ENPP1

Official Full Name

ectonucleotide pyrophosphatase/phosphodiesterase 1

Organism

Homo sapiens

Gene ID

5167

Background

This gene is a member of the ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP) family. The encoded protein is a type II transmembrane glycoprotein comprising two identical disulfide-bonded subunits. This protein has broad specificity and cleaves a variety of substrates, including phosphodiester bonds of nucleotides and nucleotide sugars and pyrophosphate bonds of nucleotides and nucleotide sugars. This protein may function to hydrolyze nucleoside 5' triphosphates to their corresponding monophosphates and may also hydrolyze diadenosine polyphosphates. Mutations in this gene have been associated with 'idiopathic' infantile arterial calcification, ossification of the posterior longitudinal ligament of the spine (OPLL), and insulin resistance. [provided by RefSeq, Jul 2008]

Synonyms

M6S1; NPP1; NPPS; PC-1; PCA1; ARHR2; COLED; PDNP1

Cat.No.	Product Name	Price
CSC-DC004946	Panoply™ Human ENPP1 Knockdown Stable Cell Line	Inquiry
CSC-SC004946	Panoply™ Human ENPP1 Over-expressing Stable Cell Line	Inquiry

Cat.No.	Product Name	Price
AD05484Z	Human ENPP1 adenoviral particles	Inquiry
LV11757L	human ENPP1 (NM_006208) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH033995	shRNA set against Rat Enpp1(NM_053535.1)	Inquiry
SHH034019	shRNA set against Mouse Enpp1(NM_008813.3)	Inquiry
SHH285913	shRNA set against Human ENPP1 (NM_006208.2)	Inquiry
SHH285917	shRNA set against Mouse ENPP1 (NM_008813.3)	Inquiry
SHH285921	shRNA set against Rat ENPP1 (NM_053535.1)	Inquiry
SHW009164	shRNA set against Danio rerio ENPP1 (NM_001030168)	Inquiry

Cat.No.	Product Name	Price
CDFH005927	Human ENPP1 cDNA Clone(NM_006208.2)	Inquiry
CDFL004143	Mouse Enpp1 cDNA Clone(NM_008813.3)	Inquiry
CDFR013259	Rat Enpp1 cDNA Clone(NM_053535.1)	Inquiry
MiUTR1M-04402	ENPP1 miRNA 3'UTR clone	Inquiry
MiUTR1R-01733	ENPP1 miRNA 3'UTR clone	Inquiry
CDCB170639	Danio rerio ENPP1 ORF Clone (NM_001030168)	Inquiry
CDCB180702	Rabbit ENPP1 ORF clone (NM_001082742.2)	Inquiry
CDCR246175	Mouse Enpp1 ORF Clone(NM_008813.3)	Inquiry
CDCR292266	Human ENPP1 ORF Clone(NM_006208.2)	Inquiry
CDCR380176	Rat Enpp1 ORF Clone(NM_053535.1)	Inquiry

Detailed Information

Exonucleotide pyrophosphotase/phosphodiesterase 1 (ENPP1) is a type 2 transmembrane glycoprotein located in the cell membrane and endoplasmic reticulum that decomposes sugar-phosphate, phosphorus sulphate, pyrophosphate, and phosphodiesterase complexes. ENPP1 is named for its ability to hydrolyze the 5' phosphatase binding band of nucleotides. The product of the ENPP1 gene affects insulin receptor signaling by inhibiting autophosphorylation of the insulin receptor beta subunit, so it is called the "gateway" of the insulin signaling pathway.

ENPP1 Function

Studies have shown that ENPP1 inhibits bone formation by producing pyrophosphate, which regulates the metabolism of bone and cartilage tissue. Therefore, the mouse model (KO) that knocks out ENPP1 and those who lack ENPP1 have heterotopic ossification of the spine, aorta, and other tissues, which affects survival. The amount of expression of ENPP1 is determined by the gene and is also regulated by other factors. Glucocorticoids and other substances that upregulate AMP can upregulate ENPP1, such as growth factors and cytokines including interleukin-1 and TNF-α. ENPP1 is widely present in the human body and is present in the main target organs of the three major insulins including liver, skeletal muscle and adipose tissue. It is also present in the heart, brain, islets, placenta, kidney, lung, salivary gland, epididymis, vas deferens, chondrocytes, Lymphocytes as well as skin fibroblasts.

Watanabe et al. showed that in the case of phosphate overload, the expression of Klotho, an anti-aging factor, requires ENPP1. This suggests that Enpp1 plays a crucial role in regulating senescence through Klotho expression under phosphate overload conditions.

Figure 1. A schematic showing regulation of aging phenotypes under phosphate overload. (Watanabe, et al. 2017)

ENPP1 Expression and Insulin Resistance

ENPP1 can cause a decrease in insulin receptor function. ENPP1 is elevated in muscle, fat, fibroblasts and other tissues in insulin resistant patients. The study found that when different tissue cells ENPP1 overexpressed, its sensitivity to insulin decreased, suggesting that when ENPP1 is increased, insulin receptor function is decreased. Moreover, ENPP1 is increased in insulin resistance patients with a decrease in insulin receptor tyrosine phosphorylation.

The researchers studied the two major insulin target tissues, muscle and fat, in non-obese non-diabetic health research subjects. In vitro and in vivo model studies have found that elevated levels of ENPP1 are associated with insulin resistance, suggesting that ENPP1 in human skeletal muscle and adipose tissue inhibits insulin activity and affects insulin receptor tyrosine kinase activity. Health Research Subjects Increased ENPP1 in insulin target organs is likely to cause insulin resistance. Transgenic animals overexpressing human ENPP1 overexpress ENPP1 in both muscle and liver, and also exhibit long-term insulin resistance.

ENPP1 and PCOS

The basic pathological changes of polycystic ovary syndrome (PCOS) are chronic persistent anovulation and hyperandrogenism. PCOS insulin resistance is rarely caused by a decrease in the number of insulin receptors and binding capacity, which is mostly due to receptor and post-receptor defects. Insulin receptors and post-receptor signaling abnormalities are the main molecular mechanisms of PCOS insulin resistance. The study found that the expression of ENPP1 mRNA in granulosa cells of patients with PCOS was higher than that of the control group, but the expression of ENPP1 in the ovary was not proportional to the serum insulin level. It can be speculated that ENPP1 may play a role in the regulation of insulin receptors and lesions in the ovary.

References:

Watanabe, R., Fujita, N., Sato, Y., Kobayashi, T., Morita, M., & Oike, T., et al. (2017). Enpp1 is an anti-aging factor that regulates klotho under phosphate overload conditions. Scientific Reports, 7(1), 7786.
Wen, M. L., Doucet, M., Stadel, R., Huang, D., Weber, K. L., & Kominsky, S. L. (2013). Enpp1: a potential facilitator of breast cancer bone metastasis. Plos One, 8(7), e66752.
Dimatteo, C., Marucci, A., Palazzo, A., Cisternino, C., Marsano, R. M., & Trischitta, V., et al. (2013). Role of somatomedin-b-like domains on enpp1 inhibition of insulin signaling. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1833(3), 552-558.

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