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P51580

- TPMT_HUMAN

UniProt

P51580 - TPMT_HUMAN

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Protein
Thiopurine S-methyltransferase
Gene
TPMT
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine.1 Publication

Catalytic activityi

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

Enzyme regulationi

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

Kineticsi

  1. KM=5.6 mM for S-adenosyl-L-methionine1 Publication
  2. KM=0.35 mM for 6-mercaptopurine

Vmax=0.6 nmol/sec/mg enzyme toward 6-mercaptopurine (at 37 degrees Celsius)

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei40 – 401Substrate By similarity
Binding sitei69 – 691S-adenosyl-L-methionine; via carbonyl oxygen
Binding sitei90 – 901S-adenosyl-L-methionine
Binding sitei152 – 1521S-adenosyl-L-methionine

GO - Molecular functioni

  1. thiopurine S-methyltransferase activity Source: ProtInc

GO - Biological processi

  1. methylation Source: Reactome
  2. nucleobase-containing compound metabolic process Source: ProtInc
  3. response to testosterone Source: Ensembl
  4. small molecule metabolic process Source: Reactome
  5. xenobiotic metabolic process Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Methyltransferase, Transferase

Keywords - Ligandi

S-adenosyl-L-methionine

Enzyme and pathway databases

ReactomeiREACT_6946. Methylation.

Names & Taxonomyi

Protein namesi
Recommended name:
Thiopurine S-methyltransferase (EC:2.1.1.67)
Alternative name(s):
Thiopurine methyltransferase
Gene namesi
Name:TPMT
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 6

Organism-specific databases

HGNCiHGNC:12014. TPMT.

Subcellular locationi

Cytoplasm UniRule annotation

GO - Cellular componenti

  1. cytosol Source: Reactome
  2. extracellular vesicular exosome Source: UniProt
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Thiopurine S-methyltransferase deficiency (TPMT deficiency) [MIM:610460]: Enzyme involved in the normal metabolic inactivation of thiopurine drugs. These drugs are generally used as immunosuppressants or cytotoxic drugs and are prescribed for a variety of clinical conditions including leukemia, autoimmune disease and organ transplantation. Patients with intermediate or no TPMT activity are at risk of toxicity after receiving standard doses of thiopurine drugs and it is shown that inter-individual differences in response to these drugs are largely determined by genetic variation at the TPMT locus.
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti80 – 801A → P in TPMT deficiency; allele TPMT*2; 100-fold reduction in activity; protein shows enhanced degradation; TPMT*2 allele frequency is 0.5%; seems to be restricted to the Caucasian population. 8 Publications
Corresponds to variant rs1800462 [ dbSNP | Ensembl ].
VAR_005637
Natural varianti154 – 1541A → T in TPMT deficiency; allele TPMT*3A and allele TPMT*3B; very low activity; protein shows enhanced degradation leading to strongly reduced protein levels; TPMT*3A is most common mutant in American Caucasians; TPMT*3A allele frequencies are 4.5% in the Caucasian; 0.8% in the African Americans and 3.2% in the Caucasian Americans population. 13 Publications
Corresponds to variant rs1800460 [ dbSNP | Ensembl ].
VAR_005638
Natural varianti215 – 2151R → H in TPMT deficiency; allele TPMT*8; intermediate activity. 2 Publications
Corresponds to variant rs56161402 [ dbSNP | Ensembl ].
VAR_008715
Natural varianti227 – 2271H → Q in TPMT deficiency; allele TPMT*7; reduced activity. 2 Publications
Corresponds to variant rs72552736 [ dbSNP | Ensembl ].
VAR_005640
Natural varianti240 – 2401Y → C in TPMT deficiency; allele TPMT*3B and allele TPMT*3C; reduced activity; protein shows enhanced degradation; TPMT*3C is the most common mutant in African-Americans and the only allele in the Japanese and Taiwanese individuals; TPMT*3C frequencies are 7.6% in Ghanaian and 0.3% in Caucasian individuals. 12 Publications
Corresponds to variant rs1142345 [ dbSNP | Ensembl ].
VAR_005641

