ENPP2 Recombinant Protein

The protein encoded by this gene functions as both a phosphodiesterase, which cleaves phosphodiester bonds at the 5' end of oligonucleotides, and a phospholipase, which catalyzes production of lysophosphatidic acid (LPA) in extracellular fluids. LPA evokes growth factor-like responses including stimulation of cell proliferation and chemotaxis. This gene product stimulates the motility of tumor cells and has angiogenic properties, and its expression is upregulated in several kinds of carcinomas. The gene product is secreted and further processed to make the biologically active form. Several alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2008]

Function: Hydrolyzes lysophospholipids to produce lysophosphatidic acid (LPA) in extracellular fluids. Major substrate is lysophosphatidylcholine. Also can act on sphingosylphosphphorylcholine producing sphingosine-1-phosphate, a modulator of cell motility. Can hydrolyze, in vitro, bis-pNPP, to some extent pNP-TMP, and barely ATP. Involved in several motility-related processes such as angiogenesis and neurite outgrowth. Acts as an angiogenic factor by stimulating migration of smooth muscle cells and microtubule formation. Stimulates migration of melanoma cells, probably via a pertussis toxin-sensitive G protein. May have a role in induction of parturition. Possible involvement in cell proliferation and adipose tissue development. Tumor cell motility-stimulating factor. Ref.9 Ref.10 Ref.11 Ref.12

Catalytic activity: 1-alkyl-sn-glycero-3-phosphoethanolamine + H2O = 1-alkyl-sn-glycerol 3-phosphate + ethanolamine. Ref.12

Cofactor: Binds 2 zinc ions per subunit

By similarity.Binds 1 calcium ion per subunit

By similarity.

Enzyme regulation: Inhibited by lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P). Inhibited by EDTA and EGTA

Probable. Ref.4 Ref.5 Ref.12

Subcellular location: Secreted. Note: Secreted by most body fluids including serum and CSF. Also by adipocytes and numerous cancer cells. Ref.4

Tissue specificity: Predominantly expressed in brain, placenta, ovary, and small intestine. Expressed in a number of carcinomas such as hepatocellular and prostate carcinoma, neuroblastoma and non-small-cell lung cancer. Expressed in body fluids such as plasma, cerebral spinal fluid (CSF), saliva, follicular and amniotic fluids. Not detected in leukocytes. Isoform 1 is more highly expressed in peripheral tissues than in the central nervous system (CNS). Adipocytes only express isoform 1. Isoform 3 is more highly expressed in the brain than in peripheral tissues. Ref.2 Ref.3 Ref.5

Induction: Up-regulated in massively obese subjects with glucose intolerance, and during adipogenesis. Ref.4 Ref.5 Ref.11 Ref.12

Post-translational modification: N-glycosylation, but not furin-cleavage, plays a critical role on secretion and on lysoPLD activity

By similarity.It has been suggested that the active SMB domain may be permitted considerable disulfide bond heterogeneity or variability, thus two alternate disulfide patterns based on 3D structures are described with 1 disulfide bond conserved in both.

Sequence similarities: Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.Contains 2 SMB (somatomedin-B) domains.

Biophysicochemical propertiesKinetic parameters:KM=0.5 mM for 16:0-LPC (at pH 8.5) Ref.5 Ref.8KM=5.5 mM for pNP-TMP (at pH 8.5)KM=11.3 mM for pNppp (isoform 1)KM=5.7 mM for pNppp (isoform 2)KM=19.8 mM for pNppp (isoform 3)Vmax=1.9 nmol/min/µg enzyme with pNppp as substrate (isoform 1)Vmax=0.67 nmol/min/µg enzyme with pNppp as substrate (isoform 2)Vmax=1.6 nmol/min/µg enzyme with pNppp as substrate (isoform 3)pH dependence:Optimum pH is 9.0 (isoform 1), 8.0 (isoform 3). Isoform 1 is less sensitive to pH. Isoform 1, isoform 2 and isoform 3 all retain some activity at pH 9.5.Temperature dependence:Isoform 1 and isoform 3 are active from 45 to 60 degrees Celsius.