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Information on EC 3.1.4.39 - alkylglycerophosphoethanolamine phosphodiesterase and Organism(s) Mus musculus and UniProt Accession Q9R1E6

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EC Tree
IUBMB Comments
Also acts on acyl and choline analogues.
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Select one or more organisms in this record: ?
This record set is specific for:
Mus musculus
UNIPROT: Q9R1E6
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Word Map
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
autotaxin (atx), lysophospholipase d, enpp2, ectonucleotide pyrophosphatase/phosphodiesterase, gdpd3, ectonucleotide pyrophosphatase/phosphodiesterase 2, heminecrolysin, pd-ialpha/atx, atx/lysopld, lyso-pld, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
lysophospholipase D
-
mATXgamma
-
NPP2alpha
-
ATX/lysoPLD
-
-
autotaxin
autotaxin (ATX)
-
-
autotaxin beta
-
-
ecto-nucleotide pyrophosphatase/phosphodiesterase-2
-
-
ectonucleotide pyrophosphatase phosphodiesterase-2
-
-
GDE1
-
-
glycerophosphodiesterase
-
-
lyso-PLD
-
-
lysophospholipase D
lysoPLD
mATX
-
-
NPP-2
-
-
nucleotide pyrophosphatase-phosphodiesterase
-
belongs to the nucleotide pyrophosphatase (NPP) family of ectoenzymes and exoenzymes
phosphodiesterase, alkylglycerophosphorylethanolamine
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of phosphoric ester
PATHWAY SOURCE
PATHWAYS
-
-, -, -
SYSTEMATIC NAME
IUBMB Comments
1-alkyl-sn-glycero-3-phosphoethanolamine ethanolaminehydrolase
Also acts on acyl and choline analogues.
CAS REGISTRY NUMBER
COMMENTARY hide
62213-15-4
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
arachidoyl-lysophosphatidylcholine + H2O
1-arachidoyl-sn-gycerol-3-phosphate + choline
show the reaction diagram
-
-
-
?
behenoyl-lysophosphatidylcholine + H2O
1-behenoyl-sn-gycerol-3-phosphate + choline
show the reaction diagram
-
-
-
?
decanoyl-lysophosphatidylcholine + H2O
1-decanoyl-sn-gycerol-3-phosphate + choline
show the reaction diagram
-
-
-
?
hexanoyl-lysophosphatidylcholine + H2O
1-hexanoyl-sn-gycerol-3-phosphate + choline
show the reaction diagram
-
-
-
?
lauroyl-lysophosphatidylcholine + H2O
1-lauroyl-sn-gycerol-3-phosphate + choline
show the reaction diagram
-
-
-
?
lysophosphatidylcholine + H2O
lysophosphatidic acid + choline
show the reaction diagram
-
lysophosphatidic acid is a bioactive phospholipid regulating a wide range of cellular responses
-
?
myristoyl-lysophosphatidylcholine + H2O
1-myristoyl-sn-gycerol-3-phosphate + choline
show the reaction diagram
-
-
-
?
octanoyl-lysophosphatidylcholine + H2O
1-octanoyl-sn-gycerol-3-phosphate + choline
show the reaction diagram
-
-
-
?
oleoyl-lysophosphatidylcholine + H2O
1-oleoyl-sn-gycerol 3-phosphate + choline
show the reaction diagram
-
-
-
?
p-nitrophenyl phenylphosphate + H2O
p-nitrophenol + phenylphosphate
show the reaction diagram
-
-
-
?
palmitoyl-lysophosphatidylcholine + H2O
1-palmitoyl-sn-gycerol-3-phosphate + choline
show the reaction diagram
-
-
-
?
stearoyl-lysophosphatidylcholine + H2O
1-stearoyl-sn-gycerol-3-phosphate + choline
show the reaction diagram
-
-
-
?
1-alkyl-sn-glycero-3-phosphocholine + H2O
1-alkyl-sn-glycerol 3-phosphate + choline
show the reaction diagram
-
-
-
-
?
1-alkyl-sn-glycero-3-phosphoethanolamine + H2O
1-alkyl-sn-glycerol 3-phosphate + ethanolamine
show the reaction diagram
1-O-alkyl-sn-glycero-3-phosphocholine + H2O
1-O-alkyl-sn-glycerol 3-phosphate + choline
show the reaction diagram
i.e. lyso-platelet-activating factor
-
-
?
arachidoyl-lysophosphatidylcholine + H2O
1-arachidoyl-sn-gycerol-3-phosphate + choline
show the reaction diagram
-
-
-
?
behenoyl-lysophosphatidylcholine + H2O
1-behenoyl-sn-gycerol-3-phosphate + choline
show the reaction diagram
-
-
-
?
bis(4-nitrophenyl)phosphate + H2O
?
show the reaction diagram
-
-
-
-
?
caproyl-lysophosphatidylcholine + H2O
1-hexanoyl-sn-gycerol-3-phosphate + choline
show the reaction diagram
-
-
-
?
capryl-lysophosphatidylcholine + H2O
1-decanoyl-sn-gycerol-3-phosphate + choline
show the reaction diagram
-
-
-
?
caprylyl-lysophosphatidylcholine + H2O
1-octanoyl-sn-gycerol-3-phosphate + choline
show the reaction diagram
-
-
-
?
