Information on EC 4.3.2.1 - argininosuccinate lyase

Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea

EC NUMBER
COMMENTARY
4.3.2.1
-
RECOMMENDED NAME
GeneOntology No.
argininosuccinate lyase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
2-(Nomega-L-arginino)succinate = fumarate + L-arginine
show the reaction diagram
-
-
-
-
2-(Nomega-L-arginino)succinate = fumarate + L-arginine
show the reaction diagram
random mechanism with the formation of two dead-end complexes: enzyme-argininosuccinate-fumarate and enzyme-argininosuccinate-arginine
-
2-(Nomega-L-arginino)succinate = fumarate + L-arginine
show the reaction diagram
stepwise E1cB mechanism, rate-limiting step probably at the C-N bond-cleavage step
-
2-(Nomega-L-arginino)succinate = fumarate + L-arginine
show the reaction diagram
random uni-bi kinetic mechanism
-
2-(Nomega-L-arginino)succinate = fumarate + L-arginine
show the reaction diagram
5 residues are essential for catalytic activity: R115, N116, T161, S283, and E296
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
elimination
Q9P870
-
elimination
-
-
elimination
-
-
elimination
-
-
C-N bond cleavage
-
PATHWAY
KEGG Link
MetaCyc Link
Alanine, aspartate and glutamate metabolism
-
Arginine and proline metabolism
-
arginine biosynthesis I (via L-ornithine)
-
arginine biosynthesis II (acetyl cycle)
-
arginine biosynthesis III (via N-acetyl-L-citrulline)
-
arginine biosynthesis IV (archaebacteria)
-
Biosynthesis of secondary metabolites
-
canavanine biosynthesis
-
citrulline-nitric oxide cycle
-
Metabolic pathways
-
urea cycle
-
SYSTEMATIC NAME
IUBMB Comments
2-(Nomega-L-arginino)succinate arginine-lyase (fumarate-forming)
-
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
ARG4
-
gene name
arginine-succinate lyase
-
-
-
-
argininosuccinase
-
-
-
-
argininosuccinase
-
-
argininosuccinase
Sulfolobus solfataricus P1
-
-
-
Argininosuccinate lyase
-
-
-
-
Argininosuccinate lyase
Q9P870
-
Argininosuccinate lyase
-
-
Argininosuccinate lyase
-
-
Argininosuccinate lyase
-
-
Argininosuccinate lyase
-
-
Argininosuccinate lyase
-
-
Argininosuccinate lyase
-
-
argininosuccinic acid lyase
-
-
-
-
Arginosuccinase
-
-
-
-
ASAL
-
-
-
-
ASL
-
-
-
-
ASL
Q9P870
-
ASL
Q9P8B5
-
ASL
-
delta2-crystallin
ASL
Q9LAE5
-
ASL
-
-
delta2 crystallin
-
-
delta2-crystallin
-
-
-
-
hASL
-
gene name
L-argininosuccinate arginine-lyase
-
-
-
-
lyase, argininosuccinate
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9027-34-3
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
fragment
UniProt
Manually annotated by BRENDA team
5 major isoform of the enzyme
-
-
Manually annotated by BRENDA team
multiple forms
-
-
Manually annotated by BRENDA team
wild type and mutant enzymes: S114A, R113N, S284A, Y323F, E296Q, r115N, N116L, T161V, S283A, and Y323I
-
-
Manually annotated by BRENDA team
ASL deficiency results in the autosomal, recessive disorder argininosuccinic aciduria
-
-
Manually annotated by BRENDA team
mutations in ASL result in the clinical condition argininosuccinic aciduria, an autosomal recessive disorder
-
-
Manually annotated by BRENDA team
mutations in ASL result the clinical condition argininosuccinate aciuria
-
-
Manually annotated by BRENDA team
subspecies Lactobacillus plantarum plantarum
-
-
Manually annotated by BRENDA team
strain PCC 73102
SwissProt
Manually annotated by BRENDA team
Gulf toadfish
-
-
Manually annotated by BRENDA team
fawn-hooded hypertensive (FHH) rats
-
-
Manually annotated by BRENDA team
male wistar rat
-
-
Manually annotated by BRENDA team
Sulfolobus solfataricus P1
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
metabolism
-
ASL synthesizes the second step in production of arginine, which is a part of the congenital urea cycle
metabolism
-
synthesizes the second last step in the conversion of ammonia into urea
metabolism
-
biological activity in liver, ileum, small intestine, heart, lung and kidney within the urea and nitric oxide cycle
metabolism
-
small heat shock protein, alphaA-crystallin, functions as a molecular chaperone, and enhances thermal stability of both delta-crystallin and ASL. Thermal unfolding of delta-crystallin or ASL in the presence of alphaA-crystallin follows a similar three-state model. A stable intermediate which retains about 30% alpha-helical structure is observed. Protection from thermal denaturation by alphaA-crystallin is by interaction with partly unfolded ASL to form high molecular weight heteroligomers. Aggregate formation of ASL is significantly reduced in the presence of alphaA-crystallin. The extent of protection of ASL at different ratios of alpahA-crystallin is described by hyperbolic curves, suggesting the preferential recognition of partly unfolded ASL by alphaA-crystallin
metabolism
-
Sulfolobus solfataricus lacks ornithine acetyltransferase and thus forms N-acetylglutamate exclusively via the energetically less favourable reaction catalysed by N-acetylglutamate synthase, investing 1 mol of acetyl CoA per mol of N-acetyl intermediate synthesized
metabolism
Sulfolobus solfataricus P1
-
Sulfolobus solfataricus lacks ornithine acetyltransferase and thus forms N-acetylglutamate exclusively via the energetically less favourable reaction catalysed by N-acetylglutamate synthase, investing 1 mol of acetyl CoA per mol of N-acetyl intermediate synthesized
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
?
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