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi152 – 1521R → E: Decreases affinity for 6-mercaptopurine. Slightly decreases catalytic activity. 1 Publication

Organism-specific databases

MIMi610460. phenotype.
Orphaneti240925. Azathioprine dose selection in the treatment of Crohn disease, leukemia and in transplantation.
240853. Azathioprine toxicity.
240863. Cisplatin toxicity.
240927. Mercaptopurine dose selection in the treatment of Crohn disease, leukemia and in transplantation.
240889. Mercaptopurine toxicity.
240999. Susceptibility to deafness due to cisplatin treatment.
241019. Susceptibility to neutropenia due to azathioprine treatment.
241021. Susceptibility to neutropenia due to mercaptopurine treatment.
3315. Thiopurine S-methyltransferase deficiency.
PharmGKBiPA356.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 245245Thiopurine S-methyltransferaseUniRule annotation
PRO_0000220102Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei14 – 141Phosphoserine2 Publications
Modified residuei58 – 581N6-acetyllysine1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP51580.
PaxDbiP51580.
PeptideAtlasiP51580.
PRIDEiP51580.

PTM databases

PhosphoSiteiP51580.

Expressioni

Gene expression databases

BgeeiP51580.
GenevestigatoriP51580.

Organism-specific databases

HPAiHPA019851.

Interactioni

Subunit structurei

Monomer.1 Publication

Protein-protein interaction databases

BioGridi113025. 3 interactions.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni18 – 214
Helixi26 – 3510
Helixi47 – 5711
Beta strandi64 – 674
Helixi75 – 817
Beta strandi85 – 895
Helixi93 – 10210
Beta strandi107 – 1115
Beta strandi119 – 1235
Beta strandi126 – 1338
Helixi135 – 1406
Beta strandi146 – 1549
Turni155 – 1573
Helixi160 – 1623
Helixi163 – 17210
Beta strandi174 – 18613
Turni189 – 1913
Helixi201 – 2088
Turni209 – 2113
Beta strandi212 – 22110
Helixi225 – 2306
Beta strandi236 – 2449

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2BZGX-ray1.58A16-245[»]
2H11X-ray1.89A/B17-245[»]
ProteinModelPortaliP51580.
SMRiP51580. Positions 17-245.

Miscellaneous databases

EvolutionaryTraceiP51580.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni29 – 4012S-adenosyl-L-methionine bindingUniRule annotation
Add
BLAST
Regioni134 – 1352S-adenosyl-L-methionine bindingUniRule annotation

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0500.
HOVERGENiHBG003037.
InParanoidiP51580.
KOiK00569.
OMAiHSVIGVE.
OrthoDBiEOG7H4DWQ.
PhylomeDBiP51580.
TreeFamiTF328951.

Family and domain databases

Gene3Di3.40.50.150. 1 hit.
HAMAPiMF_00812. Thiopur_methtran.
InterProiIPR029063. SAM-dependent_MTases-like.
IPR025835. Thiopurine_S-MeTrfase.
IPR008854. TPMT.
[Graphical view]
PfamiPF05724. TPMT. 1 hit.
[Graphical view]
PIRSFiPIRSF023956. Thiopurine_S-methyltransferase. 1 hit.
SUPFAMiSSF53335. SSF53335. 1 hit.
PROSITEiPS51585. SAM_MT_TPMT. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P51580-1 [UniParc]FASTAAdd to Basket

« Hide

MDGTRTSLDI EEYSDTEVQK NQVLTLEEWQ DKWVNGKTAF HQEQGHQLLK    50
KHLDTFLKGK SGLRVFFPLC GKAVEMKWFA DRGHSVVGVE ISELGIQEFF 100
TEQNLSYSEE PITEIPGTKV FKSSSGNISL YCCSIFDLPR TNIGKFDMIW 150
DRGALVAINP GDRKCYADTM FSLLGKKFQY LLCVLSYDPT KHPGPPFYVP 200
HAEIERLFGK ICNIRCLEKV DAFEERHKSW GIDCLFEKLY LLTEK 245
Length:245
Mass (Da):28,180
Last modified:October 1, 1996 - v1
Checksum:i190E781155B97BB9
GO

Sequence cautioni

The sequence AAB71631.1 differs from that shown. Reason: Erroneous initiation.
The sequence AAB71632.1 differs from that shown. Reason: Erroneous initiation.

