ENPP1 Antibodies

Background

ENPP1 is a type II transmembrane glycoprotein, mainly existing on the cell membrane surface of tissues such as bones and liver. The protein encoded by this gene regulates extracellular pyrophosphate levels by hydrolyzing nucleotides such as ATP, a function that is crucial for bone mineralization balance and intracellular purine metabolism. Research has found that the deficiency of ENPP1 can lead to systemic arterial calcification in infancy and early childhood, and its overexpression is closely related to insulin resistance. This gene was first identified in 1994, and its crystal structure analysis revealed a unique dimer conformation and substrate recognition mechanism. As a key target for the treatment of pathological calcification, the functional research of ENPP1 continuously provides new therapeutic ideas for metabolic diseases and cardiovascular diseases.

Structure Function Application Advantage Our Products

Structure of ENPP1

ENPP1 is a type II transmembrane glycoprotein with a molecular weight of approximately 110 kDa. Its precise molecular weight may fluctuate depending on different splicing variants and the degree of glycosylation modification.

Species	Human	Mouse	Rat
Molecular Weight (kDa)	110-130	105-115	108-118
Primary Structural Differences	Extracellular catalytic domain, short intracellular tail	Catalytic regions highly homologous to humans	Conserved phosphodiesterase active site

This protein is composed of 925 amino acid residues, and its extracellular region contains a conserved phosphodiesterase catalytic domain that generates pyrophosphate by hydrolyzing substrates such as ATP. Its tertiary structure presents a unique homodimer morphology, and the two catalytic pockets are coordinated with each other through allosteric effects. Zinc ions close to the active center directly participate in the binding and activation of nucleotide substrates, while the adjacent substrate recognition ring precisely regulates the reaction specificity to ensure highly selective catalysis of extracellular nucleotides.

Fig. 1 ENPP1 structural domains.¹

Key structural properties of ENPP1:

Extracellular nucleotide pyrophosphate/phosphate dimerization catalytic domain
Allosteric regulatory pockets formed by the homodimer interface
Zinc ion synergistic metal catalytic center

Functions of ENPP1

The main function of ENPP1 is to regulate extracellular nucleotide metabolism and pyrophosphate balance. In addition, it is also involved in various physiological and pathological processes such as pathological calcification and insulin resistance.

Function	Description
Hydrolyze extracellular ATP	Decompose ATP into AMP and pyrophosphate to initiate the extracellular nucleotide metabolic cascade.
Inhibit pathological calcification	The abnormal deposition of hydroxyapatite is inhibited by generating pyrophosphate to maintain the mineral balance of soft tissues.
Regulate insulin sensitivity	Hydrolyzed ATP reduces the activation of P2Y receptors and affects insulin signaling pathway conduction.
Innate immune regulation	Affects inflammasome activation and immune cell response by regulating extracellular ATP levels.
Bone mineralization balance	Control the concentration of pyrophosphate in the bone microenvironment to ensure the normal bone mineralization process.

The catalytic efficiency of ENPP1 is strictly regulated by its homodimer conformation. Compared with other members of the phosphodiesterase family, its unique allosteric regulation mechanism endows it with higher selectivity for nucleotide substrates, which explains its specific functional performance in various tissues.

Applications of ENPP1 and ENPP1 Antibody in Literature

1. Wang, Songnan, et al. "ENPP1 is an innate immune checkpoint of the anticancer cGAMP–STING pathway in breast cancer." Proceedings of the National Academy of Sciences 120.52 (2023): e2313693120. https://doi.org/10.1073/pnas.2313693120

The article indicates that ENPP1 inhibits the STING pathway by degrading cGAMP, promoting breast cancer metastasis. Research has found that tumors with low expression of ENPP1 exhibit "thermal tumor" characteristics, and patients respond significantly to immunotherapy. ENPP1 can serve as a biomarker and potential target for immunotherapy.

2. An, Yu, et al. "Tumor Exosomal ENPP1 Hydrolyzes cGAMP to Inhibit cGAS‐STING Signaling." Advanced Science 11.20 (2024): 2308131. https://doi.org/10.1002/advs.202308131

Research has found that exosomes secreted by tumor cells also carry ENPP1. These exosomes effectively inhibit the cGAS-STING pathway within immune cells by degrading the extracellular messenger cGAMP, thereby weakening T cell infiltration and helping tumors achieve immune escape.

3. Mercurio, Stephanie A., et al. "ENPP1 deficiency: A clinical update on the relevance of individual variants using a locus‐specific patient database." Human Mutation 43.12 (2022): 1673-1705. https://doi.org/10.1002/humu.24477

Research has found that the deficiency of ENPP1 function can lead to ENPP1 deficiency. The clinical manifestations of this disease are diverse, which can cause serious complications such as cardiovascular calcification and hypophosphatemic rickets, and the severity varies significantly among individuals. Establishing an ENPP1 variation database is crucial for improving the diagnostic rate.

4. Zhou, Yang, et al. "T Cell‐Derived Apoptotic Extracellular Vesicles Hydrolyze cGAMP to Alleviate Radiation Enteritis via Surface Enzyme ENPP1." Advanced Science 11.31 (2024): 2401634. https://doi.org/10.1002/advs.202401634

Studies have found that extracellular vesicles (ApoEVs) derived from apoptotic T cells are rich in ENPP1 on their surfaces. This enzyme can hydrolyze the radiation-induced intracellular and extracellular messenger cGAMP, thereby inhibiting the cGAS-STING pro-inflammatory pathway and ultimately effectively alleviating radiation enteritis. This reveals a new mechanism of ENPP1 in inflammatory regulation.

5. Ferreira, Carlos R., Thomas O. Carpenter, and Demetrios T. Braddock. "ENPP1 in blood and bone: skeletal and soft tissue diseases induced by ENPP1 deficiency." Annual Review of Pathology: Mechanisms of Disease 19.1 (2024): 507-540. https://doi.org/10.1146/annurev-pathmechdis-051222-121126

Research has found that ENPP1 is a key enzyme for hydrolyzing extracellular ATP. Its functional defect can lead to a contradictory mineralization: it causes both vascular calcification in infants and young children and osteoporosis in adults. This pathological mechanism provides a new perspective for understanding mineralization disorders and promotes the development of therapies targeting ENPP1.

Creative Biolabs: ENPP1 Antibodies for Research

Creative Biolabs specializes in the production of high-quality ENPP1 antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

Custom ENPP1 Antibody Development: Tailor-made solutions to meet specific research requirements.
Bulk Production: Large-scale antibody manufacturing for industry partners.
Technical Support: Expert consultation for protocol optimization and troubleshooting.
Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our ENPP1 antibodies, custom preparations, or technical support, contact us at email.

Reference

Mercurio, Stephanie A., et al. "ENPP1 deficiency: A clinical update on the relevance of individual variants using a locus‐specific patient database." Human Mutation 43.12 (2022): 1673-1705. https://doi.org/10.1002/humu.24477