Information on EC 2.1.1.67 - thiopurine S-methyltransferase

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The expected taxonomic range for this enzyme is: Mammalia

EC NUMBER
COMMENTARY hide
2.1.1.67
-
RECOMMENDED NAME
GeneOntology No.
thiopurine S-methyltransferase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine + a thiopurine = S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
also acts, more slowly, on thiopyrimidines and aromatic thiols. Not identical with EC 2.1.1.9 thiol S-methyltransferase
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
methyl group transfer
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Drug metabolism - other enzymes
-
-
SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:thiopurine S-methyltransferase
Also acts, more slowly, on thiopyrimidines and aromatic thiols. Not identical with EC 2.1.1.9 thiol S-methyltransferase.
CAS REGISTRY NUMBER
COMMENTARY hide
67339-09-7
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Mus musculus Swiss-Webster
Swiss-Webster
-
-
Manually annotated by BRENDA team
rat, Sprague-Dawley
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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 + 2,8-dihydroxy-6-thiopurine
S-adenosyl-L-homocysteine + 2,8-dihydroxy-6-methylthiopurine
show the reaction diagram
S-adenosyl-L-methionine + 2-amino-6-thiopurine
S-adenosyl-L-homocysteine + 2-amino-6-methylthiopurine
show the reaction diagram
S-adenosyl-L-methionine + 2-aminothiophenol
S-adenosyl-L-homocysteine + 2-methylsulfanylphenylamine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 2-bromothiophenol
S-adenosyl-L-homocysteine + 1-bromo-2-methylsulfanylbenzene
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 2-mercaptoethanol
S-adenosyl-L-homocysteine + 2-methylmercaptoethanol
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 2-methoxythiophenol
S-adenosyl-L-homocysteine + 1-methoxy-2-methylsulfanylbenzene
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 2-thiothymine
S-adenosyl-L-homocysteine + 2-methylthiothymine
show the reaction diagram
S-adenosyl-L-methionine + 2-thiouracil
S-adenosyl-L-homocysteine + thiouracil-2-S-methylether
show the reaction diagram
S-adenosyl-L-methionine + 3-methoxythiophenol
S-adenosyl-L-homocysteine + 1-methylsulfanyl-3-methoxybenzene
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 4-(aminomethoxy)thiophenol
S-adenosyl-L-homocysteine + 1-aminomethoxy-4-methylsulfanylbenzene
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 4-bromothiophenol
S-adenosyl-L-homocysteine + 1-bromo-4-methylsulfanylbenzene
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 4-chlorothiophenol
S-adenosyl-L-homocysteine + 1-chloro-4-methylsulfanylbenzene
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 4-fluorothiophenol
S-adenosyl-L-homocysteine + 1-fluoro-4-methylsulfanylbenzene
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 4-methoxythiophenol
S-adenosyl-L-homocysteine + 1-methoxy-4-methylsulfanylbenzene
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 4-methylthiophenol
S-adenosyl-L-homocysteine + 1-methyl-4-methylsulfanylbenzene
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 4-nitrothiophenol
S-adenosyl-L-homocysteine + 1-methylsulfanyl-4-nitrobenzene
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 4-thiobenzoate
S-adenosyl-L-homocysteine + 4-methylsulfanyl benzoate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-hydroxy-8-mercaptopurine
S-adenosyl-L-homocysteine + 6-hydroxy-8-methylmercaptopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-mercaptopurine
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-mercaptopurine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine
show the reaction diagram
S-adenosyl-L-methionine + 6-mercaptopurine nucleoside
S-adenosyl-L-homocysteine + 6-methylmercaptopurine nucleoside
show the reaction diagram
-
inactivation
-
-
?
