Autotaxin (ENPP2)

ENPP2 (Ectonucleotide pyrophosphatase/phosphodiesterase family member 2), also referred as Autotaxin, is a secreted enzyme encoded by the ENPP2 gene. This gene product stimulates the motility of tumor cells, has angiogenic properties, and its expression is upregulated in several kinds of carcinomas. The Autotaxin protein is important for generating the lipid signaling molecule lysophosphatidic acid (LPA), which is a potent mitogen, which facilitates cell proliferation and migration, neurite retraction, platelet aggregation, smooth muscle contraction, actin stress formation and cytokine and chemokine secretion. ATX has been found to catalyze the formation of cyclic phosphatidic acid (cPA), which have antitumor role by antimitogenic regulation of cell cycle, inhibition of cancer invasion and metastasis. LPA receptors and ATX are upregulated in numerous cancer cell types and show expression patterns that correlate with tumor cell invasiveness. Thus, Autotaxin has recently emerged as an attractive target for the development of anti-cancer chemotherapeutics. In addition, Serum ATX activity was found to be enhanced in relation to hepatic fibrosis in chronic liver disease due to hepatitis virus C infection.

Autotaxin (ENPP2) Related Areas

Enzyme>>Lipid Metabolism Enzymes>>Autotaxin/ENPP2

Lipid Metabolism>>Lipid Metabolism Enzymes>>Autotaxin/ENPP2

Autotaxin (ENPP2) Alternative Names

ENPP2, ATX, ATX-X, AUTOTAXIN, FLJ26803, LysoPLD, NPP2, PD-IALPHA, PDNP2 [Homo sapiens]

Enpp2, ATX, autotaxin, Npps2, PD-Ialpha, Pdnp2 [Mus musculus]

Summaries for Autotaxin (ENPP2)

Entrez Gene summary for ENPP2:

The protein encoded by this ENPP2 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. Autotaxin stimulates the motility of tumor cells and has angiogenic properties, and its expression is upregulated in several kinds of carcinomas. Autotaxin 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]

Wikipedia summary for Autotaxin:

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.

Human Autotaxin (ENPP2) Protein General Information

 

• Protein names: Autotaxin
• Sequence length: 863 AA.
• Catalytic activity: 1-alkyl-sn-glycero-3-phosphoethanolamine + H2O = 1-alkyl-sn-glycerol 3-phosphate + ethanolamine.
• Cofactor: Autotaxin binds 2 zinc ions per subunit. Autotaxin binds 1 calcium ion per subunit
• Enzyme regulation: Autotaxin is inhibited by lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P). Inhibited by EDTA and EGTA
• Sequence similarities: Autotaxin belongs to the nucleotide pyrophosphatase/phosphodiesterase family. Autotaxin contains 2 SMB (somatomedin-B) domains.
• Post-translational modification: N-glycosylation, but not furin-cleavage, plays a critical role on secretion and on lysoPLD activity.
  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.
• Induction: Autotaxin is up-regulated in massively obese subjects with glucose intolerance, and during adipogenesis.
• Subcellular location: Secreted. Note: Secreted by most body fluids including serum and CSF. Also by adipocytes and numerous cancer cells.
• Tissue specificity: Autotaxin is predominantly expressed in brain, placenta, ovary, and small intestine. Autotaxin is expressed in a number of carcinomas such as hepatocellular and prostate carcinoma, neuroblastoma and non-small-cell lung cancer. Autotaxin is 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). Autotaxin adipocytes only express isoform 1. Isoform 3 is more highly expressed in the brain than in peripheral tissues.
• Biophysicochemical properties: Kinetic parameters:
  KM=0.5 mM for 16:0-LPC (at pH 8.5)
  KM=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.

General information above from UniProt

Function for Autotaxin (ENPP2) Protein

UniProtKB:

Autotaxin hydrolyzes lysophospholipids to produce lysophosphatidic acid (LPA) in extracellular fluids. Major substrate is lysophosphatidylcholine. Autotaxin also can act on sphingosylphosphphorylcholine producing sphingosine-1-phosphate, a modulator of cell motility. Autotaxin 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. Autotaxin acts as an angiogenic factor by stimulating migration of smooth muscle cells and microtubule formation. Autotaxin stimulates migration of melanoma cells, probably via a pertussis toxin-sensitive G protein. Autotaxin may have a role in induction of parturition. Autotaxin is possible involvement in cell proliferation and adipose tissue development. Autotaxin is tumor cell motility-stimulating factor.

Genatlas:

• phosphodiesterase I, brain type/nucleotide pyrophosphatase activity
• Autotaxin is type II ectonucleotide pyrophosphate phosphodiesterase enzymehaving a lysophospholipase D activity
• Autotaxin augments invasive and metastatic potential of tumor cells
• Autotaxin plays a critical role in vascular development
• augment has a lysophospholipase D activity
• augment plays a significant role in initiating and sustaining tumor metastasis