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Literature summary for 3.1.4.39 extracted from
- Murine and human autotaxin alpha, beta, gamma isoforms: Gene organization, tissue distribution and biochemical characterization (2008), J. Biol. Chem., 283, 7776-7789.
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| expressed in three different hosts, Sf9 insect cells and CHO cells, expressed in COS cells. ATXalpha, human, 915 amino acids, lacks exon 21, this particular isoform expresses the intron 12 in which a cleavage site is present, leading to a rapid catabolism of the isoform. ATXbeta, human, 863 amino acids, lacks exons 12 and 21. Cloning of the three isoforms alpha, beta, and gamma | Homo sapiens |
| expressed in two different hosts, Sf9 insect cells and chinese hamster ovary cells, expressed in COS cells, cloning of the three isoforms alpha, beta, and gamma | Mus musculus |
| expressed in two different hosts, Sf9 insect cells and CHO cells, expressed in COS cells | Mus musculus |
| expressed in two different hosts, Sf9 insect cells and CHO cells, expressed in COS cells | Homo sapiens |
| expressed in two different hosts, Sf9 insect cells and CHO cells, expressed in COS cells, cloning of the three isoforms alpha, beta, and gamma | Mus musculus |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| DELTA323-375 | murine autotaxin beta isoform, 863 amino acids total | Mus musculus |
| DELTA323-375 | murine autotaxin gamma isoform, 889 amino acids total | Mus musculus |
| DELTA592-617 | ATXalpha isoform, 915 amino acids total | Mus musculus |
| additional information | autotaxin gamma, share 100% identity with the splice variant NPP2gamma, except for the 25-amino acid insertion located between Glu593 and Glu594 | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| EDTA | All isoforms being strongly inhibited by increasing concentrations of EDTA, 100% inhibition for 100 mM of the chelating agent; All isoforms strongly inhibited by increasing concentrations of EDTA, 100% inhibition for 100 mM of the chelating agent | Homo sapiens |  |
| EDTA | All isoforms being strongly inhibited by increasing concentrations of EDTA, 100% inhibition for 100 mM of the chelating agent; All isoforms strongly inhibited by increasing concentrations of EDTA, 100% inhibition for 100 mM of the chelating agent; strongly inhibited by increasing concentrations of EDTA, 100% inhibition for 100 mM of the chelating agent | Mus musculus | |
| EGTA | All isoforms being strongly inhibited by increasing concentrations of EGTA, 100% inhibition for 100 mM of the chelating agent; All isoforms strongly inhibited by increasing concentrations of EGTA, 100% inhibition for 100 mM of the chelating agent | Homo sapiens | |
| EGTA | All isoforms being strongly inhibited by increasing concentrations of EGTA, 100% inhibition for 100 mM of the chelating agent; All isoforms strongly inhibited by increasing concentrations of EGTA, 100% inhibition for 100 mM of the chelating agent; strongly inhibited by increasing concentrations of EGTA, 100% inhibition for 100 mM of the chelating agent | Mus musculus | |
| Human serum albumin | could be a regulator of the circulating autotaxin. When the albumin is a fatty acid-free preparation, this slight inhibition disappears; could be a regulator of the circulating autotaxin. When the albumin is a fatty acid-free preparation, this slight inhibition disappears | Homo sapiens | |
| hypericin | inhibitor of autotaxin beta; new inhibitor of autotaxin beta | Homo sapiens | |
| hypericin | inhibitor of autotaxin beta; new inhibitor of autotaxin beta; new inhibitor of autotaxin beta | Mus musculus | |
| lysophosphatidic acid | reported as an inhibitor of its own production; reported as an inhibitor of its own production | Homo sapiens | |
| lysophosphatidic acid | reported as an inhibitor of its own production; reported as an inhibitor of its own production | Mus musculus | |
| Mg2+ | concentrations ranging from 0.1 to 1000 mM; concentrations ranging from 0.1 to 1000 mM | Homo sapiens | |