?
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
?
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
?
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
-
?
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
r
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
r
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
r
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
r
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
?
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
?
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
?
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
r
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
r
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
r
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
?, r
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
?, r
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
?
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-, Q9LAE5
-
-
?
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-, Q9LAE5
-
-
r
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
last step in the biosynthesis of arginine
-
r
2-(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
-
?
2-(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
-
r
2-(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-, Q9P870
-
-
-
?
arginine + fumarate
argininosuccinate
show the reaction diagram
-
-
-
-
y
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
?
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
?
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
?
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
?
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
?
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
?
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
-
?
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
r
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
-
r
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
-
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
?
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
?
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
?
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
?
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
?
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
?
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
?
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
?
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
?
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
?
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
r
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
r
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
-
?
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
-
?
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
-
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
-
argininosuccinate
fumarate + L-Arg
show the reaction diagram
Q9P8B5
-
-
-
?
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
biological activity in liver, ileum, small intestine, heart, lung and kidney within the urea and nitric oxide cycle
-
-
?
argininosuccinate
?
show the reaction diagram
-
urea cycle enzyme, deficiency results in argininosuccinic aciduria
-
-
-
difluorofumarate + L-Arg
?
show the reaction diagram
-
-
-
-
?
fumarate + arginine
argininosuccinate
show the reaction diagram
-
-
-
-
r
fumarate + L-Arg
argininosuccinate
show the reaction diagram
-
-
-
r
fumarate + L-Arg
argininosuccinate
show the reaction diagram
-
-
-
r
fumarate + L-Arg
argininosuccinate
show the reaction diagram
-
-
-
r
fumarate + L-Arg
argininosuccinate
show the reaction diagram
-
-
-
r
fumarate + L-Arg
argininosuccinate
show the reaction diagram
-
-
-
r
fumarate + L-Arg
argininosuccinate
show the reaction diagram
-
-
-
-
fumarate + L-Arg
argininosuccinate
show the reaction diagram
-
-
-
r
fumarate + L-canavanine
?
show the reaction diagram
-
at 78% of the activity with L-Arg
-
-
?
omega-N-(L-arginino)succinate
L-arginine + fumarate
show the reaction diagram
-
-
-
-
?
omega-N-(L-arginino)succinate
L-arginine + fumarate
show the reaction diagram
-
-
-
-
?
omega-N-(L-arginino)succinate
L-arginine + fumarate
show the reaction diagram
-
-
-
-
?
monofluorofumarate + L-Arg
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
metabolic role in biosynthesis of Arg and urea
-
-
-
additional information
?
-
-
enzyme is involved in arginine biosynthesis and in urea cycle
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
r
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
r
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
r
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
r
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
r
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
r
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
r
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
r
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
r
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-, Q9LAE5
-
-
r
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
last step in the biosynthesis of arginine
-
r
2-(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
-
?
2-(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
-
r
2-(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-, Q9P870
-
-
-
?
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
-
?
