O55060 (TPMT_MOUSE) 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

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	240 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.
Subunit structure	Monomer. Ref.5
Subcellular location	Cytoplasm.
Sequence similarities	Belongs to the methyltransferase superfamily. TPMT family.

Ontologies

Keywords
Cellular component	Cytoplasm
Ligand	S-adenosyl-L-methionine
Molecular function	Methyltransferase Transferase
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	thiopurine S-methyltransferase activity Inferred from direct assay Ref.1. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 240

240

Thiopurine S-methyltransferase

PRO_0000220105

Regions

Region

24 – 35

12

S-adenosyl-L-methionine binding

Region

129 – 130

2

S-adenosyl-L-methionine binding

Sites

Binding site

35

1

Substrate

Binding site

64

1

S-adenosyl-L-methionine; via carbonyl oxygen

Binding site

85

1

S-adenosyl-L-methionine

Binding site

147

1

S-adenosyl-L-methionine

Amino acid modifications

Modified residue

53

1

N6-acetyllysine By similarity

Natural variations

Natural variant

69

1

I → V in strain: C57BL/6J.

Secondary structure

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240

Helix Strand Turn

Details...

Turn

11 – 16

6

Helix

21 – 30

10

Beta strand

38 – 40

3

Helix

42 – 52

11

Beta strand

59 – 62

4

Helix

70 – 76

7

Beta strand

80 – 84

5

Helix

88 – 97

10

Beta strand

102 – 106

5

Beta strand

114 – 118

5

Beta strand

121 – 128

8

Turn

130 – 132

3

Helix

133 – 136

4

Beta strand

141 – 149

9

Turn

150 – 152

3

Helix

155 – 157

3

Helix

158 – 167

10

Beta strand

169 – 181

13

Helix

184 – 186

3

Beta strand

189 – 191

3

Helix

196 – 203

8

Turn

204 – 206

3

Beta strand

207 – 216

10

Helix

220 – 222

3

Turn

223 – 226

4

Beta strand

231 – 239

9

Sequences

	Sequence		Length	Mass (Da)
	O55060 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: 2BA57F30E8EB72D2	FASTA	240	27,586
	10 20 30 40 50 60 MSLDMKEHPD AEVQKNQVLT LEDWKEKWVT RHISFHQEQG HQLLKKHLDT FLKGQSGLRV 70 80 90 100 110 120 FFPLCGKAIE MKWFADRGHT VVGVEISEIG IREFFAEQNL SYTEEPLAEI AGAKVFKSSS 130 140 150 160 170 180 GSISLYCCSI FDLPRANIGK FDRIWDRGAL VAINPGDHDR YADIILSLLR KEFQYLVAVL 190 200 210 220 230 240 SYDPTKHAGP PFYVPSAELK RLFGTKCSMQ CLEEVDALEE RHKAWGLDYL FEKLYLLTEK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and functional characterization of the cDNA encoding the murine thiopurine S-methyltransferase (TPMT)." Fessing M.Y., Belkov V.M., Krynetski E.Y., Evans W.E. FEBS Lett. 424:143-145(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C3H.
[2]	"Mouse thiopurine methyltransferase pharmacogenetics: cDNA cloning and characterization and processed pseudogene cloning." Adjei A.A., Johnson G.B., Otterness D.M., Weinshilboum R.M. Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE. Strain: C57BL/6J and DBA/2J.
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N. Tissue: Liver.
[4]	Krynetski E.Y., Fessing M.Y., Edick M.J., Evans W.E. Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE OF 43-227. Strain: 129/Ola.
[5]	"Structural basis of substrate recognition in thiopurine s-methyltransferase." Peng Y., Feng Q., Wilk D., Adjei A.A., Salavaggione O.E., Weinshilboum R.M., Yee V.C. Biochemistry 47:6216-6225(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEXES WITH S-ADENOSYL-L-HOMOCYSTEINE AND 6-MERCAPTOPURINE, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF046887 mRNA. Translation: AAC25919.1.
AF037043 mRNA. Translation: AAD02092.1.
AF037044 mRNA. Translation: AAD02093.1.
AF104832 , AF104825, AF104826, AF104827, AF104828, AF104829, AF104830, AF104831 Genomic DNA. Translation: AAF06075.1.
BC021598 mRNA. Translation: AAH21598.1.
AH009424 Genomic DNA. Translation: AAF74424.1.

IPI

IPI00115215.

RefSeq

NP_058065.2. NM_016785.2.

UniGene

Mm.10169.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2GB4	X-ray	1.25	A/B	1-240	[»]
3BGD	X-ray	2.00	A/B	1-240	[»]
3BGI	X-ray	1.80	A/B	1-240	[»]

ProteinModelPortal

O55060.

SMR

O55060. Positions 10-240.

ModBase

Search...

PTM databases

PhosphoSite

O55060.

Proteomic databases

PaxDb

O55060.

PRIDE

O55060.

Protocols and materials databases

DNASU

22017.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000021806; ENSMUSP00000021806; ENSMUSG00000021376.

GeneID

22017.

KEGG

mmu:22017.

UCSC

uc007qhq.2. mouse.

Organism-specific databases

CTD

7172.

MGI

MGI:98812. Tpmt.

Phylogenomic databases

eggNOG

COG0500.

GeneTree

ENSGT00390000016823.

HOGENOM

HOG000276919.

HOVERGEN

HBG003037.

InParanoid

O55060.

KO

K00569.

OrthoDB

EOG4C5CKF.

Gene expression databases

ArrayExpress

O55060.

Bgee

O55060.

CleanEx

MM_TPMT.

Genevestigator

O55060.

GermOnline

ENSMUSG00000021376. Mus musculus.

Family and domain databases

InterPro

IPR025835. Thiopurine_S-MeTrfase.
IPR008854. TPMT.
[Graphical view]

Pfam

PF05724. TPMT. 1 hit.
[Graphical view]

PIRSF

PIRSF023956. Thiopurine_S-methyltransferase. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

O55060.

NextBio

301740.

SOURCE

Search...

Entry information

Entry name

TPMT_MOUSE

Accession

Primary (citable) accession number: O55060
Secondary accession number(s): Q9JIL7, Q9QUG7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	June 1, 1998
Last modified:	April 3, 2013
This is version 100 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program