Polymorphismi

Individual variation in the toxicity and therapeutic efficacy of thiopurine drugs is associated with a common genetic polymorphism that controls levels of TPMT activity. Genetic polymorphism in the TPMT gene is such that about 90% of Caucasians have high TPMT activity, 10% have intermediate activity and 1 in 300 individuals has low activity. TPMT activity varies among ethnic groups.UniRule annotation
TPMT*3A is the only mutant allele found in the South West Asians. This is also the most common mutant allele in the Caucasians but is not found in the Chinese. All mutant alleles identified in the Chinese population were TPMT*3C. 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. These ethnic differences may be important in the clinical use of thiopurine drugs.UniRule annotation

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti49 – 491L → S Allele TPMT*5; found in a patient with intermediate enzyme activity; has very low activity when expressed in a heterologous system. 2 Publications
Corresponds to variant rs72552740 [ dbSNP | Ensembl ].
VAR_005636
Natural varianti80 – 801A → P in TPMT deficiency; allele TPMT*2; 100-fold reduction in activity; protein shows enhanced degradation; TPMT*2 allele frequency is 0.5%; seems to be restricted to the Caucasian population. 8 Publications
Corresponds to variant rs1800462 [ dbSNP | Ensembl ].
VAR_005637
Natural varianti154 – 1541A → T in TPMT deficiency; allele TPMT*3A and allele TPMT*3B; very low activity; protein shows enhanced degradation leading to strongly reduced protein levels; TPMT*3A is most common mutant in American Caucasians; TPMT*3A allele frequencies are 4.5% in the Caucasian; 0.8% in the African Americans and 3.2% in the Caucasian Americans population. 13 Publications
Corresponds to variant rs1800460 [ dbSNP | Ensembl ].
VAR_005638
Natural varianti179 – 1791Q → H.
Corresponds to variant rs6921269 [ dbSNP | Ensembl ].
VAR_052368
Natural varianti180 – 1801Y → F Allele TPMT*6; reduced activity. 2 Publications
Corresponds to variant rs75543815 [ dbSNP | Ensembl ].
VAR_005639
Natural varianti215 – 2151R → H in TPMT deficiency; allele TPMT*8; intermediate activity. 2 Publications
Corresponds to variant rs56161402 [ dbSNP | Ensembl ].
VAR_008715
Natural varianti227 – 2271H → Q in TPMT deficiency; allele TPMT*7; reduced activity. 2 Publications
Corresponds to variant rs72552736 [ dbSNP | Ensembl ].
VAR_005640
Natural varianti240 – 2401Y → C in TPMT deficiency; allele TPMT*3B and allele TPMT*3C; reduced activity; protein shows enhanced degradation; TPMT*3C is the most common mutant in African-Americans and the only allele in the Japanese and Taiwanese individuals; TPMT*3C frequencies are 7.6% in Ghanaian and 0.3% in Caucasian individuals. 12 Publications
Corresponds to variant rs1142345 [ dbSNP | Ensembl ].
VAR_005641

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
S62904 mRNA. Translation: AAB27277.1.
U12387 mRNA. Translation: AAC50130.1.
U30518
, U30512, U30513, U30514, U30515, U30516, U30517 Genomic DNA. Translation: AAC50368.1.
AF019369
, AF019364, AF019365, AF019366, AF019367, 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. Translation: CAH71233.1.
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_000367.2.
UniGeneiHs.444319.

Genome annotation databases

EnsembliENST00000309983; ENSP00000312304; ENSG00000137364.
GeneIDi7172.
KEGGihsa:7172.
UCSCiuc003ncm.3. human.

