Autotaxin

Ectonucleotide pyrophosphatase/phosphodiesterase 2
Mouse autotaxin in complex with lipid. PDB 3nkr
Identifiers
Symbols	ENPP2 ; ATX; ATX-X; AUTOTAXIN; LysoPLD; NPP2; PD-IALPHA; PDNP2
External IDs	OMIM: 601060 MGI: 1321390 HomoloGene: 4526 ChEMBL: 3691 GeneCards: ENPP2 Gene
EC number	3.1.4.39
Gene ontology Molecular function • nucleic acid binding • phosphodiesterase I activity • nucleotide diphosphatase activity • lysophospholipase activity • scavenger receptor activity • calcium ion binding • transcription factor binding • zinc ion binding • hydrolase activity • polysaccharide binding • alkylglycerophosphoethanolamine phosphodiesterase activity Cellular component • extracellular space • plasma membrane • integral component of plasma membrane Biological process • phosphate-containing compound metabolic process • receptor-mediated endocytosis • movement of cell or subcellular component • chemotaxis • immune response • G-protein coupled receptor signaling pathway • phospholipid catabolic process • positive regulation of epithelial cell migration • regulation of cell migration • phosphatidylcholine catabolic process • regulation of angiogenesis • positive regulation of peptidyl-tyrosine phosphorylation • nucleic acid phosphodiester bond hydrolysis • positive regulation of lamellipodium morphogenesis Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5168	18606
Ensembl	ENSG00000136960	ENSMUSG00000022425
UniProt	Q13822	Q9R1E6
RefSeq (mRNA)	NM_001040092	NM_001136077
RefSeq (protein)	NP_001035181	NP_001129549
Location (UCSC)	Chr 8: 119.56 – 119.67 Mb	Chr 15: 54.84 – 54.92 Mb
PubMed search	[1]	[2]

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.

Function

Autotaxin, also known as ectonucleotide pyrophosphatase/phosphodiesterase 2 (NPP2 or ENPP2), is a secreted enzyme important for generating the lipid signaling molecule lysophosphatidic acid (LPA). Autotaxin has lysophospholipase D activity that converts lysophosphatidylcholine into LPA.

Autotaxin was originally identified as a tumor cell-motility-stimulating factor; later it was shown to be LPA (which signals through Lysophospholipid receptors), the lipid product of the reaction catalyzed by autotaxin, which is responsible for its effects on cell-proliferation.

The protein encoded by this gene functions as both a phosphodiesterase, which cleaves phosphodiester bonds at the 5' end of oligonucleotides, and as 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, 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 have been identified, but the full-length nature of only two transcript variants has been determined.

Structure

The crystal structures rat and mouse autotaxin have been solved. In each case, the apo structure have been solved along with product or inhibitor bound complexes. Both proteins consist of 4 domains, 2 N-terminal somatomedin-B-like (SMB) domains which may be involved in cell-surface localisation. The catalytic domain follows and contains a deep hydrophobic pocket in which the lipid substrate binds. At the C-terminus is the inactive nuclease domain which may function to aid protein stability.

See also

• Lysophosphatidic acid
• Lysophospholipid receptors
• Lipid signaling
• Phospholipases