S-adenosyl-L-methionine + 6-mercaptopurine-riboside
S-adenosyl-L-homocysteine + 6-methylmercaptopurine-riboside
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-mercaptopurine-riboside-5'-monophosphate
S-adenosyl-L-homocysteine + 6-methylmercaptopurine-riboside-5'-monophosphate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-mercaptopurine-riboside-5'-triphosphate
S-adenosyl-L-homocysteine + 6-methylmercaptopurine-riboside-5'-triphosphate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-selenoguanine-riboside
S-adenosyl-L-homocysteine + 6-methylselenoguanine-riboside
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-selenopurine
S-adenosyl-L-homocysteine + 6-methylselenopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-selenopurine-riboside
S-adenosyl-L-homocysteine + 6-methylselenopurine-riboside
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thiodeoxyguanosine monophosphate
S-adenosyl-L-homocysteine + 6-methylthiodeoxyguanosine monophosphate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thiodeoxyinosine monophosphate
S-adenosyl-L-homocysteine + 6-methyl thiodeoxyinosine monophosphate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thioguanine
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thioguanine
S-adenosyl-L-homocysteine + 6-methylthioguanine
show the reaction diagram
S-adenosyl-L-methionine + 6-thioguanine monophosphate
S-adenosyl-L-homocysteine + 6-methylthioguanine monophosphate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thioguanine-riboside
S-adenosyl-L-homocysteine + 6-methylthioguanine-riboside
show the reaction diagram
S-adenosyl-L-methionine + 6-thioguanine-riboside-5'-monophosphate
S-adenosyl-L-homocysteine + 6-methylthioguanine-riboside-5'-monophosphate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thioguanosine monophosphate
S-adenosyl-L-homocysteine + 6-methyl thioguanosine monophosphate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thioinosine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine riboside
show the reaction diagram
S-adenosyl-L-methionine + 6-thioinosine 5'-monophosphate
S-adenosyl-L-homocysteine + 6-methylmercaptopurine ribonucleotide
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thioinosine monophosphate
S-adenosyl-L-homocysteine + 6-methyl thioinosine monophosphate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thioinosine monophosphate
S-adenosyl-L-homocysteine + 6-methylthioinosine monophosphate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thioinosine-monophosphate
S-adenosyl-L-homocysteine + 6-methylmercaptopurine-ribonucleotides
show the reaction diagram
-
-
consisting of 6-methyl-thioinosine-monophosphate, -diphosphate and triphosphate
-
?
S-adenosyl-L-methionine + 6-thioinosine-monophosphate
S-adenosyl-L-homocysteine + 6-methylthioinosine-monophosphate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thiopurine
S-adenosyl-L-homocysteine + 6-methylthiopurine
show the reaction diagram
S-adenosyl-L-methionine + 6-thiouric acid
S-adenosyl-L-homocysteine + 6-methylthiouric acid
show the reaction diagram
S-adenosyl-L-methionine + 7-methyl-6-mercaptopurine
S-adenosyl-L-homocysteine + ?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 8-hydroxy-6-mercaptopurine
S-adenosyl-L-homocysteine + 8-hydroxy-6-methylmercaptopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 9(n-propyl)6-thioguanine
S-adenosyl-L-homocysteine + 9(n-propyl)6-methylthioguanine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 9-(n-butyl)-6-mercaptopurine
S-adenosyl-L-homocysteine + 9-(n-butyl)-6-methylmercaptopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 9-ethyl-6-mercaptopurine
S-adenosyl-L-homocysteine + 9-ethyl-6-methylmercaptopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
S-adenosyl-L-methionine + azathioprine
?
show the reaction diagram
S-adenosyl-L-methionine + azathioprine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine
show the reaction diagram
S-adenosyl-L-methionine + azathioprine
S-adenosyl-L-homocysteine + azathioprine S-methylether
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + mercaptopurine
S-adenosyl-L-homocysteine + methylmercaptopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + thioguanine nucleotide
S-adenosyl-L-homocysteine + methylthioguanine
show the reaction diagram
S-adenosyl-L-methionine + thioinosine monophosphate
S-adenosyl-L-homocysteine + methylthioinosine monophosphate
show the reaction diagram
S-adenosyl-L-methionine + thioinosine triphosphate
S-adenosyl-L-homocysteine + methylthioinosine triphosphate
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + thiopurine
S-adenosyl-L-homocysteine + methylthiopurine
show the reaction diagram
-
-
-
-
?
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 + 6-mercaptopurine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thiopurine
S-adenosyl-L-homocysteine + 6-methylthiopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
additional information
?
