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Information on EC 6.3.4.5 - argininosuccinate synthase and Organism(s) Mus musculus and UniProt Accession P16460
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6.3.4.5 argininosuccinate synthaseSpecify your search results
Word Map
- 6.3.4.5
- ornithine
- citrullinemia
- arginase
- ammonia
- hyperammonemia
- deiminase
-
transcarbamylase
- l-arginine
-
pegylated
-
auxotrophic
-
adi-peg20
-
carbamyl
-
adult-onset
- coma
- argininosuccinase
- carbamoylphosphate
-
carbamoyltransferase
-
citrin
- tropoelastin
-
urea-cycle
-
consciousness
- medicine
-
ureogenesis
-
elastogenesis
-
ornithine-urea
-
elastin-derived
- jararaca
-
coinduction
-
bothrops
- n-acetylglutamate
- drug development
- molecular biology
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
Synonyms
argininosuccinate synthetase, argininosuccinate synthase, elastin-binding protein, argininosuccinate synthase 1, argininosuccinic acid synthetase, arginine succinate synthetase, citrulline-aspartate ligase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Arginine succinate synthetase
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-
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Argininosuccinate synthetase
Argininosuccinic acid synthetase
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-
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ASS
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-
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Citrulline--aspartate ligase
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Citrulline-aspartate ligase
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Elastin-binding protein
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-
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Synthetase, argininosuccinate
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-
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Argininosuccinate synthetase
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-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + L-citrulline + L-aspartate = AMP + diphosphate + 2-(Nomega-L-arginino)succinate
it is found that argininosuccinate synthetase is the major lipid A-interacting protein in liver. Argininosuccinate synthetase also inhibits the biological activities of natural lipid A and rough-type lipopolysaccharide and but not smooth-type lipopolysaccharide. Argininosuccinate synthetase enzyme activity is inhibited by lipid A and rough-type lipopolysaccharide and smooth-type lipopolysaccharide.
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
amination
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PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
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-, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
L-citrulline:L-aspartate ligase (AMP-forming)
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CAS REGISTRY NUMBER
COMMENTARY
9023-58-9
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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
ATP + citrulline + aspartate
AMP + diphosphate + 2-(Nomega-L-arginino)succinate
assay at pH 7.8, 37°C, reaction stopped by addition of molybdate buffer
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-
?
ATP + L-citrulline + L-aspartate
AMP + diphosphate + 2-(Nomega-L-arginino)succinate
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-
-
-
?
ATP + L-citrulline + L-aspartate
AMP + diphosphate + 2-(Nomega-L-arginino)succinate
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rate-limiting enzyme of the urea cycle
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-
?
ATP + L-citrulline + L-aspartate
AMP + diphosphate + L-argininosuccinate
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-
-
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?
ATP + L-citrulline + L-aspartate
AMP + diphosphate + L-argininosuccinate
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catalyzes the coupling reaction between citrulline and arginine to form argininosuccinic acid
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?
ATP + L-citrulline + L-aspartate
AMP + diphosphate + L-argininosuccinate
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the rate-limiting enzyme for converting citrulline to arginine
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?
additional information
?
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involved in L-arginine synthesis from L-citrulline, urea cycle, rate-limiting enzyme for high output NO generation, inducible enzyme, AS synthesis is more strictly regulated at the posttranscriptional than the transcriptional level in vivo
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?
additional information
?
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urea cycle, enzyme of citrulline-arginine recycling, which is important for high output production of NO in activated microglial cells, inducible enzyme
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?
additional information
?
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ASS binds to and inactivates lipopolysaccharide and lipid A, overview
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-
?
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
ATP + L-citrulline + L-aspartate
AMP + diphosphate + 2-(Nomega-L-arginino)succinate
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rate-limiting enzyme of the urea cycle
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-
?
ATP + L-citrulline + L-aspartate
AMP + diphosphate + L-argininosuccinate
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the rate-limiting enzyme for converting citrulline to arginine
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?
additional information
?
-
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involved in L-arginine synthesis from L-citrulline, urea cycle, rate-limiting enzyme for high output NO generation, inducible enzyme, AS synthesis is more strictly regulated at the posttranscriptional than the transcriptional level in vivo
-
?
additional information
?
-
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urea cycle, enzyme of citrulline-arginine recycling, which is important for high output production of NO in activated microglial cells, inducible enzyme
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?
additional information
?
