TPMT

Functionⁱ

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.Curated2 Publications

Catalytic activityⁱ

mercaptopurine
Search proteins in UniProtKB for this molecule.
Search chemical reactions in Rhea for this molecule.
See the description of this molecule in ChEBI.
+
S-adenosyl-L-methionine
Search proteins in UniProtKB for this molecule.
Search chemical reactions in Rhea for this molecule.
See the description of this molecule in ChEBI.
=
6-methylthiopurine
Search proteins in UniProtKB for this molecule.
Search chemical reactions in Rhea for this molecule.
See the description of this molecule in ChEBI.
+
H⁺
Search proteins in UniProtKB for this molecule.
Search chemical reactions in Rhea for this molecule.
See the description of this molecule in ChEBI.
+
S-adenosyl-L-homocysteine
Search proteins in UniProtKB for this molecule.
Search chemical reactions in Rhea for this molecule.
See the description of this molecule in ChEBI.
2 Publications
Manual assertion based on experiment inⁱ
- Ref.10
  "Human erythrocyte thiopurine methyltransferase: radiochemical microassay and biochemical properties."
  Weinshilboum R.M., Raymond F.A., Pazmino P.A.
  Clin. Chim. Acta 85:323-333(1978) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
- Ref.11
  "Structural basis of substrate recognition in thiopurine S-methyltransferase."
  Peng Y., Feng Q., Wilk D., Adjei A.A., Salavaggione O.E., Weinshilboum R.M., Yee V.C.
  Biochemistry 47:6216-6225(2008) [PubMed] [Europe PMC] [Abstract]
  Cited for: CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ARG-152.
EC:2.1.1.67
2 Publications
Manual assertion based on experiment inⁱ
- Ref.10
  "Human erythrocyte thiopurine methyltransferase: radiochemical microassay and biochemical properties."
  Weinshilboum R.M., Raymond F.A., Pazmino P.A.
  Clin. Chim. Acta 85:323-333(1978) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
- Ref.11
  "Structural basis of substrate recognition in thiopurine S-methyltransferase."
  Peng Y., Feng Q., Wilk D., Adjei A.A., Salavaggione O.E., Weinshilboum R.M., Yee V.C.
  Biochemistry 47:6216-6225(2008) [PubMed] [Europe PMC] [Abstract]
  Cited for: CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ARG-152.
Source:
Rhea
Search for this reaction in UniProtKB.
See the description of this reaction in Rhea.
. Show »« Hide
mercaptopurine
zoom
+
S-adenosyl-L-methionine
zoom
=
6-methylthiopurine
zoom
+
H⁺
zoom
+
S-adenosyl-L-homocysteine
zoom
6-thioguanine
Search proteins in UniProtKB for this molecule.
Search chemical reactions in Rhea for this molecule.
See the description of this molecule in ChEBI.
+
S-adenosyl-L-methionine
Search proteins in UniProtKB for this molecule.
Search chemical reactions in Rhea for this molecule.
See the description of this molecule in ChEBI.
=
6-methylthioguanine
Search proteins in UniProtKB for this molecule.
Search chemical reactions in Rhea for this molecule.
See the description of this molecule in ChEBI.
+
H⁺
Search proteins in UniProtKB for this molecule.
Search chemical reactions in Rhea for this molecule.
See the description of this molecule in ChEBI.
+
S-adenosyl-L-homocysteine
Search proteins in UniProtKB for this molecule.
Search chemical reactions in Rhea for this molecule.
See the description of this molecule in ChEBI.
1 Publication
Manual assertion based on experiment inⁱ
- Ref.10
  "Human erythrocyte thiopurine methyltransferase: radiochemical microassay and biochemical properties."
  Weinshilboum R.M., Raymond F.A., Pazmino P.A.
  Clin. Chim. Acta 85:323-333(1978) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
EC:2.1.1.67
1 Publication
Manual assertion based on experiment inⁱ
- Ref.10
  "Human erythrocyte thiopurine methyltransferase: radiochemical microassay and biochemical properties."
  Weinshilboum R.M., Raymond F.A., Pazmino P.A.
  Clin. Chim. Acta 85:323-333(1978) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
Source:
Rhea
Search for this reaction in UniProtKB.
See the description of this reaction in Rhea.
. Show »« Hide
6-thioguanine
zoom
+
S-adenosyl-L-methionine
zoom
=
6-methylthioguanine
zoom
+
H⁺
zoom
+
S-adenosyl-L-homocysteine
zoom

