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Tchem
TPMT
Thiopurine S-methyltransferase

Protein Summary
Description
Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine (also called mercaptopurine, 6-MP or its brand name Purinethol) and 6-thioguanine (also called tioguanine or 6-TG) using S-adenosyl-L-methionine as the methyl donor (PubMed:657528, PubMed:18484748). TPMT activity modulates the cytotoxic effects of thiopurine prodrugs. A natural substrate for this enzyme has yet to be identified. This gene encodes the enzyme that metabolizes thiopurine drugs via S-adenosyl-L-methionine as the S-methyl donor and S-adenosyl-L-homocysteine as a byproduct. Thiopurine drugs such as 6-mercaptopurine are used as chemotherapeutic agents. Genetic polymorphisms that affect this enzymatic activity are correlated with variations in sensitivity and toxicity to such drugs within individuals, causing thiopurine S-methyltransferase deficiency. Related pseudogenes have been identified on chromosomes 3, 18 and X. [provided by RefSeq, Aug 2014]
Illumination Graph
Knowledge Table
Most Knowledge About
Knowledge Value (0 to 1 scale)
disease perturbation
0.95
biological term
0.86
histone modification site profile
0.82
transcription factor perturbation
0.74
disease
0.7


IDG Development Level Summary
Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 188.23   (req: < 5)
Gene RIFs: 157   (req: <= 3)
Antibodies: 384   (req: <= 50)
Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 188.23   (req: >= 5)
Gene RIFs: 157   (req: > 3)
Antibodies: 384   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 5
Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 1
Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0
Active Ligands (1)
1 – 1 of 1
CHEMBL415511
chemical structure image
Protein Data Bank (2)
1 – 2 of 2
PDB Structure Id
Ligand
Method
Resolution (Å)
M.W. (kDa)
Pub Year
Title
PDB Structure Id
M.W.
Resolution
Pub Year
Pathways (48)
Biological oxidations (R-HSA-211859)

Click on a row in the table to change the structure displayed.

Items per page:
1 – 5 of 8
Data Source
Name
Explore in Pharos
Explore in Source
Reactome
Biological oxidations
Reactome
Defective TPMT causes Thiopurine S-methyltransferase deficiency (TPMT deficiency)
Reactome
Disease
Reactome
Diseases of metabolism
Reactome
Metabolic disorders of biological oxidation enzymes
Name
Explore in Pharos
Explore in Source
Biological oxidations
Defective TPMT causes Thiopurine S-methyltransferase deficiency (TPMT deficiency)
Disease
Diseases of metabolism
Metabolic disorders of biological oxidation enzymes
Protein-Protein Interactions (61)
1 – 10 of 61
ITPA
Tbio
Family: Enzyme
Novelty: 0.00285702
Score: 0.977
Data Source: STRINGDB
HPRT1
Tchem
Family: Enzyme
Novelty: 0.00042001
Score: 0.961
Data Source: STRINGDB
IMPDH1
Tclin
Family: Enzyme
Novelty: 0.01078039
Score: 0.94
Data Source: STRINGDB
GMPS
Tbio
Family: Enzyme
Novelty: 0.00301335
Score: 0.94
Data Source: STRINGDB
IMPDH2
Tclin
Family: Enzyme
Novelty: 0.00965338
Score: 0.934
Data Source: STRINGDB
XDH
Tclin
Family: Enzyme
Novelty: 0.00097175
Score: 0.933
Data Source: STRINGDB
GGH
Tchem
Family: Enzyme
Novelty: 0.00341456
Score: 0.902
Data Source: STRINGDB
SLC19A1
Tchem
Family: Transporter
Novelty: 0.00690808
Score: 0.901
Data Source: STRINGDB
NUDT15
Tbio
Family: Enzyme
Novelty: 0.01713357
Score: 0.8
Data Source: STRINGDB
CD82
Tbio
Novelty: 0.0022175
Score: 0.737
Data Source: STRINGDB
Publication Statistics
PubMed Score  188.23

PubMed score by year
PubTator Score  827.59

PubTator score by year
Amino Acid Sequence
Residue Counts
Sequence
MDGTRTSLDIEEYSDTEVQKNQVLTLEEWQDKWVNGKTAFHQEQGHQLLKKHLDTFLKGKSGLRVFFPLC
1-70
GKAVEMKWFADRGHSVVGVEISELGIQEFFTEQNLSYSEEPITEIPGTKVFKSSSGNISLYCCSIFDLPR
70-140
TNIGKFDMIWDRGALVAINPGDRKCYADTMFSLLGKKFQYLLCVLSYDPTKHPGPPFYVPHAEIERLFGK
140-210
ICNIRCLEKVDAFEERHKSWGIDCLFEKLYLLTEK
210-245
MDGTRTSLDIEEYSDTEVQKNQVLTLEEWQDKWVNGKTAFHQEQGHQLLKKHLDTFLKGKSGLRVFFPLCGKAVEMKWFADRGHSVVGVEISELGIQEFFTEQNLSYSEEPITEIPGTKVFKSSSGNISLYCCSIFDLPRTNIGKFDMIWDRGALVAINPGDRKCYADTMFSLLGKKFQYLLCVLSYDPTKHPGPPFYVPHAEIERLFGKICNIRCLEKVDAFEERHKSWGIDCLFEKLYLLTEK