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Information on EC 3.1.4.39 - alkylglycerophosphoethanolamine phosphodiesterase and Organism(s) Homo sapiens and UniProt Accession Q13822
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3.1.4.39 alkylglycerophosphoethanolamine phosphodiesteraseIUBMB Comments
Also acts on acyl and choline analogues.
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Word Map
- 3.1.4.39
-
lysophosphatidic
- lysophosphatidylcholine
- phospholipid
- fibrosis
- lysophospholipids
-
atx-lpa
- metastasis
- choline
-
protein-coupled
- melanoma
-
autocrine
-
motility-stimulating
-
ectoenzyme
-
lpa-producing
- sphingosine
- analysis
- pruritus
- drug development
-
ectonucleoside
-
lpars
- e-npps
-
motogenic
-
lpa-induced
- medicine
- molecular biology
- lysophosphatidylserine
- ntpdases
- diagnostics
-
diphosphohydrolase
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Reaction Schemes
Synonyms
autotaxin (atx), lysophospholipase d, enpp2, ectonucleotide pyrophosphatase/phosphodiesterase, gdpd3, ectonucleotide pyrophosphatase/phosphodiesterase 2, heminecrolysin, pd-ialpha/atx, lyso-pld, atx/lysopld, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ATX
ATXgamma
from human brain cDNA libary, 889 amino acids, lacks exon 12, new human variant, named autotaxin gamma
autotaxin
(ecto)nucleotide pyrophosphatase/phosphodiesterase 2 [(E)NPP2]
-
multi-functional and multi-modular, 3 splice variants/isoforms of ATX identified in both human and mouse (autotaxin alpha, beta and gamma, with autotaxin gamma being identical to PD-Ialpha)
ATX
-
-
autotaxin
autotaxin/lysoPLD
-
belongs to a family of six NPP enzymes, only autotaxin/lysoPLD has activity against phospho- and sphingolipid substrates
lysophospholipase D
lysoPLD
PD-Ialpha/ATX
-
multi-functional and multi-modular, 3 splice variants/isoforms of ATX identified in both human and mouse (autotaxin alpha, beta and gamma, with autotaxin gamma being identical to PD-Ialpha)
phosphodiesterase Ialpha/autotoxin
-
multi-functional and multi-modular, 3 splice variants/isoforms of ATX identified in both human and mouse (autotaxin alpha, beta and gamma, with autotaxin gamma being identical to phosphodiesterase Ialpha)
phosphodiesterase, alkylglycerophosphorylethanolamine
-
-
-
-
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
autotaxin
-
-
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
-
-
-
-
lysophospholipase D
-
-
lysoPLD
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of phosphoric ester
hydrolysis of phosphoric ester
hydrolysis of phosphoric ester
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
1-alkyl-sn-glycero-3-phosphoethanolamine ethanolaminehydrolase
Also acts on acyl and choline analogues.
CAS REGISTRY NUMBER
COMMENTARY
62213-15-4
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
arachidoyl-lysophosphatidylcholine + H2O
1-arachidoyl-sn-gycerol-3-phosphate + choline
-
-
-
?
behenoyl-lysophosphatidylcholine + H2O
1-behenoyl-sn-gycerol-3-phosphate + choline
-
-
-
?
decanoyl-lysophosphatidylcholine + H2O
1-decanoyl-sn-gycerol-3-phosphate + choline
-
-
-
?
hexanoyl-lysophosphatidylcholine + H2O
1-hexanoyl-sn-gycerol-3-phosphate + choline
-
-
-
?
lauroyl-lysophosphatidylcholine + H2O
1-lauroyl-sn-gycerol-3-phosphate + choline
-
-
-
?
myristoyl-lysophosphatidylcholine + H2O
1-myristoyl-sn-gycerol-3-phosphate + choline
-
-
-
?
octanoyl-lysophosphatidylcholine + H2O
1-octanoyl-sn-gycerol-3-phosphate + choline
-
-
-
?
oleoyl-lysophosphatidylcholine + H2O
1-oleoyl-sn-gycerol 3-phosphate + choline
-
-
-
?
palmitoyl-lysophosphatidylcholine + H2O
1-palmitoyl-sn-gycerol-3-phosphate + choline
-
-
-
?
stearoyl-lysophosphatidylcholine + H2O
1-stearoyl-sn-gycerol-3-phosphate + choline
-
-
-
?
1-alkyl-sn-glycero-3-phosphocholine + H2O
1-alkyl-sn-glycerol 3-phosphate + choline
-
-
-
-
?
5-[[(23R)-33-(4-[[4-(dimethylamino)phenyl]diazenyl]phenyl)-20,23-dihydroxy-20-oxido-15,33-dioxo-3,6,9,12,19,21,25-heptaoxa-16,32-diaza-20-phosphatritriacont-1-yl]carbamoyl]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid + H2O
?
-
fluorogenic substrate analogue for lysophosphatidylcholine
-
-
?
arachidoyl-lysophosphatidylcholine + H2O
1-arachidoyl-sn-gycerol-3-phosphate + choline
-
-
-
?
behenoyl-lysophosphatidylcholine + H2O
1-behenoyl-sn-gycerol-3-phosphate + choline
-
-
-
?
decanoyl-lysophosphatidylcholine + H2O
1-decanoyl-sn-gycerol-3-phosphate + choline
-
-
-
?
FS-3 + H2O
2-(6-hydroxy-3-oxo-9a,10a-dihydro-3H-xanthen-9-yl)-5-[(18-hydroxy-15-oxo-3,6,9,12-tetraoxa-16-azaoctadec-1-yl)carbamoyl]benzoic acid + (2R)-2-hydroxy-3-(phosphonooxy)propyl 6-[(4-[(E)-[4-(dimethylamino)phenyl]diazenyl]benzoyl)amino]hexanoate
-
fluorogenic lysoPLD substrate
-
-
?
hexanoyl-lysophosphatidylcholine + H2O
1-hexanoyl-sn-gycerol-3-phosphate + choline
-
-
-
?
lauroyl-lysophosphatidylcholine + H2O
1-lauroyl-sn-gycerol-3-phosphate + choline
-
-
-
?
lysophosphatidyl choline + H2O
lysophosphatidic acid + choline
best substrate, reaction of EC 3.1.4.5
-
-
?
myristoyl-lysophosphatidylcholine + H2O
1-myristoyl-sn-gycerol-3-phosphate + choline
-
-
-
?
N-arachidonoyllysophosphatidylethanolamine + H2O
lysophosphatidic acid + N-arachidonoylethanolamine
-
-
-
?
N-oleoyllysophosphatidylethanolamine + H2O
lysophosphatidic acid + N-oleoylethanolamine
-
-
-
?
N-palmitoyllysophosphatidylethanolamine + H2O
lysophosphatidic acid + N-palmitoylethanolamine
-
-
-
?
N-palmitoyllysoplasmenylethanolamine + H2O
lysoplasmenic acid + N-palmitoylethanolamine
-
-
-
?
octanoyl-lysophosphatidylcholine + H2O
1-octanoyl-sn-gycerol-3-phosphate + choline
-
-
-
?
oleoyl-lysophosphatidylcholine + H2O
1-oleoyl-sn-gycerol 3-phosphate + choline
-
-
-
?
palmitoyl-lysophosphatidylcholine + H2O
1-palmitoyl-sn-gycerol-3-phosphate + choline
-
-
-
?
stearoyl-lysophosphatidylcholine + H2O
1-stearoyl-sn-gycerol-3-phosphate + choline
-
-
-
?
[(2R)-26-(4-[(Z)-[4-(dimethylamino)phenyl]diazenyl]phenyl)-2,5-dihydroxy-5-oxido-10,26-dioxo-4,6,13,16,19,22-hexaoxa-9,25-diaza-5-phosphahexacos-1-yl 6-[(5-[5-[(3,5-dimethyl-2H-pyrrol-2-ylidene-kN)methyl]-1H-pyrrol-2-yl-kappaN]pentanoyl)amino]hexanoatato](difluoro)boron + H2O
?
-
fluorogenic substrate analogue for lysophosphatidylcholine
-
-
?
lysophosphatidyl choline + H2O
lysophosphatidic acid + choline
various concentration of lysophosphatidyl choline with or without 2.5 pM of hATX S48 are exposed to HT-1080 cells and motile area is analyzed
-
-
?
lysophosphatidylcholine + H2O
lysophosphatidic acid + choline
-
bioactive phospholipid regulating a wide range of cellular responses
-
?
lysophosphatidylcholine + H2O
lysophosphatidic acid + choline
lysophospholipase D activity
-
-
?
CPF4 + H2O
?
-
fluorescence resonance energy transfer substrate derived from bis-p-nitrophenyl phosphate
-
-
?
CPF4 + H2O
?
-
i.e. 5-([4-[(4-[[(6-chloro-7-hydroxy-2-oxo-2H-chromen-4-yl)acetyl]amino]phenoxy)(hydroxy)phosphoryl]phenyl]carbamoyl)-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid, fluorescence resonance energy transfer substrate derived from bis-p-nitrophenyl phosphate
-
-
?
lysophosphatidylcholine + H2O
lysophosphatidic acid + choline
-
-
6, 663457, 664939, 665229, 666223, 666527, 670114, 681769, 696397, 697080, 698987, 700238, 701580, 701638, 702025, 702693, 703104, 705057, 706456, 706577
-
-
?
lysophosphatidylcholine + H2O
lysophosphatidic acid + choline
-
bioactive phospholipid regulating a wide range of cellular responses
-
?
lysophosphatidylcholine + H2O
lysophosphatidic acid + choline
-
albumin-bound lipid
-
-
?
lysophosphatidylcholine + H2O
lysophosphatidic acid + choline
-
present in the plasma
-
-
?
lysophosphatidylcholine + H2O
lysophosphatidic acid + choline
-
radiolabeled substrate
-
-
?
lysophosphatidylcholine + H2O
lysophosphatidic acid + choline
-
radiolabeled substrate and fluorogenic substrate FS-3
-
-
?
additional information
?