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
-
-
-
?
argininosuccinate
fumarate + L-Arg
show the reaction diagram
-
biological activity in liver, ileum, small intestine, heart, lung and kidney within the urea and nitric oxide cycle
-
-
?
omega-N-(L-arginino)succinate
L-arginine + fumarate
show the reaction diagram
-
-
-
-
?
omega-N-(L-arginino)succinate
L-arginine + fumarate
show the reaction diagram
-
-
-
-
?
omega-N-(L-arginino)succinate
L-arginine + fumarate
show the reaction diagram
-
-
-
-
?
argininosuccinate
?
show the reaction diagram
-
urea cycle enzyme, deficiency results in argininosuccinic aciduria
-
-
-
additional information
?
-
-
metabolic role in biosynthesis of Arg and urea
-
-
-
additional information
?
-
-
enzyme is involved in arginine biosynthesis and in urea cycle
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
GDP
-
0.2 mM, slight stimulation
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1-ethyl-3-(3-diethylaminopropyl)carbodiimide
-
at pH 6
acetylenedicarboxylate
-
-
Arg
-
noncompetitive versus argininosuccinate
argininosuccinate
-
0.3 mM inhibits the reaction by 97%
bromomesaconic acid
-
argininosuccinate completely protects, Lys51 has an essential role in binding of argininosuccinate and consequently is essential in catalysis; inactivation follows pseudo-first-order kinetics
citrulline
-
competitive versus Arg and noncompetitive versus argininosuccinate and fumarate
citrulline
-
noncompetitive vs. fumarate and arginine
D-glucose
-
12.5 mM glucose decreases activity of ASL by 20%, 25 mM glucose by 50%
diethyl dicarbonate
-
-
diethyl dicarbonate
-
-
diethyl dicarbonate
-
modification of an essential His
difluorofumarate
-
pseudo-first-order process
fumarate
-
noncompetitive versus argininosuccinate
N3-(L-1-carboxy-2-nitroethyl)-L-arginine
-
-
succinate
-
dead-end inhibitor
succinate
-
noncompetitive vs. fumarate and arginine
Urea
-
competitive
monofluorofumarate
-
reversible, pseudo-first-order process
additional information
-
the antibody of the liver enzyme is an effective inhibitor of brain enzyme
-
additional information
-
mRNA expression and activity of liver argininosuccinate lyase decrease with age
-
additional information
-
acetylation at Lys288 or Lys69 decreases activity of ASL
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
Amino acids
-
extra amino acids in culture media increases activity of ASL by decreasing inhibitory acetylation rate
GTP
-
0.2 mM, stimulates
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.2
-
(Nomega-L-arginino)succinate
-
mutant c.532 G>A, pH 7.5, 37C
0.23
-
(Nomega-L-arginino)succinate
-
mutant c.1135 C>T, pH 7.5, 37C
2.6
-
(Nomega-L-arginino)succinate
-
wild-type, pH 7.5, 37C
3
-
arginine
-
-
0.007
-
argininosuccinate
-
delta-crystallin IVa
0.008
-
argininosuccinate
-
delta-crystallin IIIa
0.016
-
argininosuccinate
-
delta-crystallin Ia and delta-crystallin IIa
0.02
-
argininosuccinate
-
mutant enzyme S284A
0.022
-
argininosuccinate
-
-
0.024
-
argininosuccinate
-
delta-crystallin IVb
0.029
-
argininosuccinate
-
-
0.03
-
argininosuccinate
-
mutant enzyme R113N
0.031
-
argininosuccinate
-
delta-crystallin IIIb
0.037
-
argininosuccinate
-
Km-value at low concentrations of argininosuccinate
0.039
-
argininosuccinate
-
delta-crystallin VIb
0.042
-
argininosuccinate
-
delta-crystallin Vb
0.044
-
argininosuccinate
-
delta-crystallin VIIb
0.05
-
argininosuccinate
-
delta-crystallin IIb
0.07
-
argininosuccinate
-
wild-type enzyme
0.09
-
argininosuccinate
-
mutant enzyme S114A
0.1
-
argininosuccinate
-
-
0.1
-
argininosuccinate
-
enzyme form deltaB
0.13
-
argininosuccinate
-
enzyme form deltaC
0.144
-
argininosuccinate
-
31C
0.146
-
argininosuccinate
-
26C
0.151
-
argininosuccinate
-
21C
0.16
-
argininosuccinate
-
Km-value at high concentrations of argininosuccinate
0.183
-
argininosuccinate
-
enzyme form deltaD
0.187
-
argininosuccinate
-
enzyme form deltaE
