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UniProtKB - P51580 (TPMT_HUMAN)

Entry version 201 (25 May 2022)
Sequence version 1 (01 Oct 1996)
Previous versions | rss
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Protein

Thiopurine S-methyltransferase

Gene

TPMT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<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

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

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">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 <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

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

<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

  1. KM=18.5 µM for S-adenosyl-L-methionine (at pH 6.5 and 37 degrees Celsius)1 Publication
  2. KM=0.68 mM for 6-mercaptopurine (at pH 6.5 and 37 degrees Celsius)1 Publication
  3. KM=1.7 µM for S-adenosyl-L-methionine (at pH 7.5 and 37 degrees Celsius)1 Publication
  4. KM=0.32 mM for 6-mercaptopurine (at pH 7.5 and 37 degrees Celsius)1 Publication
  5. KM=0.20 mM for 6-thioguanine (at pH 7.5 and 37 degrees Celsius)1 Publication
  1. Vmax=1.23 nmol/sec/mg enzyme toward 6-mercaptopurine (at pH 6.5 and 37 degrees Celsius)1 Publication

pH dependencei

Optimum pH is 7.5.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei40SubstrateBy similarity1
Binding sitei69S-adenosyl-L-methionine; via carbonyl oxygen1
Binding sitei90S-adenosyl-L-methionine1
Binding sitei152S-adenosyl-L-methionine1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionMethyltransferase, Transferase
LigandS-adenosyl-L-methionine

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

More...BRENDAi		2.1.1.67, 2681

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		P51580

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-156581, Methylation
R-HSA-5578995, Defective TPMT causes TPMT deficiency

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		P51580

<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

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Thiopurine S-methyltransferase1 Publication (EC:2.1.1.672 Publications)
Alternative name(s):
Thiopurine methyltransferase1 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:TPMT
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 6

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:12014, TPMT

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		187680, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_P51580

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000137364

<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

Keywords - Cellular componenti

Cytoplasm

<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

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi152R → E: Decreases affinity for 6-mercaptopurine. Slightly decreases catalytic activity. 1 Publication1

Organism-specific databases

DisGeNET

More...DisGeNETi		7172

MalaCards human disease database

More...MalaCardsi		TPMT
MIMi610460, phenotype

Open Targets

More...OpenTargetsi		ENSG00000137364

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		413687, Azathioprine or 6-mercatopurine toxicity or dose selection
240863, Cisplatin toxicity
3315, NON RARE IN EUROPE: Thiopurine S-methyltransferase deficiency

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA356

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		P51580, Tchem

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL2500

Drug and drug target database

More...DrugBanki		DB00993, Azathioprine
DB00436, Bendroflumethiazide
DB01327, Cefazolin
DB01033, Mercaptopurine
DB01250, Olsalazine
DB01021, Trichlormethiazide

DrugCentral

More...DrugCentrali		P51580

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		TPMT

Domain mapping of disease mutations (DMDM)

More...DMDMi		1730006

<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

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00002201021 – 245Thiopurine S-methyltransferaseAdd BLAST245

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei14PhosphoserineCombined sources1
Modified residuei58N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

More...EPDi		P51580

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		P51580

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		P51580

MaxQB - The MaxQuant DataBase

More...MaxQBi		P51580

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		P51580

PeptideAtlas

More...PeptideAtlasi		P51580

PRoteomics IDEntifications database

More...PRIDEi		P51580

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		56338

PTM databases

GlyGen: Computational and Informatics Resources for Glycoscience

More...GlyGeni		P51580, 1 site, 1 O-linked glycan (1 site)

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		P51580

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		P51580

<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

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000137364, Expressed in buccal mucosa cell and 235 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		P51580, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		P51580, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000137364, Tissue enhanced (kidney, liver, thyroid gland)

<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

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Monomer.