FS-3 + H2O
?
show the reaction diagram
-
-
-
-
?
lauroyl-lysophosphatidylcholine + H2O
1-lauroyl-sn-gycerol-3-phosphate + choline
show the reaction diagram
-
-
-
?
lyso-phosphatidylcholine + H2O
lyso-phosphatidic acid + choline
show the reaction diagram
-
-
central in some key metabolic deregulations
-
?
lysophosphatidyl choline + H2O
lysophosphatidic acid + choline
show the reaction diagram
lysophosphatidyl ethanolamine + H2O
lysophosphatidic acid + ethanolamine
show the reaction diagram
-
-
-
?
lysophosphatidylcholine + H2O
lysophosphatidic acid + choline
show the reaction diagram
myristoyl-lysophosphatidylcholine + H2O
1-myristoyl-sn-gycerol-3-phosphate + choline
show the reaction diagram
-
-
-
?
N-arachidonoyl-lysophosphatidylethanolamine + H2O
lysophosphatidic acid + N-arachidonoyl-ethanolamine
show the reaction diagram
-
-
-
?
N-oleoyl-lysophosphatidylethanolamine + H2O
lysophosphatidic acid + N-oleoyl-ethanolamine
show the reaction diagram
-
-
-
?
N-palmitoyl-lysophosphatidylethanolamine + H2O
lysophosphatidic acid + N-palmitoyl-ethanolamine
show the reaction diagram
-
-
-
?
N-palmitoyl-lysoplasmenylethanolamine + H2O
lysoplasmenic acid + N-palmitoyl-ethanolamine
show the reaction diagram
-
-
-
?
N-palmitoyllysophosphatidylethanolamine + H2O
lysophosphatidic acid + N-palmitoylethanolamine
show the reaction diagram
-
-
-
?
oleoyl-lysophosphatidylcholine + H2O
1-oleoyl-sn-gycerol 3-phosphate + choline
show the reaction diagram
-
-
-
?
palmitoyl-lysophosphatidylcholine + H2O
1-palmitoyl-sn-gycerol-3-phosphate + choline
show the reaction diagram
-
-
-
?
sphingosylphosphorylcholine + H2O
sphingosine 1-phosphate + choline
show the reaction diagram
-
-
bioactive lysophospholipid, in vitro
-
?
stearoyl-lysophosphatidylcholine + H2O
1-stearoyl-sn-gycerol-3-phosphate + choline
show the reaction diagram
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
lysophosphatidylcholine + H2O
lysophosphatidic acid + choline
show the reaction diagram
-
lysophosphatidic acid is a bioactive phospholipid regulating a wide range of cellular responses
-
?
1-alkyl-sn-glycero-3-phosphocholine + H2O
1-alkyl-sn-glycerol 3-phosphate + choline
show the reaction diagram
-
-
-
-
?
1-alkyl-sn-glycero-3-phosphoethanolamine + H2O
1-alkyl-sn-glycerol 3-phosphate + ethanolamine
show the reaction diagram
-
-
-
-
r
lysophosphatidylcholine + H2O
lysophosphatidic acid + choline
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM
Co2+
check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM
Mn2+
check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM
Ni2+
check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM
Co2+
check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM
Mn2+
check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM
Ni2+
check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM
additional information
-
the catalytic domain shows a characteristic bimetallic active site
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(5Z)-2-(4-ethylpiperazin-1-yl)-5-(4-fluorobenzylidene)-1,3-thiazol-4(5H)-one
93.8% inhibition at 0.01 mM
(5Z)-2-(azepan-1-yl)-5-(4-propoxybenzylidene)-1,3-thiazol-4(5H)-one
96.6% inhibition at 0.01 mM
(5Z)-2-(morpholin-4-yl)-5-[4-(pentyloxy)benzylidene]-1,3-thiazol-4(5H)-one
93.3% inhibition at 0.01 mM
(5Z)-5-(2-chlorobenzylidene)-2-(4-methylpiperazin-1-yl)-1,3-thiazol-4(5H)-one
96.1% inhibition at 0.01 mM
(5Z)-5-(3,4-dichlorobenzylidene)-2-(4-methylpiperazin-1-yl)-1,3-thiazol-4(5H)-one
94.9% inhibition at 0.01 mM
(5Z)-5-(3,4-dichlorobenzylidene)-2-(piperazin-1-yl)-1,3-thiazol-4(5H)-one
-
(5Z)-5-(3,4-dichlorobenzylidene)-2-[4-[4-(dihydroxymethyl)benzyl]piperazin-1-yl]-1,3-thiazol-4(5H)-one
-
(5Z)-5-(3,4-dimethoxybenzylidene)-2-[4-(2-hydroxyethyl)piperazin-1-yl]-1,3-thiazol-4(5H)-one
95.3% inhibition at 0.01 mM
(5Z)-5-(3-bromobenzylidene)-2-(4-ethylpiperazin-1-yl)-1,3-thiazol-4(5H)-one
90.7% inhibition at 0.01 mM
(5Z)-5-(4-chlorobenzylidene)-2-(4-ethylpiperazin-1-yl)-1,3-thiazol-4(5H)-one
91.5% inhibition at 0.01 mM
(5Z)-5-(4-ethoxy-3-methoxybenzylidene)-2-[4-(2-hydroxyethyl)piperazin-1-yl]-1,3-thiazol-4(5H)-one
92.2% inhibition at 0.01 mM
(5Z)-5-(4-hydroxy-3,5-dimethoxybenzylidene)-2-(morpholin-4-yl)-1,3-thiazol-4(5H)-one
93.2% inhibition at 0.01 mM
(5Z)-5-benzylidene-2-(4-ethylpiperazin-1-yl)-1,3-thiazol-4(5H)-one
97.7% inhibition at 0.01 mM
4-(5-[(4,6-dioxo-2-thioxotetrahydropyrimidin-5(2H)-ylidene)methyl]furan-2-yl)benzenesulfonamide
90.1% inhibition at 0.01 mM
4-amino-6-(2-[4'-[(E)-(8-amino-1-hydroxy-5,7-disulfonaphthalen-2-yl)diazenyl]-3,3'-dimethoxybiphenyl-4-yl]hydrazinyl)-5-hydroxynaphthalene-1,3-disulfonic acid
99.0% inhibition at 0.01 mM