S-adenosyl-L-methionine + a thiopurine = S-adenosyl-L-homocysteine + a thiopurine S-methylether.
2 Publications
Manual assertion based on experiment inⁱ
- Ref.10
  "Human erythrocyte thiopurine methyltransferase: radiochemical microassay and biochemical properties."
  Weinshilboum R.M., Raymond F.A., Pazmino P.A.
  Clin. Chim. Acta 85:323-333(1978) [PubMed] [Europe PMC] [Abstract]
  Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
- Ref.11
  "Structural basis of substrate recognition in thiopurine S-methyltransferase."
  Peng Y., Feng Q., Wilk D., Adjei A.A., Salavaggione O.E., Weinshilboum R.M., Yee V.C.
  Biochemistry 47:6216-6225(2008) [PubMed] [Europe PMC] [Abstract]
  Cited for: CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ARG-152.
EC:2.1.1.67

Activity regulationⁱ

Inhibited by S-adenosyl-L-homocysteine (SAH).

Kineticsⁱ

V_max=
1.23 nmol/sec/mg enzyme toward 6-mercaptopurine (at pH 6.5 and 37 degrees Celsius)
1 Publication
Manual assertion based on experiment inⁱ
- Ref.11
  "Structural basis of substrate recognition in thiopurine S-methyltransferase."
  Peng Y., Feng Q., Wilk D., Adjei A.A., Salavaggione O.E., Weinshilboum R.M., Yee V.C.
  Biochemistry 47:6216-6225(2008) [PubMed] [Europe PMC] [Abstract]
  Cited for: CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ARG-152.

pH dependenceⁱ

Optimum pH is 7.5.1 Publication

Sites

Feature key	Position(s)	DescriptionActions	Length
Binding siteⁱ	40	SubstrateBy similarity	1
Binding siteⁱ	69	S-adenosyl-L-methionine; via carbonyl oxygen	1
Binding siteⁱ	90	S-adenosyl-L-methionine	1
Binding siteⁱ	152	S-adenosyl-L-methionine	1

GO - Molecular functionⁱ

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

drug metabolic process
Source: UniProtKB
Inferred from direct assayⁱ
- 18484748
- 657528
methylation Source: Reactome
nucleobase-containing compound metabolic process
Source: ProtInc
Traceable author statementⁱ
- 8316220

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Methyltransferase, Transferase
Ligand	S-adenosyl-L-methionine

Enzyme and pathway databases

BioCycⁱ	MetaCyc:HS06327-MONOMER
BRENDAⁱ	2.1.1.67 2681
Reactomeⁱ	R-HSA-156581 Methylation R-HSA-5578995 Defective TPMT causes Thiopurine S-methyltransferase deficiency (TPMT deficiency)

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Thiopurine S-methyltransferase1 Publication (EC:2.1.1.672 Publications) Alternative name(s): Thiopurine methyltransferase1 Publication
Gene namesⁱ	Name:TPMT
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 6

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000137364.4
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:12014 TPMT
MIMⁱ	187680 gene
neXtProtⁱ	NX_P51580

Keywords - Cellular componentⁱ

Cytoplasm

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Mutagenesisⁱ	152	R → E: Decreases affinity for 6-mercaptopurine. Slightly decreases catalytic activity. 1 Publication		1

Organism-specific databases

DisGeNET More...DisGeNETⁱ	7172
MalaCards human disease database More...MalaCardsⁱ	TPMT
MIMⁱ	610460 phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000137364
Orphanetⁱ	413687 Azathioprine or 6-mercatopurine toxicity or dose selection 240863 Cisplatin toxicity
PharmGKBⁱ	PA356

Chemistry databases

ChEMBLⁱ	CHEMBL2500
Drug and drug target database More...DrugBankⁱ	DB00993 Azathioprine DB00436 Bendroflumethiazide DB01327 Cefazolin DB01033 Mercaptopurine DB01250 Olsalazine DB01021 Trichlormethiazide

Polymorphism and mutation databases

BioMutaⁱ	TPMT
DMDMⁱ	1730006

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000220102	1 – 245	Thiopurine S-methyltransferaseAdd BLAST		245

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Modified residueⁱ	14	PhosphoserineCombined sources		1
Modified residueⁱ	58	N6-acetyllysineCombined sources		1