1 Publication

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		113025, 8 interactors

Protein interaction database and analysis system

More...IntActi		P51580, 3 interactors

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000312304

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		P51580

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		P51580, protein

<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

1245
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

AlphaFold Protein Structure Database

More...AlphaFoldDBi		P51580

Biological Magnetic Resonance Data Bank

More...BMRBi		P51580

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		P51580

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...EvolutionaryTracei		P51580

<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

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni29 – 40S-adenosyl-L-methionine bindingAdd BLAST12
Regioni134 – 135S-adenosyl-L-methionine binding2

<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

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

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		ENOG502QSF5, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00390000016823

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_085515_2_0_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		P51580

Identification of Orthologs from Complete Genome Data

More...OMAi		LWCGDFF

Database of Orthologous Groups

More...OrthoDBi		1590477at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		P51580

TreeFam database of animal gene trees

More...TreeFami		TF328951

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		3.40.50.150, 1 hit

HAMAP database of protein families

More...HAMAPi		MF_00812, Thiopur_methtran, 1 hit

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR029063, SAM-dependent_MTases
IPR025835, Thiopurine_S-MeTrfase
IPR008854, TPMT

Pfam protein domain database

More...Pfami		View protein in Pfam
PF05724, TPMT, 1 hit

PIRSF; a whole-protein classification database

More...PIRSFi		PIRSF023956, Thiopurine_S-methyltransferase, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF53335, SSF53335, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS51585, SAM_MT_TPMT, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequencei

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

P51580-1 [UniParc]FASTAAdd 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
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i190E781155B97BB9
GO

<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

The sequence AAB71631 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAB71632 differs from that shown. Reason: Erroneous initiation.Curated

<p>This subsection of the 'Sequence' section provides information on polymorphic variants. If the variant is associated with a disease state, the description of the latter can be found in the <a href="http://www.uniprot.org/manual/involvement%5Fin%5Fdisease">'Involvement in disease'</a> subsection.<p><a href='/help/polymorphism' target='_top'>More...</a></p>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 keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_00563649L → S Allele TPMT*5; has very low activity when expressed in a heterologous system. 2 PublicationsCorresponds to variant dbSNP:rs72552740Ensembl.1
Natural variantiVAR_00563780A → P Allele TPMT*2; TPMT*2 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_005638154A → T Allele TPMT*3A and allele TPMT*3B; very low activity; protein shows enhanced degradation leading to strongly reduced protein levels. 13 PublicationsCorresponds to variant dbSNP:rs1800460EnsemblClinVar.1
Natural variantiVAR_052368179Q → H. Corresponds to variant dbSNP:rs6921269Ensembl.1
Natural variantiVAR_005639180Y → F Allele TPMT*6; reduced activity. 2 PublicationsCorresponds to variant dbSNP:rs75543815Ensembl.1
Natural variantiVAR_008715215R → H Allele TPMT*8; intermediate activity. 2 PublicationsCorresponds to variant dbSNP:rs56161402EnsemblClinVar.1
Natural variantiVAR_005640227H → Q Allele TPMT*7; reduced activity. 2 PublicationsCorresponds to variant dbSNP:rs72552736Ensembl.1
Natural variantiVAR_005641240Y → C Allele TPMT*3B and allele TPMT*3C; reduced activity; protein shows enhanced degradation. 12 PublicationsCorresponds to variant dbSNP:rs1142345EnsemblClinVar.1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...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

Protein sequence database of the Protein Information Resource

More...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

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000309983.5; ENSP00000312304.4; ENSG00000137364.5

Database of genes from NCBI RefSeq genomes

More...GeneIDi		7172

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:7172

Matched Annotation from NCBI and EMBL-EBI (MANE) - Phase one

More...MANE-Selecti		ENST00000309983.5; ENSP00000312304.4; NM_000367.5; NP_000358.1

UCSC genome browser

More...UCSCi		uc003ncm.4, human

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<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

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
CCDSiCCDS4543.1
PIRiI57946
RefSeqiNP_000358.1, NM_000367.4
NP_001333746.1, NM_001346817.1
NP_001333747.1, NM_001346818.1

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 entryMethodResolution (Å)ChainPositionsPDBsum
2BZGX-ray1.58A16-245[»]
2H11X-ray1.89A/B17-245[»]
AlphaFoldDBiP51580
BMRBiP51580
SMRiP51580
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi113025, 8 interactors
IntActiP51580, 3 interactors
STRINGi9606.ENSP00000312304