-
-
S-adenosyl-L-methionine and sinefungin prevent degradation of TPMT by stabilizing ist native structure
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
-
baseline activity 102%
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2,3-Dithiopropanol
2,4-dithiopyrimidine
2,8-dihydroxy-6-mercaptopurine
-
-
2-Amino-6-thiopurine
2-Hydroxy-6-mercaptopurine
-
-
2-mercaptoethanol
2-methylthio-4-hydroxypyrimidine
2-Methylthiouracil
3,4,5-triiodobenzoic acid
-
-
3,4-dimethoxy-5-hydroxybenzoic acid
-
-
3,4-dimethoxybenzoic acid
-
-
3,5-dichlorobenzoic acid
-
-
3,5-dihydroxy-4-methoxybenzoic acid
-
-
3,5-dimethylbenzoic acid
-
-
3,5-dinitrobenzoic acid
-
-
3-bromo-5-hydroxy-4-methoxybenzoic acid
-
-
3-chloro-5-hydroxy-4-methoxybenzoic acid
-
-
3-hydroxy-4,5-dimethoxybenzoic acid
-
-
3-hydroxy-4-methoxy-5-(dimethylamino)benzoic acid
-
-
3-hydroxy-4-methoxy-5-nitrobenzoic acid
-
-
3-hydroxy-4-methoxybenzoic acid
-
-
3-hydroxy-5-iodo-4-methoxybenzoic acid
-
-
4-hydroxy-3-methoxybenzoic acid
-
-
5-amino-salicylic acid
-
-
5-Aminosalicylate
-
-
5-methyl-2,4-dithiopyrimidine
6-hydroxy-2-thiopurine
6-Mercaptopurine
6-methylmercaptopurine
-
-
6-methylthiopurine
6-Thioguanine
-
mixed inhibitor of 6-mercaptopurine methylation
aspirin
-
-
Azathioprine
-
IC50: 0.43-0.532 mM
bendroflumethiazide
Benzoic acid
celecoxib
-
-
diclofenac
-
-
Disulfiram
-
-
Ethacrynic acid
-
-
flurbiprofen
-
-
Furosemide
glutathione
Ibuprofen
-
-
Ketoprofen
-
-
L-cysteine
L-homocysteine
L-homocysteine thiolactone
lornoxicam
-
-
Mefenamic acid
-
-
meloxicam
-
-
mesalazine
N-ethylmaleimide
-
-
nabumetone
-
-
naproxen
-
-
olsalazine
paracetamol
-
-
piretanide
-
IC50: 0.3-0.313 mM
piroxicam
-
-
S-adenosyl-L-homocysteine
-
-
S-adenosyl-L-methionine
S-Methylglutathione
-
-
sulfasalazine
Sulphasalazine
-
-
testosterone
-
; IC50: 0.03-0.072 mM
tolfenamic acid
-
-
trichlormethiazide
tropolone
-
-
additional information
-
low levels of methionine can result in low S-adenosyl-L-methionine levels and consequently decreased TPMT activity
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
S-adenosyl-L-methionine
-
S-adenosyl-L-methionine acts as a positive modulator of TPMT activity, the effect of S-adenosyl-L-methionine appears to be restricted to protein stabilisation rather than an increase of TPMT expression
SKF-525A
-
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
168
2-mercaptoethanol
-
-
1.7 - 2
2-Thiouracil
0.138
6-hydroxy-8-mercaptopurine
-
-
0.00035 - 0.99
6-Mercaptopurine
1.17
6-mercaptopurine-riboside
-
-
1.27
6-mercaptopurine-riboside-5'-monophosphate
-
-
0.89
6-mercaptopurine-riboside-5'-triphosphate
-
-
0.139
6-selenoguanine-riboside
-
-
0.0291
6-selenopurine
-
-
0.0518
6-selenopurine-riboside
-
-
0.1314
6-thiodeoxyguanosine
-
recombinant enzyme, expressed in yeast
0.0127
6-thiodeoxyinosine
-
recombinant enzyme, expressed in yeast
0.0137 - 1.45
6-Thioguanine
0.761
6-thioguanine-riboside
-
-
1.04
6-thioguanine-riboside-5'-monophosphate
-
-
-
0.0261
6-thioguanosine
-
recombinant enzyme, expressed in yeast
0.0271
6-thioguanosine 5-monophosphate
-
recombinant enzyme, expressed in yeast
0.0551
6-thioinosine
-
recombinant enzyme, expressed in yeast
0.0257
6-thioinosine 5'-monophosphate
-
recombinant enzyme, expressed in yeast
0.2
6-Thiopurine
-
-
0.231
7-methyl-6-mercaptourine
-
-
-
0.0961
8-hydroxy-6-mercaptopurine
-
-
0.292
9-(n-butyl)6-mercaptopurine
-
-
0.159
9-(n-propyl)-6-thioguanine
-
-
0.372
9-ethyl-6-mercaptopurine
-
-
0.0024 - 0.0463
S-adenosyl-L-methionine
additional information
additional information
-
various thiophenols as substrates, Km 0.0008-0.0078
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.027
2-Hydroxy-6-mercaptopurine
-
-
0.01 - 0.0113
3,4-dimethoxy-5-hydroxybenzoic acid
0.00802 - 0.0113
6-Mercaptopurine
0.45 - 0.9
6-Thioguanine
2.413
celecoxib
-
-
0.722
diclofenac
-
-
1.524
flurbiprofen
-
-
1.043
Ibuprofen
-
-
0.172
Ketoprofen
-
-
1.41
lornoxicam
-
-
0.039
Mefenamic acid
-
-
4.238
meloxicam
-
-
4.3
nabumetone
-
-
0.052
naproxen
-
-
0.208
olsalazine
-
-
5.162
paracetamol
-
-
2.589
piroxicam
-
-
0.00075
S-adenosyl-L-homocysteine
-
-
0.05
tolfenamic acid
-
-
0.85
tropolone
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.43 - 0.532
Azathioprine
Homo sapiens
-
IC50: 0.43-0.532 mM
2.416
celecoxib
Homo sapiens
-
-
1.582
diclofenac
Homo sapiens
-
-
1.649
flurbiprofen
Homo sapiens
-
-
0.015 - 0.019
Furosemide
Homo sapiens
-
IC50: 0.015-0.019 mM, has the potential to inhibit thiopurine S-methyltransferase in patients with chronic inflammatory bowel disease
1.968
Ibuprofen
Homo sapiens
-
-
1.013
Ketoprofen
Homo sapiens
-
-
2.135
lornoxicam
Homo sapiens
-
-
0.039
Mefenamic acid
Homo sapiens
