Autotaxin
Encyclopedia
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
.
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 receptor
s), 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.
rat autotaxin
and mouse autotaxin have been solved and deposited in the PDB
. 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 is aid protein stability.
For more information, see the QUIPS article at PDBe
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that in humans is encoded by the ENPP2 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
Autotaxin, also known as ectonucleotide pyrophosphatase/phosphodiesterase 2 (NPP2 or ENPP2), is a secreted enzyme important for generating the lipid signalingLipid signaling
Lipid signaling, broadly defined, refers to any biological signaling event involving a lipid messenger that binds a protein target, such as a receptor, kinase or phosphatase, which in turn mediate the effects of these lipids on specific cellular responses...
molecule lysophosphatidic acid
Lysophosphatidic acid
Lysophosphatidic acid is a phospholipid derivative that can act as a signaling molecule.-Function:LPA acts as a potent mitogen due to its activation of three high-affinity G-protein-coupled receptors called LPA1, LPA2, and LPA3...
(LPA). Autotaxin has lysophospholipase D
Phospholipase D
Phospholipase D is an enzyme which is located in the plasma membrane and catalyzes the hydrolysis of phosphatidylcholine to form phosphatidic acid , releasing the soluble choline headgroup into the cytosol...
activity that converts lysophosphatidylcholine
Phosphatidylcholine
Phosphatidylcholines are a class of phospholipids that incorporate choline as a headgroup.They are a major component of biological membranes and can be easily obtained from a variety of readily available sources such as egg yolk or soy beans from which they are mechanically extracted or chemically...
into LPA
Lysophosphatidic acid
Lysophosphatidic acid is a phospholipid derivative that can act as a signaling molecule.-Function:LPA acts as a potent mitogen due to its activation of three high-affinity G-protein-coupled receptors called LPA1, LPA2, and LPA3...
.
Autotaxin was originally identified as a tumor cell-motility-stimulating factor; later it was shown to be LPA
Lysophosphatidic acid
Lysophosphatidic acid is a phospholipid derivative that can act as a signaling molecule.-Function:LPA acts as a potent mitogen due to its activation of three high-affinity G-protein-coupled receptors called LPA1, LPA2, and LPA3...
(which signals through Lysophospholipid receptor
Lysophospholipid receptor
The lysophospholipid receptor group are members of the G protein-coupled receptor family of integral membrane proteins that are important for lipid signaling. In humans, there are eight LPL receptors, each encoded by a separate gene...
s), the lipid
Lipid signaling
Lipid signaling, broadly defined, refers to any biological signaling event involving a lipid messenger that binds a protein target, such as a receptor, kinase or phosphatase, which in turn mediate the effects of these lipids on specific cellular responses...
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
Phosphodiesterase
A phosphodiesterase is any enzyme that breaks a phosphodiester bond. Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below...
, which cleaves phosphodiester bonds at the 5' end of oligonucleotides, and as a phospholipase
Phospholipase
A phospholipase is an enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances. There are four major classes, termed A, B, C and D, distinguished by the type of reaction which they catalyze:*Phospholipase A...
, 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 structuresX-ray crystallography
X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...
rat autotaxin
and mouse autotaxin have been solved and deposited in the PDB
Protein Data Bank
The Protein Data Bank is a repository for the 3-D structural data of large biological molecules, such as proteins and nucleic acids....
. 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
Somatomedin B
Somatomedin B is a serum factor of unknown function, is a small cysteine-rich peptide, derived proteolytically from the N-terminus of the cell-substrate adhesion protein vitronectin...
-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 is aid protein stability.
For more information, see the QUIPS article at PDBe
See also
- Lysophosphatidic acidLysophosphatidic acidLysophosphatidic acid is a phospholipid derivative that can act as a signaling molecule.-Function:LPA acts as a potent mitogen due to its activation of three high-affinity G-protein-coupled receptors called LPA1, LPA2, and LPA3...
- Lysophospholipid receptorLysophospholipid receptorThe lysophospholipid receptor group are members of the G protein-coupled receptor family of integral membrane proteins that are important for lipid signaling. In humans, there are eight LPL receptors, each encoded by a separate gene...
s - Lipid signalingLipid signalingLipid signaling, broadly defined, refers to any biological signaling event involving a lipid messenger that binds a protein target, such as a receptor, kinase or phosphatase, which in turn mediate the effects of these lipids on specific cellular responses...
- PhospholipasePhospholipaseA phospholipase is an enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances. There are four major classes, termed A, B, C and D, distinguished by the type of reaction which they catalyze:*Phospholipase A...
s