ID   TPMT_RAT                Reviewed;         240 AA.
AC   Q9Z0T0;
DT   24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   03-AUG-2022, entry version 110.
DE   RecName: Full=Thiopurine S-methyltransferase;
DE            EC=2.1.1.67;
DE   AltName: Full=Thiopurine methyltransferase;
GN   Name=Tpmt;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Sprague-Dawley;
RA   Krynetski E.Y., Fessing M.Y., Evans W.E.;
RL   Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Catalyzes the S-methylation of thiopurine drugs such as 6-
CC       mercaptopurine (also called mercaptopurine, 6-MP or its brand name
CC       Purinethol) using S-adenosyl-L-methionine as the methyl donor. TPMT
CC       activity modulates the cytotoxic effects of thiopurine prodrugs. A
CC       natural substrate for this enzyme has yet to be identified.
CC       {ECO:0000250|UniProtKB:O55060}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=S-adenosyl-L-methionine + a thiopurine = S-adenosyl-L-
CC         homocysteine + a thiopurine S-methylether.; EC=2.1.1.67;
CC         Evidence={ECO:0000250|UniProtKB:O55060};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=mercaptopurine + S-adenosyl-L-methionine = 6-methylthiopurine
CC         + H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:12609,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:28279, ChEBI:CHEBI:50667,
CC         ChEBI:CHEBI:57856, ChEBI:CHEBI:59789; EC=2.1.1.67;
CC         Evidence={ECO:0000250|UniProtKB:O55060};
CC   -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:O55060}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC       superfamily. TPMT family. {ECO:0000305}.
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DR   EMBL; AF120100; AAD17293.1; -; mRNA.
DR   RefSeq; XP_006253832.1; XM_006253770.3.
DR   AlphaFoldDB; Q9Z0T0; -.
DR   SMR; Q9Z0T0; -.
DR   iPTMnet; Q9Z0T0; -.
DR   PhosphoSitePlus; Q9Z0T0; -.
DR   jPOST; Q9Z0T0; -.
DR   GeneID; 690050; -.
DR   UCSC; RGD:620089; rat.
DR   CTD; 7172; -.
DR   RGD; 1585162; Tpmt.
DR   VEuPathDB; HostDB:ENSRNOG00000016468; -.
DR   HOGENOM; CLU_085515_2_0_1; -.
DR   PhylomeDB; Q9Z0T0; -.
DR   Reactome; R-RNO-156581; Methylation.
DR   Reactome; R-RNO-9748787; Azathioprine ADME.
DR   PRO; PR:Q9Z0T0; -.
DR   Proteomes; UP000002494; Chromosome 17.
DR   Bgee; ENSRNOG00000016468; Expressed in kidney and 20 other tissues.
DR   ExpressionAtlas; Q9Z0T0; baseline and differential.
DR   Genevisible; Q9Z0T0; RN.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:1904047; F:S-adenosyl-L-methionine binding; ISO:RGD.
DR   GO; GO:0008119; F:thiopurine S-methyltransferase activity; ISO:RGD.
DR   GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR   GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR   GO; GO:0033574; P:response to testosterone; IEP:RGD.
DR   GO; GO:0006805; P:xenobiotic metabolic process; ISO:RGD.
DR   Gene3D; 3.40.50.150; -; 1.
DR   HAMAP; MF_00812; Thiopur_methtran; 1.
DR   InterPro; IPR029063; SAM-dependent_MTases_sf.
DR   InterPro; IPR025835; Thiopurine_S-MeTrfase.
DR   InterPro; IPR008854; TPMT.
DR   Pfam; PF05724; TPMT; 1.
DR   PIRSF; PIRSF023956; Thiopurine_S-methyltransferase; 1.
DR   SUPFAM; SSF53335; SSF53335; 1.
DR   PROSITE; PS51585; SAM_MT_TPMT; 1.
PE   2: Evidence at transcript level;
KW   Acetylation; Cytoplasm; Methyltransferase; Reference proteome;
KW   S-adenosyl-L-methionine; Transferase.
FT   CHAIN           1..240
FT                   /note="Thiopurine S-methyltransferase"
FT                   /id="PRO_0000220113"
FT   BINDING         24..35
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250"
FT   BINDING         35
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         64
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250"
FT   BINDING         85
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250"
FT   BINDING         129..130
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250"
FT   BINDING         147
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         53
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P51580"
SQ   SEQUENCE   240 AA;  27692 MW;  04608B546BBDC1E3 CRC64;
     MSLGIKEHPD AEVQKNRVLT LDDWQDKWVT RHIAFHQEQG HQLLKKHFDT FLKGQSGLRV
     FFPLCGKAIE MKWFADRGHT VVGVEISEIG IREFFAEQNL SYTEEPLTEI AGAKVFKSSS
     GNISLYCCSI FDLPRANIGK FDRIWDRGAL VAVNPGDRDR YADIILSLLR KGYHYLLVVL
     SYDPTKHTGP PFYVPDAELK KLFGTKCNMQ CLEEVDALEE RHKTWGVDYF FEKLYLLTEK