-
Catalytic ability of ATX for p-nitrophenyl thymidine 5'-monophosphate and adenosine triphosphate hydrolysis are low compared with nucleotide pyrophosphatases-1/phosphodiesterases
-
-
?
additional information
?
-
-
Catalytic ability of ATX for p-nitrophenyl thymidine 5'-monophosphate and adenosine triphosphate hydrolysis are low compared with nucleotide pyrophosphatases-1/phosphodiesterases
-
-
?
additional information
?
-
-
There are no major differences in the respective specificities of the various isoforms, main substrate is lauroyl lysophosphatidylcholine
-
-
?
additional information
?
-
There are no major differences in the respective specificities of the various isoforms, main substrate is lauroyl lysophosphatidylcholine
-
-
?
additional information
?
-
-
the plasma enzyme hydrolyzes acyl-, alkyl- and alkenyl-lysophophatidylcholines
-
?
additional information
?
-
-
There are no major differences in the respective specificities of the various isoforms, main substrate is lauroyl-lysophosphatidylcholine
-
-
?
additional information
?
-
There are no major differences in the respective specificities of the various isoforms, main substrate is lauroyl-lysophosphatidylcholine
-
-
?
additional information
?
-
-
activity implicated in a large variety of biological processes (during normal development and under pathological conditions). Developmental roles include adipogenesis, intestinal cell motility and neurite morphology, a contribution to disease is described for alzheimer's disease, chronic hepatitis C, multiple sclerosis, neuropathic pain, obesity, rheumatoid arthritis
-
-
?
additional information
?
-
-
assay development devised to quantify 4-nitrophenol from hydrolysis of chromogenic substrate by serum lysoPLD without tedious lipid extraction procedures
-
-
?
additional information
?
-
-
lysophospholipase D generates lysophosphatidic acid from lysophosphatidylcholine
-
-
?
additional information
?
-
-
reaction mechanism of NBD-LPC hydrolysis, overview. Artificial substrates FS-3 and pNP-TMP are used for kinetic studies, overview
-
-
?
additional information
?
-
-
the enzyme hydrolyzes extracellular lysophospholipids into the lipid mediator lysophosphatidic acid, a ligand for specific G protein-coupled receptors
-
-
?
additional information
?
-
-
the recombinant enzyme promotes MDA-MB-231 breast cancer cell and mouse aortic vascular smooth muscle cell migration in lysophosphatidic acid-dependent and -independent ways. The enzyme also shows nucleotide phosphodiesterase activity with nucleotide derivative 4-nitrophenyl-TMP as a substrate
-
-
?
additional information
?
-
poor substrate: glycerophospho-N-palmitoylethanolamine
-
-
?
additional information
?
-
-
poor substrate: glycerophospho-N-palmitoylethanolamine
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
1-alkyl-sn-glycero-3-phosphocholine + H2O
1-alkyl-sn-glycerol 3-phosphate + choline
-
-
-
-
?
lysophosphatidylcholine + H2O
lysophosphatidic acid + choline
-
bioactive phospholipid regulating a wide range of cellular responses
-
?
lysophosphatidylcholine + H2O
lysophosphatidic acid + choline
lysophospholipase D activity
-
-
?
lysophosphatidylcholine + H2O
lysophosphatidic acid + choline
-
-
-
-
?
lysophosphatidylcholine + H2O
lysophosphatidic acid + choline
-
bioactive phospholipid regulating a wide range of cellular responses
-
?
lysophosphatidylcholine + H2O
lysophosphatidic acid + choline
-
present in the plasma
-
-
?
additional information
?
-
-
activity implicated in a large variety of biological processes (during normal development and under pathological conditions). Developmental roles include adipogenesis, intestinal cell motility and neurite morphology, a contribution to disease is described for alzheimer's disease, chronic hepatitis C, multiple sclerosis, neuropathic pain, obesity, rheumatoid arthritis
-
-
?
additional information
?
-
-
the enzyme hydrolyzes extracellular lysophospholipids into the lipid mediator lysophosphatidic acid, a ligand for specific G protein-coupled receptors
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Co2+
Mg2+
Mn2+
check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM
Ni2+
Zn2+
check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM
Ca2+
Co2+
check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM
Mg2+
Mn2+
Ni2+
check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM
Zn2+
additional information
-
the catalytic domain shows a characteristic bimetallic active site
Ca2+
check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM
Ca2+
similar stimulation of LysoPLD activity by addition of Ca2+ and Mg2+ occurs. Mg2+ or Ca2+ may act to stabilize the structure of ATX or shield the electric charge of the substrate
Co2+
activity of hATX S48 protein is significantly stimulated by addition of Co2+
Co2+
check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM
Mg2+
check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM
Mg2+
similar stimulation of LysoPLD activity by addition of Ca2+ and Mg2+ occurs. Mg2+ or Ca2+ may act to stabilize the structure of ATX or shield the electric charge of the substrate
Ni2+
check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM
Ni2+
Mg2+-ATP treated sample is applied to the Ni2+ charged chelating sepharose. Most effective affinity chelating metal
Ca2+
check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM
Mg2+
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
Zn2+
check the sensitivity to metals for the human and murine isoforms, concentrations ranging from 0.1 to 1000 mM
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
EDTA
All isoforms strongly inhibited by increasing concentrations of EDTA, 100% inhibition for 100 mM of the chelating agent
EGTA
All isoforms strongly inhibited by increasing concentrations of EGTA, 100% inhibition for 100 mM of the chelating agent
Human serum albumin
could be a regulator of the circulating autotaxin. When the albumin is a fatty acid-free preparation, this slight inhibition disappears
-
2-(4-[[(2,3-dichlorophenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
72.3% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(2,4,6-mesitylphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
53.5% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(2,5-dichlorophenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
mixed inhibition, 5.4% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(2-benzothiadiazolphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
63.2% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(2-chlorophenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
83.5% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(2-fluorophenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
77.3% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(2-iodophenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
68.4% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(2-methoxyphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
97.6% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(2-methylesterphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
51.2% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(3,5-bis(trifluoromethyl)phenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
competitive inhibition, 34.1% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(3,5-dimethylphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
competitive inhibition, 30.4% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(3-benzothiadiazolphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
competitive inhibition, 28.6% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(3-chlorophenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
mixed inhibition, 9.7% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(3-fluorophenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
40.5% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(3-iodophenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
mixed inhibition, 8.6% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(3-methoxyphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
40.9% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(3-methylphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
competitive inhibition, 41.9% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(3-trifluoromethylphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
competitive inhibition, 0.3% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(4-carboxylphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
72.7% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(4-chlorophenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
competitive inhibition, 42.4% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(4-dimethylaminonaphthylphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
59.9% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(4-fluorophenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
48.9% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(4-iodophenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
mixed inhibition, 32.7% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(4-methoxyphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
79.7% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(4-methylphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
49.9% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(4-morpholinosulfonylphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
64.1% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(4-pyrazolephenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
68.6% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(4-trifluoromethylphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
noncompetitive inhibition, 36.2% residual activity at 0.001 mM using FS-3 as substrate
2-(4-[[(phenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid phenyl