4-chloro-N-methyl-N-{2-[2-(methylsulfonyl)hydrazinyl]-2-oxoethyl}benzenesulfonamide
70.7% inhibition at 0.01 mM
4-[4-[(5Z)-5-(3,4-dichlorobenzylidene)-4-oxo-4,5-dihydro-1,3-thiazol-2-yl]piperazin-1-yl]butane-1-sulfonic acid
-
5-[4-[(5Z)-5-(3,4-dichlorobenzylidene)-4-oxo-4,5-dihydro-1,3-thiazol-2-yl]piperazin-1-yl]pentanoic acid
-
hypericin
lysophosphatidic acid
reported as an inhibitor of its own production
Mg2+
concentrations ranging from 0.1 to 1000 mM
murine serum albumin
could be a regulator of the circulating autotaxin. When the albumin is a fatty acid-free preparation, this slight inhibition disappears
-
N-(2-chlorophenyl)-2-([(2E)-2-[1-(pyridin-2-yl)ethylidene]hydrazinyl]carbonothioyl)hydrazinecarbothioamide
71.5% inhibition at 0.01 mM
Zn2+
concentrations ranging from 0.1 to 1000 mM
[2-([4-[(5Z)-5-(3,4-dichlorobenzylidene)-4-oxo-4,5-dihydro-1,3-thiazol-2-yl]piperazin-1-yl]methyl)phenyl]boronic acid
binding structure, overview
[3-([4-[(5Z)-5-(3,4-dichlorobenzylidene)-4-oxo-4,5-dihydro-1,3-thiazol-2-yl]piperazin-1-yl]methyl)phenyl]boronic acid
binding structure, overview
[4-([4-[(5Z)-5-(3,4-dichlorobenzylidene)-4-oxo-4,5-dihydro-1,3-thiazol-2-yl]piperazin-1-yl]methyl)phenyl]boronic acid
binding structure, overview
(5Z)-3-benzyl-5-[(1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)methylidene]-1,3-thiazolidine-2,4-dione
-
-
1-acyl glycerol 3-phosphate
-
also fatty alcohol phosphates (structurally 1-acyl glycerol 3-phosphate analogs)
1-bromo-3(s)-hydroxy-4-(palmitoyloxy) butylphosphonate
-
inhibitory in vitro and in vivo
3-([4-[(Z)-(3-benzyl-2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-3-ethoxyphenoxy]methyl)benzoic acid
-
-
3-[(4-[(Z)-[3-(4-fluorobenzyl)-2,4-dioxo-1,3-thiazolidin-5-ylidene]methyl]-3-methoxyphenoxy)methyl]benzoic acid
-
competitive inhibition, 35% residual ATX activity at 0.005 mM
3-[(4-[(Z)-[3-(4-fluorobenzyl)-2,4-dioxo-1,3-thiazolidin-5-ylidene]methyl]phenoxy)methyl]benzoic acid
-
competitive inhibition, 7% residual ATX activity at 0.005 mM
bithionol
-
inhibitory in vitro and in vivo
brefeldin-A
-
inhibitor of trans-Golgi transport, inhibits secretion of ATX
Ca2+
-
-
EGTA
All isoforms strongly inhibited by increasing concentrations of EGTA, 100% inhibition for 100 mM of the chelating agent
Globomycin
-
Treatment with the signal peptidase inhibitor inhibits ATX secretion by adipocytes treated for 6 h
hypericin
new inhibitor of autotaxin beta
Ki16425
-
inhibits the migratory response of lysophosphatidic acid1-expressing cells to both lysophosphatidic acid and ATX
lactacystin
-
proteasome inhibitor, restores the detection of ATX in cell homogenate of the mutants DELTAV12-V22 and DELTAV12-G27, Synthesis and secretion of ATX are highly dependent on the hydrophobic core of the signal peptide, but not on the amino acid composition the putative signal peptidase cleavage site
lysophosphatidic acid
reported as an inhibitor of its own production
Mg2+
manganese inhibits the catalytic activities, concentrations ranging from 0.1 to 1000 mM
murine serum albumin
could be a regulator of the circulating autotaxin. When the albumin is a fatty acid-free preparation, this slight inhibition disappears
-
N-glycosidase
-
treatment with N-glycosidase inhibits lysophospholipase D activity of ATX. N-glycosylation of ATX strongly influences its secretion and its lysoPLD activity
-
tunicamycin
-
inhibits secretion of ATX
Zn2+
zinc inhibits the catalytic activities, concentrations ranging from 0.1 to 1000 mM
[3-[(4-[(Z)-[3-(4-fluorobenzyl)-2,4-dioxo-1,3-thiazolidin-5-ylidene]methyl]phenoxy)methyl]phenyl]boronic acid
-
mixed-type inhibition, complete inhibition at 0.005 mM
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
heparin
-
enhances the lysoPLD activity of isozyme ATXalpha toward lysophosphatidylcholine up to 2fold, but it has no detectable effect on the activity of isozyme ATXbeta
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.1
1-alkyl-sn-glycero-3-phosphoethanolamine
-
achieved under optimal assay conditions, almost same results in blood plasma
0.32
1-O-alkyl-sn-glycero-3-phosphocholine
pH 7.4, temperature not specified in the publication
0.094 - 1
lysophosphatidylcholine
additional information
additional information
-
capable of hydrolyzing sphingosylphosphorylcholine with a significantly higher km-value, also able to hydrolyze nucleotide triphosphates di-adenosine polyphosphates and artificial phosphodiester substrates such as p-nitrophenyl thymidine phosphate with Km-values close to 1 and optimal activity observed at alkaline pH
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.077
1-O-alkyl-sn-glycero-3-phosphocholine
