ID   TPMT_MUSSP              Reviewed;         240 AA.
AC   Q9QX22;
DT   24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   03-AUG-2022, entry version 81.
DE   RecName: Full=Thiopurine S-methyltransferase;
DE            EC=2.1.1.67;
DE   AltName: Full=Thiopurine methyltransferase;
GN   Name=Tpmt;
OS   Mus spretus (Western Mediterranean mouse) (Algerian mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10096;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=EI;
RA   Adjei A.A., Johnson G.B., Otterness D.M., Weinshilboum R.M.;
RT   "Mouse thiopurine methyltransferase pharmacogenetics: cDNA cloning and
RT   characterization and processed pseudogene cloning.";
RL   Submitted (DEC-1997) 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; AF037045; AAD02094.1; -; mRNA.
DR   AlphaFoldDB; Q9QX22; -.
DR   SMR; Q9QX22; -.
DR   PRIDE; Q9QX22; -.
DR   MGI; MGI:98812; Tpmt.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:1904047; F:S-adenosyl-L-methionine binding; IEA:Ensembl.
DR   GO; GO:0008119; F:thiopurine S-methyltransferase activity; IBA:GO_Central.
DR   GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR   GO; GO:0006805; P:xenobiotic metabolic process; IEA:Ensembl.
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; S-adenosyl-L-methionine;
KW   Transferase.
FT   CHAIN           1..240
FT                   /note="Thiopurine S-methyltransferase"
FT                   /id="PRO_0000220106"
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;  27618 MW;  860A0DC5BD6FBA4C CRC64;
     MSLDMKEHPD AEVQKNRVLT LEDWKDKWVT RHISFHQEQG HQLLKKHLDT FLKGQSGLRV
     FFPLCGKAVE MKWFADRGHT VVGVEISEIG IREFFAEQNL SYTEEPLAEI AGAKVFKSSS
     GSISLYCCSI FDLPRANIGK FDRIWDRGAL VAINPGDHDR YADIILSLLR KEFQYLMAVL
     SYDPTKHAGP PFYVPSAELK RLFGTKCSMQ CLEEVDALEE RHKAWGLDYL FEKLYLLTEK