-
56.4% residual activity at 0.001 mM using FS-3 as substrate
2-amino-2-(2-(4-octylphenyl) ethyl)propan-1,3-diol
-
synonyms FTY720, finolimod, competitive inhibition
cyclohexanaminium hydrogen [4-([3-[2-(2-methoxyethoxy)ethoxy]propanoyl]amino)benzyl]phosphonate
-
-
cyclohexanaminium hydrogen [fluoro[4-(heptanoylamino)phenyl]methyl]phosphonate
-
-
cyclohexanaminium hydrogen [[4-(decanoylamino)phenyl](fluoro)methyl]phosphonate
-
-
cyclohexanaminium hydrogen [[4-(decanoylamino)phenyl](hydroxy)methyl]phosphonate
-
-
cyclohexanaminium hydrogen [[4-(heptanoylamino)phenyl](hydroxy)methyl]phosphonate
-
-
EGTA
All isoforms being strongly inhibited by increasing concentrations of EGTA, 100% inhibition for 100 mM of the chelating agent
FTY720P
-
binds apo-ATX and an ATX with bound FS-3/products complex, noncompetitive/mixed inhibition
Human serum albumin
could be a regulator of the circulating autotaxin. When the albumin is a fatty acid-free preparation, this slight inhibition disappears
-
[(2R,3S)-3-(hexadecanoylamino)-2-hydroxy-4-[4-(pyridin-2-ylmethoxy)phenyl]butyl]phosphonic acid
-
-
[(2R,3S)-3-(hexadecanoylamino)-2-hydroxy-4-[4-[(4-methoxy-3,5-dimethylbenzyl)oxy]phenyl]butyl]phosphonic acid
-
-
[(2R,3S)-3-(hexadecanoylamino)-2-hydroxy-4-[4-[(4-methoxy-3,5-dimethylpyridin-2-yl)methoxy]phenyl]butyl]phosphonic acid
-
i.e. VPC8a202
[(2R,3S)-3-(hexadecanoylamino)-2-hydroxy-4-[4-[(4-methoxy-3-methylbenzyl)oxy]phenyl]butyl]phosphonic acid
-
-
[(2R,3S)-3-(hexadecanoylamino)-2-hydroxy-4-[4-[(4-methoxypyridin-2-yl)methoxy]phenyl]butyl]phosphonic acid
-
-
[(2R,3S)-4-(4-[[3,5-dimethyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methoxy]phenyl)-3-(hexadecanoylamino)-2-hydroxybutyl]phosphonic acid
-
-
[(2R,3S)-4-[4-(benzyloxy)phenyl]-3-(hexadecanoylamino)-2-hydroxybutyl]phosphonic acid
-
-
[(2R,3S)-4-[4-[(2,4-dichlorobenzyl)oxy]phenyl]-3-(hexadecanoylamino)-2-hydroxybutyl]phosphonic acid
-
-
[(2R,3S)-4-[4-[(3,5-dimethyl-4-propoxypyridin-2-yl)methoxy]phenyl]-3-(hexadecanoylamino)-2-hydroxybutyl]phosphonic acid
-
-
[(2R,3S)-4-[4-[(3,5-dimethylbenzyl)oxy]phenyl]-3-(hexadecanoylamino)-2-hydroxybutyl]phosphonic acid
-
-
[(2R,3S)-4-[4-[(3,5-dimethylpyridin-2-yl)methoxy]phenyl]-3-(hexadecanoylamino)-2-hydroxybutyl]phosphonic acid
-
-
[(2R,3S)-4-[4-[(4-ethoxy-3,5-dimethylpyridin-2-yl)methoxy]phenyl]-3-(hexadecanoylamino)-2-hydroxybutyl]phosphonic acid
-
-
EDTA
All isoforms being strongly inhibited by increasing concentrations of EDTA, 100% inhibition for 100 mM of the chelating agent
H2L 7905958
-
competitive inhibition with respect to ATX-mediated FS-3 hydrolysis and non-competitive inhibition with respect to ATX-mediated 4-nitrophenyl-TMP hydrolysis
H2L 7905958
-
potent ATX inhibitor, complete inhibition of FS-3 hydrolysis at 0.01 mM, competitive inhibitor
L-histidine
-
15-20 mM, noncompetitive, 75% inhibition, inhibition can be reversed by 20fold lower concentrations of zinc or cobalt salts
PF8380
-
the inhibitor shows adequate oral bioavailability and potency in reducing lysophosphatidic acid levels in plasma and at sites of infl ammation
additional information
-
not inhibited by 2-(4-[[(2-trifluoromethylphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
additional information
-
inhibitor development and synthesis, anti and syn forms of the molecules show different effects on the inhibitory potency, homology model docking study, overview
-
additional information
-
the low hydrophobicity of an inhibitor is a critical factor in its preference for the binding to a noncatalytic binding site over a catalytic binding site in ATX. Structure-activity relationship of inhibition on lysoPLD activity by polyphenols, overview. Resveratrol, caffeine, L-amino acids, tyrosine, phenylalanine, and 3-(3,4-dihydroxyphenyl)alanine, and phenolic antioxidants (propyl gallate, BHT, BHA), methyl (R)-(+)-2-(4-hydroxyphenoxy)propionate, 3-(4-hydroxyphenyl)-1-propanol, and 4-(4-hydroxyphenyl)-2-butanone are inactive. Also inactive are flavonols kaempferol, tamarixetin, flavones luteolin, apigenin, chrysin, flavanols (+)-catechin, (-)-epicatechin, isoflavones daidzein, genistein
-
additional information
-
the low hydrophobicity of an inhibitor is a critical factor in its preference for the binding to a noncatalytic binding site over a catalytic binding site in ATX. Structure-activity relationship of inhibition on lysoPLD activity by polyphenols, overview. Resveratrol, caffeine, L-amino acids, tyrosine, phenylalanine, and 3-(3,4-dihydroxyphenyl)alanine, and phenolic antioxidants (propyl gallate, BHT, BHA), methyl (R)-(þ)-2-(4-hydroxyphenoxy)propionate, 3-(4-hydroxyphenyl)-1-propanol, and 4-(4-hydroxyphenyl)-2-butanone are inactive. Also inactive are flavonols kaempferol, tamarixetin, flavones luteolin, apigenin, chrysin, flavanols (+)-catechin, (-)-epicatechin, isoflavones daidzein, genistein
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
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
integrins
-
ATX activity against exogenously provided and cell-associated substrates is increased by integrin binding
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0063
5-[[(23R)-33-(4-[[4-(dimethylamino)phenyl]diazenyl]phenyl)-20,23-dihydroxy-20-oxido-15,33-dioxo-3,6,9,12,19,21,25-heptaoxa-16,32-diaza-20-phosphatritriacont-1-yl]carbamoyl]-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoic acid
-
-
0.7
4-nitrophenyl-TMP
-
wild type enzyme, in 50 mM Tris pH 7.4, 5 mM CaCl2, 1 mg/ml bovine serum albumin, at 37°C
4.8
4-nitrophenyl-TMP
-
mutant enzyme H226Q, in 50 mM Tris pH 7.4, 5 mM CaCl2, 1 mg/ml bovine serum albumin, at 37°C
0.0026
FS-3
-
wild type enzyme, in 50 mM Tris pH 7.4, 5 mM CaCl2, 1 mg/ml bovine serum albumin, at 37°C
0.019
FS-3
-
mutant enzyme H226Q, in 50 mM Tris pH 7.4, 5 mM CaCl2, 1 mg/ml bovine serum albumin, at 37°C
0.1
lysophosphatidylcholine
-
kinetic analysis of recombinant autotaxin/lysoPLD using [14C] lysophosphatidylcholine substrate
0.47
lysophosphatidylcholine
-
in presence of 0.25 mM Zn2+ plus 10 mM L-histidine
0.066
lysophosphatidylcholine 16:0
-
wild type enzyme, in 50 mM Tris pH 7.4, 5 mM CaCl2, 1 mg/ml bovine serum albumin, at 37°C
0.094
lysophosphatidylcholine 16:0
-
mutant enzyme H420Q, in 50 mM Tris pH 7.4, 5 mM CaCl2, 1 mg/ml bovine serum albumin, at 37°C
0.12
lysophosphatidylcholine 16:0
-
mutant enzyme H434Q, in 50 mM Tris pH 7.4, 5 mM CaCl2, 1 mg/ml bovine serum albumin, at 37°C
0.126
lysophosphatidylcholine 16:0
-
mutant enzyme H226Q, in 50 mM Tris pH 7.4, 5 mM CaCl2, 1 mg/ml bovine serum albumin, at 37°C
0.089
lysophosphatidylcholine 18:0
-
wild type enzyme, in 50 mM Tris pH 7.4, 5 mM CaCl2, 1 mg/ml bovine serum albumin, at 37°C
0.115
lysophosphatidylcholine 18:0
-
mutant enzyme H420Q, in 50 mM Tris pH 7.4, 5 mM CaCl2, 1 mg/ml bovine serum albumin, at 37°C
0.27
lysophosphatidylcholine 18:0
-
mutant enzyme H226Q, in 50 mM Tris pH 7.4, 5 mM CaCl2, 1 mg/ml bovine serum albumin, at 37°C
0.069
lysophosphatidylcholine 18:1
-
mutant enzyme H420Q, in 50 mM Tris pH 7.4, 5 mM CaCl2, 1 mg/ml bovine serum albumin, at 37°C
0.073
lysophosphatidylcholine 18:1
-
wild type enzyme, in 50 mM Tris pH 7.4, 5 mM CaCl2, 1 mg/ml bovine serum albumin, at 37°C
0.105
lysophosphatidylcholine 18:1
-
mutant enzyme H434Q, in 50 mM Tris pH 7.4, 5 mM CaCl2, 1 mg/ml bovine serum albumin, at 37°C
0.126
lysophosphatidylcholine 18:1
-
mutant enzyme H226Q, in 50 mM Tris pH 7.4, 5 mM CaCl2, 1 mg/ml bovine serum albumin, at 37°C
additional information
additional information
-
affinity for lysophosphatidylcholine is significantly higher than for nucleotides
-
additional information
additional information
-
steady-state, single-turnover, and transient kinetics, kinetic analysis and modeling, using artificial fluorescent substrate FS-3, overview
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0034
2-(4-[[(2,5-dichlorophenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.004
2-(4-[[(3,5-bis(trifluoromethyl)phenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.0042
2-(4-[[(3,5-dimethylphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.0071
2-(4-[[(3-benzothiadiazolphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.0026
2-(4-[[(3-chlorophenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.0074
2-(4-[[(3-iodophenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.0045
2-(4-[[(3-methylphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.0007
2-(4-[[(3-trifluoromethylphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.0057
2-(4-[[(4-chlorophenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.0132
2-(4-[[(4-iodophenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.0132
2-(4-[[(4-trifluoromethylphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.0002
2-amino-2-(2-(4-octylphenyl) ethyl)propan-1,3-diol
-
substrate p-nitrophenyl thymidine 5-monophosphate, pH 8.0, 30 min of incubation at 37°C, measuring absorbance at 405 nm, twofold higher KI compared to inhibitor S1P
0.000018
cyclohexanaminium hydrogen [4-(decanoylamino)benzyl]phosphonate
-
pH and temperature not specified in the publication
0.000512
cyclohexanaminium hydrogen [4-(heptanoylamino)benzyl]phosphonate
-
pH and temperature not specified in the publication
0.000009
cyclohexanaminium hydrogen [4-(tetradecanoylamino)benzyl]phosphonate
-
pH and temperature not specified in the publication
0.000834
cyclohexanaminium hydrogen [fluoro[4-(heptanoylamino)phenyl]methyl]phosphonate
-
pH and temperature not specified in the publication
0.0000061 - 0.000072
cyclohexanaminium hydrogen [[4-(decanoylamino)phenyl](fluoro)methyl]phosphonate
0.000024 - 0.0000242
cyclohexanaminium hydrogen [[4-(decanoylamino)phenyl](hydroxy)methyl]phosphonate
0.001009
cyclohexanaminium hydrogen [[4-(heptanoylamino)phenyl](hydroxy)methyl]phosphonate
-
pH and temperature not specified in the publication
0.0225 - 0.027