pH 7.4, temperature not specified in the publication
0.032
lysophosphatidylcholine
pH 7.4, temperature not specified in the publication
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.24
1-O-alkyl-sn-glycero-3-phosphocholine
pH 7.4, temperature not specified in the publication
0.031
lysophosphatidylcholine
pH 7.4, temperature not specified in the publication
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0001
1-acyl glycerol 3-phosphate
-
CPF4 FRET assay (change of fluorescence intensity), inihibition involves both a reduction in vmax and an increase in km, binding affinity is 1000fold stronger than to 1-alkyl-sn-glycero-3-phosphoethanolamine and analogue substrates
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00017
(5Z)-5-(3,4-dichlorobenzylidene)-2-(piperazin-1-yl)-1,3-thiazol-4(5H)-one
Mus musculus
pH 9.0, 37°C
0.000025
(5Z)-5-(3,4-dichlorobenzylidene)-2-[4-[4-(dihydroxymethyl)benzyl]piperazin-1-yl]-1,3-thiazol-4(5H)-one
Mus musculus
pH 9.0, 37°C
0.00023
4-[4-[(5Z)-5-(3,4-dichlorobenzylidene)-4-oxo-4,5-dihydro-1,3-thiazol-2-yl]piperazin-1-yl]butane-1-sulfonic acid
Mus musculus
pH 9.0, 37°C
0.00039
5-[4-[(5Z)-5-(3,4-dichlorobenzylidene)-4-oxo-4,5-dihydro-1,3-thiazol-2-yl]piperazin-1-yl]pentanoic acid
Mus musculus
pH 9.0, 37°C
0.0016 - 0.0026
hypericin
0.00002 - 0.000038
lysophosphatidic acid
0.187 - 0.251
murine serum albumin
-
0.00058
[2-([4-[(5Z)-5-(3,4-dichlorobenzylidene)-4-oxo-4,5-dihydro-1,3-thiazol-2-yl]piperazin-1-yl]methyl)phenyl]boronic acid
Mus musculus
pH 9.0, 37°C
0.000013
[3-([4-[(5Z)-5-(3,4-dichlorobenzylidene)-4-oxo-4,5-dihydro-1,3-thiazol-2-yl]piperazin-1-yl]methyl)phenyl]boronic acid
Mus musculus
pH 9.0, 37°C
0.000022
[4-([4-[(5Z)-5-(3,4-dichlorobenzylidene)-4-oxo-4,5-dihydro-1,3-thiazol-2-yl]piperazin-1-yl]methyl)phenyl]boronic acid
Mus musculus
pH 9.0, 37°C
0.00011
(5Z)-3-benzyl-5-[(1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl)methylidene]-1,3-thiazolidine-2,4-dione
Mus musculus
-
in Tris-HCl buffer (pH 7.4) at 37°C
0.000161
3-([4-[(Z)-(3-benzyl-2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-3-ethoxyphenoxy]methyl)benzoic acid
Mus musculus
-
in Tris-HCl buffer (pH 7.4) at 37°C
0.0025
3-[(4-[(Z)-[3-(4-fluorobenzyl)-2,4-dioxo-1,3-thiazolidin-5-ylidene]methyl]-3-methoxyphenoxy)methyl]benzoic acid
Mus musculus
-
in Tris-HCl buffer (pH 7.4) at 37°C
0.0017
3-[(4-[(Z)-[3-(4-fluorobenzyl)-2,4-dioxo-1,3-thiazolidin-5-ylidene]methyl]phenoxy)methyl]benzoic acid
Mus musculus
-
in Tris-HCl buffer (pH 7.4) at 37°C
0.0028
hypericin
Mus musculus
tested on murine autotaxin beta
0.000018
lysophosphatidic acid
Mus musculus
reported as an inhibitor of its own production, incubating murine autotaxin beta with lysophosphatidic acid
0.317
murine serum albumin
Mus musculus
incubating murine autotaxin beta with murine serum albumin
-
0.000028
[3-[(4-[(Z)-[3-(4-fluorobenzyl)-2,4-dioxo-1,3-thiazolidin-5-ylidene]methyl]phenoxy)methyl]phenyl]boronic acid
Mus musculus
-
in Tris-HCl buffer (pH 7.4) at 37°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0051
Murine autotaxin gamma, p-nitrophenyl phenylphosphonate as a substrate, Vmax 1.8 nmol p-nitrophenyl/min
0.0163
Murine autotaxin alpha, p-nitrophenyl phenylphosphonate as a substrate, Vmax 0.35 nanomol p-nitrophenyl/min
0.0919
Murine autotaxin beta, para-nitrophenyl phenylphosphonate as a substrate, Vmax 1.9 nmol para-nitrophenyl/min
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 9.5
purified isoforms show pH dependence
5.5 - 9.5
purified isoforms show pH dependence
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
assay at
45 - 55
murine isoform gamma is maximally active at 45–55°C
37
-
assay at
45 - 55
murine isoform beta maximally active at 45–55°C
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 60
5 - 60
purified isoforms show temperature dependence
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
despite a lower expression, murine autotaxin alpha is detected in brain and adipose tissue
Manually annotated by BRENDA team
-
present in circulating blood. ATX is responsible for bulk lysophosphatidic acid production in plasma. Stabilizes blood vessels and is required for embryonic vasculature by producing lysophosphatidic acid
Manually annotated by BRENDA team
-
intestinal, colonic microvessels, high endothelial venules-like vessels
Manually annotated by BRENDA team
highest expression level
Manually annotated by BRENDA team
-
during embryonic development. In vivo expression of autotaxin in the brain during development and following neurotrauma
Manually annotated by BRENDA team
-
from E7.5 to E9.5, Enpp2 mRNA is abundantly expressed in the visceral endoderm cells