Keywords - PTMⁱ

Acetylation, Phosphoprotein

Proteomic databases

EPDⁱ	P51580
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	P51580
PaxDbⁱ	P51580
PeptideAtlas More...PeptideAtlasⁱ	P51580
PRIDEⁱ	P51580
ProteomicsDBⁱ	56338

PTM databases

iPTMnetⁱ	P51580
PhosphoSitePlusⁱ	P51580

Expressionⁱ

Gene expression databases

Bgeeⁱ	ENSG00000137364 Expressed in 222 organ(s), highest expression level in buccal mucosa cell
ExpressionAtlasⁱ	P51580 baseline and differential
Genevisibleⁱ	P51580 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	HPA019851

HPAⁱ

HPA019851

Interactionⁱ

Subunit structureⁱ

Monomer.1 Publication

Protein-protein interaction databases

BioGridⁱ	113025, 1 interactor
STRINGⁱ	9606.ENSP00000312304

Chemistry databases

BindingDBⁱ

P51580

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Turnⁱ	18 – 21	Combined sources	4
Helixⁱ	26 – 35	Combined sources	10
Helixⁱ	47 – 57	Combined sources	11
Beta strandⁱ	64 – 67	Combined sources	4
Helixⁱ	75 – 81	Combined sources	7
Beta strandⁱ	85 – 89	Combined sources	5
Helixⁱ	93 – 102	Combined sources	10
Beta strandⁱ	107 – 111	Combined sources	5
Beta strandⁱ	119 – 123	Combined sources	5
Beta strandⁱ	126 – 133	Combined sources	8
Helixⁱ	135 – 140	Combined sources	6
Beta strandⁱ	146 – 154	Combined sources	9
Turnⁱ	155 – 157	Combined sources	3
Helixⁱ	160 – 162	Combined sources	3
Helixⁱ	163 – 172	Combined sources	10
Beta strandⁱ	174 – 186	Combined sources	13
Turnⁱ	189 – 191	Combined sources	3
Helixⁱ	201 – 208	Combined sources	8
Turnⁱ	209 – 211	Combined sources	3
Beta strandⁱ	212 – 221	Combined sources	10
Helixⁱ	225 – 230	Combined sources	6
Beta strandⁱ	236 – 244	Combined sources	9

Show more details

3D structure databases

ProteinModelPortalⁱ	P51580
SMRⁱ	P51580
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	P51580

EvolutionaryTraceⁱ

P51580

Family & Domainsⁱ

Region

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Regionⁱ	29 – 40	S-adenosyl-L-methionine bindingAdd BLAST		12
Regionⁱ	134 – 135	S-adenosyl-L-methionine binding		2

Sequence similaritiesⁱ

Belongs to the class I-like SAM-binding methyltransferase superfamily. TPMT family.Curated

Phylogenomic databases

eggNOGⁱ	ENOG410IGTR Eukaryota ENOG4111GNF LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00390000016823
HOVERGENⁱ	HBG003037
InParanoidⁱ	P51580
KEGG Orthology (KO) More...KOⁱ	K00569
OMAⁱ	GFHQEQG
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0VS2
PhylomeDBⁱ	P51580
TreeFamⁱ	TF328951

Family and domain databases

HAMAPⁱ	MF_00812 Thiopur_methtran, 1 hit
InterProⁱ	View protein in InterPro IPR029063 SAM-dependent_MTases IPR025835 Thiopurine_S-MeTrfase IPR008854 TPMT
PANTHERⁱ	PTHR10259 PTHR10259, 1 hit
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF05724 TPMT, 1 hit
PIRSFⁱ	PIRSF023956 Thiopurine_S-methyltransferase, 1 hit
SUPFAMⁱ	SSF53335 SSF53335, 1 hit
PROSITEⁱ	View protein in PROSITE PS51585 SAM_MT_TPMT, 1 hit

Sequenceⁱ

Sequence statusⁱ: Complete.