0.2
-
argininosuccinate
-
-
0.26
-
argininosuccinate
-
pH 7.5, 37C
0.35
-
argininosuccinate
-
-
0.4
-
argininosuccinate
-
-
1.7
-
argininosuccinate
-
mutant enzyme Y323F
0.046
-
difluorofumarate
-
-
0.045
-
disodium argininosuccinate
-
wild type, 25 C, 10 mM Tris-HCl, pH 7.5, 1 mM EDTA
0.069
-
disodium argininosuccinate
-
mutant W9R, 25 C, 10 mM Tris-HCl, pH 7.5, 1 mM EDTA
0.083
-
disodium argininosuccinate
-
mutant TRUN1-8, 25 C, 10 mM Tris-HCl, pH 7.5, 1 mM EDTA
0.105
-
disodium argininosuccinate
-
mutant TRUN1-9, 25 C, 10 mM Tris-HCl, pH 7.5, 1 mM EDTA
0.106
-
disodium argininosuccinate
-
mutant W9Y, 25 C, 10 mM Tris-HCl, pH 7.5, 1 mM EDTA
0.111
-
disodium argininosuccinate
-
mutant W9F, 25 C, 10 mM Tris-HCl, pH 7.5, 1 mM EDTA
0.112
-
disodium argininosuccinate
-
mutant W9A, 25 C, 10 mM Tris-HCl, pH 7.5, 1 mM EDTA
0.115
-
disodium argininosuccinate
-
mutant W9M, 25 C, 10 mM Tris-HCl, pH 7.5, 1 mM EDTA
0.119
-
disodium argininosuccinate
-
211-chimera, 25 C, 10 mM Tris-HCl, pH 7.5, 1 mM EDTA
0.212
-
disodium argininosuccinate
-
mutant M9F/E115D, 25 C, 10 mM Tris-HCl, pH 7.5, 1 mM EDTA
0.255
-
disodium argininosuccinate
-
mutant D115A, 25 C, 10 mM Tris-HCl, pH 7.5, 1 mM EDTA
0.273
-
disodium argininosuccinate
-
mutant D115E, 25 C, 10 mM Tris-HCl, pH 7.5, 1 mM EDTA
0.294
-
disodium argininosuccinate
-
mutant M9W/E115D, 25 C, 10 mM Tris-HCl, pH 7.5, 1 mM EDTA
0.61
-
disodium argininosuccinate
-
mutant M9Y/E115D, 25 C, 10 mM Tris-HCl, pH 7.5, 1 mM EDTA
2.724
-
disodium argininosuccinate
-
mutant M9W, 25 C, 10 mM Tris-HCl, pH 7.5, 1 mM EDTA
3.159
-
disodium argininosuccinate
-
mutant M9W/V14S, 25 C, 10 mM Tris-HCl, pH 7.5, 1 mM EDTA
0.067
-
fumarate
-
-
4.5
-
fumarate
-
-
5.3
-
fumarate
-
-
1.4
-
monofluorofumarate
-
-
additional information
-
additional information
-
-
-
additional information
-
additional information
-
Km-values of the multiple form of delta-crystallin
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.12
-
argininosuccinate
-
mutant enzyme S284A
0.43
-
argininosuccinate
-
mutant enzyme Y323F
0.62
-
argininosuccinate
-
mutant enzyme R113N
2.42
-
argininosuccinate
-
mutant enzyme S114A
3.28
-
argininosuccinate
-
-
4.9
-
argininosuccinate
-
wild-type enzyme
2500
-
argininosuccinate
-
-
2930
-
argininosuccinate
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.0012
-
-
activity in lung homogenate
0.003
-
-
pH and temperature not specified in the publication, activity in cell culture in growth medium with 0.5% peptone and 0.1%yeast extract
0.003
-
-
pH and temperature not specified in the publication, activity in cell culture in growth medium with 0.2% yeast extract
0.006
-
-
pH and temperature not specified in the publication, activity in cell culture in minimal growth medium with 20 mM glucose and 5 mM NH4+
3
-
-
mutant c.C1153T, pH 7.5, 37C
5
-
-
mutant c.A943G, pH 7.5, 37C
8
-
-
formation of argininosuccinate
8
-
-
synthesis of argininosuccinate
8.6
-
-
pRH1, units/mg
10.3
-
-
cleavage of argininosuccinate
10.3
-
-
deamination of argininosuccinate
20
-
-
-
20
-
-
mutant c.T299C, pH 7.5, 37C
23
-
-
-
23
-
-
mutant c.A857G, pH 7.5, 37C
41
-
-
mutant c.A566G, pH 7.5, 37C
208
-
-
mutant c.G532A, pH 7.5, 37C
280
-
-
mutant c.C1135T, pH 7.5, 37C
4227
-
-
wild-type, pH 7.5, 37C
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.8
7.2
-
formation of argininosuccinate
7.4
-
-
activity assay
7.5
-
-
a plateau above pH 7.5, cleavage of argininosuccinate; a plateau below pH 7.5, formation of argininosuccinate
7.5
-
-
formation of argininosuccinate
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
30
-
-
activity assay
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.2
-
-
isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
striatal neurons
Manually annotated by BRENDA team
-
low mRNA content
Manually annotated by BRENDA team
-
