ID   TPMT_CANLF              Reviewed;         245 AA.
AC   Q8HX86;
DT   03-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   03-AUG-2022, entry version 115.
DE   RecName: Full=Thiopurine S-methyltransferase;
DE            EC=2.1.1.67;
DE   AltName: Full=Thiopurine methyltransferase;
GN   Name=TPMT;
OS   Canis lupus familiaris (Dog) (Canis familiaris).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX   NCBI_TaxID=9615;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANT GLY-97.
RX   PubMed=12464800; DOI=10.1097/00008571-200212000-00005;
RA   Salavaggione O.E., Kidd L., Prondzinski J.L., Szumlanski C.L.,
RA   Pankratz V.S., Wang L., Trepanier L., Weinshilboum R.M.;
RT   "Canine red blood cell thiopurine S-methyltransferase: companion animal
RT   pharmacogenetics.";
RL   Pharmacogenetics 12:713-724(2002).
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:P51580};
CC   -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P51580}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC       superfamily. TPMT family. {ECO:0000305}.
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DR   EMBL; AY057077; AAL18009.1; -; mRNA.
DR   EMBL; AY057087; AAL18006.1; -; Genomic_DNA.
DR   EMBL; AY057080; AAL18006.1; JOINED; Genomic_DNA.
DR   EMBL; AY057081; AAL18006.1; JOINED; Genomic_DNA.
DR   EMBL; AY057082; AAL18006.1; JOINED; Genomic_DNA.
DR   EMBL; AY057083; AAL18006.1; JOINED; Genomic_DNA.
DR   EMBL; AY057084; AAL18006.1; JOINED; Genomic_DNA.
DR   EMBL; AY057085; AAL18006.1; JOINED; Genomic_DNA.
DR   EMBL; AY057086; AAL18006.1; JOINED; Genomic_DNA.
DR   RefSeq; NP_001003015.1; NM_001003015.1.
DR   RefSeq; XP_005640012.1; XM_005639955.2.
DR   RefSeq; XP_005640013.1; XM_005639956.2.
DR   RefSeq; XP_013965954.1; XM_014110479.1.
DR   AlphaFoldDB; Q8HX86; -.
DR   SMR; Q8HX86; -.
DR   STRING; 9615.ENSCAFP00000014924; -.
DR   PaxDb; Q8HX86; -.
DR   Ensembl; ENSCAFT00030024981; ENSCAFP00030021817; ENSCAFG00030013471.
DR   Ensembl; ENSCAFT00845050687; ENSCAFP00845039735; ENSCAFG00845028681.
DR   GeneID; 403536; -.
DR   KEGG; cfa:403536; -.
DR   CTD; 7172; -.
DR   VEuPathDB; HostDB:ENSCAFG00845028681; -.
DR   eggNOG; ENOG502QSF5; Eukaryota.
DR   GeneTree; ENSGT00390000016823; -.
DR   HOGENOM; CLU_085515_2_0_1; -.
DR   InParanoid; Q8HX86; -.
DR   OMA; LWCGDFF; -.
DR   OrthoDB; 1590477at2759; -.
DR   TreeFam; TF328951; -.
DR   Reactome; R-CFA-156581; Methylation.
DR   Reactome; R-CFA-9748787; Azathioprine ADME.
DR   Proteomes; UP000002254; Chromosome 35.
DR   Bgee; ENSCAFG00000010160; Expressed in metanephros cortex and 49 other tissues.
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; Reference proteome;
KW   S-adenosyl-L-methionine; Transferase.
FT   CHAIN           1..245
FT                   /note="Thiopurine S-methyltransferase"
FT                   /id="PRO_0000220097"
FT   BINDING         29..40
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250"
FT   BINDING         40
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         69
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250"
FT   BINDING         90
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250"
FT   BINDING         152
FT                   /ligand="S-adenosyl-L-methionine"
FT                   /ligand_id="ChEBI:CHEBI:59789"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         58
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P51580"
FT   VARIANT         97
FT                   /note="R -> G"
FT                   /evidence="ECO:0000269|PubMed:12464800"
SQ   SEQUENCE   245 AA;  28428 MW;  FF248133D3F8EF5A CRC64;
     MDKTRTFLDV KEYPDTEVQK NRVLTLEEWQ EKWVSRRIGF HQEQGHKLLK KHLDTFLKGE
     NGLRVFFPLC GKAVEMKWFA DRGHSVVGVE ISELGIREFF AEQNLSYTEE PIVEIPGGKI
     FKSSSGNISL YCCSLFDLPR ANIGKFDRIW DRGALVAINP GDRERYADIM LSLTRKGFHY
     LLAVLCYDPT KHAGPPFYVP EAEIKKLFGS ICNIHCLEKV DVFEEQHKSW GIDYIIEKLY
     LFTEK