[(2R,3S)-3-(hexadecanoylamino)-2-hydroxy-4-[4-(pyridin-2-ylmethoxy)phenyl]butyl]phosphonic acid
0.0047 - 0.2175
[(2R,3S)-3-(hexadecanoylamino)-2-hydroxy-4-[4-[(4-methoxy-3,5-dimethylbenzyl)oxy]phenyl]butyl]phosphonic acid
0.001 - 0.0111
[(2R,3S)-3-(hexadecanoylamino)-2-hydroxy-4-[4-[(4-methoxy-3,5-dimethylpyridin-2-yl)methoxy]phenyl]butyl]phosphonic acid
0.0088 - 0.0265
[(2R,3S)-3-(hexadecanoylamino)-2-hydroxy-4-[4-[(4-methoxy-3-methylbenzyl)oxy]phenyl]butyl]phosphonic acid
0.083
[(2R,3S)-3-(hexadecanoylamino)-2-hydroxy-4-[4-[(4-methoxypyridin-2-yl)methoxy]phenyl]butyl]phosphonic acid
-
anti configuration, pH and temperature not specified in the publication
0.0016 - 0.0035
[(2R,3S)-4-(4-[[3,5-dimethyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methoxy]phenyl)-3-(hexadecanoylamino)-2-hydroxybutyl]phosphonic acid
0.0039 - 0.0116
[(2R,3S)-4-[4-(benzyloxy)phenyl]-3-(hexadecanoylamino)-2-hydroxybutyl]phosphonic acid
0.0889 - 0.399
[(2R,3S)-4-[4-[(2,4-dichlorobenzyl)oxy]phenyl]-3-(hexadecanoylamino)-2-hydroxybutyl]phosphonic acid
0.0015 - 1.059
[(2R,3S)-4-[4-[(3,5-dimethyl-4-propoxypyridin-2-yl)methoxy]phenyl]-3-(hexadecanoylamino)-2-hydroxybutyl]phosphonic acid
0.0043 - 0.0062
[(2R,3S)-4-[4-[(3,5-dimethylbenzyl)oxy]phenyl]-3-(hexadecanoylamino)-2-hydroxybutyl]phosphonic acid
0.0044
[(2R,3S)-4-[4-[(3,5-dimethylpyridin-2-yl)methoxy]phenyl]-3-(hexadecanoylamino)-2-hydroxybutyl]phosphonic acid
-
syn configuration, pH and temperature not specified in the publication
0.011 - 0.5841
[(2R,3S)-4-[4-[(4-ethoxy-3,5-dimethylpyridin-2-yl)methoxy]phenyl]-3-(hexadecanoylamino)-2-hydroxybutyl]phosphonic acid
0.0000061
cyclohexanaminium hydrogen [[4-(decanoylamino)phenyl](fluoro)methyl]phosphonate
-
pH and temperature not specified in the publication
0.000072
cyclohexanaminium hydrogen [[4-(decanoylamino)phenyl](fluoro)methyl]phosphonate
-
pH and temperature not specified in the publication
0.000024
cyclohexanaminium hydrogen [[4-(decanoylamino)phenyl](hydroxy)methyl]phosphonate
-
pH and temperature not specified in the publication
0.0000242
cyclohexanaminium hydrogen [[4-(decanoylamino)phenyl](hydroxy)methyl]phosphonate
-
pH and temperature not specified in the publication
0.0019
H2L 7905958
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.0225
[(2R,3S)-3-(hexadecanoylamino)-2-hydroxy-4-[4-(pyridin-2-ylmethoxy)phenyl]butyl]phosphonic acid
-
anti configuration, pH and temperature not specified in the publication
0.027
[(2R,3S)-3-(hexadecanoylamino)-2-hydroxy-4-[4-(pyridin-2-ylmethoxy)phenyl]butyl]phosphonic acid
-
syn configuration, pH and temperature not specified in the publication
0.0047
[(2R,3S)-3-(hexadecanoylamino)-2-hydroxy-4-[4-[(4-methoxy-3,5-dimethylbenzyl)oxy]phenyl]butyl]phosphonic acid
-
syn configuration, pH and temperature not specified in the publication
0.2175
[(2R,3S)-3-(hexadecanoylamino)-2-hydroxy-4-[4-[(4-methoxy-3,5-dimethylbenzyl)oxy]phenyl]butyl]phosphonic acid
-
anti configuration, pH and temperature not specified in the publication
0.001
[(2R,3S)-3-(hexadecanoylamino)-2-hydroxy-4-[4-[(4-methoxy-3,5-dimethylpyridin-2-yl)methoxy]phenyl]butyl]phosphonic acid
-
syn configuration, pH and temperature not specified in the publication
0.0111
[(2R,3S)-3-(hexadecanoylamino)-2-hydroxy-4-[4-[(4-methoxy-3,5-dimethylpyridin-2-yl)methoxy]phenyl]butyl]phosphonic acid
-
anti configuration, pH and temperature not specified in the publication
0.0088
[(2R,3S)-3-(hexadecanoylamino)-2-hydroxy-4-[4-[(4-methoxy-3-methylbenzyl)oxy]phenyl]butyl]phosphonic acid
-
syn configuration, pH and temperature not specified in the publication
0.0265
[(2R,3S)-3-(hexadecanoylamino)-2-hydroxy-4-[4-[(4-methoxy-3-methylbenzyl)oxy]phenyl]butyl]phosphonic acid
-
anti configuration, pH and temperature not specified in the publication
0.0016
[(2R,3S)-4-(4-[[3,5-dimethyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methoxy]phenyl)-3-(hexadecanoylamino)-2-hydroxybutyl]phosphonic acid
-
syn configuration, pH and temperature not specified in the publication
0.0035
[(2R,3S)-4-(4-[[3,5-dimethyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methoxy]phenyl)-3-(hexadecanoylamino)-2-hydroxybutyl]phosphonic acid
-
anti configuration, pH and temperature not specified in the publication
0.0039
[(2R,3S)-4-[4-(benzyloxy)phenyl]-3-(hexadecanoylamino)-2-hydroxybutyl]phosphonic acid
-
anti configuration, pH and temperature not specified in the publication
0.0116
[(2R,3S)-4-[4-(benzyloxy)phenyl]-3-(hexadecanoylamino)-2-hydroxybutyl]phosphonic acid
-
syn configuration, pH and temperature not specified in the publication
0.0889
[(2R,3S)-4-[4-[(2,4-dichlorobenzyl)oxy]phenyl]-3-(hexadecanoylamino)-2-hydroxybutyl]phosphonic acid
-
syn configuration, pH and temperature not specified in the publication
0.399
[(2R,3S)-4-[4-[(2,4-dichlorobenzyl)oxy]phenyl]-3-(hexadecanoylamino)-2-hydroxybutyl]phosphonic acid
-
anti configuration, pH and temperature not specified in the publication
0.0015
[(2R,3S)-4-[4-[(3,5-dimethyl-4-propoxypyridin-2-yl)methoxy]phenyl]-3-(hexadecanoylamino)-2-hydroxybutyl]phosphonic acid
-
syn configuration, pH and temperature not specified in the publication
1.059
[(2R,3S)-4-[4-[(3,5-dimethyl-4-propoxypyridin-2-yl)methoxy]phenyl]-3-(hexadecanoylamino)-2-hydroxybutyl]phosphonic acid
-
anti configuration, pH and temperature not specified in the publication
0.0043
[(2R,3S)-4-[4-[(3,5-dimethylbenzyl)oxy]phenyl]-3-(hexadecanoylamino)-2-hydroxybutyl]phosphonic acid
-
syn configuration, pH and temperature not specified in the publication
0.0062
[(2R,3S)-4-[4-[(3,5-dimethylbenzyl)oxy]phenyl]-3-(hexadecanoylamino)-2-hydroxybutyl]phosphonic acid
-
anti configuration, pH and temperature not specified in the publication
0.011
[(2R,3S)-4-[4-[(4-ethoxy-3,5-dimethylpyridin-2-yl)methoxy]phenyl]-3-(hexadecanoylamino)-2-hydroxybutyl]phosphonic acid
-
anti configuration, pH and temperature not specified in the publication
0.5841
[(2R,3S)-4-[4-[(4-ethoxy-3,5-dimethylpyridin-2-yl)methoxy]phenyl]-3-(hexadecanoylamino)-2-hydroxybutyl]phosphonic acid
-
syn configuration, pH and temperature not specified in the publication
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.1035
Human serum albumin
Homo sapiens
incubating human autotaxin gamma with human serum albumin
-
0.000016
lysophosphatidic acid
Homo sapiens
reported as an inhibitor of its own production, incubating human autotaxin gamma with lysophosphatidic acid
0.0013
2-(4-[[(2,5-dichlorophenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
Homo sapiens
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.0341
2-(4-[[(3,5-bis(trifluoromethyl)phenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
Homo sapiens
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.0304
2-(4-[[(3,5-dimethylphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
Homo sapiens
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.0286
2-(4-[[(3-benzothiadiazolphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
Homo sapiens
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.0097
2-(4-[[(3-chlorophenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
Homo sapiens
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.0161
2-(4-[[(3-fluorophenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
Homo sapiens
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.0016
2-(4-[[(3-iodophenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
Homo sapiens
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.0177
2-(4-[[(3-methoxyphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
Homo sapiens
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.0135
2-(4-[[(3-methylphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
Homo sapiens
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.0009
2-(4-[[(3-trifluoromethylphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
Homo sapiens
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.0107
2-(4-[[(4-chlorophenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
Homo sapiens
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.0177
2-(4-[[(4-fluorophenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
Homo sapiens
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.0015
2-(4-[[(4-iodophenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
Homo sapiens
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.0161
2-(4-[[(4-methylphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
Homo sapiens
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.0327
2-(4-[[(4-trifluoromethylphenyl)amino]carbonothioyl]-1-piperazinyl)-8-ethyl-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid
Homo sapiens
-
1 mM each CaCl2 and MgCl2, 5 mM KCl, and 140 mM NaCl, in 50 mM Tris, pH 8.0, at 37°C
0.0003
2-amino-2-(2-(4-octylphenyl) ethyl)propan-1,3-diol
Homo sapiens
-
to 0.0004, substrate p-nitrophenyl thymidine 5-monophosphate, pH 8.0, 30 min of incubation at 37°C, measuring absorbance at 405 nm, compared to inhibitor S1P 0.0001 mM
0.0753
Human serum albumin
Homo sapiens
incubating human autotaxin beta with human serum albumin
-
0.000017
lysophosphatidic acid
Homo sapiens
reported as an inhibitor of its own production, incubating human autotaxin beta with lysophosphatidic acid
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0997
Human autotaxin gamma, p-nitrophenyl phenylphosphonate as a substrate, Vmax 1.6 nmol p-nitrophenyl/min
0.00847
human autotaxin alpha, p-nitrophenyl phenylphosphonate as a substrate, Vmax 0.67 nmol p-nitrophenyl/min
0.135
Human autotaxin beta, p-nitrophenyl phenylphosphonate as a substrate, Vmax 1.9 nmol p-nitrophenyl/min
additional information
additional information
biochemical and cell biological activity of hATX S48 protein measured
additional information
-
biochemical and cell biological activity of hATX S48 protein measured
additional information
-
phosphodiesterase activity of recombinant autotaxin is measured by using p-nitrophenyl phenylphosphonate substrate