| Mg2+ | concentrations ranging from 0.1 to 1000 mM; manganese inhibits the catalytic activities, concentrations ranging from 0.1 to 1000 mM | Mus musculus | |
| murine serum albumin | could be a regulator of the circulating autotaxin. When the albumin is a fatty acid-free preparation, this slight inhibition disappears; could be a regulator of the circulating autotaxin. When the albumin is a fatty acid-free preparation, this slight inhibition disappears | Mus musculus | |
| Zn2+ | concentrations ranging from 0.1 to 1000 mM; concentrations ranging from 0.1 to 1000 mM | Homo sapiens | |
| Zn2+ | concentrations ranging from 0.1 to 1000 mM; zinc inhibits the catalytic activities, concentrations ranging from 0.1 to 1000 mM | Mus musculus | |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| extracellular | - |
Mus musculus | - |
- |
| extracellular | - |
Homo sapiens | - |
- |
| extracellular | in human, the highest levels of mRNA expression for the autotaxin gamma variant is detected in total brain, whereas significantly lower expression levels are observed in peripheral tissues | Homo sapiens | - |
- |
| extracellular | in mouse, the autotaxin gamma variant shows little variation in its distribution, the various levels of expression are apparently lower | Mus musculus | - |
- |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Ca2+ | check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM | Mus musculus | |
| Ca2+ | check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM | Homo sapiens | |
| Co2+ | check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM | Mus musculus | |
| Co2+ | check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM | Homo sapiens | |
| Mg2+ | check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM | Mus musculus | |
| Mg2+ | check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM | Homo sapiens | |
| Mn2+ | check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM | Mus musculus | |
| Mn2+ | check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM | Homo sapiens | |
| Ni2+ | check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM | Mus musculus | |
| Ni2+ | check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM | Homo sapiens | |
| Zn2+ | check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM | Mus musculus | |
| Zn2+ | check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM | Homo sapiens | |
Molecular Weight [Da]
| Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|
| 55000 | 66000 | analyzed by SDS-PAGE, two Western blots using either chicken antiautotaxin antibodies or anti-M2 FLAG antibodies, for the alpha isoform, a 5566-kDa double band is visible. Major band is detected at 66 kDa | Homo sapiens |
| 55000 | 66000 | analyzed by SDS-PAGE, two Western blots using either chicken antiautotaxin antibodies or anti-M2 FLAG antibodies, for the alpha isoform, a 5566-kDa double band is visible. Major band is detected at 66 kDa | Mus musculus |
| 90000 | - |
shorter versions of the beta isoform at 90 kDa | Mus musculus |
| 90000 | - |
shorter versions of the beta isoform at 90 kDa | Homo sapiens |
| 100000 | - |
full-length beta isoform | Homo sapiens |
| 100000 | - |
full-length gamma isoform | Mus musculus |
| 100000 | - |
full-length gamma isoform | Homo sapiens |
| 100000 | - |
the full-length beta isoform | Mus musculus |
| 105300 | - |
mass spectrometry analysis of purified human autotaxin alpha isoform reveals a large peak around 105300 Da. This could be due to the presence of glycan structures on the protein. The 66-kDa band disappears under nonreduced conditions and is not detected by mass spectrometry analysis of the native molecule. N-terminal sequencing analysis of the second band (66 kDa) gives the sequence KVAPKRR corresponding to position 341 of the protein. alpha isoform is indeed cleaved between Arg340 and Lys341 | Homo sapiens |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| lysophosphatidylcholine + H2O | Homo sapiens | - |
lysophosphatidic acid + choline | bioactive phospholipid regulating a wide range of cellular responses | ? | |
| lysophosphatidylcholine + H2O | Mus musculus | - |
