ENPP2

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]

Full Name

Ectonucleotide Pyrophosphatase/Phosphodiesterase 2

Research Area

Hydrolyzes lysophospholipids to produce the signaling molecule lysophosphatidic acid (LPA) in extracellular fluids (PubMed:15769751, PubMed:26371182, PubMed:27754931, PubMed:14500380, PubMed:12354767,).

Major substrate is lysophosphatidylcholine (PubMed:12176993, PubMed:27754931, PubMed:14500380).

Also can act on sphingosylphosphorylcholine producing sphingosine-1-phosphate, a modulator of cell motility (PubMed:14500380).

Can hydrolyze, in vitro, bis-pNPP, to some extent pNP-TMP, and barely ATP (PubMed:15769751, PubMed:12176993).

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 (PubMed:11559573).

Stimulates migration of melanoma cells, probably via a pertussis toxin-sensitive G protein (PubMed:1733949).

May have a role in induction of parturition (PubMed:12176993).

Possible involvement in cell proliferation and adipose tissue development (Probable). Tumor cell motility-stimulating factor (PubMed:1733949, PubMed:11559573).

Required for LPA production in activated platelets, cleaves the sn-1 lysophospholipids to generate sn-1 lysophosphatidic acids containing predominantly 18:2 and 20:4 fatty acids (PubMed:21393252).

Shows a preference for the sn-1 to the sn-2 isomer of 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) (PubMed:21393252).

Biological Process

Cell motility Source: UniProtKB
Chemotaxis Source: UniProtKB
Immune response Source: InterPro
Phosphatidylcholine catabolic process Source: UniProtKB
Phospholipid catabolic process Source: UniProtKB
Positive regulation of epithelial cell migration Source: UniProtKB
Positive regulation of lamellipodium morphogenesis Source: UniProtKB
Positive regulation of peptidyl-tyrosine phosphorylation Source: UniProtKB
Regulation of angiogenesis Source: InterPro
Regulation of cell migration Source: UniProtKB
Sphingolipid catabolic process Source: UniProtKB

Cellular Location

Secreted

PTM

N-glycosylation, but not furin-cleavage, plays a critical role on secretion and on lysoPLD activity.
The interdomain disulfide bond between Cys-414 and Cys-806 is essential for catalytic activity.