additional information
phosphodiesterase activity of recombinant autotaxin is measured by using p-nitrophenyl phenylphosphonate substrate
additional information
-
autotaxin/lysoPLD activity is determined at the indicated substrate concentrations using conditioned medium from V5-autotaxin expressing cells as the source of enzyme and radiolabeled lysophosphatidylcholine as substrate
additional information
-
lysoPLD activity is assessed, based on the amount of choline released with lysophosphatidylcholine as the substrate, absorption spectrometry. Amounts of the substrate lysophosphatidylcholine and the product lysophosphatidic acid are also checked simultaneously. Changes in the lysoPLD activity and lysophosphatidylcholine and lysophosphatidic acid concentrations in incubated serum. Concentrations of lysophosphatidylcholine and lysophosphatidic acid increase upon incubation, the levels increase significantly as compared with those in the controls (no incubation) after 60-min incubations. Dramatic increase in the lysophosphatidic acid concentration is observed, and the lysophosphatidic acid level after 180-min incubation is about 15times higher than in the control
additional information
-
phosphodiesterase activity of recombinant autotaxin is measured by using p-nitrophenyl phenylphosphonate substrate
additional information
phosphodiesterase activity of recombinant autotaxin is measured by using p-nitrophenyl phenylphosphonate substrate
additional information
-
approx. 0 mmol/ml/min, serum from a patient with preterm labor, detection of dilution dependency of choline-producing activity of sera, diluted 100fold (serum + saline), absence of exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx. 0 mmol/ml/min, serum from a patient with severe pre-eclampsia, detection of dilution dependency of choline-producing activity of sera, diluted 30fold (serum + saline), absence of exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate , 37°C
additional information
-
approx. 0 mmol/ml/min, serum from a woman with normal pregnancy, detection of dilution dependency of choline-producing activity of sera, diluted 1fold (serum + saline), absence of exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx. 10 mmol/ml/min, serum from a woman with normal pregnancy, detection of dilution dependency of choline-producing activity of sera, diluted 30fold (serum + saline), absence of exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx. 100 mmol/ml/min, serum from a patient with preterm labor, detection of dilution dependency of choline-producing activity of sera, diluted 1fold (serum + saline), presence of 0.15 mM exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate , 37°C
additional information
-
approx. 1000 mmol/ml/min, serum from a patient with preterm labor, detection of dilution dependency of choline-producing activity of sera, diluted 100fold (serum + saline), presence of 0.15 mM exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx. 104 micromol/ml/min, serum from a patient with severe pre-eclampsia, diluted 3.3fold (serum + saline), presence of 0.15 mM exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx. 1100 mmol/ml/min, serum from a patient with severe pre-eclampsia, detection of dilution dependency of choline-producing activity of sera, diluted 100fold (serum + saline), presence of 0.15 mM exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx. 118 micromol/ml/min, serum from a patient with preterm labor (30.1 +/- 0.8 gestational weeks; n is 21), diluted 3.3fold (serum + saline), presence of 0.15 mM exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx. 139 micromol/ml/min, serum from a patient with preterm labor (30.1 +/- 0.8 gestational weeks; n is 21), diluted 3.3fold (serum + saline), presence of 0.15 mM exogenous 18:2-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx. 146 micromol/ml/min, serum from a patient with severe pre-eclampsia, diluted 3.3fold (serum + saline), presence of 0.15 mM exogenous 18:2-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx. 15 mmol/ml/min, serum from a patient with severe pre-eclampsia, detection of dilution dependency of choline-producing activity of sera, diluted 100fold (serum + saline), absence of exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx. 15 mmol/ml/min, serum from a woman with normal pregnancy, detection of dilution dependency of choline-producing activity of sera, diluted 100fold (serum + saline), absence of exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate , 37°C
additional information
-
approx. 150 mmol/ml/min, serum from a woman with normal pregnancy, detection of dilution dependency of choline-producing activity of sera, diluted 1fold (serum + saline), presence of 0.15 mM exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate , 37°C
additional information
-
approx. 153 micromol/ml/min, serum from a woman with normal pregnancy (35.8 +/- 0.7 gestational weeks; n is 25), diluted 3.3fold (serum + saline), presence of 0.15 mM exogenous 18:2-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx. 180 mmol/ml/min, serum from a patient with severe pre-eclampsia, detection of dilution dependency of choline-producing activity of sera, diluted 1fold (serum + saline), presence of 0.15 mM exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx. 200 mmol/ml/min, serum from a woman with normal pregnancy, detection of dilution dependency of choline-producing activity of sera, diluted 3.3fold (serum + saline), presence of 0.15 mM exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate , 37°C
additional information
-
approx. 300 mmol/ml/min, serum from a patient with preterm labor, detection of dilution dependency of choline-producing activity of sera, diluted 3.3fold (serum + saline), presence of 0.15 mM exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx. 350 mmol/ml/min, serum from a patient with severe pre-eclampsia, detection of dilution dependency of choline-producing activity of sera, diluted 3.3fold (serum + saline), presence of 0.15 mM exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx. 400 mmol/ml/min, serum from a woman with normal pregnancy, detection of dilution dependency of choline-producing activity of sera, diluted 10fold (serum + saline), presence of 0.15 mM exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate , 37°C
additional information
-
approx. 450 mmol/ml/min, serum from a patient with preterm labor, detection of dilution dependency of choline-producing activity of sera, diluted 10fold (serum + saline), presence of 0.15 mM exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx. 450 mmol/ml/min, serum from a patient with severe pre-eclampsia, detection of dilution dependency of choline-producing activity of sera, diluted 10fold (serum + saline), presence of 0.15 mM exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx. 450 mmol/ml/min, serum from a woman with normal pregnancy, detection of dilution dependency of choline-producing activity of sera, diluted 30fold (serum + saline), presence of 0.15 mM exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate , 37°C
additional information
-
approx. 49 micromol/ml/min, serum from a patient with moderate pre-eclampsia, diluted 3.3fold (serum + saline), presence of 0.15 mM exogenous 18:2-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx. 5 mmol/ml/min, serum from a woman with normal pregnancy, detection of dilution dependency of choline-producing activity of sera, diluted 10fold (serum + saline), absence of exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx. 500 mmol/ml/min, serum from a patient with preterm labor, detection of dilution dependency of choline-producing activity of sera, diluted 30fold (serum + saline), presence of 0.15 mM exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx. 500 mmol/ml/min, serum from a patient with severe pre-eclampsia, detection of dilution dependency of choline-producing activity of sera, diluted 30fold (serum + saline), presence of 0.15 mM exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx. 60 mmol/ml/min, serum from a patient with preterm labor, detection of dilution dependency of choline-producing activity of sera, diluted 1fold (serum + saline), absence of exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx. 65 mmol/ml/min, serum from a patient with preterm labor, detection of dilution dependency of choline-producing activity of sera, diluted 10fold (serum + saline), absence of exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate , 37°C
additional information
-
approx. 65 mmol/ml/min, serum from a patient with preterm labor, detection of dilution dependency of choline-producing activity of sera, diluted 3.3fold (serum + saline), absence of exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx. 65 mmol/ml/min, serum from a patient with severe pre-eclampsia, detection of dilution dependency of choline-producing activity of sera, diluted 1fold (serum + saline), absence of exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx. 700 mmol/ml/min, serum from a woman with normal pregnancy, detection of dilution dependency of choline-producing activity of sera, diluted 100fold (serum + saline), presence of 0.15 mM exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx. 8 mmol/ml/min, serum from a patient with preterm labor, detection of dilution dependency of choline-producing activity of sera, diluted 30fold (serum + saline), absence of exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate , 37°C
additional information
-
approx. 8 mmol/ml/min, serum from a woman with normal pregnancy, detection of dilution dependency of choline-producing activity of sera, diluted 3.3fold (serum + saline), absence of exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate , 37°C
additional information
-
