Information on EC 2.1.1.67 - thiopurine S-methyltransferase

-

168

2-mercaptoethanol

-

1.7 - 2

2-Thiouracil

0.138

6-hydroxy-8-mercaptopurine

-

0.00035 - 0.99

6-Mercaptopurine

24 entries

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

36 entries

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

Mus musculus

-

485515

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

-

0.0109

methanetellurol

pH 6.8, 37°C

776531

-

0.0024 - 0.0463

S-adenosyl-L-methionine

16 entries

0.0035

tellurite

pH 6.8, 37°C

776531

additional information

-

various thiophenols as substrates, Km 0.0008-0.0078

485518

-

0.027

2-Hydroxy-6-mercaptopurine

-

0.01 - 0.0113

3,4-dimethoxy-5-hydroxybenzoic acid

3 entries

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

-

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

-

0.00000716

-

TMPT reference activity after recovery of the bone marrow suppression

690118

0.00003033

-

elevated TPMT activity during the recovery phase of a bone marrow suppression, following the pancytopenic period

690118

1.03

-

Mus musculus Swiss-Webster

additional information

6.5

6.6

-

6.7

-

7.4

7.5

-

TPMT activity assay

686326, 687983, 690118, 686161

3.5 - 8.6

-

37

-

-

-

UniProt

-

-

Swiss-Webster

485515

-

Oryctolagus cuniculus

-

SwissProt

-

SwissProt

-

SwissProt

-

-

primary cell

-

low mRNA level

-

embryonic kidney cell line

peripheral blood mononuclear cell

-

embryonic kidney cell line with inducible thiopurine methyltransferase

-

-

-

-

-

-

-

lymphoblastoid cell line

-

-

-

-

-

low mRNA level

-

-

-

-

intermediate mRNA level

-

intermediate mRNA level

Highest Expressing Human Cell Lines

Filter by:

Cell Line Links

Gene Links

evolution

malfunction

metabolism

thiopurine drugs, azathioprine, mercaptopurine, and thioguanine, are widely used in the treatment of several malignant and nonmalignant diseases. Patients with low-activity variants of thiopurine S-methyltransferase can be affected by pronounced pharmacologic effects when receiving thiopurine medications

778459

physiological function

Pseudomonas syringae pv. pisi

additional information

28000

-

485522, 485526, 686157

30000

-

2 isozymes, gel filtration

485519

33000

determined by SDS-PAGE and immunoblotting

685039

35000

36000

-

gel filtration

?

-

x * 35000, SDS-PAGE

718804

monomer

-

688415

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

238G>C

460G>A

460G>A/719A>G

-

TPMT*3A polymorphism, low or no TPMT activity

686574

539A>T

-

TPMT variant

719A>G

A154T

A154T/Y240C

A154Y

-

thiopurine S-methyltransferase polymorphism, G to A transition at position 460

A167G

A179G/G460A

the variant is associated with low enzyme activity

733706

A180P

-

the mutation affects TMPT activity

A719G

A80P

C132Y

C212R

C216T

the mutant exhibits reduced activity compared to the wild type enzyme

734843

E28V

3 entries

E98X

-

the mutation affects TMPT activity

703267

F208L

-

the mutation is associated with a decrease in enzyme activity

G144R

G238C

G36S

G460A

G71R

H227Q

K119T

K122T

K238E

L49S

L69V

M1V

Q179H

polymorphism c.537G>T, TPMT*24

Q42E

R152A

mutant to probe, whether this residue is important for catalysis

R152A/R226A

mutant to probe, whether this residue is important for catalysis

R152E

mutant to probe, whether this residue is important for catalysis

R152H

mutant to probe, whether this residue is important for catalysis

R163H

R163P

R215H

R226A

mutant to probe, whether this residue is important for catalysis

R226E

mutant to probe, whether this residue is important for catalysis

R226H

mutant to probe, whether this residue is important for catalysis

S125L

TPMT*2

TPMT*23

-

polymorphism, single nucleotide substitution, C500G

TPMT*3A

TPMT*3B

TPMT*3C

Y107D

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

Y180F

Y240C

A154T

-

polymorphism TPMT*3B

A154T/Y240C

-

polymorphism TPMT*3A

A154T/Y240C/E98STOP

-

polymorphism TPMT*3D

A80P

-

polymorphism TPMT*2

C132Y

-

polymorphism TPMT*11

E28V

-

polymorphism TPMT*13

G144R

-

polymorphism TPMT*10

G36S/K238E

-

polymorphism TPMT*20

G71R

-

polymorphism TPMT*18

H227E

-

polymorphism TPMT*7

K122T

-

polymorphism TPMT*19

L49S

-

polymorphism TPMT*5

L69V

-

polymorphism TPMT*21

Q42E

-

polymorphism TPMT*17

R163H

-

polymorphism TPMT*16

R163P

-

polymorphism TPMT*22

R215H

-

polymorphism TPMT*8

S125L

-

polymorphism TPMT*12

Y180F

-

polymorphism TPMT*6

Y240C

-

polymorphism TPMT*3C

additional information

45 - 56

46.4

melting temperature of the wild type enzyme without ligand

755704

46.8

melting temperature of the wild type enzyme in complex with S-adenosyl-L-methionine

755704

55

-

the melting temperature of the wild type enzyme is at 55°C

718942

S-adenosyl-L-methionine is responsible for direct stabilization of the enzyme

-

718804

80°C, activity in cell lysate is stable during storage

-

-

2 isozymes

-

cytosolic fractions of transformed Saccharomyces cerevisiae cells are prepared

685039

Ni-NTA column chromatography and Superdex 200 gel filtration

Ni-NTA column chromatography and Superdex S200 gel filtration

partially

-

using a Ni2+-NTA resin and a gel-filtration column

-

8 entries

a 8.7 kb fragment encompassing part of exon III through a portion of intron 6 is subcloned into the pZERO-2 vector

Mus musculus

-

685945

baculovirus expressed

-

485525

cDNA cloned and heterologous expressed in rabbit reticulocytes and wheat germ lysate

Mus musculus

O55060

485526

cDNA cloning, heterologous expression in yeast

-

485522, 485523

enhanced green fluorescent protein-tagged enzyme is expressed in Escherichia coli, Jurkat, Hep-G2, and HEK-293 cells

-

703564

expressed in COS-1 cells

702164

expressed in Escherichia coli BL21-Codon Plus (DE3)-RIL cells

expressed in Escherichia coli BL21-CodonPlus (DE3)-RIL cells

755704

expression in Escherichia coli

776531

for cloning of the TPMT fragment the TOPO TA cloning kit is used

-

689358

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

-

689365

into the yeast expression vector pYeDP60 for transformation of Saccharomyces cerevisiae cells

685039

retroviral gene transfer

-

485528

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

-

689362

azathioprine therapy can raise TPMT activity

-

703355

decreased activity of TPMT is associated with hematopoietic toxicity after administration of standard doses of 6- mercaptopurine or azathioprine

-

704818

longitudinal induction of thiopurine methyltransferase activity is observed during 6-thioguanine treatment

-

701941

S-adenosyl-L-methionine has no effect on TPMT mRNA expression

-

706092

smokers have significantly higher TPMT activity than nonsmokers

-

706092

the restriction of L-methionine in cell growth media reversibly decreases enzyme activity and protein levels