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
mouse and human enzymes show high structural homology
physiological function
the enzyme is the predominant contributor to lysophosphatidic acid production in the human body, especially in the blood, and therefore has important roles in various physiological functions, including development of vasculature and lymphocyte trafficking
malfunction
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
ENPP2_MOUSE
862
1
98885
Swiss-Prot
Secretory Pathway (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
100000
full-length gamma isoform
55000 - 66000
analyzed by SDS-PAGE, two Western blots using either chicken antiautotaxin antibodies or anti-M2 FLAG antibodies, for the alpha isoform, a 55–66-kDa double band is visible. Major band is detected at 66 kDa
100000
110000
-
from HEC cells (isolation from mouse lymph nodes using immunomagnetic beads coupled to antibody MECA-79), SDS-PAGE, immunoblot
120000
-
analyzed by Western blot, ATX is undetectable in conditioned media from undifferentiated 3T3F442A preadipocytes. Conditioned media treated with N-glycosidase and O-glycosidase, N-glycosidase leads to a reduction of 9.6 kDa apparent molecular weight of ATX, O-glycosidase is without influence
90000
shorter versions of the beta isoform at 90 kDa
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 37000, SDS-PAGE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
-
-
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structure determination and analysis of enzyme in complexes with inhibitors 2BoA, 3BoA, and 4BoA, at 1.95 A, 1.90 A, and 1.75 A resolution
ATX alone and in complex with LPAs with different acyl-chain lengths and saturations, X-ray diffraction structure determination and analysis at 1.7-2.0 A resolution
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
DELTA323-375
murine autotaxin gamma isoform, 889 amino acids total
DELTA592-617
ATXalpha isoform, 915 amino acids total
DELTA202-363
-
COS cells transfected with mutated ATX express catalytically inactive phosphodiesterase and lysophospholipase D. Lethality of the ATX-/-embryos. ATX-dependent LPA production is due to the catalytic activity of the enzyme
DELTA323-375
murine autotaxin beta isoform, 863 amino acids total
DELTAA30-G41
-
deletion mutants are generated from plasmid pcDNA-mATX, encompasses furin site
DELTAA30-I33
-
deletion mutants are generated from plasmid pcDNA-mATX, between signal peptidase and furin site
DELTAA36-E40
-
deletion mutants are generated from plasmid pcDNA-mATX
DELTAC25
-
deletion mutants are generated from plasmid pcDNA-mATX, amino acid -3 referring to the potential signal peptidase cleavage site
DELTAE40-P43
-
deletion mutants are generated from plasmid pcDNA-mATX
DELTAG27
-
deletion mutants are generated from plasmid pcDNA-mATX, amino acid -1 referring to the potential signal peptidase cleavage site
DELTAG27-A30
-
deletion mutants are generated from plasmid pcDNA-mATX, contain potential signal peptidase clevage site
DELTAG27-R35
-
deletion mutants are generated from plasmid pcDNA-mATX, encompasses both furin and signal peptidase cleavage sites
DELTAL46-S49
-
deletion mutants are generated from plasmid pcDNA-mATX
DELTAN23
-
deletion mutants are generated from plasmid pcDNA-mATX, amino acid -5 referring to the potential signal peptidase cleavage site
DELTAN23-G27
-
deletion mutants are generated from plasmid pcDNA-mATX, encompasses -1 and -3 amino acids referring to the potential signal peptidase clevage site
DELTAN410
-
deletion mutants are generated from plasmid pcDNA-mATX, contains a N-glycosylation site, point deletion of the amino-acid N410 inhibits lysophospholipase D activity of ATX, does not modify the ATX secretion and strongly inhibits ATX activity
DELTAN53
-
deletion mutants are generated from plasmid pcDNA-mATX, contains a N-glycosylation site, does not modify the ATX secretion and slightly reduces (25%) ATX activity
DELTAN53/DELTAN410
-
deletion mutants are generated from plasmid pcDNA-mATX, two N-glycosylation sites, double point deletion of the amino-acids N53 and N410 inhibits secretion of ATX, without altering the ATX amount in cell homogenate
DELTAP43-L46
-
deletion mutants are generated from plasmid pcDNA-mATX
DELTAR32-R35
-
deletion mutants are generated from plasmid pcDNA-mATX, furine site
DELTAS49-N53
-
deletion mutants are generated from plasmid pcDNA-mATX, contains N-glycosylation site
DELTAV12-G27
-
deletion mutants are generated from plasmid pcDNA-mATX, hydrophobic domain of signal peptide and signal peptide cleavage site, ATX secretion is suppressed
DELTAV12-V22
-
deletion mutants are generated from plasmid pcDNA-mATX, hydrophobic domain of signal peptide, ATX secretion is suppressed