approx. 80 mmol/ml/min, serum from a patient with severe pre-eclampsia, detection of dilution dependency of choline-producing activity of sera, diluted 3.3fold (serum + saline), absence of exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx. 90 micromol/ml/min, serum from a woman with normal pregnancy (35.8 +/- 0.7 gestational weeks; n is 25), diluted 3.3fold (serum + saline), presence of 0.15 mM exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx. 92 micromol/ml/min, serum from a patient with moderate pre-eclampsia, diluted 3.3fold (serum + saline), presence of 0.15 mM exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate, 37°C
additional information
-
approx.50 mmol/ml/min, serum from a patient with severe pre-eclampsia, detection of dilution dependency of choline-producing activity of sera, diluted 10fold (serum + saline), absence of exogenous 16:0-lysophosphatidylcholine, radiolabeled substrate , 37°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
9
alpha isoform is almost insensitive to pH, whereas the beta isoform presents a maximal activity at pH 9
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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
Various concentrations of hATX S48 protein are exposed to HT-1080 cells and motile area is analyzed. hATX S48 protein also affects cell proliferation
-
LysoPLD activity is determined in culture medium from control cells or cells expressing V5-autotaxin (ATX)
-
Detection of lysophospholipase D/autotoxin (lysoPLD/ATX) antigen in the urine samples of patients with nephrotic syndrome, both with active and inactive disease states. LysoPLD/ATX antigen detection in the urine and its concentrations seem to be correlated with the total urinary protein concentrations
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
-
serum lysoPLD/ATX activity might be substantially altered when the urinary protein excretion is enhanced. Correlation between the lysoPLD/ATX activity and albumin concentration in the serum. Analysis of the serum lysophospholipase D/autotoxin (lysoPLD/ATX) activity and albumin in patients with nephrotic syndrome
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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
-
-
expression of V5-tagged autotaxin/lysoPLD in HEK293 cells, Western blotting experiments reveal that most of the recombinant autotaxin/lysoPLDaccumulates extracellularly
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
additional information
malfunction
-
a recombinant ATX mutant, lacking lysoPLD activity, or heat-inactived ATX also induces lung epithelial cell migration
malfunction
-
ATX SMB2 mutants with impaired binding to beta3 integrins display reduced LPA generating capacity. Mutation of a charged, surface-exposed residue at the N-terminus of the ATX SMB2 domain significantly reduces binding of ATX to platelet integrins. The effects of ATX on platelet and cell-associated LPA production, but not hydrolysis of small molecule or detergent-solubilized substrates, are attenuated by point mutations in the SMB2 that impair integrin binding
physiological function
-
ATX promotes the migrations of THP-1 and Jurkat cells via Gi-signaling pathway
physiological function
-
expression of autotaxin by cancer cells controls osteolytic bone metastasis formation
physiological function
-
the autotaxin-lysophosphatidic acid receptor axis plays a causal role in breast tumorigenesis and cancer-related inflammation
physiological function
-
the enzyme controls the blood concentration of lysophosphatidic acid
physiological function
-
ATX moderately facilitates platelet adhesion to fibrinogen, synergistic effect of platelet activation and ATX on LPA generation. ATX binding to platelet integrins enables agonist-stimulated LPA production. The lysophospholipase D generates the bioactive lipid mediator lysophosphatidic acid. Integrin-bound ATX can access cell surface substrates and deliver LPA to cell surface receptors
physiological function
-
ATX stimulates tumour-cell migration, angiogenesis and metastasis
physiological function
-
autotaxin is a catalytic protein, which possesses lysophospholipase D activity producing lysophosphatidic acid, and is involved in cellular membrane lipid metabolism and remodeling. It acts as a culprit protein for cancer, which potently stimulates cancer cell proliferation and tumor cell motility, augments the tumorigenicity and induces angiogenic responses. Lysophosphatidic acid 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 also catalyzes the formation of cyclic phosphatidic acid, which have antitumor role by antimitogenic regulation of cell cycle, inhibition of cancer invasion and metastasis
physiological function
-
autotaxin is a secreted lysophospholipase D that hydrolyzes lysophosphatidylcholine into lysophosphatidic acid, initiating signaling cascades leading to cancer metastasis, wound healing, and angiogenesis
physiological function
-
autotaxin is a secreted soluble enzyme that generates lysophosphatidic acid through its lysophospholipase D activity
physiological function
-
autotaxin is an enzyme present in the blood and responsible for biosynthesis of lysophosphatidic acid
physiological function
-
lysophospholipase D hydrolyzes lysophosphatidylcholine to form the bioactive lipid lysophosphatidic acid
physiological function
-
secreted autotaxin, which exhibits lysophospholipase D activity, stimulates lung epithelial cell migration through lysophosphatidic acid generation-dependent and -independent pathways lung cell migration is a crucial step for re-epithelialization that in turn is essential for remodelling and repair after lung injury, overview. Extracellular ATX stimulates cell migration through G?i-coupled LPA receptors, cytoskeleton rearrangement, phosphorylation of PKC delta and cortactin at the leading edge of migrating cells. Cortactin regulates ATX-V5-induced cell migration
physiological function
-
the enzyme and its reaction product lysophosphatidic acid have a critical role in lymphocyte migration to secondary lymphoid organs, involvement of the enzyme in inflammatory bowel disease patients, the enzyme/lysophosphatidic acid has a role in the migration of lymphocytes to the inflamed intestine
physiological function
-
the enzyme is involved in synthesis of lysophosphatidic acid, a phospholipid growth factor acting via specific receptors (LPA1R to LPA6R) and involved in several pathologies including obesity. ATX/LPA signaling impairs glucose homeostasis, regulation of obesity involves the enzyme, overview
physiological function
-
the enzyme is the primary lysophosphatidic acid-producing phospholipase. Enzyme-lysophosphatidic acid signaling is essential for development and has been implicated in a great diversity of (patho)physiological processes, ranging from lymphocyte homing to tumor progression. Isozyme ATX alpha but not ATX beta binds abundantly to cultured mammalian cells in a manner strictly dependent on heparan sulfate. By mediating bindings to heparan sulfate proteoglycans, the isozyme ATXalpha insertion loop likely serves to target LPA production close to the lysophosphatidic acid receptors
physiological function
-
the enzyme promotes MDA-MB-231 breast cancer cell and mouse aortic vascular smooth muscle cell migration in lysophosphatidic acid-dependent and -independent ways, overview. The enzyme binds to integrin adhesion receptors required for cell migration. Integrin-mediated cell surface binding results in enzyme uptake and intracellular trafficking, critical for the ability of the enzyme to promote rapid directionally persistent MDA-MB-231 cell migration
additional information
-
ATX interacts with integrins, possible role for the solvent-exposed surface of the N-terminal tandem somatomedin B-like domains in binding to platelet integrin alphaIIbbeta3. The opposite face of the somatomedin B-like domain interacts with the catalytic phosphodiesterase domain to form a hydrophobic channel through which lysophospholipid substrates enter and leave the active site. Integrin binding therefore localizes ATX activity to the cell surface, providing a mechanism to generate LPA in the vicinity of its receptors
additional information
-
extracelluar ATX binds to the LPA receptor and integrin beta4 complex on A-549 cell surface
additional information
-
the ability of ATX to drive cell migration is enhanced by the presence of the ATX substrate lysophosphocholine
additional information
-
Thr210 coordinates one of the two catalytic zinc ions and hydrogen bonds with the phosphate or sulfate in the active site. Kinetics of ATX depend strongly on the substrate identity, suggesting that ATX could display different kinetic profiles for the various in vivo substrates
additional information
-
the tripartite catalytic domain shows shallow groove and a deep hydrophobic pocket, and an open tunnel, which forms a sort of T-junction with the shallow groove, substrate binding structure, overview. The enzyme contains a SMB domain that mediates the binding to cell surface integrins
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). ENPP2_HUMAN
863
1
98994
Swiss-Prot
Secretory Pathway (Reliability: 4)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
100000
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
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
100000
-
immunoblotting, 3D1 antibody (1/500), a polyclonal antibody raised against the peptide sequence in autotaxin CKKPDQHFKPYMKQHLPKRL and a polyclonal antibody to amino acids 541-720 of autotoxin
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
domains discovered are adjacent somatomedin B-like domain, nuclease-like domain and a single EF hand-like motif, modulator of oligodendrocyte remodeling and focal adhesion organization (MORFO) domain is located at the C-terminal end of the protein and entails the nuclease-like domain not thought to be catalytically active and functions independently of ATX's enzymatic activity