Polymorphism databases

DMDMi1730006.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
S62904 mRNA. Translation: AAB27277.1 .
U12387 mRNA. Translation: AAC50130.1 .
U30518
, U30512 , U30513 , U30514 , U30515 , U30516 , U30517 Genomic DNA. Translation: AAC50368.1 .
AF019369
, AF019364 , AF019365 , AF019366 , AF019367 , 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. Translation: CAH71233.1 .
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_000367.2.
UniGenei Hs.444319.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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. Positions 17-245.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 113025. 3 interactions.

Chemistry

ChEMBLi CHEMBL2500.
DrugBanki DB01033. Mercaptopurine.

PTM databases

PhosphoSitei P51580.

Polymorphism databases

DMDMi 1730006.

Proteomic databases

MaxQBi P51580.
PaxDbi P51580.
PeptideAtlasi P51580.
PRIDEi P51580.

Protocols and materials databases

DNASUi 7172.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000309983 ; ENSP00000312304 ; ENSG00000137364 .
GeneIDi 7172.
KEGGi hsa:7172.
UCSCi uc003ncm.3. human.

Organism-specific databases

CTDi 7172.
GeneCardsi GC06M018072.
HGNCi HGNC:12014. TPMT.
HPAi HPA019851.
MIMi 187680. gene.
610460. phenotype.
neXtProti NX_P51580.
Orphaneti 240925. Azathioprine dose selection in the treatment of Crohn disease, leukemia and in transplantation.
240853. Azathioprine toxicity.
240863. Cisplatin toxicity.
240927. Mercaptopurine dose selection in the treatment of Crohn disease, leukemia and in transplantation.
240889. Mercaptopurine toxicity.
240999. Susceptibility to deafness due to cisplatin treatment.
241019. Susceptibility to neutropenia due to azathioprine treatment.
241021. Susceptibility to neutropenia due to mercaptopurine treatment.
3315. Thiopurine S-methyltransferase deficiency.
PharmGKBi PA356.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0500.
HOVERGENi HBG003037.
InParanoidi P51580.
KOi K00569.
OMAi HSVIGVE.
OrthoDBi EOG7H4DWQ.
PhylomeDBi P51580.
TreeFami TF328951.

Enzyme and pathway databases

Reactomei REACT_6946. Methylation.

Miscellaneous databases

EvolutionaryTracei P51580.
GeneWikii Thiopurine_methyltransferase.
GenomeRNAii 7172.
NextBioi 28108.
PROi P51580.
SOURCEi Search...

Gene expression databases

Bgeei P51580.
Genevestigatori P51580.

