UniProt:P51580 TPMT

chain
  • chain:1-245
checksum 190E781155B97BB9
comment
  • FUNCTION Catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine (also called mercaptopurine, 6-MP or its brand name Purinethol) and 6-thioguanine (also called tioguanine or 6-TG) using S-adenosyl-L-methionine as the methyl donor (PubMed:657528, PubMed:18484748). TPMT activity modulates the cytotoxic effects of thiopurine prodrugs. A natural substrate for this enzyme has yet to be identified.ACTIVITY REGULATION Inhibited by S-adenosyl-L-homocysteine (SAH).SUBUNIT Monomer.POLYMORPHISM Polymorphic variations define TPMT activity levels that are variable among ethnic groups. 90% of Caucasians have high TPMT activity, 10% have intermediate activity, and 1 in 300 individuals has low activity (PubMed:10208641). These differences influence the clinical use and therapeutic efficacy of thiopurine drugs, generally used as immunosuppressants or cytotoxic drugs in conditions including leukemia, autoimmune disease and organ transplantation. Intermediate or low TPMT activity is associated with thiopurine intolerance and patients are at risk of toxicity after receiving standard doses of thiopurine drugs [MIM:610460] (PubMed:10751626, PubMed:15819814, PubMed:16220112, PubMed:16476125, PubMed:16789994, PubMed:7862671, PubMed:8561894, PubMed:8644731, PubMed:9246020, PubMed:9336428, PubMed:9711875, PubMed:9931345, PubMed:9931346). The most prevalent TPMT alleles associated with TPMT deficiency are TPMT*2 and TPMT*3A. The proteins encoded by TPMT*2 and TPMT*3A mutant are degraded more rapidly by an ATP-dependent proteasome-mediated pathway (PubMed:9177237, PubMed:8644731).POLYMORPHISM TPMT*3A is the most common allele in the Caucasians and American Caucasians; it is the only mutant allele found in the South West Asians; it is not found in the Chinese. TPMT*3C is common in African-Americans and is the only allele in Chinese, Japanese and Taiwanese individuals. 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.SIMILARITY Belongs to the class I-like SAM-binding methyltransferase superfamily. TPMT family.
crossReference
databaseName UniProt
dbId 66307
description
  • recommendedName: fullName evidence="20"Thiopurine S-methyltransferase ecNumber evidence="9 10"2.1.1.67/ecNumber alternativeName: fullName evidence="21"Thiopurine methyltransferase
displayName UniProt:P51580 TPMT
geneName
  • TPMT
identifier P51580
isSequenceChanged false
keyword
  • 3D-structure
  • Acetylation
  • Cytoplasm
  • Direct protein sequencing
  • Methyltransferase
  • Phosphoprotein
  • Reference proteome
  • S-adenosyl-L-methionine
  • Transferase
modified [InstanceEdit:11703684] Shorser, Solomon, 2021-05-28
name
  • TPMT
otherIdentifier
  • 0002350301
  • 11727822_a_at
  • 11727823_x_at
  • 11727824_at
  • 11727825_x_at
  • 17015975
  • 203671_at
  • 203672_x_at
  • 2944026
  • 2944027
  • 2944028
  • 2944029
  • 2944030
  • 2944031
  • 2944034
  • 2944035
  • 2944037
  • 2944038
  • 2944040
  • 2944042
  • 2944043
  • 2944044
  • 2944045
  • 2944050
  • 32810_at
  • 3787362
  • 3787364
  • 7172
  • 8124134
  • A_23_P214108
  • A_24_P397498
  • A_33_P3317321
  • GE62974
  • GO:0003674
  • GO:0005515
  • GO:0005575
  • GO:0005622
  • GO:0005737
  • GO:0005829
  • GO:0006139
  • GO:0008119
  • GO:0008150
  • GO:0008168
  • GO:0008757
  • GO:0016740
  • GO:0017144
  • GO:0032259
  • GO:0034641
  • GO:1904047
  • HMNXSV003028526
  • Hs.296922.0.A4_3p_at
  • ILMN_1740185
  • ILMN_1760212
  • PH_hs_0024285
  • S62904_s_at
  • TC06001301.hg
  • U12387_s_at
  • g805083_3p_a_at
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • TPMT_HUMAN
  • O14806
  • O15423
  • O15424
  • O15425
  • O15426
  • O15515
  • O15548
  • O43213
  • Q5VUK6
  • Q9UBE6
  • Q9UBT8
  • Q9UE62
sequenceLength 245
species [Species:48887] Homo sapiens
url http://purl.uniprot.org/uniprot/P51580
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