lysophosphatidic acid + choline | lysophosphatidic acid is a bioactive phospholipid regulating a wide range of cellular responses | ? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
| Homo sapiens | Q13822 | gamma isoform | - |
| Mus musculus | - |
- |
- |
| Mus musculus | Q9R1E6 | gamma isoform | - |
| Mus musculus | Q9R1E6 | alpha isoform | - |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| glycoprotein | - |
Homo sapiens |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
- |
Mus musculus |
- |
Homo sapiens |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| adipose tissue | despite a lower expression, murine autotaxin alpha is detected in brain and adipose tissue | Mus musculus | - |
| brain | autotaxin beta is expressed in brain and peripheral tissues. Tissue distribution of the three isoforms alpha, beta, and gamma | Mus musculus | - |
| brain | autotaxin gamma is expressed in brain and peripheral tissues. Tissue distribution of the three isoforms alpha, beta, and gamma | Mus musculus | - |
| brain | cloning and tissue distribution of the three isoforms alpha, beta, and gamma. Human isoform total autotaxin mRNA expression, quantitative PCR is presented in 21 tissues | Homo sapiens | - |
| brain | tissue distribution of the three isoforms alpha, beta, and gamma | Mus musculus | - |
| central nervous system | high levels of expression are detected in peripheral tissues, lower expression levels are observed in the central nervous system. Autotaxin isoform alpha exhibits the lowest expression levels both in the central nervous system and peripheral tissues among the three isoforms. Tissue distribution of the three isoforms alpha, beta, and gamma | Homo sapiens | - |
Specific Activity [micromol/min/mg]
| Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
|---|---|---|---|
| additional information | - |
phosphodiesterase activity of recombinant autotaxin is measured by using p-nitrophenyl phenylphosphonate substrate | Mus musculus |
| additional information | - |
phosphodiesterase activity of recombinant autotaxin is measured by using p-nitrophenyl phenylphosphonate substrate | Homo sapiens |
| additional information | - |
phosphodiesterase activity of recombinant autotaxin is measured by using p-nitrophenyl-phenylphosphonate substrate | Mus musculus |
| additional information | - |
phosphodiesterase activity of recombinant autotaxin is measured by using para-nitrophenyl phenylphosphonate substrate | Mus musculus |
| 0.0051 | - |
Murine autotaxin gamma, p-nitrophenyl phenylphosphonate as a substrate, Vmax 1.8 nmol p-nitrophenyl/min | Mus musculus |
| 0.00847 | - |
human autotaxin alpha, p-nitrophenyl phenylphosphonate as a substrate, Vmax 0.67 nmol p-nitrophenyl/min | Homo sapiens |
| 0.0163 | - |
Murine autotaxin alpha, p-nitrophenyl phenylphosphonate as a substrate, Vmax 0.35 nanomol p-nitrophenyl/min | Mus musculus |
| 0.0919 | - |
Murine autotaxin beta, para-nitrophenyl phenylphosphonate as a substrate, Vmax 1.9 nmol para-nitrophenyl/min | Mus musculus |
| 0.0997 | - |
Human autotaxin gamma, p-nitrophenyl phenylphosphonate as a substrate, Vmax 1.6 nmol p-nitrophenyl/min | Homo sapiens |
| 0.135 | - |
Human autotaxin beta, p-nitrophenyl phenylphosphonate as a substrate, Vmax 1.9 nmol p-nitrophenyl/min | Homo sapiens |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| arachidoyl-lysophosphatidylcholine + H2O | - |
Mus musculus | 1-arachidoyl-sn-gycerol-3-phosphate + choline | - |
? | |
| arachidoyl-lysophosphatidylcholine + H2O | - |
Homo sapiens | 1-arachidoyl-sn-gycerol-3-phosphate + choline | - |
? | |
| behenoyl-lysophosphatidylcholine + H2O | - |
Mus musculus | 1-behenoyl-sn-gycerol-3-phosphate + choline | - |
? | |
| behenoyl-lysophosphatidylcholine + H2O | - |
Homo sapiens | 1-behenoyl-sn-gycerol-3-phosphate + choline | - |
? | |
| caproyl-lysophosphatidylcholine + H2O | - |
Mus musculus | 1-hexanoyl-sn-gycerol-3-phosphate + choline | - |
? | |
| capryl-lysophosphatidylcholine + H2O | - |
Mus musculus | 1-decanoyl-sn-gycerol-3-phosphate + choline | - |
? | |
| caprylyl-lysophosphatidylcholine + H2O | - |
