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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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.
Catalytic activity	S-adenosyl-L-methionine + a thiopurine = S-adenosyl-L-homocysteine + a thiopurine S-methylether.
Enzyme regulation	Inhibited by S-adenosyl-L-homocysteine (SAH).
Subunit structure	Monomer.
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	Defects in TPMT are the cause of thiopurine S-methyltransferase deficiency (TPMT deficiency) [MIM:610460]. TPMT is an 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.
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 protein encoded by TPMT*2 and TPMT*3A mutant alleles are degradated more rapidely by an ATP-dependent proteasome-mediated pathway.
Sequence similarities	Belongs to the methyltransferase superfamily. TPMT family.
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. Source: ProtInc 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. 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

Sites

Binding site

33

1

S-adenosyl-L-methionine

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.10 Ref.11 Ref.12 Ref.13

Modified residue

58

1

N6-acetyllysine Ref.14

Natural variations

Natural variant

49

1

L → S Allele TPMT*5. Ref.5
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.26 Ref.27
Corresponds to variant rs1800462 [ dbSNP | Ensembl ].

VAR_005637

Natural variant

154

1

A → T in TPMT deficiency; allele TPMT*3A and allele TPMT*3B; lower activity; protein shows enhanced degradation; 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.18 Ref.19 Ref.20 Ref.21 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27
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. Ref.5

VAR_005639

Natural variant

215

1

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

VAR_008715

Natural variant

227

1

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

VAR_005640

Natural variant

240

1

Y → C in TPMT deficiency; allele TPMT*3B and allele TPMT*3C; lower 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.18 Ref.19 Ref.21 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27
Corresponds to variant rs1142345 [ dbSNP | Ensembl ].

VAR_005641

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: 8316220] [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: 7628307] [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: 8561894] [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: 9453052] [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: 9246020] [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: 14574404] [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: 15489334] [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: 9711875] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 210-245, VARIANT TPMT DEFICIENCY GLN-227.
[10]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"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: 18318008] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14, MASS SPECTROMETRY. Tissue: Liver.
[12]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[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: 19690332] [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., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]	"The crystal structure of human thiopurine S-methyltransferase in complex with SAH." Structural genomics consortium (SGC) Submitted (AUG-2005) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.58 ANGSTROMS) OF 16-245.
[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: 7862671] [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: 8644731] [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: 9336428] [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: 9177237] [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: 9931345] [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: 9931346] [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: 10208641] [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: 10751626] [Abstract] Cited for: VARIANTS TPMT DEFICIENCY PRO-80; THR-154 AND CYS-240, FREQUENCY AND DISTRIBUTION OF ALLELES.
[25]	"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: 15819814] [Abstract] Cited for: VARIANTS TPMT DEFICIENCY THR-154 AND CYS-240.
[26]	"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: 16476125] [Abstract] Cited for: VARIANTS TPMT DEFICIENCY PRO-80; THR-154 AND CYS-240, FREQUENCY AND DISTRIBUTION OF ALLELES.
[27]	"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: 16789994] [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.

SMR

P51580. Positions 17-245.

ModBase

Search...

Protein-protein interaction databases

STRING

P51580.

PTM databases

PhosphoSite

P51580.

Polymorphism databases

DMDM

1730006.

Proteomic databases

PeptideAtlas

P51580.

PRIDE

P51580.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000309983; ENSP00000312304; ENSG00000137364.

GeneID

7172.

KEGG

hsa:7172.

UCSC

uc003ncm.1. human.

Organism-specific databases

CTD

7172.

GeneCards

GC06M018072.

H-InvDB

HIX0018948.

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.
240889. Mercaptopurine toxicity.
240999. Susceptibility to deafness due to cisplatin treatment.
241019. Susceptibility to neutropenia due to azathioprine treatment.
3315. Thiopurine S-methyltransferase deficiency.

PharmGKB

PA356.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG05434.

HOVERGEN

HBG003037.

InParanoid

P51580.

OMA

QGDIFTL.

OrthoDB

EOG4C5CKF.

PhylomeDB

P51580.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P51580.

Bgee

P51580.

Genevestigator

P51580.

GermOnline

ENSG00000137364. Homo sapiens.

Family and domain databases

InterPro

IPR008854. Thiopurine_S-MeTrfase.
IPR016822. Thiopurine_S-MeTrfase_sub.
[Graphical view]

KO

K00569.

PANTHER

PTHR10259. PTHR10259. 1 hit.

Pfam

PF05724. TPMT. 1 hit.
[Graphical view]

PIRSF

PIRSF023956. Thiopurine_S-methyltransferase. 1 hit.

ProtoNet

Search...

Other

DrugBank

DB01033. Mercaptopurine.

NextBio

28108.

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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:	December 14, 2011
This is version 122 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.