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P51580 (TPMT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Thiopurine S-methyltransferase

EC=2.1.1.67
Alternative name(s):
Thiopurine methyltransferase
Gene names
Name:TPMT
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length245 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine. Ref.10

Catalytic activity

S-adenosyl-L-methionine + a thiopurine = S-adenosyl-L-homocysteine + a thiopurine S-methylether. Ref.10

Enzyme regulation

Inhibited by S-adenosyl-L-homocysteine (SAH). HAMAP-Rule MF_00812

Subunit structure

Monomer. Ref.16

Subcellular location

Cytoplasm HAMAP-Rule MF_00812.

Polymorphism

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. HAMAP-Rule MF_00812

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. HAMAP-Rule MF_00812

Involvement in disease

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.

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.

Sequence similarities

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

Biophysicochemical properties

Kinetic parameters:

KM=5.6 mM for S-adenosyl-L-methionine Ref.10

KM=0.35 mM for 6-mercaptopurine

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

Sequence caution

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

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 245245Thiopurine S-methyltransferase HAMAP-Rule MF_00812
PRO_0000220102

Regions

Region29 – 4012S-adenosyl-L-methionine binding HAMAP-Rule MF_00812
Region134 – 1352S-adenosyl-L-methionine binding HAMAP-Rule MF_00812

Sites

Binding site401Substrate By similarity
Binding site691S-adenosyl-L-methionine; via carbonyl oxygen
Binding site901S-adenosyl-L-methionine
Binding site1521S-adenosyl-L-methionine

Amino acid modifications

Modified residue141Phosphoserine Ref.11 Ref.13
Modified residue581N6-acetyllysine Ref.14

Natural variations

Natural variant491L → S Allele TPMT*5; found in a patient with intermediate enzyme activity; has very low activity when expressed in a heterologous system. Ref.5 Ref.25
Corresponds to variant rs72552740 [ dbSNP | Ensembl ].
VAR_005636
Natural variant801A → 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. Ref.17 Ref.20 Ref.21 Ref.23 Ref.24 Ref.25 Ref.27 Ref.28
Corresponds to variant rs1800462 [ dbSNP | Ensembl ].
VAR_005637
Natural variant1541A → 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. Ref.3 Ref.5 Ref.16 Ref.18 Ref.19 Ref.20 Ref.21 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28
Corresponds to variant rs1800460 [ dbSNP | Ensembl ].
VAR_005638
Natural variant1791Q → H.
Corresponds to variant rs6921269 [ dbSNP | Ensembl ].
VAR_052368
Natural variant1801Y → F Allele TPMT*6; reduced activity. Ref.5 Ref.25
Corresponds to variant rs75543815 [ dbSNP | Ensembl ].
VAR_005639
Natural variant2151R → H in TPMT deficiency; allele TPMT*8; intermediate activity. Ref.22 Ref.25
Corresponds to variant rs56161402 [ dbSNP | Ensembl ].
VAR_008715
Natural variant2271H → Q in TPMT deficiency; allele TPMT*7; reduced activity. Ref.9 Ref.25
Corresponds to variant rs72552736 [ dbSNP | Ensembl ].
VAR_005640
Natural variant2401Y → 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. Ref.3 Ref.5 Ref.16 Ref.18 Ref.19 Ref.21 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28
Corresponds to variant rs1142345 [ dbSNP | Ensembl ].
VAR_005641

Experimental info

Mutagenesis1521R → E: Decreases affinity for 6-mercaptopurine. Slightly decreases catalytic activity. Ref.10

Secondary structure

......................................... 245
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P51580 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 190E781155B97BB9

FASTA24528,180
        10         20         30         40         50         60 
MDGTRTSLDI EEYSDTEVQK NQVLTLEEWQ DKWVNGKTAF HQEQGHQLLK KHLDTFLKGK 

        70         80         90        100        110        120 
SGLRVFFPLC GKAVEMKWFA DRGHSVVGVE ISELGIQEFF TEQNLSYSEE PITEIPGTKV 

       130        140        150        160        170        180 
FKSSSGNISL YCCSIFDLPR TNIGKFDMIW DRGALVAINP GDRKCYADTM FSLLGKKFQY 

       190        200        210        220        230        240 
LLCVLSYDPT KHPGPPFYVP HAEIERLFGK ICNIRCLEKV DAFEERHKSW GIDCLFEKLY 


LLTEK 

« Hide

References

« Hide 'large scale' references
[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]"Human thiopurine methyltransferase pharmacogenetics: gene sequence polymorphisms."
Otterness D., Szumlanski C., Lennard L., Klemetsdal B., Aarbakke J., Park-Hah J.O., Iven H., Schmiegelow K., Branum E., O'Brien J., Weinshilboum R.M.
Clin. Pharmacol. Ther. 62:60-73(1997) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
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]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
S62904 mRNA. Translation: AAB27277.1.
U12387 mRNA. Translation: AAC50130.1.
U30518 expand/collapse EMBL AC list , U30512, U30513, U30514, U30515, U30516, U30517 Genomic DNA. Translation: AAC50368.1.
AF019369 expand/collapse EMBL AC list , 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.
PIRI57946.
RefSeqNP_000358.1. NM_000367.2.
UniGeneHs.444319.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2BZGX-ray1.58A16-245[»]
2H11X-ray1.89A/B16-245[»]
ProteinModelPortalP51580.
SMRP51580. Positions 17-245.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113025. 3 interactions.

Chemistry

ChEMBLCHEMBL2500.
DrugBankDB01033. Mercaptopurine.

PTM databases

PhosphoSiteP51580.

Polymorphism databases

DMDM1730006.

Proteomic databases

PaxDbP51580.
PeptideAtlasP51580.
PRIDEP51580.

Protocols and materials databases

DNASU7172.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000309983; ENSP00000312304; ENSG00000137364.
GeneID7172.
KEGGhsa:7172.
UCSCuc003ncm.3. human.

Organism-specific databases

CTD7172.
GeneCardsGC06M018072.
HGNCHGNC:12014. TPMT.
HPAHPA019851.
MIM187680. gene.
610460. phenotype.
neXtProtNX_P51580.
Orphanet240925. 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.
PharmGKBPA356.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0500.
HOVERGENHBG003037.
InParanoidP51580.
KOK00569.
OMACGDFFAL.
OrthoDBEOG7H4DWQ.
PhylomeDBP51580.
TreeFamTF328951.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

BgeeP51580.
GenevestigatorP51580.

Family and domain databases

HAMAPMF_00812. Thiopur_methtran.
InterProIPR025835. Thiopurine_S-MeTrfase.
IPR008854. TPMT.
[Graphical view]
PfamPF05724. TPMT. 1 hit.
[Graphical view]
PIRSFPIRSF023956. Thiopurine_S-methyltransferase. 1 hit.
PROSITEPS51585. SAM_MT_TPMT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP51580.
GeneWikiThiopurine_methyltransferase.
GenomeRNAi7172.
NextBio28108.
PROP51580.
SOURCESearch...

Entry information

Entry nameTPMT_HUMAN
AccessionPrimary (citable) accession number: P51580
Secondary accession number(s): O14806 expand/collapse secondary AC list , O15423, O15424, O15425, O15426, O15515, O15548, O43213, Q5VUK6, Q9UBE6, Q9UBT8, Q9UE62
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: April 16, 2014
This is version 143 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

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

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM