Q26998 (UPP_TOXGO) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Uracil phosphoribosyltransferase
Short name=UPRT
Short name=UPRTase
EC=2.4.2.9

Alternative name(s):
UMP pyrophosphorylase

Gene names

Name:

uprt

Organism

Toxoplasma gondii

Taxonomic identifier

5811 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Alveolata › Apicomplexa › Conoidasida › Coccidia › Eucoccidiorida › Eimeriorina › Sarcocystidae › Toxoplasma

Protein attributes

Sequence length	244 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the conversion of uracil and 5-phospho-alpha-D-ribose 1-diphosphate (PRPP) to UMP and diphosphate. Ref.1
Catalytic activity	UMP + diphosphate = uracil + 5-phospho-alpha-D-ribose 1-diphosphate.
Cofactor	Binds 1 Mg2+ ion per subunit. The magnesium is bound as Mg-PRPP. Ref.3
Enzyme regulation	Allosterically activated by GTP. Binding of GTP leads to 5-time activation of the enzyme. Ref.3
Pathway	Pyrimidine metabolism; UMP biosynthesis via salvage pathway; UMP from uracil: step 1/1.
Subunit structure	Monomer. Forms homodimers in presence of substrates and homotetramers in the presence of GTP. Ref.1 Ref.3
Sequence similarities	Belongs to the UPRTase family.
Biophysicochemical properties	Kinetic parameters: KM=3.5 µM for uracil Ref.1 Ref.3 KM=216 µM for 5-phospho-alpha-D-ribose 1-diphosphate (in the absence of GTP) KM=37.4 µM for 5-phospho-alpha-D-ribose 1-diphosphate (in the presence of GTP) Vmax=0.45 µmol/min/mg enzyme

Ontologies

Keywords
Ligand	GTP-binding Nucleotide-binding
Molecular function	Glycosyltransferase Transferase
Technical term	3D-structure Allosteric enzyme Direct protein sequencing
Gene Ontology (GO)
Biological_process	UMP salvage Inferred from electronic annotation. Source: UniProtKB-UniPathway
Molecular_function	GTP binding Inferred from electronic annotation. Source: UniProtKB-KW uracil phosphoribosyltransferase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 244

244

Uracil phosphoribosyltransferase

PRO_0000120783

Regions

Nucleotide binding

102 – 105

4

GTP

Region

169 – 172

4

5-phospho-alpha-D-ribose 1-diphosphate binding

Region

234 – 236

3

Uracil binding

Sites

Binding site

59

1

GTP

Binding site

68

1

GTP

Binding site

112

1

5-phospho-alpha-D-ribose 1-diphosphate

Binding site

129

1

GTP

Binding site

137

1

5-phospho-alpha-D-ribose 1-diphosphate

Binding site

158

1

GTP

Binding site

164

1

5-phospho-alpha-D-ribose 1-diphosphate

Binding site

229

1

Uracil; via amide nitrogen

Binding site

235

1

5-phospho-alpha-D-ribose 1-diphosphate

Experimental info

Mutagenesis

59

1

K → A: GTP-induced enzymatic activation is reduced 4-fold. Ref.3

Mutagenesis

68

1

R → A: GTP-induced enzymatic activation is reduced 2-fold. Ref.3

Mutagenesis

128

1

C → V: No effect on activity. Far less oxidation sensitive than wild-type. Ref.2

Mutagenesis

150

1

K → A: GTP-induced enzymatic activation is reduced 4-fold. Ref.3

Mutagenesis

235

1

D → A or N: No enzymatic activity. Ref.3

Secondary structure

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244

Helix Strand Turn

Details...