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ASS binds to and inactivates lipopolysaccharide and lipid A, overview
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-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
alpha-methyl-DL-aspartic acid
specific inhibitor for Ass1, can significantly increase the rate of embryonic reabsorption
diphosphoryl lipid A (DPL)
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DPL from Escherichia coli, inhibits argininosuccinate synthetase in a dose-dependent manner, concentration for half inhibition of argininosuccinate synthetase enzyme activity: 0.039 mg/ml
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monophosphoryl lipid A (MPL)
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MPL from Escherichia coli, inhibits argininosuccinate synthetase in a dose-dependent manner, concentration for half inhibition of argininosuccinate synthetase enzyme activity: 0.270 mg/ml
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R-lipopolysaccharide (LPS)
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rough-type LPS from Escherichia coli, inhibits argininosuccinate synthetase in a dose-dependent manner, concentration for half inhibition of argininosuccinate synthetase enzyme activity: 0.230 mg/ml
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recombinant mycoplasma arginine deiminase
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36% decrease in AS activity after rADI treatment
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S-lipopolysaccharide (LPS)
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smooth-type-LPS from Escherichia coli, inhibits argininosuccinate synthetase in a dose-dependent manner, concentration for half inhibition of argininosuccinate synthetase enzyme activity: 0.024 mg/ml
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sodium 2-deoxy-2-(3S-(9-phenyl-nonanoyl-oxy) tetradecanoyl) amino-3-O-(9-phenyl-nonanoyl)-D-glucopyranose 4-sulfate
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synthesized lipid A analog, inhibits argininosuccinate synthetase in a dose-dependent manner, concentration for half inhibition of argininosuccinate synthetase enzyme activity: 0.0065 mg/ml
additional information
-
study of the effect of recombinant mycoplasma arginine deiminase on cell proliferation, good correlation of the high resistance to this treatment with a high AS activity in the cell line
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
lipopolysaccharide
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argininosuccinate synthase accumulates in circulation within 1 h after treatment with both lipopolysaccharide alone and hepatotoxic combination of lipopolysaccharide and D-Galactosamine. Enzyme physically binds to lipopolysaccharide
additional information
interaction with Bj-BPP-10c, snake venom anti-hypertensive peptide of Botrops jararaca, activates the catalytic activity of argininosuccinate snythetase in a dose-dependent manner
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additional information
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AS mRNA is 4-6fold induced by Escherichia coli lipopolysaccharide and mouse interferon-gamma, kinetics of induction
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additional information
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inducible enzyme, immunostimulation of AS synthesis with lipopolysaccharide or cytokines, such as TNF-alpha, interleukin 1 and interferon-gamma
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
Mus musculus
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substrate: diphosphoryl lipid A, IC50: 0.039 mg/ml
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additional information
additional information
Mus musculus
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substrate: monophosphoryl lipid A, IC50: 0.270 mg/ml
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additional information
additional information
Mus musculus
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substrate: R-lipopolysaccharide, IC50: 0.230 mg/ml
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additional information
additional information
Mus musculus
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substrate: S-lipopolysaccharide, IC50: 0.024 mg/ml
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additional information
additional information
Mus musculus
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substrate: sodium 2-deoxy-2-(3S-(9-phenyl-nonanoyl-oxy) tetradecanoyl) amino-3-O-(p-phenyl-nonanoyl)-D-glucopyranose 4-sulfate (ONO-4007), IC50: 0.0065 mg/ml
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
Ass1 is highly expressed in mouse decidua and uterine stromal cells undergoing decidualization, and argininosuccinate lyase Asl is weakly expressed in mouse decidua and uterine stromal cells undergoing decidualization
Ass1 is highly expressed in mouse decidua and uterine stromal cells undergoing decidualization, and argininosuccinate lyase Asl is weakly expressed in mouse decidua and uterine stromal cells undergoing decidualization
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
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recombinant argininosuccinate synthase reduces lipolysaccharide cytotoxicity, TNF-alpha production, and increases cell viability in cultured mouse macrophages, even when added one h following lipopolysaccharide challenge. Intraperitoneal injection of recombinant argininosuccinate synthase at 5 mg/kg after treatment with a high dose of lipopolysaccharide remarkably increases survival of rodents, with a concomitant decrease of sepsis markers TNF-alpha, C-reactive protein, and lactate dehydrogenase levels in blood
physiological function
part of citrulline-NO cycle, limiting step in NO synthesis
physiological function
