? | |
GTP + H2O | - |
Homo sapiens | GMP + diphosphate | - |
? | |
GTP + H2O | - |
Rattus norvegicus | GMP + diphosphate | - |
? | |
additional information | NPP1 hydrolyzes a wide range of phosphodiester bonds, e.g. in nucleoside triphosphates, (cyclic) dinucleotides, and nucleotide sugars yielding nucleoside 5'-monophosphates as products. Its main substrate is ATP which is cleaved to AMP and diphosphate. Purine nucleotides (ATP and GTP) are better substrates than pyrimidine nucleotides (CTP and UTP) | Mus musculus | ? | - |
- |
|
additional information | NPP1 hydrolyzes a wide range of phosphodiester bonds, e.g. in nucleoside triphosphates, (cyclic) dinucleotides, and nucleotide sugars yielding nucleoside 5'-monophosphates as products. Its main substrate is ATP which is cleaved to AMP and diphosphate. Purine nucleotides (ATP and GTP) are better substrates than pyrimidine nucleotides (CTP and UTP) | Rattus norvegicus | ? | - |
- |
|
additional information | NPP1 hydrolyzes a wide range of phosphodiester bonds, e.g. in nucleoside triphosphates, (cyclic) dinucleotides, and nucleotide sugars yielding nucleoside 5'-monophosphates as products. Its main substrate is ATP which is cleaved to AMP and diphosphate. Purine nucleotides (ATP and GTP) are better substrates than pyrimidine nucleotides (CTP and UTP). Besides, NPP1 metabolizes other nucleotides, e.g. nicotinamide adenine dinucleotide (NAD+), 3'-phosphoadenosine-5'-phosphosulfate (PAPS), diadenosine polyphosphates like diadenosine triphosphate (AP3A) or diadenosine tetraphosphate (AP4A), and UDP-glucose | Homo sapiens | ? | - |
- |
|
NAD+ + H2O | - |
Homo sapiens | NMN + AMP | - |
? | |
thiamine diphosphate + H2O | - |
Homo sapiens | thiamine + diphosphate | - |
? | |
UTP + H2O | - |
Mus musculus | UMP + diphosphate | - |
? | |
UTP + H2O | - |
Homo sapiens | UMP + diphosphate | - |
? | |
UTP + H2O | - |
Rattus norvegicus | UMP + diphosphate | - |
? |
Subunits | Comment | Organism |
---|---|---|
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 | Mus musculus |
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 | Homo sapiens |
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 | Rattus norvegicus |
Synonyms | Comment | Organism |
---|---|---|
More | see also EC 3.1.4.1 | Mus musculus |
More | see also EC 3.1.4.1 | Homo sapiens |
More | see also EC 3.1.4.1 | Rattus norvegicus |
NPP1 | - |
Mus musculus |
NPP1 | - |
Homo sapiens |
NPP1 | - |
Rattus norvegicus |
nucleotide pyrophosphatase/phosphodiesterase 1 | - |
Mus musculus |
nucleotide pyrophosphatase/phosphodiesterase 1 | - |
Homo sapiens |
nucleotide pyrophosphatase/phosphodiesterase 1 | - |
Rattus norvegicus |
Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
1.96 | - |
UTP | pH and temperature not specified in the publication, soluble enzyme | Homo sapiens | |
2.16 | - |
cAMP | pH and temperature not specified in the publication, soluble enzyme | Homo sapiens | |
2.51 | - |
4-nitrophenyl-5'-adenosine monophosphate | pH and temperature not specified in the publication, soluble enzyme | Homo sapiens | |
5.36 | - |
2',3''-cGAMP | pH and temperature not specified in the publication, soluble enzyme | Homo sapiens | |
5.51 | - |
ATP | pH and temperature not specified in the publication, soluble enzyme | Homo sapiens | |
5.65 | - |
Ap4A | pH and temperature not specified in the publication, soluble enzyme | Homo sapiens | |
8.7 | - |
CTP | pH and temperature not specified in the publication | Mus musculus | |
16 | - |
ATP | pH and temperature not specified in the publication | Mus musculus | |
22.3 | - |
4-nitrophenyl-5'-thymidine monophosphate | pH and temperature not specified in the publication, soluble enzyme | Homo sapiens | |
200 | - |