Beta strand

14 – 16

3

Helix

22 – 32

11

Beta strand

36 – 38

3

Helix

43 – 53

11

Helix

59 – 78

20

Beta strand

83 – 89

7

Turn

91 – 93

3

Beta strand

95 – 101

7

Beta strand

105 – 111

7

Turn

112 – 114

3

Helix

115 – 124

10

Beta strand

130 – 137

8

Beta strand

139 – 141

3

Beta strand

144 – 150

7

Helix

155 – 157

3

Beta strand

158 – 163

6

Beta strand

165 – 169

5

Helix

171 – 183

13

Helix

187 – 189

3

Beta strand

190 – 197

8

Helix

199 – 208

10

Beta strand

212 – 219

8

Beta strand

221 – 223

3

Beta strand

229 – 231

3

Helix

236 – 241

6

Sequences

	Sequence		Length	Mass (Da)
	Q26998 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 1810CC234B2CE60F	FASTA	244	27,646
	10 20 30 40 50 60 MAQVPASGKL LVDPRYSTND QEESILQDII TRFPNVVLMK QTAQLRAMMT IIRDKETPKE 70 80 90 100 110 120 EFVFYADRLI RLLIEEALNE LPFEKKEVTT PLDVSYHGVS FYSKICGVSI VRAGESMESG 130 140 150 160 170 180 LRAVCRGCRI GKILIQRDET TAEPKLIYEK LPADIRDRWV MLLDPMCATA GSVCKAIEVL 190 200 210 220 230 240 LRLGVKEERI IFVNILAAPQ GIERVFKEYP KVRMVTAAVD ICLNSRYYIV PGIGDFGDRY FGTM

References

[1]	"Expression, purification, and characterization of uracil phosphoribosyltransferase from Toxoplasma gondii." Carter D., Donald R.G.K., Roos D., Ullman B. Mol. Biochem. Parasitol. 87:137-144(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-6, FUNCTION, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES. Strain: RH / EP.
[2]	"Crystal structures of Toxoplasma gondii uracil phosphoribosyltransferase reveal the atomic basis of pyrimidine discrimination and prodrug binding." Schumacher M.A., Carter D., Scott D.M., Roos D.S., Ullman B., Brennan R.G. EMBO J. 17:3219-3232(1998) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF MUTANT VAL-128 APOENZYME AND IN COMPLEXES WITH SUBSTRATES AND 5-FLUOROURACIL, MUTAGENESIS OF CYS-128.
[3]	"The structural mechanism of GTP stabilized oligomerization and catalytic activation of the Toxoplasma gondii uracil phosphoribosyltransferase." Schumacher M.A., Bashor C.J., Song M.H., Otsu K., Zhu S., Parry R.J., Ullman B., Brennan R.G. Proc. Natl. Acad. Sci. U.S.A. 99:78-83(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF MUTANT VAL-128 IN COMPLEXES WITH URACIL; SUBSTRATE ANALOG AND GTP, COFACTOR, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, MUTAGENESIS OF LYS-59; ARG-68; LYS-150 AND ASP-235.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U10246 Genomic DNA. Translation: AAB60213.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BD3	X-ray	1.93	A/B/C/D	2-244	[»]
1BD4	X-ray	2.20	A/B/C/D	2-244	[»]
1JLR	X-ray	2.45	A/B/C/D	2-244	[»]
1JLS	X-ray	2.50	A/B/C/D	2-244	[»]
1UPF	X-ray	2.30	A/B/C/D	21-244	[»]
1UPU	X-ray	2.50	A/B/C/D	21-244	[»]

ProteinModelPortal

Q26998.

SMR

Q26998. Positions 10-244.

ModBase

Search...

Proteomic databases

PRIDE

Q26998.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Phylogenomic databases

OMA

LFYDKLP.

Enzyme and pathway databases

BRENDA

2.4.2.9. 6411.

UniPathway

UPA00574; UER00636.

Family and domain databases

ProtoNet

Search...

Other

DrugBank

DB00544. Fluorouracil.

EvolutionaryTrace

Q26998.

Entry information

Entry name

UPP_TOXGO

Accession

Primary (citable) accession number: Q26998

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	April 3, 2013
This is version 69 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)