Nucleotide diphosphatase 1
| Nucleotide diphosphatase 1 | ||
|---|---|---|
| Mass / length primary structure | 925 amino acids | |
| Secondary to quaternary structure | Homodimer; Type 2 membrane protein | |
| Cofactor | 2 A 2+ | |
| Identifier | ||
| Gene name (s) | ENPP1 ARHR2; COLED; M6S1; NPP1; NPPS; PC-1; PCA1; PDNP1 | |
| External IDs | ||
| Enzyme classification | ||
| EC, category | 3.6.1.9 , hydrolase | |
| Response type | Hydrolysis of phosphoric acid esters | |
| Substrate | Dinucleotide + H 2 O | |
| Products | 2 mononucleotides | |
| Occurrence | ||
| Parent taxon | Eukaryotes | |
| Orthologue | ||
| human | House mouse | |
| Entrez | 5167 | 18605 |
| Ensemble | ENSG00000197594 | ENSMUSG00000037370 |
| UniProt | P22413 | P06802 |
| Refseq (mRNA) | NM_006208 | NM_001308327 |
| Refseq (protein) | NP_006199 | NP_001295256 |
| Gene locus | Chr 6: 131.81 - 131.9 Mb | Chr 10: 24.64 - 24.71 Mb |
| PubMed search | 5167 |
18605
|
Nucleotide diphosphatase (NPPase) (more precisely, Ectonukleotid pyrophosphatase / phosphodiesterase ) hot enzymes , the hydrolytic cleavage of FAD and other dinucleotides to catalyze . This reaction is important for the breakdown of these substances and NPPases occur in animals and plants. Humans have two genes that code for NPPases : ENPP1 and ENPP3 .
The NPPases are membrane proteins . NPPase 1 is mainly found on the surface of plasma cells .
Mutations in the ENPP1 gene can lead to NPPase 1 deficiency, which can lead to ossification of the longitudinal posterior ligament (OLPP) and infantile arterial calcification (IIAC). Overproduction of the enzyme has been shown in several tissue types from people with insulin resistance , and enzyme variants have been associated with type 2 diabetes and its complications in many studies. The cause is the binding of overproduced NPPase 1 to the insulin receptor and the resulting inhibition of the signal transduction of insulin . For these reasons, NPPase is a pharmaceutical target for the treatment of these diseases.
Catalyzed reactions
Nucleotide diphosphatase 1 and nucleotide diphosphatase 3 are able to function both as diphosphatase ( EC 3.6.1.9 ) and as diesterase ( EC 3.1.4.1 ) and thus not only different dinucleotides such as NAD + , NADP + , FAD , Degrade CoA and even UDP-glucose , but also triphosphates like ATP , GTP , CTP , TTP and UTP ; also diadenosine polyphosphates and cAMP .
+ H 2 O + AMP 
As an example, the cleavage of FAD into FMN and AMP is shown.
More functions
Through its role in regulating the diphosphate content, NPPase 1 has a role in bone growth ; it also appears to participate in the nucleotide-sugar metabolism in the ER and in the Golgi apparatus and to be a factor in insulin sensitivity.
regulation
Both NPPases are inhibited by low ATP concentrations with subsequent phosphorylation of the enzyme.
Individual evidence
- ↑ a b c UniProt P22413 , UniProt O14638
- ↑ UniProt P22413
- ↑ Ira D. Goldfine, Betty A. Maddux, Jack F. Youngren, Gerald Reaven, Domenico Accili, Vincenzo Trischitta, Riccardo Vigneri, Lucia Frittitta: The role of membrane glycoprotein plasma cell antigen 1 / ectonucleotide pyrophosphatase phosphodiesterase 1 in the pathogenesis of insulin resistance and related abnormalities . In: Endocr. Rev. Band 29 , no. 1 , February 2008, p. 62–75 , doi : 10.1210 / er.2007-0004 , PMID 18199690 , PMC 2244935 (free full text).
- ↑ Nicola Abate; Manisha Chandalia; Rosa Di Paola; Daniel W Foster; Scott M Grundy; Vincenzo Trischitta: Mechanisms of disease: Ectonucleotide pyrophosphatase phosphodiesterase 1 as a 'gatekeeper' of insulin receptors . In: Nat Clin Pract Endocrinol Metab . tape 2 , no. December 12 , 2006, pp. 694-701 , doi : 10.1038 / ncpendmet0367 , PMID 17143316 .