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
glycoprotein
proteolytic modification
-
ATX is synthesized as a preproenzyme and proteolytically processed, the mature protein is secreted
glycoprotein
-
ATX is synthesized as pre-pro-enzyme and secreted upon removal of the N-terminal signal peptide and further trimming by a furine-type protease
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant ATX alpha isoform, hanging-drop vapour diffusion method, X-ray diffraction structure determination and analysis at 3.0 A resolution
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
H226Q
-
the mutation impairs substrate hydrolysis, with hydrolysis of artificial substrates being disproportionately lower than that of lysophosphatidylcholine
H420Q
-
the mutation does not inhibit the wild type migration response or hydrolytic activity
H434Q
-
the mutation impairs substrate hydrolysis, with hydrolysis of artificial substrates being disproportionately lower than that of lysophosphatidylcholine
additional information
additional information
-
autotaxin gamma, share 100% identity with the splice variant NPP2gamma, except for the 25-amino acid insertion located between Glu593 and Glu594
additional information
autotaxin gamma, share 100% identity with the splice variant NPP2gamma, except for the 25-amino acid insertion located between Glu593 and Glu594
additional information
rhATX S48 site-directed mutagenesis, recombinant human ATX, creation of a full-length recombinant molecule by using prokaryotic cells. Shows lysoPLD enzymatic activity. hATX S48 Ser-48-C terminal of human ATX-T (L46720) cDNA is amplified. hATX S48 protein shows both lysoPLD and PDE activity
additional information
-
rhATX S48 site-directed mutagenesis, recombinant human ATX, creation of a full-length recombinant molecule by using prokaryotic cells. Shows lysoPLD enzymatic activity. hATX S48 Ser-48-C terminal of human ATX-T (L46720) cDNA is amplified. hATX S48 protein shows both lysoPLD and PDE activity
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
activity decreases when binding to bead-linked anti-ATX-antibody, remaining enzyme activity is measured (radiolabled substrate). Afterwards the precipitated beads are incubated with 100 mM glycine buffer, 48°C, 1 h for recovering the enzyme activity. Subsequently the remaining enzyme activity is measured (radiolabeled substrate). Results: endogenous substrate 20% activity can be recovered (75% lost before) for serum from a woman with normal pregnancy, 6% activity can be recovered (76% lost before) for serum from a patient with severe pre-eclampsia, 13% activity can be recovered (70% lost due to antibody binding) for serum from a patient with preterm labor. Results exogenous substrate 80% activity can be recovered (75% lost before) for serum from a woman with normal pregnancy, 6% activity can be recovered (70% lost before) for serum from a patient with severe pre-eclampsia, 13% activity can be recovered (90% lost due to antibody binding) for serum from a patient with preterm labor
-
lysoPLD activity is found to be very stable, the activity shows no change even after 180-min incubation at 37°C
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
gel filtration, SDSPAGE. Establish purification protocol for recombinant hATX S48 protein. Introduction of the construction of an expression system with Escherichia coli and purification methods for the active recombinant molecule of human ATX
from CHO cells: sequential metal ion affinity and gel filtration chromatography, exchanged into phosphate-buffered saline and concentrated to 1 mg/ml of monomeric autotaxin by centrifugal filtration
-
prepared from a Vaccinia viral lysate through the concanavalin A-agarose step
-
recombinant ATX-Fc fusion protein from HEK-293 cells cell medium by affinity chromatography with protein A sepharose followed by cleavage with thrombin. Detagged ATX protein is further purified to essential homogeneity by gel filtration
-
recombinant His-tagged ATX alpha isoform from Escherichia coli strain BL21 (DE3) by nickel affinity chromatography and gel filtration
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21 and Escherichia coli TOP10 strain. Construction of an expression system with Escherichia coli and purification methods for the active recombinant molecule of human ATX
expressed in two different hosts, Sf9 insect cells and CHO cells, expressed in COS cells
transfection of FTC-238 cells with pEGFP-C3/ATX-construct for secretion of expressed ATX and with pD38tm/ATX-construct for production of membrane-anchored ATX respectively. sATX clones show higher cell motility than mATX clones (transwell filter assay), addition of interleukin-1beta to culture medium reduces cell motility due to downregulating ATX gene activity (mRNA expression level analysed by quantitative-RT-PCR), colony soft agar assay of sATX-clones results in bigger amount and bigger diameter of colonies compared to mATX-clones
alpha isoform of ATX, overexpression of the His-tagged enzyme in Escherichia coli strain BL21 (DE3)
-
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
functional expression of the ATX-Fc fusion protein in HEK-293 cells with secretion of the enzyme to the medium
-
functional overexpression of V5-tagged ATX and secretion into conditioned medium
-
generate mouse overexpressing circulating autotaxin: amplification of human 1-antitrypsin (A1AT) promoter by PCR (from a Yac clone obtained from ATCC), injection of DNA into pronuclei of 1-cellstage FVB mouse embryos, transfer of injected cells into the oviduct of pseudopregnant female mouse. Transfection of CHO cells with a vector for expression of a fusion protein containing the human immunoglobulin-kappa chain leader sequence, a His-tag, and a cDNA-sequence encoding aminoacids 52-915 of human autotaxin-gamma
-
human ATX cDNA cloned with a C-terminal His-tag in pcDNA3 for transfection of HEK293T cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
autotaxin activity is unaffected by treatment with eicosapentaenoic acid and docosahexaenoic acid, and aspirin has no effect on any endpoint
-
enhanced enzyme expression in the inflamed mucosa from Crohn's disease and ulcerative colitis patients, the enzyme expression is remarkably higher in the actively inflamed mucosa than in the quiescent mucosa in the same patient
-
enzyme expression is up-regulated in obese patients in relationship with insulin resistance and impaired glucose tolerance
-
lipopolysaccharides challenge induces ATX expression and release into the medium
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
ATX is one of the target molecules for cancer therapy, therefore the immuno-neutralization by an antibody which is able to recognize the catalytic site, or the low molecular weight chemical inhibitors based on structural biology should be a useful tool for prevention or treatment of tumor progression and metastasis
medicine
autotaxin gene expression is significantly higher in neoplastic endometrium compared with normal tissue. The expression of autotaxin is significantly elevated in type I endometrial cancer compared to type II, in premenopausal women and in patients affected either by obesity or diabetes
analysis
-
the purified ATX protein is enzymatically active and biologically functional, offering a useful tool for further biological and structural studies of this important enzyme
diagnostics
-
lysoPLD assay can be applied to clinical laboratory testing. Serum lysoPLD activity in healthy female subjects is significantly higher than that in male subjects. It seems likely that lysoPLD and its product lysophosphatidic acid participate in female reproductive biology. lysoPLD assay method seems to be promising for laboratory testing because it allows easy handling of the samples
drug development
medicine
medicine
-
survival factor, preventing serum-deprivation induced apoptosis in fibroblasts through extracellular activation of LPA signaling pathway
medicine
-
tumor cell motility-stimulating factor, implicated in the progression of tumor
medicine
-
the autotaxin-lysophosphatidic acid receptor axis is a rich therapeutic target in cancer
medicine
-
autotaxin is an attractive target for the anticancer therapeutics that inhibit angiogenesis, invasion, and migration
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ward, W.H.J.; Fersht, A.R.
Asymmetry of tyrosyl-tRNA synthetase in solution
Biochemistry
27
1041-1049
1988
Homo sapiens
Xie, Y.; Meier, K.E.
Lysophospholipase D and its role in LPA production
Cell. Signal.
16
975-981
2004
Bos taurus, Oryctolagus cuniculus, Homo sapiens, Rattus norvegicus
Kishi, Y.; Okudaira, S.; Kishi, M.; Hama, K.; Shida, D.; Kitayama, J.; Yamori, T.; Aoki, J.; Fujimaki, T.; Arai, H.
Autotaxin is overexpressed in glioblastoma multiforme and contributes to cell motility of glioblastoma by converting lysophosphatidylcoholine to lysophosphatidic acid
J. Biol. Chem.
281
17492-17500
2006
Homo sapiens
Song, J.; Clair, T.; Noh, J.H.; Eun, J.W.; Ryu, S.Y.; Lee, S.N.; Ahn, Y.M.; Kim, S.Y.; Lee, S.H.; Park, W.S.; Yoo, N.J.; Lee, J.Y.; Nam, S.W.
Autotaxin (lysoPLD/NPP2) protects fibroblasts from apoptosis through its enzymatic product, lysophosphatidic acid, utilizing albumin-bound substrate
Biochem. Biophys. Res. Commun.
337
967-975
2005
Homo sapiens
Tanaka, M.; Kishi, Y.; Takanezawa, Y.; Kakehi, Y.; Aoki, J.; Arai, H.
Prostatic acid phosphatase degrades lysophosphatidic acid in seminal plasma
FEBS Lett.
571
197-204
2004
Homo sapiens
Kehlen, A.; Englert, N.; Seifert, A.; Klonisch, T.; Dralle, H.; Langner, J.; Hoang-Vu, C.
Expression, regulation and function of autotaxin in thyroid carcinomas
Int. J. Cancer
109
833-838
2004
Homo sapiens
Clair, T.; Koh, E.; Ptaszynska, M.; Bandle, R.W.; Liotta, L.A.; Schiffmann, E.; Stracke, M.L.
