Information on EC 2.1.1.2 - guanidinoacetate N-methyltransferase

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The expected taxonomic range for this enzyme is: Chordata

EC NUMBER
COMMENTARY hide
2.1.1.2
-
RECOMMENDED NAME
GeneOntology No.
guanidinoacetate N-methyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine + guanidinoacetate = S-adenosyl-L-homocysteine + creatine
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
methyl group transfer
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Arginine and proline metabolism
-
-
creatine biosynthesis
-
-
glycine metabolism
-
-
Glycine, serine and threonine metabolism
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Metabolic pathways
-
-
SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:N-guanidinoacetate methyltransferase
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CAS REGISTRY NUMBER
COMMENTARY hide
9029-75-8
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
spiny mouse
-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + guanidinoacetate
S-adenosyl-L-homocysteine + creatine
show the reaction diagram
S-adenosyl-L-methionine + guanidinoacetic acid + glutathione
?
show the reaction diagram
-
assay at pH 7.4, 37C, 1 h, reaction stopped with 5% trichloroacetic acid
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + guanidinoacetate
S-adenosyl-L-homocysteine + creatine
show the reaction diagram
additional information
?
-
-
together with creatine/phosphocreatine shuttle system involved in brain energy homeostasis through a neuron-glial relationship
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-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3-deaza-S-adenosyl-L-homocysteine
DTNB
-
2 mol DTNB per mol enzyme causes complete inactivation
glutathione
iodoacetate
-
-
N-ethylmaleimide
-
irreversible
p-chloromercuribenzoate
S-adenosyl-L-homocysteine
S-adenosylhomocysteine
-
sinefungin
additional information
-
complete and irreversible inactivation by ultraviolet irradiation
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-mercaptoethanol
-
-
cysteine
dithiothreitol
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-
glutathione
additional information
-
hepatic GAMT activity does not differ between rats fed creatine-free or creatine-supplemented diets
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.011 - 2.3
Guanidinoacetate
0.002 - 0.049
S-adenosyl-L-methionine
additional information
additional information
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0788 - 0.081
Guanidinoacetate
1 - 3.8
S-adenosyl-L-methionine
additional information
additional information
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.039
3-deaza-S-adenosyl-L-homocysteine
-
-
0.016
adenosylhomocysteine
-
-
0.0004
S-adenosyl-L-homocysteine
-
-
0.006 - 0.018
sinefungin
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00035
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brain
0.0005
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liver of sarcoma-bearing mice
0.00053
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S180 cell
0.00057
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Ehrlich ascites carcinoma cell
0.0006
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liver of normal mice; sarcoma
0.0007
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intestine
0.00084
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muscle
0.0019
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kidney
0.0058
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pancreas
0.022
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purified enzyme
0.0286
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liver
0.12
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native enzyme
0.13
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recombinant enzyme
0.16
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purified enzyme
27.2
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purified enzyme
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
weak GAMT expression is detected in the epithelium of alimentary tract
Manually annotated by BRENDA team
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highest enzyme level
Manually annotated by BRENDA team
in embryos at 12.5 days of gestation guanidinoacetate N-methyltransferase is detectable in the hepatic primordium only, with all other tissues being negative. Non-radioactive in situ hybridization (58C for 40 h in 5 x SSC, 50% formamide and 40 microg/ml salmon sperm DNA) with digoxigenin-labeled antisense and sense riboprobes (400 ng/ml) for rat guanidinoacetate N-methyltransferase. guanidinoacetate N-methyltransferase proteins are detected with rabbit polyclonal antibodies
Manually annotated by BRENDA team
in embryos at 18.5 days of gestation guanidinoacetate N-methyltransferase is detectable. Non-radioactive in situ hybridization (58C for 40 h in 5 x SSC, 50% formamide and 40 microg/ml salmon sperm DNA) with digoxigenin-labeled antisense and sense riboprobes (400 ng/ml) for rat guanidinoacetate N-methyltransferase. guanidinoacetate N-methyltransferase proteins are detected with rabbit polyclonal antibodies
Manually annotated by BRENDA team
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low activity
Manually annotated by BRENDA team
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-
Manually annotated by BRENDA team
GAMT is strongly expressed in all neurons and glia cells of neural cord
Manually annotated by BRENDA team
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low enzyme level
Manually annotated by BRENDA team
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S180 cells
Manually annotated by BRENDA team
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mainly found in Sertoli cells of seminiferous tubules
Manually annotated by BRENDA team
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L197P mutation in exon 6: guanidinoacetate increases to 2566 microMol/l, creatine decreases to 3.7 microMol/l
Manually annotated by BRENDA team
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low enzyme level
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GAMT is only located in the cytoplasm of epithelial cells but not in nuclei
Manually annotated by BRENDA team
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perinuclear localization