present in neurones and nerve fibres in the myenteric plexus of the lower oesophagael sphincter, antrum, pylorus, ileum and colon, in the submucosal plexus of ileum and colon, in longitudinal muscle of ileum and colon, nerve bundles of circular muscles
Manually annotated by BRENDA team
-
ASL expression is time-dependently reduced in hypoxia
Manually annotated by BRENDA team
P04424
using DNA
Manually annotated by BRENDA team
-
predominant expression
Manually annotated by BRENDA team
-
mRNA detectable
Manually annotated by BRENDA team
-
neurons of the myenteric plexus
Manually annotated by BRENDA team
-
low mRNA content
Manually annotated by BRENDA team
-
nerve fibers of smooth muscle layer
Manually annotated by BRENDA team
additional information
-
not found in oligodendrocytes
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
50000
-
-
SDS-PAGE
51700
-
-
SDS-PAGE
52340
-
Q9P870
the asl open reading frame encodes a protein of 464 amino acids with a calculated mass of 52337 Da
187000
-
-
equilibrium sedimentation
190000
-
-
disc gel electrophoresis
190000
-
-
gel filtration
200000
-
-
gel filtration
202000
-
-
gel filtration
215000
-
-, Q9LAE5
native PAGE, recombinant ASL
218000
-
-
gel filtration
220000
-
Q8DVX5, -
gel filtration, recombinant fusion protein
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
4 * 50000, SDS-PAGE
?
-
x * 51663, calculation from nucleotide sequence
?
-
x * 51944, calculation from nucleotide sequence
?
-
x * 55000, SDS-PAGE
hexamer
-
5 or 6 * 39000, SDS-PAGE
pentamer
-
5 or 6 * 39000, SDS-PAGE
tetramer
-
4 * 50000, SDS-PAGE
tetramer
-
4 * 49000, SDS-PAGE
tetramer
-
4 * 50000, SDS-PAGE
tetramer
-
4 * 50400, equilibrium sedimentation in presence of urea and guanidine hydrochloride
tetramer
-
4 * 50000, SDS-PAGE
tetramer
-
4 * 51600, deduced from nucleotide sequence
tetramer
-, Q9LAE5
4 * 53000, SDS-PAGe, recombinant ASL
tetramer
-
-
tetramer
Q8DVX5, -
4 * 51500, calculated
homotetramer
-
-
additional information
-
small heat shock protein, alphaA-crystallin, functions as a molecular chaperone, and enhances thermal stability of both delta-crystallin and ASL. Thermal unfolding of delta-crystallin or ASL in the presence of alphaA-crystallin follows a similar three-state model. A stable intermediate which retains about 30% alpha-helical structure is observed. Protection from thermal denaturation by alphaA-crystallin is by interaction with partly unfolded ASL to form high molecular weight heteroligomers. Aggregate formation of ASL is significantly reduced in the presence of alphaA-crystallin. The extent of protection of ASL at different ratios of alpahA-crystallin is described by hyperbolic curves, suggesting the preferential recognition of partly unfolded ASL by alphaA-crystallin
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
side-chain modification
-
acetylation at Lys288 or Lys69 in liver decreases activity of ASL
additional information
-
origin of the multiple forms is due to post-translational oxidative modification of the protein
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
S283A mutant, hanging-drop vapor diffusion at room temperatur, 9 mg/ml protein in 10 mM Tris-HCl, pH 7.5 and 1 mM EDTA is preincubated with 75 mM argininosuccinate, subsequently 0.005 ml drops of the solution are mixed with an equal ammount of precipitating solution consisting of 12% polyethylene glycol 2000 MME, 300 mM MgCl2, 100 mM HEPES, pH 7.4, crystals diffract to 1.96 A resolution
-
apoenzyme and complex of double loop mutant with sulfate, growing at room temperature using the hanging drop vapor diffusion method, molecular replacement at 2.2 A resolution for the DLM-sulfate complex, 2.5 A resolution for the apoenzyme
-
crystallized from a highly concentrated sample of purified recombinant alpha-methylacyl-CoA-racemase with arginosuccinate lyase as a minor impurity, growing at room temperature in mother liquid consisting of 1.26 M ammonium phosphate pH 7.0, small bipyramidal crystals, molecular replacement at 2.44 A resolution