L-histidine inhibits production of lysophosphatidic acid by the tumor-associated cytokine, autotaxin
Lipids Health Dis.
4
DOI:10.1186/1476-511X-4-5
2005
Homo sapiens
-
Ferguson, C.G.; Bigman, C.S.; Richardson, R.D.; van Meeteren, L.A.; Moolenaar, W.H.; Prestwich, G.D.
Fluorogenic phospholipid substrate to detect lysophospholipase D/autotaxin activity
Org. Lett.
8
2023-2026
2006
Homo sapiens
Clair, T.; Koh, E.; Ptaszynska, M.; Bandle, R.W.; Liotta, L.A.; Schiffmann, E.; Stracke, M.L.
L-histidine inhibits production of lysophosphatidic acid by the tumor-associated cytokine, autotaxin
Lipids Health Dis.
4
5-5
2005
Homo sapiens
Nakamura, K.; Ohkawa, R.; Okubo, S.; Tozuka, M.; Okada, M.; Aoki, S.; Aoki, J.; Arai, H.; Ikeda, H.; Yatomi, Y.
Measurement of lysophospholipase D/autotaxin activity in human serum samples
Clin. Biochem.
40
274-277
2007
Homo sapiens
Nakamura, K.; Nangaku, M.; Ohkawa, R.; Okubo, S.; Yokota, H.; Ikeda, H.; Aoki, J.; Yatomi, Y.
Analysis of serum and urinary lysophospholipase D/autotaxin in nephrotic syndrome
Clin. Chem. Lab. Med.
46
150-151
2008
Homo sapiens
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)
Morris, A.J.; Smyth, S.S.
Measurement of autotaxin/lysophospholipase D activity
Methods Enzymol.
434
89-104
2007
Homo sapiens, Mammalia
Haga, A.; Hashimoto, K.; Tanaka, N.; Nakamura, K.T.; Deyashiki, Y.
Scalable purification and characterization of the extracellular domain of human autotaxin from prokaryotic cells
Protein Expr. Purif.
59
9-17
2008
Homo sapiens (Q13822), Homo sapiens
Yuelling, L.M.; Fuss, B.
Autotaxin (ATX): a multi-functional and multi-modular protein possessing enzymatic lysoPLD activity and matricellular properties
Biochim. Biophys. Acta
1781
525-530
2008
Homo sapiens
van Meeteren, L.A.; Brinkmann, V.; Saulnier-Blache, J.S.; Lynch, K.R.; Moolenaar, W.H.
Anticancer activity of FTY720: phosphorylated FTY720 inhibits autotaxin, a metastasis-enhancing and angiogenic lysophospholipase D
Cancer Lett.
266
203-208
2008
Homo sapiens
Pamuklar, Z.; Federico, L.; Liu, S.; Umezu-Goto, M.; Dong, A.; Panchatcharam, M.; Fulerson, Z.; Berdyshev, E.; Natarajan, V.; Fang, X.; van Meeteren, L.A.; Moolenaar, W.H.; Mills, G.B.; Morris, A.J.; Smyth, S.S.
Autotaxin/lysopholipase D and lysophosphatidic acid regulate murine hemostasis and thrombosis
J. Biol. Chem.
284
7385-7394
2009
Homo sapiens
Tokumura, A.; Kume, T.; Taira, S.; Yasuda, K.; Kanzaki, H.
Altered activity of lysophospholipase D, which produces bioactive lysophosphatidic acid and choline, in serum from women with pathological pregnancy
Mol. Hum. Reprod.
15
301-310
2009
Homo sapiens
Seifert, A.; Klonisch, T.; Wulfaenger, J.; Haag, F.; Dralle, H.; Langner, J.; Hoang-Vu, C.; Kehlen, A.
The cellular localization of autotaxin impacts on its biological functions in human thyroid carcinoma cells
Oncol. Rep.
19
1485-1491
2008
Homo sapiens (Q13822), Homo sapiens
Wakelam, M.; Powner, D.; Pettitt, T.
Determination of phospholipase D, lysophospholipase D and DG kinase signaling pathways in disease states by mass spectrometry
Adv. Enzyme Regul.
48
254-260
2008
Homo sapiens
Iwasawa, Y.; Fujii, T.; Nagamatsu, T.; Kawana, K.; Okudaira, S.; Miura, S.; Matsumoto, J.; Tomio, A.; Hyodo, H.; Yamashita, T.; Oda, K.; Kozuma, S.; Aoki, J.; Yatomi, Y.; Taketani, Y.
Expression of autotaxin, an ectoenzyme that produces lysophosphatidic acid, in human placenta
Am. J. Reprod. Immunol.
62
90-95
2009
Homo sapiens
Li, S.; Zhang, J.
Lipopolysaccharide induces autotaxin expression in human monocytic THP-1 cells
Biochem. Biophys. Res. Commun.
378
264-268
2009
Homo sapiens
Hoeglund, A.B.; Howard, A.L.; Wanjala, I.W.; Pham, T.C.; Parrill, A.L.; Baker, D.L.
Characterization of non-lipid autotaxin inhibitors
Bioorg. Med. Chem.
18
769-776
2010
Homo sapiens
Liu, S.; Murph, M.; Panupinthu, N.; Mills, G.B.
ATX-LPA receptor axis in inflammation and cancer
Cell Cycle
8
3695-3701
2009
Homo sapiens
Hoeglund, A.B.; Bostic, H.E.; Howard, A.L.; Wanjala, I.W.; Best, M.D.; Baker, D.L.; Parrill, A.L.
Optimization of a pipemidic acid autotaxin inhibitor
J. Med. Chem.
53
1056-1066
2010
Homo sapiens
Koh, E.; Bandle, R.W.; Roberts, D.D.; Stracke, M.L.; Clair, T.
Novel point mutations attenuate autotaxin activity
Lipids Health Dis.
8
4-4
2009
Homo sapiens
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
Block, R.C.; Duff, R.; Lawrence, P.; Kakinami, L.; Brenna, J.T.; Shearer, G.C.; Meednu, N.; Mousa, S.; Friedman, A.; Harris, W.S.; Larson, M.; Georas, S.
The effects of EPA, DHA, and aspirin ingestion on plasma lysophospholipids and autotaxin
Prostaglandins Leukot. Essent. Fatty Acids
82
87-95
2010
Homo sapiens
Inoue, K.; Tanaka, N.; Haga, A.; Yamasaki, K.; Umeda, T.; Kusakabe, Y.; Sakamoto, Y.; Nonaka, T.; Deyashiki, Y.; Nakamura, K.T.
Crystallization and preliminary X-ray crystallographic analysis of human autotaxin
Acta Crystallogr. Sect. F
67
450-453
2011
Homo sapiens
Tania, M.; Khan, A.; Zhang, H.; Li, J.; Song, Y.
Autotaxin: a protein with two faces
Biochem. Biophys. Res. Commun.
401
493-497
2010
Homo sapiens
Zhao, J.; He, D.; Berdyshev, E.; Zhong, M.; Salgia, R.; Morris, A.J.; Smyth, S.S.; Natarajan, V.; Zhao, Y.
Autotaxin induces lung epithelial cell migration through lysoPLD activity-dependent and -independent pathways
Biochem. J.
439
45-55
2011
Homo sapiens
East, J.E.; Kennedy, A.J.; Tomsig, J.L.; De Leon, A.R.; Lynch, K.R.; Macdonald, T.L.
Synthesis and structure-activity relationships of tyrosine-based inhibitors of autotaxin (ATX)
Bioorg. Med. Chem. Lett.
20
7132-7136
2010
Homo sapiens
Jiang, G.; Madan, D.; Prestwich, G.D.
Aromatic phosphonates inhibit the lysophospholipase D activity of autotaxin
Bioorg. Med. Chem. Lett.
21
5098-5101
2011
Homo sapiens
Song, Y.; Dilger, E.; Bell, J.; Barton, W.A.; Fang, X.
Large scale purification and characterization of recombinant human autotaxin/lysophospholipase D from mammalian cells
BMB Rep.
43
541-546
2010
Homo sapiens
Ueda, K.; Yoshihara, M.; Nakao, M.; Tanaka, T.; Sano, S.; Fukuzawa, K.; Tokumura, A.
Evaluation of inhibitory actions of flavonols and related substances on lysophospholipase D activity of serum autotaxin by a convenient assay using a chromogenic substrate
J. Agric. Food Chem.
58
6053-6063
2010
Homo sapiens
Saunders, L.P.; Cao, W.; Chang, W.C.; Albright, R.A.; Braddock, D.T.; De La Cruz, E.M.
Kinetic analysis of autotaxin reveals substrate-specific catalytic pathways and a mechanism for lysophosphatidic acid distribution
J. Biol. Chem.
286
30130-30141
2011
Homo sapiens
Fulkerson, Z.; Wu, T.; Sunkara, M.; Kooi, C.V.; Morris, A.J.; Smyth, S.S.
Binding of autotaxin to integrins localizes lysophosphatidic acid production to platelets and mammalian cells
J. Biol. Chem.
286
34654-34663
2011
Homo sapiens
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
Wu, T.; Kooi, C.V.; Shah, P.; Charnigo, R.; Huang, C.; Smyth, S.S.; Morris, A.J.
Integrin-mediated cell surface recruitment of autotaxin promotes persistent directional cell migration
FASEB J.
28
861-870
2014
Homo sapiens
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.
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
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
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