ENPP2

Autotaxin, also known as ectonucleotide pyrophosphatase/phosphodiesterase family member 2 (E-NPP 2), is an enzyme that in humans is encoded by the ENPP2 gene.

== Structure == Autotaxin is a multi-domain protein with a modular architecture. From the N- to the C-terminus, it comprises two consecutive N-terminal cysteine-rich somatomedin B-like (SMB) domains, followed by a central catalytic phosphodiesterase (PDE) domain and a C-terminal nuclease-like (NUC) domain. The two SMB domains mediate protein–protein interactions, particularly through integrin-dependent binding to cell surfaces. The catalytic PDE domain, which is structurally related to alkaline phosphatases, harbors the enzyme's lysophospholipase D activity responsible for converting lysophosphatidylcholine into lysophosphatidic acid (LPA). The C-terminal NUC domain, although catalytically inactive, is structurally linked to the PDE domain and contributes to substrate binding and overall protein stability. A region at the extreme C-terminus, sometimes referred to as the MORFO domain, overlaps with the NUC region and has been associated with oligodendrocyte remodeling. Thus, the domain organization from N- to C-terminus is: SMB1–SMB2–PDE–NUC, with the MORFO domain often considered part of or overlapping with the NUC domain.