UTP | pH and temperature not specified in the publication | Mus musculus | |
820 | - |
GTP | pH and temperature not specified in the publication | Mus musculus |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
0.0005 | 0.056 | alpha-borano-beta,gamma-MetATP | pH and temperature not specified in the publication, membrane enzyme, versus 4-nitrophenyl-5'-thymidine monophosphate | Homo sapiens | |
0.00128 | - |
alpha,beta-metADP | pH and temperature not specified in the publication, soluble enzyme, versus 4-nitrophenyl-5'-thymidine monophosphate | Homo sapiens | |
0.002 | 0.0045 | gamma-S-adenosine 5'-(alpha,beta-methylene)triphosphate | pH and temperature not specified in the publication, membrane enzyme | Homo sapiens | |
0.00218 | - |
2-MeSADP | pH and temperature not specified in the publication, soluble enzyme, versus 4-nitrophenyl-5'-thymidine monophosphate | Homo sapiens | |
0.0022 | - |
alpha,beta-metATP | pH and temperature not specified in the publication, versus 4-nitrophenyl-5'-thymidine monophosphate | Rattus norvegicus | |
0.00296 | - |
benzoyl-ATP | pH and temperature not specified in the publication, membrane enzyme, versus 4-nitrophenyl-5'-thymidine monophosphate | Homo sapiens | |
0.00332 | - |
alpha,beta-metATP | pH and temperature not specified in the publication, soluble enzyme, versus 4-nitrophenyl-5'-thymidine monophosphate | Homo sapiens | |
0.00342 | - |
dialADP | pH and temperature not specified in the publication, membrane enzyme, versus 4-nitrophenyl-5'-thymidine monophosphate | Homo sapiens | |
0.00409 | - |
dialATP | pH and temperature not specified in the publication, soluble enzyme, versus 4-nitrophenyl-5'-thymidine monophosphate | Homo sapiens | |
0.00447 | - |
2-MeSATP | pH and temperature not specified in the publication, soluble enzyme, versus 4-nitrophenyl-5'-thymidine monophosphate | Homo sapiens | |
0.00503 | - |
dialADP | pH and temperature not specified in the publication, soluble enzyme, versus 4-nitrophenyl-5'-thymidine monophosphate | Homo sapiens | |
0.00508 | - |
dialATP | pH and temperature not specified in the publication, soluble enzyme, versus 4-nitrophenyl-5'-adenosine monophosphate | Homo sapiens | |
0.00509 | - |
dialADP | pH and temperature not specified in the publication, soluble enzyme, versus 4-nitrophenyl-5'-adenosine monophosphate | Homo sapiens | |
0.00514 | 0.00562 | dialADP | pH and temperature not specified in the publication, soluble enzyme, versus ATP | Homo sapiens | |
0.00682 | 0.00696 | dialATP | pH and temperature not specified in the publication, soluble enzyme, versus ATP | Homo sapiens | |
0.00819 | - |
alpha,beta-metATP | pH and temperature not specified in the publication, soluble enzyme, versus 4-nitrophenyl-5'-adenosine monophosphate | Homo sapiens | |
0.0096 | - |
alpha,beta-metADP | pH and temperature not specified in the publication, versus 4-nitrophenyl-5'-thymidine monophosphate | Rattus norvegicus | |
0.0098 | - |
dialATP | pH and temperature not specified in the publication | Rattus norvegicus | |
0.013 | 0.0269 | alpha,beta-metATP | pH and temperature not specified in the publication, soluble enzyme, versus ATP | Homo sapiens | |
0.0146 | - |
benzoyl-ATP | pH and temperature not specified in the publication, soluble enzyme, versus ATP | Homo sapiens | |
0.0165 | - |
alpha,beta-metADP | pH and temperature not specified in the publication, membrane enzyme, versus 4-nitrophenyl-5'-thymidine monophosphate | Homo sapiens | |
0.0165 | 0.0243 | alpha,beta-metADP | pH and temperature not specified in the publication, soluble enzyme, versus ATP | Homo sapiens | |
0.0205 | - |
benzoyl-ATP | pH and temperature not specified in the publication | Rattus norvegicus | |
0.0213 | 0.0253 | 2-MeSATP | pH and temperature not specified in the publication, soluble enzyme, versus ATP | Homo sapiens | |