P51580-1 [UniParc]FASTA Add to basket

« Hide

        10         20         30         40         50
MDGTRTSLDI EEYSDTEVQK NQVLTLEEWQ DKWVNGKTAF HQEQGHQLLK 
        60         70         80         90        100
KHLDTFLKGK SGLRVFFPLC GKAVEMKWFA DRGHSVVGVE ISELGIQEFF 
       110        120        130        140        150
TEQNLSYSEE PITEIPGTKV FKSSSGNISL YCCSIFDLPR TNIGKFDMIW 
       160        170        180        190        200
DRGALVAINP GDRKCYADTM FSLLGKKFQY LLCVLSYDPT KHPGPPFYVP 
       210        220        230        240 
HAEIERLFGK ICNIRCLEKV DAFEERHKSW GIDCLFEKLY LLTEK

Length:245

Mass (Da):28,180

Last modified:October 1, 1996 - v1

Checksum:ⁱ190E781155B97BB9

GO

Sequence cautionⁱ

The sequence AAB71631 differs from that shown. Reason: Erroneous initiation.Curated

The sequence AAB71632 differs from that shown. Reason: Erroneous initiation.Curated

Polymorphismⁱ

Polymorphic variations define TPMT activity levels that are variable among ethnic groups. 90% of Caucasians have high TPMT activity, 10% have intermediate activity, and 1 in 300 individuals has low activity (PubMed:10208641). These differences influence the clinical use and therapeutic efficacy of thiopurine drugs, generally used as immunosuppressants or cytotoxic drugs in conditions including leukemia, autoimmune disease and organ transplantation. Intermediate or low TPMT activity is associated with thiopurine intolerance and patients are at risk of toxicity after receiving standard doses of thiopurine drugs [MIMⁱ:610460] (PubMed:10751626, PubMed:15819814, PubMed:16220112, PubMed:16476125, PubMed:16789994, PubMed:7862671, PubMed:8561894, PubMed:8644731, PubMed:9246020, PubMed:9336428, PubMed:9711875, PubMed:9931345, PubMed:9931346). The most prevalent TPMT alleles associated with TPMT deficiency are TPMT*2 and TPMT*3A. The proteins encoded by TPMT*2 and TPMT*3A mutant are degraded more rapidly by an ATP-dependent proteasome-mediated pathway (PubMed:9177237, PubMed:8644731).15 Publications

TPMT*3A is the most common allele in the Caucasians and American Caucasians; it is the only mutant allele found in the South West Asians; it is not found in the Chinese. TPMT*3C is common in African-Americans and is the only allele in Chinese, Japanese and Taiwanese individuals. This allele is found at a low frequency in the Caucasians. This suggests that TPMT*3C is the oldest mutation, with TPMT*3B being acquired later to form the TPMT*3A allele in the Caucasian and South West Asian populations. TPMT*2 appears to be a more recent allele, which has only been detected in Caucasians to date.3 Publications

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_005636	49	L → S Polymorphism; allele TPMT*5; has very low activity when expressed in a heterologous system. 2 PublicationsCorresponds to variant dbSNP:rs72552740Ensembl.	1
Natural variantⁱVAR_005637	80	A → P Polymorphism; allele TPMT2; TPMT2 allele frequency is 0.5%; seems to be restricted to the Caucasian population; 100-fold reduction in activity; protein shows enhanced degradation. 8 PublicationsCorresponds to variant dbSNP:rs1800462EnsemblClinVar.	1
Natural variantⁱVAR_005638	154	A → T Polymorphism; allele TPMT3A and allele TPMT3B; very low activity; protein shows enhanced degradation leading to strongly reduced protein levels. 13 PublicationsCorresponds to variant dbSNP:rs1800460EnsemblClinVar.	1
Natural variantⁱVAR_052368	179	Q → H. Corresponds to variant dbSNP:rs6921269Ensembl.	1
Natural variantⁱVAR_005639	180	Y → F Polymorphism; allele TPMT*6; reduced activity. 2 PublicationsCorresponds to variant dbSNP:rs75543815Ensembl.	1
Natural variantⁱVAR_008715	215	R → H Polymorphism; allele TPMT*8; intermediate activity. 2 PublicationsCorresponds to variant dbSNP:rs56161402EnsemblClinVar.	1
Natural variantⁱVAR_005640	227	H → Q Polymorphism; allele TPMT*7; reduced activity. 2 PublicationsCorresponds to variant dbSNP:rs72552736Ensembl.	1
Natural variantⁱVAR_005641	240	Y → C Polymorphism; allele TPMT3B and allele TPMT3C; reduced activity; protein shows enhanced degradation. 12 PublicationsCorresponds to variant dbSNP:rs1142345EnsemblClinVar.	1