argininosuccinate synthase 1 (ASS1), is directly transactivated by p53 in response to genotoxic stress, resulting in the rearrangement of arginine metabolism. x-Ray irradiation promotes the systemic induction of Ass1 and concomitantly increases plasma arginine levels in p53+/+ mice but not in p53-/- mice. Ass1+/- mice exhibit hypersensitivity to whole-body irradiation owing to increased apoptosis in the small intestinal crypts. ASS1 plays a pivotal role in limiting Akt phosphorylation. Aberrant activation of Akt resulting from ASS1 loss disrupts Akt-mediated cell survival signaling activity under genotoxic stress
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). ASSY_MOUSE
412
0
46584
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
analysis by native gel electrophoresis shows that argininosuccinate synthetase can bind bacterial lipopolysaccharide and lipid A
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argininosuccinate synthetase is purified from mouse liver. Livers are excised from 20 male mice (C3H/He strain, age 7-8 weeks) and homogenized in 100 mM Tris-HCl (pH 7.5) containing 1 mM citrulline and 1 mM aspartic acid. Homogenate is centrifuged. After salting-out with (NH4)2SO4. The sample is subjected to anion-exchange chromatography on DE-52. Concentrated samples are loaded on a column of Sephacryl S-300 HR. The collected first peak fractions are dialyzed and subjected to anion-exchange chromatography on UNO S-1
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
argininosuccinate synthase 1 (ASS1), is directly transactivated by p53 in response to genotoxic stress, resulting in the rearrangement of arginine metabolism. x-Ray irradiation promotes the systemic induction of Ass1
Ass1 expression is upregulated significantly at implantation site on day 5 of pregnancy. Ass1 expression is induced by cAMP through PKA/p-Creb signaling pathway
L-Arg at high concentration down-regulates Ass1 and Asl expression by negative feedback to maintain L-Arg homeostasis
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
medicine
argininosuccinate synthase Ass contributes to ethanol plus Fas/CD95 agonistic antibody Jo2-mediated liver injury. NOS2 induction, 3-nitrotyrosine adducts formation and elevated nitrites, nitrates and S-nitrosothiols are higher in livers from wild-type mice than from Ass+/- mice
medicine
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AS and GTP cyclohydrolase I are intimately associated with inflammatory arthritis, they may be important modulators of arthritis and may represent novel targets for modulation of disease activity
medicine
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citrulline-arginine recycling enzyme, intervention in the supply of arginine may represent a new therapeutic approach to the treatment of NO-mediated neurodegenerative damage in the brain
medicine
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argininosuccinate synthetase is inhibited by endotoxin, implying that bacterial products might potentially regulate the arginine metabolism in the host and perturb NO synthesis
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Patejunas, G.; Bradley, A.; Beaudet, A.L.; O'Brien, W.E.
Generation of a mouse model for citrullinemia by targeted disruption of the argininosuccinate synthetase gene
Somat. Cell Mol. Genet.
20
55-60
1994
Mus musculus
Shen, L.J.; Lin, W.C.; Beloussow, K.; Shen, W.C.
Resistance to the anti-proliferative activity of recombinant arginine deiminase in cell culture correlates with the endogenous enzyme, argininosuccinate synthetase
Cancer Lett.
191
165-170
2003
Canis lupus familiaris, Homo sapiens, Mus musculus
Hukkanen, M.; Platts, L.A.M.; Haralambous, S.; Ainola, M.; Konttinen, Y.T.; Kollias, G.; Polak, J.M.
Induction of inducible nitric oxide synthase, argininosuccinate synthase, and GTP cyclohydrolase I in arthritic joints of human tumor necrosis factor-alpha transgenic mice
J. Rheumatol.
30
652-659
2003
Mus musculus
Kawahara, K.; Gotoh, T.; Oyadomari, S.; Kajizono, M.; Kuniyasu, A.; Ohsawa, K.; Imai, Y.; Kohsaka, S.; Nakayama, H.; Mori, M.
Co-induction of argininosuccinate synthetase, cationic amino acid transporter-2, and nitric oxide synthase in activated murine microglial cells
Mol. Brain Res.
90
165-173
2001
Mus musculus, Rattus norvegicus
Satoh, M.; Iwahori, T.; Sugawara, N.; Yamazaki, M.
Liver argininosuccinate synthase binds to bacterial lipopolysaccharides and lipid A and inactivates their biological activities
J. Endotoxin Res.
12
21-38
2006
Mus musculus
Satoh, M.; Ando, S.; Shinoda, T.; Yamazaki, M.
Clearance of bacterial lipopolysaccharides and lipid A by the liver and the role of argininosuccinate synthase
Innate Immun.
14
51-60
2008
Mus musculus
Guerreiro, J.R.; Lameu, C.; Oliveira, E.F.; Klitzke, C.F.; Melo, R.L.; Linares, E.; Augusto, O.; Fox, J.W.; Lebrun, I.; Serrano, S.M.; Camargo, A.C.
Argininosuccinate synthetase is a functional target for a snake venom anti-hypertensive peptide: role in arginine and nitric oxide production
J. Biol. Chem.
284
20022-20033
2009
Homo sapiens, Mus musculus (P16460)
Prima, V.; Wang, A.; Molina, G.; Wang, K.K.; Svetlov, S.I.
Inhibition of LPS toxicity by hepatic argininosuccinate synthase (ASS): Novel roles for ASS in innate immune responses to bacterial infection
Int. Immunopharmacol.
11
1180-1188
2011
Mus musculus, Homo sapiens (P00966)
Lu, Y.; Ward, S.; Nieto, N.
Ethanol plus the Jo2 fas agonistic antibody-induced liver injury is attenuated in mice with partial ablation of argininosuccinate synthase
Alcoholism
38
649-656
2014
Mus musculus (P16460)
Huang, Z.; Wang, T.S.; Zhao, Y.C.; Zuo, R.J.; Deng, W.B.; Chi, Y.J.; Yang, Z.M.
Cyclic adenosine monophosphate-induced argininosuccinate synthase 1 expression is essential during mouse decidualization
Mol. Cell. Endocrinol.
388
20-31
2014
Mus musculus (P16460), Mus musculus
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