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
31500
-
gel filtration
60000
Western Blot analyses shows the presences of the guanidinoacetate N-methyltransferase-EGFP fusion protein
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
-
crystallization data
monomer
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SDS-PAGE, gel filtration
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
in complex with S-adenosyl-L-methionine in monoclinic and tetragonal modification
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in complex with S-adenosylhomocysteine and guanidinoacetate, and in complex with S-adenosyl-homocysteine and guanidine
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4
-
remains active for 24 h
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
inactivated during purification, can be reactivated by addition of a thiol
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, 10 mM phosphate buffer, pH 7.2, 1 mM EDTA, 0.1 M NaCl, concentrated by ultrafiltration
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-50C, cell homogenate, enzyme activity is stable for at least 6 months
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-60C, purified enzyme, stable for months
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
inactivated during purification, can be reactivated by addition of a thiol
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Saos2, U2OS, and A-549 cells
genotyping, overexpression of wild-type and mutant enzymes as EGFP-fusion proteins in a primary enzyme-deficient human fibroblast cell line, homozygous for a frameshift mutation
in Escherichia coli
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recombinant enzyme truncated at amino acid 37 from N-terminus
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the open reading frame of the guanidinoacetate N-methyltransferase gene (NM_000156) from a fibroblast cell line is transfected into primary fibroblasts from a guanidinoacetate N-methyltransferase-deficient patient (Trp20Ser) or transient transected in HeLa cells.
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
both RNA and protein levels of GAMT are increased in a p53-dependent manner after various inducers of genotoxic stress (etoposide, H2O2, and gamma-irradiation), glucose deprivation induces GAMT in a p53-dependent manner, GAMT mRNA and protein are increased in several tissues of glucose-deprived p53 wild-type mice while remaining unchanged in the same tissues of p53 null mice
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GAMT induction in response to DNA damage is dependent upon p53, GAMT also shows p53-dependent induction in response to exogenously expressed p53 and genotoxic stress, metabolic stress induces GAMT expression to regulate creatine levels in a p53-dependent manner
GAMT mRNA expression is relatively low until 34 days gestation, in the fetal liver GAMT mRNA and protein expression are also relatively low until 34-37 days gestation, between mid-gestation and term neither GAMT mRNA nor protein can be detected in the placenta
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high expression in tumor cells
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no transcript of GAMT is detected from fertilized egg to blastula stage
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A54P
naturally occuring mutation from enzyme deficiency patients, no recombinant expression of the mutant achieved, inactive mutant
A74P
naturally occuring mutation from enzyme deficiency patients, no recombinant expression of the mutant achieved, inactive mutant
C169Y
naturally occuring mutation from enzyme deficiency patients, no recombinant expression of the mutant achieved
D135N
naturally occuring mutation from enzyme deficiency patients, inactive mutant
G68C
naturally occuring mutation from enzyme deficiency patients, no recombinant expression of the mutant achieved
H147Y
naturally occuring mutation from enzyme deficiency patients, almost inactive mutant
H51P
naturally occuring mutation from enzyme deficiency patients, no recombinant expression of the mutant achieved
L166P
naturally occuring mutation from enzyme deficiency patients, inactive mutant
N92D
naturally occuring mutation from enzyme deficiency patients, inactive mutant
P8T
naturally occuring mutation from enzyme deficiency patients, the mutant shows similar activity as the wild-type enzyme
R208P
naturally occuring mutation from enzyme deficiency patients, almost inactive mutant
T136M
naturally occuring mutation from enzyme deficiency patients, inactive mutant
W45R
naturally occuring mutation from enzyme deficiency patients, inactive mutant
Y27H
naturally occuring mutation from enzyme deficiency patients, the mutant shows similar activity as the wild-type enzyme
D129A
-
active enzyme
D129N
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active enzyme
D134A
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inactive
D134E
-
lower activity than wild type enzyme
D134N
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much lower activity than wild type enzyme
D92N
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lower activity than wild type enzyme
E45D
decrease in kcat-value, increase in Km-value of S-adenosyl-L-methionine
E45Q
decrease in kcat-value, increase in Km-value of S-adenosyl-L-methionine
E45S
no residual activity
E89Q
-
lower activity than wild type enzyme
G67A
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inactive enzyme
G69A
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inactive enzyme
T135A
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lower activity than wild type enzyme
W143F
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lower activity than wild type enzyme
W143L
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lower activity than wild type enzyme
Y133F
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lower activity than wild type enzyme
Y133V
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lower activity than wild type enzyme
Y221F
decrease in kcat-value
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
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nonradioactive method for measuring enzyme activity in lymphoblasts by using HPLC with UV detector
medicine