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	S62904 mRNA Translation: AAB27277.1 U12387 mRNA Translation: AAC50130.1 U30518 U30517 Genomic DNA Translation: AAC50368.1 AF019369 AF019368 Genomic DNA Translation: AAC51865.1 U81562 Genomic DNA Translation: AAB71625.1 U81563 Genomic DNA Translation: AAB71626.1 U81564 Genomic DNA Translation: AAB71627.1 U81565 Genomic DNA Translation: AAB71628.1 U81566 Genomic DNA Translation: AAB71629.1 U81567 Genomic DNA Translation: AAB71630.1 U81568 Genomic DNA Translation: AAB71631.1 Different initiation. U81569 Genomic DNA Translation: AAB71632.1 Different initiation. U81570 Genomic DNA Translation: AAB71633.1 U81571 Genomic DNA Translation: AAB71634.1 U81572 Genomic DNA Translation: AAB71635.1 U81573 Genomic DNA Translation: AAB71636.1 AB045146 Genomic DNA Translation: BAA97037.1 AL589723 Genomic DNA No translation available. BC009596 mRNA Translation: AAH09596.1 AF035426 Genomic DNA Translation: AAC32289.1 AF021876 mRNA Translation: AAB80746.1 AF021877 mRNA Translation: AAB80747.1
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS4543.1
PIRⁱ	I57946
NCBI Reference Sequences More...RefSeqⁱ	NP_000358.1, NM_000367.4 NP_001333746.1, NM_001346817.1 NP_001333747.1, NM_001346818.1
UniGeneⁱ	Hs.444319

Genome annotation databases

Ensemblⁱ	ENST00000309983; ENSP00000312304; ENSG00000137364
GeneIDⁱ	7172
KEGGⁱ	hsa:7172
UCSC genome browser More...UCSCⁱ	uc003ncm.4 human

Keywords - Coding sequence diversityⁱ

Polymorphism

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
P51580	Thiopurine S-methyltransferase, isoform CRA_d		HUMAN		245	UniRef100_P51580

Protein	Similar proteins		Species	Score	Length	Source
P51580	Thiopurine S-methyltransferase		PONPY		245	UniRef90_P51580
Thiopurine S-methyltransferase		PANTR		245
Thiopurine S-methyltransferase		GORGO		245
Thiopurine S-methyltransferase		CHLAE		245
Thiopurine S-methyltransferase, isoform CRA_d		HUMAN		245
+31

Protein	Similar proteins		Species	Score	Length	Source
P51580	Thiopurine S-methyltransferase		PONPY		245	UniRef50_P51580
Thiopurine S-methyltransferase		PANTR		245
Thiopurine S-methyltransferase		GORGO		245
Thiopurine S-methyltransferase		CHLAE		245
Thiopurine S-methyltransferase	)	MOUSE		240
+253

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	S62904 mRNA Translation: AAB27277.1 U12387 mRNA Translation: AAC50130.1 U30518 U30517 Genomic DNA Translation: AAC50368.1 AF019369 AF019368 Genomic DNA Translation: AAC51865.1 U81562 Genomic DNA Translation: AAB71625.1 U81563 Genomic DNA Translation: AAB71626.1 U81564 Genomic DNA Translation: AAB71627.1 U81565 Genomic DNA Translation: AAB71628.1 U81566 Genomic DNA Translation: AAB71629.1 U81567 Genomic DNA Translation: AAB71630.1 U81568 Genomic DNA Translation: AAB71631.1 Different initiation. U81569 Genomic DNA Translation: AAB71632.1 Different initiation. U81570 Genomic DNA Translation: AAB71633.1 U81571 Genomic DNA Translation: AAB71634.1 U81572 Genomic DNA Translation: AAB71635.1 U81573 Genomic DNA Translation: AAB71636.1 AB045146 Genomic DNA Translation: BAA97037.1 AL589723 Genomic DNA No translation available. BC009596 mRNA Translation: AAH09596.1 AF035426 Genomic DNA Translation: AAC32289.1 AF021876 mRNA Translation: AAB80746.1 AF021877 mRNA Translation: AAB80747.1
CCDSⁱ	CCDS4543.1
PIRⁱ	I57946
RefSeqⁱ	NP_000358.1, NM_000367.4 NP_001333746.1, NM_001346817.1 NP_001333747.1, NM_001346818.1
UniGeneⁱ	Hs.444319

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	2BZG	X-ray	1.58	A	16-245	[»]
	2H11	X-ray	1.89	A/B	17-245	[»]
ProteinModelPortalⁱ	P51580
SMRⁱ	P51580
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	113025, 1 interactor
STRINGⁱ	9606.ENSP00000312304