Family and domain databases

Gene3Di 3.40.50.150. 1 hit.
HAMAPi MF_00812. Thiopur_methtran.
InterProi IPR029063. SAM-dependent_MTases-like.
IPR025835. Thiopurine_S-MeTrfase.
IPR008854. TPMT.
[Graphical view ]
Pfami PF05724. TPMT. 1 hit.
[Graphical view ]
PIRSFi PIRSF023956. Thiopurine_S-methyltransferase. 1 hit.
SUPFAMi SSF53335. SSF53335. 1 hit.
PROSITEi PS51585. SAM_MT_TPMT. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Human thiopurine methyltransferase: molecular cloning and expression of T84 colon carcinoma cell cDNA."
    Honchel R., Aksoy I.A., Szumlanski C., Wood T.C., Otterness D.M., Wieben E.D., Weinshilboum R.M.
    Mol. Pharmacol. 43:878-887(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
    Tissue: Kidney.
  2. "Thiopurine methyltransferase pharmacogenetics. Cloning of human liver cDNA and a processed pseudogene on human chromosome 18q21.1."
    Lee D., Szumlanski C.L., Houtman J., Honchel R., Rojas K., Overhauser J., Weiben E.D., Weinshilboum R.M.
    Drug Metab. Dispos. 23:398-405(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "Thiopurine methyltransferase pharmacogenetics: human gene cloning and characterization of a common polymorphism."
    Szumlanski C., Otterness D., Her C., Lee D., Brandriff B., Kelsell D., Spurr N., Lennard L., Wieben E., Weinshilboum R.M.
    DNA Cell Biol. 15:17-30(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS TPMT DEFICIENCY THR-154 AND CYS-240.
  4. "Promoter and intronic sequences of the human thiopurine S-methyltransferase (TPMT) gene isolated from a human PAC1 genomic library."
    Krynetski E.Y., Fessing M.Y., Yates C.R., Sun D., Schuetz J.D., Evans W.E.
    Pharm. Res. 14:1672-1678(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-49 AND PHE-180, VARIANTS TPMT DEFICIENCY THR-154 AND CYS-240.
  6. "Genomic structure of thiopurine S-methyltransferase gene."
    Nakamura Y.
    Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  7. "The DNA sequence and analysis of human chromosome 6."
    Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D.
    , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
    Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  8. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Bone marrow.
  9. "Detection of known and new mutations in the thiopurine S-methyltransferase gene by single-strand conformation polymorphism analysis."
    Spire-Vayron de la Moureyre C., Debuysere H., Sabbagh N., Marez D., Vinner E., Chevalier E.D., Lo-Guidice J.-M., Broly F.
    Hum. Mutat. 12:177-185(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 210-245, VARIANT TPMT DEFICIENCY GLN-227.
  10. "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.
  11. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  12. "Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography."
    Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., Zou H., Gu J.
    Proteomics 8:1346-1361(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  13. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  14. "Lysine acetylation targets protein complexes and co-regulates major cellular functions."
    Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
    Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-58, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  15. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  16. "Structural basis of allele variation of human thiopurine-S-methyltransferase."
    Wu H., Horton J.R., Battaile K., Allali-Hassani A., Martin F., Zeng H., Loppnau P., Vedadi M., Bochkarev A., Plotnikov A.N., Cheng X.
    Proteins 67:198-208(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) OF 16-245 IN COMPLEX WITH S-ADENOSYL-L-HOMOCYSTEINE, SUBUNIT, CHARACTERIZATION OF VARIANTS TPMT DEFICIENCY THR-154 AND CYS-240.
  17. "A single point mutation leading to loss of catalytic activity in human thiopurine S-methyltransferase."
    Krynetski E.Y., Schuetz J.D., Galpin A.J., Pui C.-H., Relling M.V., Evans W.E.
    Proc. Natl. Acad. Sci. U.S.A. 92:949-953(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT TPMT DEFICIENCY PRO-80.
  18. "Thiopurine S-methyltransferase deficiency: two nucleotide transitions define the most prevalent mutant allele associated with loss of catalytic activity in Caucasians."
    Tai H.-L., Krynetski E.Y., Yates C.R., Loennechen T., Fessing M.Y., Krynetskaia N.F., Evans W.E.
    Am. J. Hum. Genet. 58:694-702(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS TPMT DEFICIENCY THR-154 AND CYS-240.
  19. "Azathioprine-induced severe pancytopenia due to a homozygous two-point mutation of the thiopurine methyltransferase gene in a patient with juvenile HLA-B27-associated spondylarthritis."