-
hanging-drop vapor diffusion, crystal structure of Q286R mutant at 2.65 A
-
to 2.5 A resolution, space group R3
Q8DVX5, -
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.5
8.5
-
stable for at least 20 min
7
-
-
at 4C and at 25C, 8 h, stable
8.2
-
-
25C, about 40% loss of activity after 8 h; 4C, about 60% loss of activity after 4 h
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4
-
-
Tris-HCl buffer, pH 8.5, 50% loss of activity after 2.3 h
38
-
-
30 min, stable
49
-
-
20 min, 50% inactivation
52
-
-
20 min, 50% inactivation
54
-
-
mid-point temperature transition 2
57
-
-
mid-point temperature transition 1 and 3
58
-
-
mid-point temperature transition 3, presence of alphaA-crystallin
60
-
-
20 min, 50% inactivation
60
-
-
30 min, enzyme form deltaIIb and deltaIVb are stable
65
-
-
complete denaturation
83
-
-
mid-point temperature transition 1, presence of alphaA-crystallin
85
-
-
mid-point temperature transition 2, presence of alphaA-crystallin
additional information
-
-
enzyme forms with higher isoelectric point are much more thermostable than those with lower pI values
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
Arg or phosphate ions protect from cold inactivation
-
phosphate, arsenate, 20% dimethylsulfoxide or 20% glycerol protects against cold inactivation
-
ASL undergoes cold dissociation via a dimer intermediate
-
repeated freezing and thawing does not appreciably alter the activity
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
0C, Tris buffer, pH 8.5, 50% loss of activity after 2.5 h
-
4C, Tris-HCl buffer, pH 8.5, 50% loss of activity after 2.3 h
-
frozen in 0.1 M potassium phosphate, pH 7.0, stable
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant His-tagged ASL
-
leaf extract is centrifuged, the supernatant lyophilized, the resuspended material is partially purified on a G-15 Sephadex and a Q-Sepharose FF column
-
brain
-
kidney
-
liver ASL
-
recombinant ASL
-
recombinant His-tagged ASL
-, Q9LAE5
recombinant protein
Q8DVX5, -
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
into the pGEM-T vector for sequence analysis
Q9P870
expression in Escherichia coli
-
expression in Saccharomyces cerevisiae and in Escherichia coli
-
expressed as His tag enzyme
-
expressed as His tag enzymes
-
expression in Escherichia coli argH auxotroph, deficient in argininosuccinate lyase
-
expression in mouse cells
-
cloning of cDNA
-
expression in Escherichia coli
-
expression in Escherichia coli and COS-7 cells
-
overexpressed in HEK293T cells or in Escherichia coli
-
cloning of argH gene encoding ASL
-
expression in Escherichia coli
-, Q9LAE5
expression in Escherichia coli
Q8DVX5, -
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
mRNA levels in liver decrease significantly when gulf toadfishes are crowded by 7 days
-
expression of ASL is significantly decreased to 50% in Shunt lambs
-
threefold repression of enzyme formation by arginine
-
threefold repression of enzyme formation by arginine
Sulfolobus solfataricus P1
-
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
E296Q
-
retains only 0.001% residual activity
N116L
-
no activity
R115N
-
no activity
S283A
-
no activity
S384A
-
catalytic efficiency is decreased by an order of magnitude in comparison to wild-type delta II crystallin
T161V
-
no activity
Y323F
-
catalytic efficiency is decreased by an order of magnitude in comparison to wild-type delta II crystallin
Y323I
-
no activity
A41G/I43M
-
mutant without enzyme activity
D115A
-
mutant with 45% enzyme activity
D115E
-
mutant with 42.6% enzyme activity
E115D
-
mutant without enzyme activity
I143M
-
mutant without enzyme activity
M9F/E115D
-
mutant with 3.3% enzyme activity
M9W
-
mutant with 2.0% enzyme activity
M9W/E115D
-
mutant with 17% enzyme activity
M9W/V14S
-
mutant with 1.9% enzyme activity
TRUN1-8
-
mutant with 37% enzyme activity
TRUN1-9
-