0.0237 | 0.0328 | 2-MeSADP | pH and temperature not specified in the publication, soluble enzyme, versus ATP | Homo sapiens | |
0.0354 | - |
2-MeSADP | pH and temperature not specified in the publication, soluble enzyme, versus 4-nitrophenyl-5'-adenosine monophosphate | Homo sapiens | |
0.0399 | - |
2-MeSATP | pH and temperature not specified in the publication, soluble enzyme, versus 4-nitrophenyl-5'-adenosine monophosphate | Homo sapiens |
General Information | Comment | Organism |
---|---|---|
evolution | ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) is a metalloenzyme that belongs to the NPP family, which comprises seven subtypes (NPP1-7) | Mus musculus |
evolution | ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) is a metalloenzyme that belongs to the NPP family, which comprises seven subtypes (NPP1-7) | Homo sapiens |
evolution | ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) is a metalloenzyme that belongs to the NPP family, which comprises seven subtypes (NPP1-7) | Rattus norvegicus |
malfunction | the blockade of NPP1 can increase the concentration of ATP and 2',3''-cGAMP, but at the same time it can decrease the concentration of adenosine by reducing the concentration of its precursor AMP. This all can lead to an enhancement of the immune response in the body. Lentiviral shRNA-knockdown of NPP1 expression in a human glioblastoma cell line (NCH421k cells) reduces cell proliferation, increased accumulation of cells in the G1/G0 cell cycle phase and induced cell death. The mechanism for this effect may be based on the increased activation of cell apoptosis inducing P2X7 receptor activation owing to the accumulation of undegraded ATP (the main substrate of NPP1) by the knockdown of NPP1 function. Furthermore, the reduced production of extracellular adenosine by a blockade of NPP1 function may also reduce the adenosine induced angiogenesis as well as cell proliferation and differentiation by stimulating P1 receptors. Thus, NPP1 inhibitors may have antineoplastic effects on neuronal tumor cells. Increased expression of NPP1 in the chondrocytes, which is age-related, leads to the overproduction of diphosphate | Homo sapiens |
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 | Mus musculus |
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 | Homo sapiens |
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 | Rattus norvegicus |
kcat/KM Value [1/mMs-1] | kcat/KM Value Maximum [1/mMs-1] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
7.25 | - |
CTP | pH and temperature not specified in the publication | Mus musculus | |
13.35 | - |
4-nitrophenyl-5'-adenosine monophosphate | pH and temperature not specified in the publication, soluble enzyme | Homo sapiens | |
18.95 | - |
cAMP | pH and temperature not specified in the publication, soluble enzyme | Homo sapiens | |
34.6 | - |
UTP | pH and temperature not specified in the publication, soluble enzyme | Homo sapiens | |
46.5 | - |
UTP | pH and temperature not specified in the publication | Mus musculus | |
100.45 | - |
4-nitrophenyl-5'-thymidine monophosphate | pH and temperature not specified in the publication, soluble enzyme | Homo sapiens | |
164.4 | - |
2',3''-cGAMP | pH and temperature not specified in the publication, soluble enzyme | Homo sapiens | |
195.2 | - |
GTP | pH and temperature not specified in the publication | Mus musculus | |
275.6 | - |
Ap4A | pH and temperature not specified in the publication, soluble enzyme | Homo sapiens | |
347.8 | - |
ATP | pH and temperature not specified in the publication | Mus musculus | |
674.4 | - |
ATP | pH and temperature not specified in the publication, soluble enzyme | Homo sapiens |