    Leipold G., Schuetz E., Haas J.P., Oellerich M.
    Arthritis Rheum. 40:1896-1898(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS TPMT DEFICIENCY THR-154 AND CYS-240.
  20. "Enhanced proteolysis of thiopurine S-methyltransferase (TPMT) encoded by mutant alleles in humans (TPMT*3A, TPMT*2): mechanisms for the genetic polymorphism of TPMT activity."
    Tai H.-L., Krynetski E.Y., Schuetz E.G., Yanishevski Y., Evans W.E.
    Proc. Natl. Acad. Sci. U.S.A. 94:6444-6449(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION OF VARIANTS TPMT DEFICIENCY PRO-80 AND THR-154, MECHANISM FOR THE GENETIC POLYMORPHISM OF TPMT ACTIVITY.
  21. "Thiopurine methyltransferase alleles in British and Ghanaian populations."
    Ameyaw M.-M., Collie-Duguid E.S.R., Powrie R.H., Ofori-Adjei D., McLeod H.L.
    Hum. Mol. Genet. 8:367-370(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS TPMT DEFICIENCY PRO-80; THR-154 AND CYS-240.
  22. "Polymorphism of the thiopurine S-methyltransferase gene in African-Americans."
    Hon Y.Y., Fessing M.Y., Pui C.-H., Relling M.V., Krynetski E.Y., Evans W.E.
    Hum. Mol. Genet. 8:371-376(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT TPMT DEFICIENCY HIS-215.
  23. "The frequency and distribution of thiopurine methyltransferase alleles in Caucasian and Asian populations."
    Collie-Duguid E.S.R., Pritchard S.C., Powrie R.H., Sludden J., Collier D.A., Li T., McLeod H.L.
    Pharmacogenetics 9:37-42(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS TPMT DEFICIENCY PRO-80; THR-154 AND CYS-240, FREQUENCY AND DISTRIBUTION OF ALLELES.
  24. "Genetic analysis of thiopurine methyltransferase polymorphism in a Japanese population."
    Hiratsuka M., Inoue T., Omori F., Agatsuma Y., Mizugaki M.
    Mutat. Res. 448:91-95(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS TPMT DEFICIENCY PRO-80; THR-154 AND CYS-240, FREQUENCY AND DISTRIBUTION OF ALLELES.
  25. "Thiopurine S-methyltransferase pharmacogenetics: variant allele functional and comparative genomics."
    Salavaggione O.E., Wang L., Wiepert M., Yee V.C., Weinshilboum R.M.
    Pharmacogenet. Genomics 15:801-815(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS TPMT DEFICIENCY PRO-80; THR-154; HIS-215; GLN-227 AND CYS-240, VARIANTS SER-49 AND PHE-180, CHARACTERIZATION OF VARIANTS TPMT DEFICIENCY PRO-80; THR-154; HIS-215; GLN-227 AND CYS-240, CHARACTERIZATION OF VARIANTS SER-49 AND PHE-180.
  26. "Severe azathioprine-induced myelotoxicity in a kidney transplant patient with thiopurine S-methyltransferase-deficient genotype (TPMT*3A/*3C)."
    Kurzawski M., Dziewanowski K., Ciechanowski K., Drozdzik M.
    Transpl. Int. 18:623-625(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS TPMT DEFICIENCY THR-154 AND CYS-240.
  27. "Molecular analysis of thiopurine S-methyltransferase alleles in Taiwan aborigines and Taiwanese."
    Lu H.-F., Shih M.-C., Chang Y.-S., Chang J.-Y., Ko Y.-C., Chang S.-J., Chang J.-G.
    J. Clin. Pharm. Ther. 31:93-98(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS TPMT DEFICIENCY PRO-80; THR-154 AND CYS-240, FREQUENCY AND DISTRIBUTION OF ALLELES.
  28. "Frequency of the thiopurine S-methyltransferase alleles in the ancient genetic population isolate of Sardinia."
    Rossino R., Vincis C., Alves S., Prata M.J., Macis M.D., Nucaro A.L., Schirru E., Congia M.
    J. Clin. Pharm. Ther. 31:283-287(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS TPMT DEFICIENCY PRO-80; THR-154 AND CYS-240, FREQUENCY AND DISTRIBUTION OF ALLELES.

Entry informationi

Entry nameiTPMT_HUMAN
AccessioniPrimary (citable) accession number: P51580
Secondary accession number(s): O14806
, O15423, O15424, O15425, O15426, O15515, O15548, O43213, Q5VUK6, Q9UBE6, Q9UBT8, Q9UE62
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: September 3, 2014
This is version 147 of the entry and version 1 of the sequence. [Complete history]
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.

Miscellaneousi

Miscellaneous

TPMT deficiency inherited by TPMT*2 and TPMT*3A alleles, are the most prevalent mutant TPMT in humans. TPMT deficiency is associated with lower cellular levels of TPMT protein, and the proteins encoded by TPMT*2 and TPMT*3A mutant alleles are degraded more rapidly by an ATP-dependent proteasome-mediated pathway.

Keywords - Technical termi

3D-structure, Complete proteome, 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 polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  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

External Data

Dasty 3

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