mutant with 2.1% enzyme activity
W9A
-
mutant with 1.9% enzyme activity
W9F
-
mutant with 11.3% enzyme activity
W9M
-
mutant with 1.0% enzyme activity
W9R
-
mutant with 3% enzyme activity
W9Y
-
mutant with 49.5% enzyme activity
A398D
-
no activity, 15.55 of wild-type activity if coexpressed with Q286R
D31N
P04424
missense mutation found in patients with late onset of argininosuccinic aciduria, residual activity
D87G
-
no activity, 35.2% of wild-type activity if coexpressed with Q286R
E73K
P04424
missense mutation found in patient with neonatal onset of argininosuccinic aciduria, enzyme inactive
K288R
-
132% of wild-type activity
M360T
-
no actiivty, 10% of wild-type activity if coexpressed with Q286R
Q286R
-
frequently complementing allele, 2% of wild-type kcat
Q286R
-
3% of wild-type activity
Q286R
P04424
missense mutation found in patient with neonatal onset of argininosuccinic aciduria, enzyme inactive
R113Q
P04424
missense mutation found in patient with neonatal onset of argininosuccinic aciduria, enzyme inactive
R12Q
-
6% of wild-type kcat
R182Q
P04424
missense mutation found in patient with late onset of argininosuccinic aciduria, enzyme inactive
R186Q
P04424
missense mutation found in patient with neonatal onset of argininosuccinic aciduria, residual activity
R236W
P04424
missense mutation found in patient with neonatal onset of argininosuccinic aciduria, enzyme inactive
R297Q
P04424
missense mutation found in patient with late onset of argininosuccinic aciduria, residual activity
R456W missense mutation found in patient with neonatal onset of argininosuccinic aciduria
P04424
, residual activity
V178M
P04424
missense mutation combined with mutation R186Q on the other allele found in patient with neonatal onset of argininosuccinic aciduria, enzyme activity reduced compared to wild-type
V335L
P04424
missense mutation found in patients with late onset of argininosuccinic aciduria, enzyme activity reduced compared to wild-type
M9Y/E115D
-
mutant with 5.5% enzyme activity
additional information
-
double loop mutant DLM, enzymatically inactive
M382R
P04424
missense mutation found in patient with neonatal onset of argininosuccinic aciduria, residual activity
additional information
-
the mutations E86A and R113W identified on separate alleles are most likely to determine ASL-deficiency in a severely affected patient with neonatal onset of the disease
additional information
-
expression of mutant ASL proteins in Escherichia coli. The known classical p.Q286R, the novel classical p.K315E and the known mutations p.I100T, p.E189G and p.R385C, which all have been linked to a mild phenotype of argininosuccinic aciduria, show no significant residual activity. There is some enzyme activity detected with the p.V178M (5% of wild-type), and p.R379C (10% of wild-type) mutations in which Km values for argininosuccinic acid differs significantly from the wild-type ASL protein
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
argininosuccinate lyase is a valuable marker for estimating hepatopathy
medicine
-
expression of mutant ASL proteins in Escherichia coli. The known classical p.Q286R, the novel classical p.K315E and the known mutations p.I100T, p.E189G and p.R385C, which all have been linked to a mild phenotype of argininosuccinic aciduria, show no significant residual activity. There is some enzyme activity detected with the p.V178M (5% of wild-type), and p.R379C (10% of wild-type) mutations in which Km values for argininosuccinic acid differs significantly from the wild-type ASL protein
medicine
-
transient ischemia induces changes in the number and percentage of the nNOS+ neurons also expressing argininosuccinate lyase
medicine
-
argininosuccinate lyase is present in activated microglia cells in the ischemic rat
analysis
-
the rapid and sensitive assay method is used to detect increases in the activity in serum from patients with liver diseases