Chemistry databases

BindingDBiP51580
ChEMBLiCHEMBL2500
DrugBankiDB00993, Azathioprine
DB00436, Bendroflumethiazide
DB01327, Cefazolin
DB01033, Mercaptopurine
DB01250, Olsalazine
DB01021, Trichlormethiazide
DrugCentraliP51580

PTM databases

GlyGeniP51580, 1 site, 1 O-linked glycan (1 site)
iPTMnetiP51580
PhosphoSitePlusiP51580

Genetic variation databases

BioMutaiTPMT
DMDMi1730006

Proteomic databases

EPDiP51580
jPOSTiP51580
MassIVEiP51580
MaxQBiP51580
PaxDbiP51580
PeptideAtlasiP51580
PRIDEiP51580
ProteomicsDBi56338

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...Antibodypediai		10352, 424 antibodies from 32 providers

The DNASU plasmid repository

More...DNASUi		7172

Genome annotation databases

EnsembliENST00000309983.5; ENSP00000312304.4; ENSG00000137364.5
GeneIDi7172
KEGGihsa:7172
MANE-SelectiENST00000309983.5; ENSP00000312304.4; NM_000367.5; NP_000358.1
UCSCiuc003ncm.4, human

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		7172
DisGeNETi7172

GeneCards: human genes, protein and diseases

More...GeneCardsi		TPMT
HGNCiHGNC:12014, TPMT
HPAiENSG00000137364, Tissue enhanced (kidney, liver, thyroid gland)
MalaCardsiTPMT
MIMi187680, gene
610460, phenotype
neXtProtiNX_P51580
OpenTargetsiENSG00000137364
Orphaneti413687, Azathioprine or 6-mercatopurine toxicity or dose selection
240863, Cisplatin toxicity
3315, NON RARE IN EUROPE: Thiopurine S-methyltransferase deficiency
PharmGKBiPA356
VEuPathDBiHostDB:ENSG00000137364

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiENOG502QSF5, Eukaryota
GeneTreeiENSGT00390000016823
HOGENOMiCLU_085515_2_0_1
InParanoidiP51580
OMAiLWCGDFF
OrthoDBi1590477at2759
PhylomeDBiP51580
TreeFamiTF328951

Enzyme and pathway databases

BRENDAi2.1.1.67, 2681
PathwayCommonsiP51580
ReactomeiR-HSA-156581, Methylation
R-HSA-5578995, Defective TPMT causes TPMT deficiency
SignaLinkiP51580

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		7172, 9 hits in 1038 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		TPMT, human
EvolutionaryTraceiP51580

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		Thiopurine_methyltransferase

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		7172
PharosiP51580, Tchem

Protein Ontology

More...PROi		PR:P51580
RNActiP51580, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000137364, Expressed in buccal mucosa cell and 235 other tissues
ExpressionAtlasiP51580, baseline and differential
GenevisibleiP51580, HS

Family and domain databases

Gene3Di3.40.50.150, 1 hit
HAMAPiMF_00812, Thiopur_methtran, 1 hit
InterProiView protein in InterPro
IPR029063, SAM-dependent_MTases
IPR025835, Thiopurine_S-MeTrfase
IPR008854, TPMT
PfamiView protein in Pfam
PF05724, TPMT, 1 hit
PIRSFiPIRSF023956, Thiopurine_S-methyltransferase, 1 hit
SUPFAMiSSF53335, SSF53335, 1 hit
PROSITEiView protein in PROSITE
PS51585, SAM_MT_TPMT, 1 hit

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<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 subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiTPMT_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P51580
Secondary accession number(s): O14806
, O15423, O15424, O15425, O15426, O15515, O15548, O43213, Q5VUK6, Q9UBE6, Q9UBT8, Q9UE62
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: May 25, 2022
This is version 201 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

<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

3D-structure, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with genetic variants
    List of human entries with genetic variants
  3. Human variants curated from literature reports
    Index of human variants curated from literature reports
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families
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