ENPP2 Human
Description
Molecular Structure and Biochemical Properties
ENPP2 is a 94–101 kDa protein with distinct structural domains:
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N-terminal intracellular domain
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Transmembrane domain
The enzyme exhibits optimal activity at neutral pH (7.5–8.0) and requires Zn²⁺/Mg²⁺ cofactors . Unlike other ENPP family members, ENPP2 shows weak nucleotide hydrolysis but strong lysoPLD activity (>1,000-fold higher) .
Biological Functions
ENPP2 regulates multiple pathways through LPA production:
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Cell motility: Enhances tumor invasion via LPA-mediated activation of Rho GTPases
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Angiogenesis: Promotes endothelial cell migration (EC50 = 0.5–1 nM)
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Neural development: Essential for embryonic neural tube formation
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Inflammation: Upregulates CXCL1 chemokine in atherosclerosis models (2.3-fold increase vs controls)
Key enzymatic reaction:
This reaction shows substrate preference for sn-1 acyl-LPC over sn-2 variants (Kₐ = 120 μM vs 450 μM) .
Cancer
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Hepatocellular carcinoma (HCC): High ENPP2 expression correlates with:
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Breast cancer: Serum ENPP2 levels >2 ng/mL predict poor chemotherapy response (AUC = 0.81)
Cardiovascular Disease
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Atherosclerosis: Endothelial-specific ENPP2 knockout reduces:
Metabolic Disorders
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Obesity: Plasma LPA18:2 levels correlate with body mass index (r = 0.62, p < 0.001)
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Diabetes: ENPP2 activity increases 3.1-fold in diabetic nephropathy patients
Therapeutic Targeting
Current inhibitors under investigation:
| Compound Type | Example | IC₅₀ | Clinical Phase |
|---|---|---|---|
| Small molecule | HA155 | 8 nM | Preclinical |
| Antibody | PAT-048 | 0.2 μg/mL | Phase I |
| Natural product | Sanguinarine | 1.2 μM | Preclinical |
In mouse xenograft models, HA155 reduces tumor volume by 78% (p < 0.01) compared to controls .
Research Applications
Recombinant human ENPP2 (e.g., Catalog #5255-EN) is used for:
Product Specs
Ectonucleotide Pyrophosphatase-2 (ENPP2), a member of the ectonucleotide pyrophosphatase family, plays a crucial role in nucleotide metabolism and inflammatory responses. This enzyme hydrolyzes the phosphodiester bond in triphosphate nucleotides, producing pyrophosphate. Unlike ENPP-1 and ENPP-3, ENPP2 exhibits weak nucleotide activity but possesses lysophospholipase D activity, enabling the formation of lysophosphatidic acid (LPA) and choline from lysophosphatidylcholine. Notably, both ENPP-2 and LPA are implicated in inflammatory diseases such as arthritis and asthma.
Recombinant human ENPP2, expressed in HEK293 cells, is a single, glycosylated polypeptide chain with a molecular weight of 94.9 kDa. The protein consists of 825 amino acids (residues 49-863) and includes a C-terminal 6-histidine tag for purification purposes. Purification is achieved using proprietary chromatographic techniques.
Sterile, colorless solution.
The ENPP2 solution is provided at a concentration of 0.25 mg/ml in phosphate-buffered saline (PBS) at pH 7.4 with 10% glycerol.
For short-term storage (up to 2-4 weeks), the ENPP2 solution should be stored at 4°C. For long-term storage, it is recommended to freeze the solution at -20°C. The addition of a carrier protein (0.1% HSA or BSA) is advisable for extended storage periods. To maintain protein integrity, avoid repeated freeze-thaw cycles.
The purity of ENPP2 is determined to be greater than 90% using SDS-PAGE analysis.
The specific activity of ENPP2, measured as the amount of enzyme that hydrolyzes 1 nanomole of bis(p-nitrophenyl) phosphate per minute at pH 8.7 and 37°C, is greater than 15,000 units/mg.
ENPP2, ATX, PDNP2, ATX-X, NPP2, PD-IALPHA, Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 isoform 2, ectonucleotide pyrophosphatase/phosphodiesterase 2, ENPP2, E-NPP 2, AUTOTAXIN, Extracellular lysophospholipase D, LysoPLD.
HEK293 Cells.
DGSMDSPWTN ISGSCKGRCF ELQEAGPPDC RCDNLCKSYT SCCHDFDELC LKTARGWECT KDRCGEVRNE ENACHCSEDC LARGDCCTNY QVVCKGESHW VDDDCEEIKA AECPAGFVRP PLIIFSVDGF RASYMKKGSK VMPNIEKLRS CGTHSPYMRP VYPTKTFPNL YTLATGLYPE SHGIVGNSMY DPVFDATFHL RGREKFNHRW WGGQPLWITA TKQGVKAGTF FWSVVIPHER RILTILQWLT LPDHERPSVY AFYSEQPDFS GHKYGPFGPE MTNPLREIDK IVGQLMDGLK QLKLHRCVNV IFVGDHGMED VTCDRTEFLS NYLTNVDDIT LVPGTLGRIR SKFSNNAKYD PKAIIANLTC KKPDQHFKPY LKQHLPKRLH YANNRRIEDI HLLVERRWHV ARKPLDVYKK PSGKCFFQGD HGFDNKVNSM QTVFVGYGST FKYKTKVPPF ENIELYNVMC DLLGLKPAPN NGTHGSLNHL LRTNTFRPTM PEEVTRPNYP GIMYLQSDFD LGCTCDDKVE PKNKLDELNK RLHTKGSTEE RHLLYGRPAV LYRTRYDILY HTDFESGYSE IFLMPLWTSY TVSKQAEVSS VPDHLTSCVR PDVRVSPSFS QNCLAYKNDK QMSYGFLFPP YLSSSPEAKY DAFLVTNMVP MYPAFKRVWN YFQRVLVKKY ASERNGVNVI SGPIFDYDYD GLHDTEDKIK QYVEGSSIPV PTHYYSIITS CLDFTQPADK CDGPLSVSSF ILPHRPDNEE SCNSSEDESK WVEELMKMHT ARVRDIEHLT SLDFFRKTSR SYPEILTLKT YLHTYESEIH HHHHH
Product Science Overview
ENPP2 is a secreted enzyme that primarily functions as a lysophospholipase D (lysoPLD). It hydrolyzes lysophosphatidylcholine (LPC) to produce lysophosphatidic acid (LPA), a bioactive lipid mediator involved in cell proliferation, survival, and migration . The enzyme is synthesized as a zymogen and undergoes maturation to become biologically active. It consists of several domains:
ENPP2 is constitutively active and is regulated by a negative feedback loop involving LPA . It is secreted primarily by adipose tissue and endothelial cells and can be found in various biological fluids, including blood, cerebrospinal fluid, and saliva . The enzyme’s activity is crucial for the production of LPA, which evokes growth factor-like responses, including stimulation of cell proliferation and chemotaxis .
ENPP2 has been implicated in several pathological conditions. Its expression is upregulated in various carcinomas, and it stimulates the motility of tumor cells, contributing to cancer progression and metastasis . Additionally, ENPP2 is associated with diseases such as autoimmune pancreatitis and teratocarcinoma .
Recombinant human ENPP2 is produced in HEK293 cells and is a single, glycosylated polypeptide chain containing 825 amino acids. It has a molecular mass of approximately 94.9 kDa and is purified using proprietary chromatographic techniques . This recombinant form is used in research to study the enzyme’s function and its role in various diseases.
