P51580 (TPMT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Thiopurine S-methyltransferase
EC=2.1.1.67

Alternative name(s):
Thiopurine methyltransferase

Gene names

Name:

TPMT

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	245 AA.
Sequence status	Complete.
Protein existence	Evidence 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).
Subunit structure	Monomer. Ref.16
Subcellular location	Cytoplasm.
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. 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.
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 immunosupressants 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 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.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	S-adenosyl-L-methionine
Molecular function	Methyltransferase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	nucleobase-containing compound metabolic process Traceable author statement Ref.1. Source: ProtInc small molecule metabolic process Traceable author statement. Source: Reactome xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	thiopurine S-methyltransferase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 245

245

Thiopurine S-methyltransferase

PRO_0000220102

Regions

Region

29 – 40

12

S-adenosyl-L-methionine binding

Region

134 – 135

2

S-adenosyl-L-methionine binding

Sites

Binding site

40

1

Substrate By similarity

Binding site

69

1

S-adenosyl-L-methionine; via carbonyl oxygen

Binding site

90

1

S-adenosyl-L-methionine

Binding site

152

1

S-adenosyl-L-methionine

Amino acid modifications

Modified residue

14

1

Phosphoserine Ref.11 Ref.13

Modified residue

58

1

N6-acetyllysine Ref.14

Natural variations

Natural variant

49

1

L → 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 variant

80

1

A → 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 variant

154

1

A → 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 variant

179

1

Q → H.
Corresponds to variant rs6921269 [ dbSNP | Ensembl ].

VAR_052368

Natural variant

180

1

Y → F Allele TPMT*6; reduced activity. Ref.5 Ref.25

VAR_005639

Natural variant

215

1

R → H in TPMT deficiency; allele TPMT*8; intermediate activity. Ref.22 Ref.25
Corresponds to variant rs56161402 [ dbSNP | Ensembl ].

VAR_008715

Natural variant

227

1

H → Q in TPMT deficiency; allele TPMT*7; reduced activity. Ref.9 Ref.25
Corresponds to variant rs72552736 [ dbSNP | Ensembl ].

VAR_005640

Natural variant

240

1

Y → 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

Mutagenesis

152

1

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

Secondary structure

1

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245

Helix Strand Turn

Details...

Turn

18 – 21

4

Helix

26 – 35

10

Helix

47 – 57

11

Beta strand

64 – 67

4

Helix

75 – 81

7

Beta strand

85 – 89

5

Helix

93 – 102

10

Beta strand

107 – 111

5

Beta strand

119 – 123

5

Beta strand

126 – 133

8

Helix

135 – 140

6

Beta strand

146 – 154

9

Turn

155 – 157

3

Helix

160 – 162

3

Helix

163 – 172

10

Beta strand

174 – 186

13

Turn

189 – 191

3

Helix

201 – 208

8

Turn

209 – 211

3

Beta strand

212 – 221

10

Helix

225 – 230

6

Beta strand

236 – 244

9

Sequences

	Sequence		Length	Mass (Da)
	P51580 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 190E781155B97BB9	FASTA	245	28,180
	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

References

	« Hide 'large scale' referencesShow '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. , 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY.
[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 , 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.

IPI

IPI00019400.

PIR

I57946.

RefSeq

NP_000358.1. NM_000367.2.

UniGene

Hs.444319.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2BZG	X-ray	1.58	A	16-245	[»]
2H11	X-ray	1.89	A/B	16-245	[»]

ProteinModelPortal

P51580.

ModBase

Search...

PTM databases

PhosphoSite

P51580.

Polymorphism databases

DMDM

1730006.

Proteomic databases

PaxDb

P51580.

PeptideAtlas

P51580.

PRIDE

P51580.

Protocols and materials databases

DNASU

7172.

StructuralBiologyKnowledgebase

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Genome annotation databases

Ensembl

ENST00000309983; ENSP00000312304; ENSG00000137364.

GeneID

7172.

KEGG

hsa:7172.

UCSC

uc003ncm.3. human.

Organism-specific databases

CTD

7172.

GeneCards

GC06M018072.

HGNC

HGNC:12014. TPMT.

HPA

HPA019851.

MIM

187680. gene.
610460. phenotype.

neXtProt

NX_P51580.

Orphanet

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.

PharmGKB

PA356.

GenAtlas

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Phylogenomic databases

eggNOG

COG0500.

HOVERGEN

HBG003037.

InParanoid

P51580.

KO

K00569.

OMA

GKSLDMC.

OrthoDB

EOG4C5CKF.

PhylomeDB

P51580.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

Bgee

P51580.

Genevestigator

P51580.

GermOnline

ENSG00000137364. Homo sapiens.

Family and domain databases

InterPro

IPR025835. Thiopurine_S-MeTrfase.
IPR008854. TPMT.
[Graphical view]

Pfam

PF05724. TPMT. 1 hit.
[Graphical view]

PIRSF

PIRSF023956. Thiopurine_S-methyltransferase. 1 hit.

ProtoNet

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Other

ChEMBL

CHEMBL2500.

DrugBank

DB01033. Mercaptopurine.

EvolutionaryTrace

P51580.

GenomeRNAi

7172.

NextBio

28108.

SOURCE

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Entry information

Entry name

TPMT_HUMAN

Accession

Primary (citable) accession number: P51580
Secondary accession number(s): O14806 , 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:	May 1, 2013
This is version 133 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.