-
-
4.292
meloxicam
Homo sapiens
-
-
4.341
nabumetone
Homo sapiens
-
-
0.079
naproxen
Homo sapiens
-
-
1.474
olsalazine
Homo sapiens
-
-
5.168
paracetamol
Homo sapiens
-
-
0.3 - 0.313
piretanide
Homo sapiens
-
IC50: 0.3-0.313 mM
2.589
piroxicam
Homo sapiens
-
-
0.03 - 0.072
testosterone
Homo sapiens
-
IC50: 0.03-0.072 mM
0.063
tolfenamic acid
Homo sapiens
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00000716
-
TMPT reference activity after recovery of the bone marrow suppression
0.00003033
-
elevated TPMT activity during the recovery phase of a bone marrow suppression, following the pancytopenic period
1.03
-
-
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
-
TPMT activity assay
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
3.5 - 8.6
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
primary cell
Manually annotated by BRENDA team
-
embryonic kidney cell line with inducible thiopurine methyltransferase
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30000
-
2 isozymes, gel filtration
33000
-
determined by SDS-PAGE and immunoblotting
35000
-
-
36000
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
-
x * 35000, SDS-PAGE
monomer
-
-
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
two crystal structures of murine TPMT are determined, as a binary complex with the product S-adenosyl-L-homocysteine and as a ternary complex with S-adenosyl-L-homocysteine and the substrate 6-mercaptopurine, to 1.8 and 2.0 A resolution, respectively
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
45 - 56
55
-
the melting temperature of the wild type enzyme is at 55C
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
S-adenosyl-L-methionine is responsible for direct stabilization of the enzyme
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
80C, activity in cell lysate is stable during storage
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
2 isozymes
-
cytosolic fractions of transformed Saccharomyces cerevisiae cells are prepared
-
Ni-NTA column chromatography and Superdex 200 gel filtration
-
using a Ni2+-NTA resin and a gel-filtration column
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a 8.7 kb fragment encompassing part of exon III through a portion of intron 6 is subcloned into the pZERO-2 vector
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baculovirus expressed
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cDNA cloned and heterologous expressed in rabbit reticulocytes and wheat germ lysate
cDNA cloning, heterologous expression in yeast
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enhanced green fluorescent protein-tagged enzyme is expressed in Escherichia coli, Jurkat, Hep-G2, and HEK-293 cells
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expressed in COS-1 cells
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expressed in Escherichia coli BL21-Codon Plus (DE3)-RIL cells
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for cloning of the TPMT fragment the TOPO TA cloning kit is used
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into the pCR2.1-TOPO vector, used as a template to generate point mutations, the variants are sequenced and cloned into the mammalian expression vector pCMV6-XL5, into the pENTR/D-TOPO vector and subsequently into the pcDNA-DEST40 vector
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into the yeast expression vector pYeDP60 for transformation of Saccharomyces cerevisiae cells
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retroviral gene transfer
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the full-length coding region is amplified by PCR from a eukaryotic expression plasmid and cloned into the pET-28a vector for expression in Escherichia coli BL21DE3 cells
to assess the functional effect of the trinucleotide repeat variants in the promoter, the wild-type and variant TPMT promoters are amplified and cloned into the promoter-less pGL3-Basic vector
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
azathioprine therapy can raise TPMT activity
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decreased activity of TPMT is associated with hematopoietic toxicity after administration of standard doses of 6- mercaptopurine or azathioprine
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longitudinal induction of thiopurine methyltransferase activity is observed during 6-thioguanine treatment
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S-adenosyl-L-methionine has no effect on TPMT mRNA expression
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smokers have significantly higher TPMT activity than nonsmokers
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the restriction of L-methionine in cell growth media reversibly decreases enzyme activity and protein levels
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TPMT activity is significantly higher in wild type children than in wild type adults (18-68 years), wild type infants from 0.08-5 years has a 9% higher average TPMT activity than the other wild type groups, only in children from 0.08-2 years is the TPMT activity higher in males than in females
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
238G>C
460G>A
460G>A/719A>G
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TPMT*3A polymorphism, low or no TPMT activity
539A>T
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TPMT variant
719A>G
A154T/Y240C
A154Y
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thiopurine S-methyltransferase polymorphism, G to A transition at position 460
A179G/G460A
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the variant is associated with low enzyme activity
A180P
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the mutation affects TMPT activity
C216T
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the mutant exhibits reduced activity compared to the wild type enzyme
E98X
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the mutation affects TMPT activity
F208L
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the mutation is associated with a decrease in enzyme activity
Q179H
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polymorphism c.537G>T, TPMT*24
R152A
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mutant to probe, whether this residue is important for catalysis
R152A/R226A
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mutant to probe, whether this residue is important for catalysis
R152E
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mutant to probe, whether this residue is important for catalysis
R152H
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mutant to probe, whether this residue is important for catalysis
R226A
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mutant to probe, whether this residue is important for catalysis
R226E
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mutant to probe, whether this residue is important for catalysis
R226H
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mutant to probe, whether this residue is important for catalysis
TPMT*2
TPMT*23
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polymorphism, single nucleotide substitution, C500G
TPMT*3A
TPMT*3B
TPMT*3C
Y107D
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the mutant shows less than 10% activity compared to the wild type enzyme, the variant allozyme shows a striking decrease in both immunoreactive protein level and enzyme activity after transient expression in COS-1 cells, the mutant is less stable than the wild type TPMT allozyme
A154T
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polymorphism TPMT*3B
A154T/Y240C
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polymorphism TPMT*3A
A154T/Y240C/E98STOP
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polymorphism TPMT*3D
A80P
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polymorphism TPMT*2
C132Y
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polymorphism TPMT*11
E28V
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polymorphism TPMT*13
G144R
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polymorphism TPMT*10
G36S/K238E
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polymorphism TPMT*20
G71R
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polymorphism TPMT*18
H227E
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polymorphism TPMT*7
K122T
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polymorphism TPMT*19
L49S
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polymorphism TPMT*5
L69V
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polymorphism TPMT*21
Q42E
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polymorphism TPMT*17
R163H
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polymorphism TPMT*16
R163P
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polymorphism TPMT*22
R215H
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polymorphism TPMT*8
S125L
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polymorphism TPMT*12
Y180F
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polymorphism TPMT*6
Y240C
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polymorphism TPMT*3C
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
diagnostics
medicine
Show AA Sequence (1214 entries)
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