F249A
-
the mutant shows decreased lysoPLD activity and differences in the fatty acid preferences compared to the wild-type enzyme
F274A
-
the mutant shows decreased lysoPLD activity and differences in the fatty acid preferences compared to the wild-type enzyme
L213A
-
the mutant shows decreased lysoPLD activity and differences in the fatty acid preferences compared to the wild-type enzyme
L243A
-
the mutant shows decreased lysoPLD activity and differences in the fatty acid preferences compared to the wild-type enzyme
M512A
-
the mutant shows decreased lysoPLD activity and differences in the fatty acid preferences compared to the wild-type enzyme
N230A
-
almost inactive mutant
T209A
-
catalytically inactive
T210A
W254A
-
the mutant shows decreased lysoPLD activity and differences in the fatty acid preferences compared to the wild-type enzyme
Y306A
-
the mutant shows decreased lysoPLD activity and differences in the fatty acid preferences compared to the wild-type enzyme
additional information
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
two recombinant mouse ATX proteins (wild-type ATX and catalytically inactive T209A mutant ATX) with a His tag at the N-terminus are expressed and purified using a baculovirus system and nickel column chromatography
-
Western blot in cell homogenates requires a pre-purification with concanavalin A-sepharose
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
expressed in two different hosts, Sf9 insect cells and CHO cells, expressed in COS cells
atx-/-, atx+/-, and atx+/+ uncover the physiological role of ATX and to identify the endogenous product of ATX, ATX gene is targeted with an ATXgene-targeting vector. Plasma lysoPLD activity, plasma lysophosphatidic acid concentrations and plasma ATX protein level in atx+/-mice are about half the values found in atx+/+ mice. Embryos, early blood vessels appear to form properly, but fail to develop into mature vessels. ATX-null mice are lethal around embryonic day 10.5. Despite the reduced LPA level, heterozygous mice appear phenotypically normal. Viability and fecundity are similar to those in wild-type mice. Morphologies of atx+/+ and atx-/-embryo proper at E8.5, E9.5, and E10.5. Defects in vascular remodeling in atx-/-embryos shown. ATX and LPA stabilize preformed vessels and prevent endothelial disassembly in allantois explants
-
cloned from 129S6/Sv mouse brain, expression in COS-7 cells
-
co-transfection of MBEC4 cells with 2 plasmids, mlysoPLDpCAGGS26 and pSV2-neo, screening by Western blotting and immunocytochemistry with an anti-ATX mAb (4F1)14 and by measuring the lysoPLD activities of the culture media
-
expressed in B-103 cells
-
expressed in COS-7 cells
-
expressed in COS-7 cells (ATCC: CRL-1651) and HEK 293 cells. Compared distribution of overexpressed ATX in COS-7 and HEK293 cells
-
expressed in two different hosts, Sf9 insect cells and CHO cells, expressed in COS cells, cloning of the three isoforms alpha, beta, and gamma
expression in HEK-293 cell
expression in Sf9 cell
isolation of cDNA encoding ATX from HEC cDNA library and transfection of COS-7 African green monkey kidney cells, recombinant expression and purification and immunoblot analysis for showing that HECs synthesize and secrete ATX
-
real-time quantitative PCR expression analysis
-
recombinant expression of GDE1 in COS-7 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme expression is up-regulated in obese mice in relationship with insulin resistance and impaired glucose tolerance
-
phospholipase Cgamma activation drives increased production of autotaxin in endothelial cells
-
the concentration and enzyme activity of ATX are not affected by nerve injury
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
-
tumor cell motility-stimulating factor, represents a potential target for cancer therapy
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hama, K.; Aoki, J.; Fukaya, M.; Kishi, Y.; Sakai, T.; Suzuki, R.; Ohta, H.; Yamori, T.; Watanabe, M.; Chun, J.; Arai, H.
Lysophosphatidic acid and autotaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA1
J. Biol. Chem.
279
17634-17639
2004
Mus musculus
Manually annotated by BRENDA team
Pradere, J.P.; Tarnus, E.; Gres, S.; Valet, P.; Saulnier-Blache, J.S.
Secretion and lysophospholipase D activity of autotaxin by adipocytes are controlled by N-glycosylation and signal peptidase
Biochim. Biophys. Acta
1771
93-102
2007
Mus musculus
Manually annotated by BRENDA team
Savaskan, N.E.; Rocha, L.; Kotter, M.R.; Baer, A.; Lubec, G.; van Meeteren, L.A.; Kishi, Y.; Aoki, J.; Moolenaar, W.H.; Nitsch, R.; Braeuer, A.U.
