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Protein

Thiopurine S-methyltransferase

Gene

Tpmt

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine (also called mercaptopurine, 6-MP or its brand name Purinethol) using S-adenosyl-L-methionine as the methyl donor (PubMed:18484748). TPMT activity modulates the cytotoxic effects of thiopurine prodrugs. A natural substrate for this enzyme has yet to be identified.Curated1 Publication

Catalytic activityi

S-adenosyl-L-methionine + a thiopurine = S-adenosyl-L-homocysteine + a thiopurine S-methylether.1 Publication
Mercaptopurine + S-adenosyl-L-methionine = 6-methylthiopurine + S-adenosyl-L-homocysteine.1 Publication

Kineticsi

  1. KM=5.6 µM for S-adenosyl-L-methionine (at pH 6.5 and 37 degrees Celsius)1 Publication
  2. KM=0.35 mM for 6-mercaptopurine (at pH 6.5 and 37 degrees Celsius)1 Publication
  1. Vmax=0.604 nmol/sec/mg enzyme toward 6-mercaptopurine (at pH 6.5 and 37 degrees Celsius)1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei35Substrate1
Binding sitei64S-adenosyl-L-methionine; via carbonyl oxygen1
Binding sitei85S-adenosyl-L-methionine1
Binding sitei147S-adenosyl-L-methionine1

GO - Molecular functioni

  • S-adenosyl-L-methionine binding Source: MGI
  • thiopurine S-methyltransferase activity Source: MGI

GO - Biological processi

Keywordsi

Molecular functionMethyltransferase, Transferase
LigandS-adenosyl-L-methionine

Enzyme and pathway databases

BRENDAi2.1.1.67 3474

Names & Taxonomyi

Protein namesi
Recommended name:
Thiopurine S-methyltransferase1 Publication (EC:2.1.1.671 Publication)
Alternative name(s):
Thiopurine methyltransferase
Gene namesi
Name:Tpmt
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:98812 Tpmt

Subcellular locationi

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002201051 – 240Thiopurine S-methyltransferaseAdd BLAST240

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei34PhosphoserineCombined sources1
Modified residuei53N6-acetyllysineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiO55060
PaxDbiO55060
PeptideAtlasiO55060
PRIDEiO55060

PTM databases

iPTMnetiO55060
PhosphoSitePlusiO55060

Expressioni

Gene expression databases

CleanExiMM_TPMT

Interactioni

Subunit structurei

Monomer.1 Publication

Protein-protein interaction databases

IntActiO55060, 2 interactors
MINTiO55060
STRINGi10090.ENSMUSP00000021806

Structurei

Secondary structure

1240
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO55060
SMRiO55060
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO55060

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni24 – 35S-adenosyl-L-methionine bindingAdd BLAST12
Regioni129 – 130S-adenosyl-L-methionine binding2

Sequence similaritiesi

Phylogenomic databases

eggNOGiENOG410IGTR Eukaryota
ENOG4111GNF LUCA
HOGENOMiHOG000276919
HOVERGENiHBG003037
InParanoidiO55060
KOiK00569
PhylomeDBiO55060
TreeFamiTF328951

Family and domain databases

HAMAPiMF_00812 Thiopur_methtran, 1 hit
InterProiView protein in InterPro
IPR029063 SAM-dependent_MTases
IPR025835 Thiopurine_S-MeTrfase
IPR008854 TPMT
PANTHERiPTHR10259 PTHR10259, 1 hit
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

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 7 potential isoforms that are computationally mapped.Show allAlign All

O55060-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MSLDMKEHPD AEVQKNQVLT LEDWKEKWVT RHISFHQEQG HQLLKKHLDT
60 70 80 90 100
FLKGQSGLRV FFPLCGKAIE MKWFADRGHT VVGVEISEIG IREFFAEQNL
110 120 130 140 150
SYTEEPLAEI AGAKVFKSSS GSISLYCCSI FDLPRANIGK FDRIWDRGAL
160 170 180 190 200
VAINPGDHDR YADIILSLLR KEFQYLVAVL SYDPTKHAGP PFYVPSAELK
210 220 230 240
RLFGTKCSMQ CLEEVDALEE RHKAWGLDYL FEKLYLLTEK
Length:240
Mass (Da):27,586
Last modified:June 1, 1998 - v1
Checksum:i2BA57F30E8EB72D2
GO

Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0R4J018A0A0R4J018_MOUSE
Thiopurine S-methyltransferase
Tpmt
240Annotation score:
D3Z380D3Z380_MOUSE
Thiopurine S-methyltransferase
Tpmt
205Annotation score:
D3Z217D3Z217_MOUSE
Thiopurine S-methyltransferase
Tpmt
182Annotation score:
D3YWK6D3YWK6_MOUSE
Thiopurine S-methyltransferase
Tpmt
188Annotation score:
D6RIK3D6RIK3_MOUSE
Thiopurine S-methyltransferase
Tpmt
188Annotation score:
A0A286YCA5A0A286YCA5_MOUSE
Thiopurine S-methyltransferase
Tpmt
83Annotation score:
D3Z0R1D3Z0R1_MOUSE
Thiopurine S-methyltransferase
Tpmt
93Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti69I → V in strain: C57BL/6J. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF046887 mRNA Translation: AAC25919.1
AF037043 mRNA Translation: AAD02092.1
AF037044 mRNA Translation: AAD02093.1
AF104832
, AF104825, AF104826, AF104827, AF104828, AF104829, AF104830, AF104831 Genomic DNA Translation: AAF06075.1
BC021598 mRNA Translation: AAH21598.1
AH009424 Genomic DNA Translation: AAF74424.1
CCDSiCCDS26488.1
RefSeqiNP_058065.2, NM_016785.2
XP_006516989.1, XM_006516926.2
UniGeneiMm.10169

Genome annotation databases

GeneIDi22017
KEGGimmu:22017
UCSCiuc007qhq.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF046887 mRNA Translation: AAC25919.1
AF037043 mRNA Translation: AAD02092.1
AF037044 mRNA Translation: AAD02093.1
AF104832
, AF104825, AF104826, AF104827, AF104828, AF104829, AF104830, AF104831 Genomic DNA Translation: AAF06075.1
BC021598 mRNA Translation: AAH21598.1
AH009424 Genomic DNA Translation: AAF74424.1
CCDSiCCDS26488.1
RefSeqiNP_058065.2, NM_016785.2
XP_006516989.1, XM_006516926.2
UniGeneiMm.10169

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2GB4X-ray1.25A/B1-240[»]
3BGDX-ray2.00A/B1-240[»]
3BGIX-ray1.80A/B1-240[»]
ProteinModelPortaliO55060
SMRiO55060
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO55060, 2 interactors
MINTiO55060
STRINGi10090.ENSMUSP00000021806

PTM databases

iPTMnetiO55060
PhosphoSitePlusiO55060

Proteomic databases

MaxQBiO55060
PaxDbiO55060
PeptideAtlasiO55060
PRIDEiO55060

Protocols and materials databases

DNASUi22017
Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi22017
KEGGimmu:22017
UCSCiuc007qhq.2 mouse

Organism-specific databases

CTDi7172
MGIiMGI:98812 Tpmt

Phylogenomic databases

eggNOGiENOG410IGTR Eukaryota
ENOG4111GNF LUCA
HOGENOMiHOG000276919
HOVERGENiHBG003037
InParanoidiO55060
KOiK00569
PhylomeDBiO55060
TreeFamiTF328951

Enzyme and pathway databases

BRENDAi2.1.1.67 3474

Miscellaneous databases

EvolutionaryTraceiO55060
PROiPR:O55060
SOURCEiSearch...

Gene expression databases

CleanExiMM_TPMT

Family and domain databases

HAMAPiMF_00812 Thiopur_methtran, 1 hit
InterProiView protein in InterPro
IPR029063 SAM-dependent_MTases
IPR025835 Thiopurine_S-MeTrfase
IPR008854 TPMT
PANTHERiPTHR10259 PTHR10259, 1 hit
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
ProtoNetiSearch...

Entry informationi

Entry nameiTPMT_MOUSE
AccessioniPrimary (citable) accession number: O55060
Secondary accession number(s): Q9JIL7, Q9QUG7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: June 1, 1998
Last modified: July 18, 2018
This is version 137 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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