Mus musculus | 1-octanoyl-sn-gycerol-3-phosphate + choline | - |
? | |
| decanoyl-lysophosphatidylcholine + H2O | - |
Homo sapiens | 1-decanoyl-sn-gycerol-3-phosphate + choline | - |
? | |
| decanoyl-lysophosphatidylcholine + H2O | - |
Mus musculus | 1-decanoyl-sn-gycerol-3-phosphate + choline | - |
? | |
| hexanoyl-lysophosphatidylcholine + H2O | - |
Homo sapiens | 1-hexanoyl-sn-gycerol-3-phosphate + choline | - |
? | |
| hexanoyl-lysophosphatidylcholine + H2O | - |
Mus musculus | 1-hexanoyl-sn-gycerol-3-phosphate + choline | - |
? | |
| lauroyl-lysophosphatidylcholine + H2O | - |
Mus musculus | 1-lauroyl-sn-gycerol-3-phosphate + choline | - |
? | |
| lauroyl-lysophosphatidylcholine + H2O | - |
Homo sapiens | 1-lauroyl-sn-gycerol-3-phosphate + choline | - |
? | |
| lysophosphatidylcholine + H2O | - |
Homo sapiens | lysophosphatidic acid + choline | bioactive phospholipid regulating a wide range of cellular responses | ? | |
| lysophosphatidylcholine + H2O | - |
Mus musculus | lysophosphatidic acid + choline | lysophosphatidic acid is a bioactive phospholipid regulating a wide range of cellular responses | ? | |
| additional information | no major differences in the respective specificities of the various isoforms, main substrate is lauroyl lysophosphatidylcholine | Mus musculus | ? | - |
? | |
| additional information | There are no major differences in the respective specificities of the various isoforms, main substrate is lauroyl lysophosphatidylcholine | Mus musculus | ? | - |
? | |
| additional information | There are no major differences in the respective specificities of the various isoforms, main substrate is lauroyl lysophosphatidylcholine | Homo sapiens | ? | - |
? | |
| additional information | There are no major differences in the respective specificities of the various isoforms, main substrate is lauroyl-lysophosphatidylcholine | Homo sapiens | ? | - |
? | |
| additional information | There are no major differences in the respective specificities of the various isoforms, main substrate is lauroyl-lysophosphatidylcholine | Mus musculus | ? | - |
? | |
| myristoyl-lysophosphatidylcholine + H2O | - |
Mus musculus | 1-myristoyl-sn-gycerol-3-phosphate + choline | - |
? | |
| myristoyl-lysophosphatidylcholine + H2O | - |
Homo sapiens | 1-myristoyl-sn-gycerol-3-phosphate + choline | - |
? | |
| octanoyl-lysophosphatidylcholine + H2O | - |
Homo sapiens | 1-octanoyl-sn-gycerol-3-phosphate + choline | - |
? | |
| octanoyl-lysophosphatidylcholine + H2O | - |
Mus musculus | 1-octanoyl-sn-gycerol-3-phosphate + choline | - |
? | |
| oleoyl-lysophosphatidylcholine + H2O | - |
Mus musculus | 1-oleoyl-sn-gycerol 3-phosphate + choline | - |
? | |
| oleoyl-lysophosphatidylcholine + H2O | - |
Homo sapiens | 1-oleoyl-sn-gycerol 3-phosphate + choline | - |
? | |
| p-nitrophenyl phenylphosphate + H2O | - |
Mus musculus | p-nitrophenol + phenylphosphate | - |
? | |
| palmitoyl-lysophosphatidylcholine + H2O | - |
Mus musculus | 1-palmitoyl-sn-gycerol-3-phosphate + choline | - |
? | |
| palmitoyl-lysophosphatidylcholine + H2O | - |
Homo sapiens | 1-palmitoyl-sn-gycerol-3-phosphate + choline | - |
? | |
| stearoyl-lysophosphatidylcholine + H2O | - |
Mus musculus | 1-stearoyl-sn-gycerol-3-phosphate + choline | - |
? | |
| stearoyl-lysophosphatidylcholine + H2O | - |
Homo sapiens | 1-stearoyl-sn-gycerol-3-phosphate + choline | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| ATXgamma | from human brain cDNA libary, 889 amino acids, lacks exon 12, new human variant, named autotaxin gamma | Homo sapiens |
| autotaxin | type II ectonucleotide pyrophosphate phosphodiesterase enzyme, member of the nucleotide pyrophosphatase/phosphodiesterase family of ectoenzymes (E-NPP) that hydrolyze phosphodiester bonds of various nucleotides and nucleotide derivatives | Mus musculus |
| autotaxin | type II ectonucleotide pyrophosphate phosphodiesterase enzyme, member of the nucleotide pyrophosphatase/phosphodiesterase family of ectoenzymes (E-NPP) that hydrolyze phosphodiester bonds of various nucleotides and nucleotide derivatives | Homo sapiens |