Autotaxin (NPP-2) in the brain: cell type-specific expression and regulation during development and after neurotrauma
Cell. Mol. Life Sci.
64
230-243
2007
Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Ferry, G.; Giganti, A.; Coge, F.; Bertaux, F.; Thiam, K.; Boutin, J.A.
Functional invalidation of the autotaxin gene by a single amino acid mutation in mouse is lethal
FEBS Lett.
581
3572-3578
2007
Mus musculus
Manually annotated by BRENDA team
Tanaka, M.; Okudaira, S.; Kishi, Y.; Ohkawa, R.; Iseki, S.; Ota, M.; Noji, S.; Yatomi, Y.; Aoki, J.; Arai, H.
Autotaxin stabilizes blood vessels and is required for embryonic vasculature by producing lysophosphatidic acid
J. Biol. Chem.
281
25822-25830
2006
Mus musculus
Manually annotated by BRENDA team
Giganti, A.; Rodriguez, M.; Fould, B.; Moulharat, N.; Coge, F.; Chomarat, P.; Galizzi, J.P.; Valet, P.; Saulnier-Blache, J.S.; Boutin, J.A.; Ferry, G.
Murine and human autotaxin alpha, beta, gamma isoforms: Gene organization, tissue distribution and biochemical characterization
J. Biol. Chem.
283
7776-7789
2008
Homo sapiens, Homo sapiens (Q13822), Mus musculus, Mus musculus (Q9R1E6)
Manually annotated by BRENDA team
van Meeteren, L.A.; Ruurs, P.; Stortelers, C.; Bouwman, P.; van Rooijen, M.A.; Pradere, J.P.; Pettit, T.R.; Wakelam, M.J.; Saulnier-Blache, J.S.; Mummery, C.L.; Moolenaar, W.H.; Jonkers, J.
Autotaxin, a secreted lysophospholipase D, is essential for blood vessel formation during development
Mol. Cell. Biol.
26
5015-5022
2006
Mus musculus
Manually annotated by BRENDA team
Nakasaki, T.; Tanaka, T.; Okudaira, S.; Hirosawa, M.; Umemoto, E.; Otani, K.; Jin, S.; Bai, Z.; Hayasaka, H.; Fukui, Y.; Aozasa, K.; Fujita, N.; Tsuruo, T.; Ozono, K.; Aoki, J.; Miyasaka, M.
Involvement of the lysophosphatidic acid-generating enzyme autotaxin in lymphocyte-endothelial cell interactions
Am. J. Pathol.
173
1566-1576
2008
Mus musculus
Manually annotated by BRENDA team
Federico, L.; Pamuklar, Z.; Smyth, S.S.; Morris, A.J.
Therapeutic potential of autotaxin/lysophospholipase d inhibitors
Curr. Drug Targets
9
698-708
2008
Mus musculus
Manually annotated by BRENDA team
Kanda, H.; Newton, R.; Klein, R.; Morita, Y.; Gunn, M.D.; Rosen, S.D.
Autotaxin, an ectoenzyme that produces lysophosphatidic acid, promotes the entry of lymphocytes into secondary lymphoid organs
Nat. Immunol.
9
415-423
2008
Mus musculus
Manually annotated by BRENDA team
Fotopoulou, S.; Oikonomou, N.; Grigorieva, E.; Nikitopoulou, I.; Paparountas, T.; Thanassopoulou, A.; Zhao, Z.; Xu, Y.; Kontoyiannis, D.L.; Remboutsika, E.; Aidinis, V.
ATX expression and LPA signalling are vital for the development of the nervous system
Dev. Biol.
339
451-464
2010
Mus musculus
Manually annotated by BRENDA team
Endo, T.; Kano, K.; Motoki, R.; Hama, K.; Okudaira, S.; Ishida, M.; Ogiso, H.; Tanaka, M.; Matsuki, N.; Taguchi, R.; Kanai, M.; Shibasaki, M.; Arai, H.; Aoki, J.
Lysophosphatidylmethanol is a pan lysophosphatidic acid receptor agonist and is produced by autotaxin in blood
J. Biochem.
146
283-293
2009
Mus musculus
Manually annotated by BRENDA team
Koike, S.; Keino-Masu, K.; Ohto, T.; Sugiyama, F.; Takahashi, S.; Masu, M.
Autotaxin/lysophospholipase D-mediated lysophosphatidic acid signaling is required to form distinctive large lysosomes in the visceral endoderm cells of the mouse yolk sac
J. Biol. Chem.
284
33561-33570
2009
Mus musculus
Manually annotated by BRENDA team
Ma, L.; Uchida, H.; Nagai, J.; Inoue, M.; Aoki, J.; Ueda, H.
Evidence for de novo synthesis of lysophosphatidic acid in the spinal cord through phospholipase A2 and autotaxin in nerve injury-induced neuropathic pain
J. Pharmacol. Exp. Ther.
333
540-546
2010
Mus musculus
Manually annotated by BRENDA team
Im, E.; Motiejunaite, R.; Aranda, J.; Park, E.Y.; Federico, L.; Kim, T.I.; Clair, T.; Stracke, M.L.; Smyth, S.; Kazlauskas, A.