Chemistry databases

BindingDBⁱ	P51580
ChEMBLⁱ	CHEMBL2500
DrugBankⁱ	DB00993 Azathioprine DB00436 Bendroflumethiazide DB01327 Cefazolin DB01033 Mercaptopurine DB01250 Olsalazine DB01021 Trichlormethiazide

PTM databases

iPTMnetⁱ	P51580
PhosphoSitePlusⁱ	P51580

Polymorphism and mutation databases

BioMutaⁱ	TPMT
DMDMⁱ	1730006

Proteomic databases

EPDⁱ	P51580
MaxQBⁱ	P51580
PaxDbⁱ	P51580
PeptideAtlasⁱ	P51580
PRIDEⁱ	P51580
ProteomicsDBⁱ	56338

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	7172
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENST00000309983; ENSP00000312304; ENSG00000137364
GeneIDⁱ	7172
KEGGⁱ	hsa:7172
UCSCⁱ	uc003ncm.4 human

Organism-specific databases

CTDⁱ	7172
DisGeNETⁱ	7172
EuPathDBⁱ	HostDB:ENSG00000137364.4
GeneCardsⁱ	TPMT
HGNCⁱ	HGNC:12014 TPMT
HPAⁱ	HPA019851
MalaCardsⁱ	TPMT
MIMⁱ	187680 gene 610460 phenotype
neXtProtⁱ	NX_P51580
OpenTargetsⁱ	ENSG00000137364
Orphanetⁱ	413687 Azathioprine or 6-mercatopurine toxicity or dose selection 240863 Cisplatin toxicity
PharmGKBⁱ	PA356
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	ENOG410IGTR Eukaryota ENOG4111GNF LUCA
GeneTreeⁱ	ENSGT00390000016823
HOVERGENⁱ	HBG003037
InParanoidⁱ	P51580
KOⁱ	K00569
OMAⁱ	GFHQEQG
OrthoDBⁱ	EOG091G0VS2
PhylomeDBⁱ	P51580
TreeFamⁱ	TF328951

Enzyme and pathway databases

BioCycⁱ	MetaCyc:HS06327-MONOMER
BRENDAⁱ	2.1.1.67 2681
Reactomeⁱ	R-HSA-156581 Methylation R-HSA-5578995 Defective TPMT causes Thiopurine S-methyltransferase deficiency (TPMT deficiency)

Miscellaneous databases

ChiTaRSⁱ	TPMT human
EvolutionaryTraceⁱ	P51580
GeneWikiⁱ	Thiopurine_methyltransferase
GenomeRNAiⁱ	7172
Protein Ontology More...PROⁱ	PR:P51580
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000137364 Expressed in 222 organ(s), highest expression level in buccal mucosa cell
ExpressionAtlasⁱ	P51580 baseline and differential
Genevisibleⁱ	P51580 HS

Family and domain databases

HAMAPⁱ	MF_00812 Thiopur_methtran, 1 hit
InterProⁱ	View protein in InterPro IPR029063 SAM-dependent_MTases IPR025835 Thiopurine_S-MeTrfase IPR008854 TPMT
PANTHERⁱ	PTHR10259 PTHR10259, 1 hit
Pfamⁱ	View protein in Pfam PF05724 TPMT, 1 hit
PIRSFⁱ	PIRSF023956 Thiopurine_S-methyltransferase, 1 hit
SUPFAMⁱ	SSF53335 SSF53335, 1 hit
PROSITEⁱ	View protein in PROSITE PS51585 SAM_MT_TPMT, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	TPMT_HUMAN
Accessionⁱ	P51580Primary (citable) accession number: P51580 Secondary accession number(s): O14806 Q9UE62
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
	Last sequence update:	October 1, 1996
	Last modified:	December 5, 2018
	This is version 184 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

PDB cross-references
Index of Protein Data Bank (PDB) cross-references
SIMILARITY comments
Index of protein domains and families
Human chromosome 6
Human chromosome 6: entries, gene names and cross-references to MIM
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

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UniProtKB - P51580 (TPMT_HUMAN)

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Thiopurine S-methyltransferase

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the ‘Function’ section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

pH dependencei

Sites

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GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

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Cytosol

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

Organism-specific databases

Chemistry databases

Polymorphism and mutation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

Chemistry databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Region

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

Family and domain databases

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

Natural variant

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

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Chemistry databases

PTM databases

Polymorphism and mutation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

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Functionⁱ

Catalytic activityⁱ

Kineticsⁱ

pH dependenceⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Sequence cautionⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