| autotaxin beta | - |
Mus musculus |
| autotaxin gamma | - |
Homo sapiens |
| hATX | - |
Homo sapiens |
| human autotaxin alpha | - |
Homo sapiens |
| human autotaxin beta | - |
Homo sapiens |
| lyso-PLD | - |
Mus musculus |
| lyso-PLD | - |
Homo sapiens |
| lysophospholipase D | - |
Mus musculus |
| lysophospholipase D | - |
Homo sapiens |
| mATX | - |
Mus musculus |
| mATXgamma | - |
Mus musculus |
| NPP2alpha | - |
Homo sapiens |
| NPP2alpha | - |
Mus musculus |
| NPP2gamma | - |
Homo sapiens |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 45 | 55 | murine isoform beta maximally active at 4555°C | Mus musculus |
| 45 | 55 | murine isoform gamma is maximally active at 4555°C | Mus musculus |
| 45 | 60 | purified isoforms show temperature dependence | Homo sapiens |
| 45 | 60 | purified isoforms show temperature dependence. beta isoform plateaus from 45 to 60°C, alpha isoform remains not much sensitive to temperature and little active | Homo sapiens |
Temperature Range [°C]
| Temperature Minimum [°C] | Temperature Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 5 | 60 | - |
Homo sapiens |
| 5 | 60 | alpha isoform has no obvious maximal temperature for activity | Mus musculus |
| 5 | 60 | purified isoforms show temperature dependence | Mus musculus |
Temperature Stability [°C]
| Temperature Stability Minimum [°C] | Temperature Stability Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 60 | - |
gamma isoform is still active at high temperature (60°C) | Homo sapiens |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 8 | - |
- |
Mus musculus |
| 8 | - |
gamma isoform presents a maximal activity at pH 8 | Homo sapiens |
| 9 | - |
alpha isoform is almost insensitive to pH, whereas the beta isoform presents a maximal activity at pH 9 | Homo sapiens |
pH Range
| pH Minimum | pH Maximum | Comment | Organism |
|---|---|---|---|
| 5.5 | 9.5 | purified isoforms show pH dependence | Mus musculus |
| 5.5 | 9.5 | purified isoforms show pH dependence | Homo sapiens |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 0.000016 | - |
reported as an inhibitor of its own production, incubating human autotaxin gamma with lysophosphatidic acid | Homo sapiens | lysophosphatidic acid | |
| 0.000017 | - |
reported as an inhibitor of its own production, incubating human autotaxin beta with lysophosphatidic acid | Homo sapiens | lysophosphatidic acid | |
| 0.000018 | - |
reported as an inhibitor of its own production, incubating murine autotaxin beta with lysophosphatidic acid | Mus musculus | lysophosphatidic acid | |
| 0.00002 | - |
reported as an inhibitor of its own production, incubating murine autotaxin gamma with lysophosphatidic acid | Mus musculus | lysophosphatidic acid | |
| 0.000038 | - |
reported as an inhibitor of its own production, incubating human autotaxin alpha with lysophosphatidic acid | Homo sapiens | lysophosphatidic acid | |
| 0.000038 | - |
reported as an inhibitor of its own production, incubating murine autotaxin alpha with lysophosphatidic acid | Mus musculus | lysophosphatidic acid | |
| 0.0016 | - |
tested on murine autotaxin alpha | Mus musculus | hypericin | |
| 0.0025 | - |
tested on human autotaxin gamma | Homo sapiens | hypericin | |
| 0.0026 | - |
tested on murine autotaxin gamma | Mus musculus | hypericin | |
| 0.0028 | - |
tested on murine autotaxin beta | Mus musculus | hypericin | |
| 0.0029 | - |
tested on human autotaxin beta | Homo sapiens | hypericin | |
| 0.0753 | - |
incubating human autotaxin beta with human serum albumin | Homo sapiens | Human serum albumin | |
| 0.1035 | - |
incubating human autotaxin gamma with human serum albumin | Homo sapiens | Human serum albumin | |
| 0.187 | - |
incubating murine autotaxin alpha with murine serum albumin | Mus musculus | murine serum albumin | |
| 0.251 | - |
incubating murine autotaxin gamma with murine serum albumin | Mus musculus | murine serum albumin | |
| 0.317 | - |
incubating murine autotaxin beta with murine serum albumin | Mus musculus | murine serum albumin |
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