PLCgamma activation drives increased production of autotaxin in endothelial cells and LPA-dependent regression
Mol. Cell. Biol.
30
2401-2410
2010
Mus musculus
Manually annotated by BRENDA team
David, M.; Wannecq, E.; Descotes, F.; Jansen, S.; Deux, B.; Ribeiro, J.; Serre, C.M.; Gres, S.; Bendriss-Vermare, N.; Bollen, M.; Saez, S.; Aoki, J.; Saulnier-Blache, J.S.; Clezardin, P.; Peyruchaud, O.
Cancer cell expression of autotaxin controls bone metastasis formation in mouse through lysophosphatidic acid-dependent activation of osteoclasts
PLoS ONE
5
e9741
2010
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Albers, H.M.; Dong, A.; van Meeteren, L.A.; Egan, D.A.; Sunkara, M.; van Tilburg, E.W.; Schuurman, K.; van Tellingen, O.; Morris, A.J.; Smyth, S.S.; Moolenaar, W.H.; Ovaa, H.
Boronic acid-based inhibitor of autotaxin reveals rapid turnover of LPA in the circulation
Proc. Natl. Acad. Sci. USA
107
7257-7262
2010
Mus musculus
Manually annotated by BRENDA team
Tsuboi, K.; Okamoto, Y.; Ikematsu, N.; Inoue, M.; Shimizu, Y.; Uyama, T.; Wang, J.; Deutsch, D.G.; Burns, M.P.; Ulloa, N.M.; Tokumura, A.; Ueda, N.
Enzymatic formation of N-acylethanolamines from N-acylethanolamine plasmalogen through N-acylphosphatidylethanolamine-hydrolyzing phospholipase D-dependent and -independent pathways
Biochim. Biophys. Acta
1811
565-577
2011
Mus musculus
Manually annotated by BRENDA team
Nishimasu, H.; Okudaira, S.; Hama, K.; Mihara, E.; Dohmae, N.; Inoue, A.; Ishitani, R.; Takagi, J.; Aoki, J.; Nureki, O.
Crystal structure of autotaxin and insight into GPCR activation by lipid mediators
Nat. Struct. Mol. Biol.
18
205-212
2011
Mus musculus
Manually annotated by BRENDA team
Kawaguchi, M.; Okabe, T.; Okudaira, S.; Nishimasu, H.; Ishitani, R.; Kojima, H.; Nureki, O.; Aoki, J.; Nagano, T.
Screening and X-ray crystal structure-based optimization of autotaxin (ENPP2) inhibitors, using a newly developed fluorescence probe
ACS Chem. Biol.
8
1713-1721
2013
Danio rerio, Mus musculus (Q9R1E6)
Manually annotated by BRENDA team
Rancoule, C.; Dusaulcy, R.; Treguer, K.; Gres, S.; Attane, C.; Saulnier-Blache, J.S.
Involvement of autotaxin/lysophosphatidic acid signaling in obesity and impaired glucose homeostasis
Biochimie
96
140-143
2014
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Perrakis, A.; Moolenaar, W.H.
Autotaxin: structure-function and signaling
J. Lipid Res.
55
1010-1018
2014
Homo sapiens, Mus musculus, Streptomyces chromofuscus, Loxosceles sp.
Manually annotated by BRENDA team
Hozumi, H.; Hokari, R.; Kurihara, C.; Narimatsu, K.; Sato, H.; Sato, S.; Ueda, T.; Higashiyama, M.; Okada, Y.; Watanabe, C.; Komoto, S.; Tomita, K.; Kawaguchi, A.; Nagao, S.; Miura, S.
Involvement of autotaxin/lysophospholipase D expression in intestinal vessels in aggravation of intestinal damage through lymphocyte migration
Lab. Invest.
93
508-519
2013
Homo sapiens, Mus musculus, Mus musculus BALB/c
Manually annotated by BRENDA team
Tsuboi, K.; Okamoto, Y.; Rahman, I.A.; Uyama, T.; Inoue, T.; Tokumura, A.; Ueda, N.
Glycerophosphodiesterase GDE4 as a novel lysophospholipase D a possible involvement in bioactive N-acylethanolamine biosynthesis
Biochim. Biophys. Acta
1851
537-548
2015
Mus musculus (Q9CRY7), Mus musculus
Manually annotated by BRENDA team
Rahman, I.A.; Tsuboi, K.; Hussain, Z.; Yamashita, R.; Okamoto, Y.; Uyama, T.; Yamazaki, N.; Tanaka, T.; Tokumura, A.; Ueda, N.
Calcium-dependent generation of N-acylethanolamines and lysophosphatidic acids by glycerophosphodiesterase GDE7
Biochim. Biophys. Acta
1861
1881-1892
2016
Homo sapiens (Q7L5L3), Homo sapiens, Mus musculus (Q99LY2), Mus musculus
Manually annotated by BRENDA team
Ohshima, N.; Kudo, T.; Yamashita, Y.; Mariggio, S.; Araki, M.; Honda, A.; Nagano, T.; Isaji, C.; Kato, N.; Corda, D.; Izumi, T.; Yanaka, N.
New members of the mammalian glycerophosphodiester phosphodiesterase family GDE4 and GDE7 produce lysophosphatidic acid by lysophospholipase D activity
J. Biol. Chem.
290
4260-4271
2015
Mus musculus (Q9CRY7)
Manually annotated by BRENDA team