TPMT

Protein identityUniProt · HPA

UniProt accession

P51580

Gene

TPMT

Ensembl

ENSG00000137364

Chromosome

6

Canonical length

245 aa

Protein class

Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Predicted intracellular proteins

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

245 residues, UniProt reviewed canonical sequence.

>P51580|TPMT
     1  MDGTRTSLDI EEYSDTEVQK NQVLTLEEWQ DKWVNGKTAF HQEQGHQLLK KHLDTFLKGK
    61  SGLRVFFPLC GKAVEMKWFA DRGHSVVGVE ISELGIQEFF TEQNLSYSEE PITEIPGTKV
   121  FKSSSGNISL YCCSIFDLPR TNIGKFDMIW DRGALVAINP GDRKCYADTM FSLLGKKFQY
   181  LLCVLSYDPT KHPGPPFYVP HAEIERLFGK ICNIRCLEKV DAFEERHKSW GIDCLFEKLY
   241  LLTEK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TPMT can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.26

Highest tissue expression

72 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.15

gnomAD pLI

0

gnomAD missense Z

0.29

DepMap mean gene effect

0.03

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• methylation
• nucleobase-containing compound metabolic process
• xenobiotic catabolic process
• xenobiotic metabolic process

Molecular functions

• S-adenosyl-L-methionine binding
• thiopurine S-methyltransferase activity

Cellular components

• cytosol

Protein domainsUniProt · Pfam · InterPro

• S-adenosyl-L-methionine-dependent methyltransferase superfamily
• TPMT family
• Thiopurine S-methyltransferase
• Thiopurine S-methyltransferase (TPMT)

KeywordsUniProt

• Acetylation
• Cytoplasm
• Methyltransferase
• Phosphoprotein
• S-adenosyl-L-methionine
• Transferase