ID UPP_TOXGO Reviewed; 244 AA. AC Q26998; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 27-MAR-2024, entry version 110. DE RecName: Full=Uracil phosphoribosyltransferase; DE Short=UPRT; DE Short=UPRTase; DE EC=2.4.2.9 {ECO:0000269|PubMed:11773618, ECO:0000269|PubMed:9247925}; DE AltName: Full=UMP pyrophosphorylase; GN Name=uprt; OS Toxoplasma gondii. OC Eukaryota; Sar; Alveolata; Apicomplexa; Conoidasida; Coccidia; OC Eucoccidiorida; Eimeriorina; Sarcocystidae; Toxoplasma. OX NCBI_TaxID=5811; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-6, FUNCTION, RP SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, AND CATALYTIC ACTIVITY. RC STRAIN=RH / EP; RX PubMed=9247925; DOI=10.1016/s0166-6851(97)00058-3; RA Carter D., Donald R.G.K., Roos D., Ullman B.; RT "Expression, purification, and characterization of uracil RT phosphoribosyltransferase from Toxoplasma gondii."; RL Mol. Biochem. Parasitol. 87:137-144(1997). RN [2] RP X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF MUTANT VAL-128 APOENZYME AND IN RP COMPLEXES WITH SUBSTRATES AND 5-FLUOROURACIL, AND MUTAGENESIS OF CYS-128. RX PubMed=9628859; DOI=10.1093/emboj/17.12.3219; RA Schumacher M.A., Carter D., Scott D.M., Roos D.S., Ullman B., Brennan R.G.; RT "Crystal structures of Toxoplasma gondii uracil phosphoribosyltransferase RT reveal the atomic basis of pyrimidine discrimination and prodrug binding."; RL EMBO J. 17:3219-3232(1998). RN [3] RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF MUTANT VAL-128 IN COMPLEXES WITH RP URACIL; SUBSTRATE ANALOG AND GTP, COFACTOR, SUBUNIT, BIOPHYSICOCHEMICAL RP PROPERTIES, ACTIVITY REGULATION, MUTAGENESIS OF LYS-59; ARG-68; LYS-150 AND RP ASP-235, AND CATALYTIC ACTIVITY. RX PubMed=11773618; DOI=10.1073/pnas.012399599; RA Schumacher M.A., Bashor C.J., Song M.H., Otsu K., Zhu S., Parry R.J., RA Ullman B., Brennan R.G.; RT "The structural mechanism of GTP stabilized oligomerization and catalytic RT activation of the Toxoplasma gondii uracil phosphoribosyltransferase."; RL Proc. Natl. Acad. Sci. U.S.A. 99:78-83(2002). CC -!- FUNCTION: Catalyzes the conversion of uracil and 5-phospho-alpha-D- CC ribose 1-diphosphate (PRPP) to UMP and diphosphate. CC {ECO:0000269|PubMed:9247925}. CC -!- CATALYTIC ACTIVITY: CC Reaction=diphosphate + UMP = 5-phospho-alpha-D-ribose 1-diphosphate + CC uracil; Xref=Rhea:RHEA:13017, ChEBI:CHEBI:17568, ChEBI:CHEBI:33019, CC ChEBI:CHEBI:57865, ChEBI:CHEBI:58017; EC=2.4.2.9; CC Evidence={ECO:0000269|PubMed:11773618, ECO:0000269|PubMed:9247925}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:11773618}; CC Note=Binds 1 Mg(2+) ion per subunit. The magnesium is bound as Mg-PRPP. CC {ECO:0000269|PubMed:11773618}; CC -!- ACTIVITY REGULATION: Allosterically activated by GTP. Binding of GTP CC leads to 5-time activation of the enzyme. CC {ECO:0000269|PubMed:11773618}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=3.5 uM for uracil {ECO:0000269|PubMed:11773618, CC ECO:0000269|PubMed:9247925}; CC KM=216 uM for 5-phospho-alpha-D-ribose 1-diphosphate (in the absence CC of GTP) {ECO:0000269|PubMed:11773618, ECO:0000269|PubMed:9247925}; CC KM=37.4 uM for 5-phospho-alpha-D-ribose 1-diphosphate (in the CC presence of GTP) {ECO:0000269|PubMed:11773618, CC ECO:0000269|PubMed:9247925}; CC Vmax=0.45 umol/min/mg enzyme {ECO:0000269|PubMed:11773618, CC ECO:0000269|PubMed:9247925}; CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via salvage pathway; CC UMP from uracil: step 1/1. CC -!- SUBUNIT: Monomer. Forms homodimers in presence of substrates and CC homotetramers in the presence of GTP. {ECO:0000269|PubMed:11773618, CC ECO:0000269|PubMed:9247925}. CC -!- SIMILARITY: Belongs to the UPRTase family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U10246; AAB60213.1; -; Genomic_DNA. DR PDB; 1BD3; X-ray; 1.93 A; A/B/C/D=2-244. DR PDB; 1BD4; X-ray; 2.20 A; A/B/C/D=2-244. DR PDB; 1JLR; X-ray; 2.45 A; A/B/C/D=2-244. DR PDB; 1JLS; X-ray; 2.50 A; A/B/C/D=2-244. DR PDB; 1UPF; X-ray; 2.30 A; A/B/C/D=21-244. DR PDB; 1UPU; X-ray; 2.50 A; A/B/C/D=21-244. DR PDBsum; 1BD3; -. DR PDBsum; 1BD4; -. DR PDBsum; 1JLR; -. DR PDBsum; 1JLS; -. DR PDBsum; 1UPF; -. DR PDBsum; 1UPU; -. DR AlphaFoldDB; Q26998; -. DR SMR; Q26998; -. DR EnsemblProtists; TGME49_312480-t26_1; TGME49_312480-t26_1; TGME49_312480. DR VEuPathDB; ToxoDB:TGARI_312480; -. DR VEuPathDB; ToxoDB:TGCAST_312480; -. DR VEuPathDB; ToxoDB:TGCOUG_312480; -. DR VEuPathDB; ToxoDB:TGDOM2_312480; -. DR VEuPathDB; ToxoDB:TGFOU_312480; -. DR VEuPathDB; ToxoDB:TGGT1_312480; -. DR VEuPathDB; ToxoDB:TGMAS_312480; -. DR VEuPathDB; ToxoDB:TGME49_312480; -. DR VEuPathDB; ToxoDB:TGP89_312480; -. DR VEuPathDB; ToxoDB:TGPRC2_312480; -. DR VEuPathDB; ToxoDB:TGRH88_051740; -. DR VEuPathDB; ToxoDB:TGRUB_312480; -. DR VEuPathDB; ToxoDB:TGVAND_312480; -. DR VEuPathDB; ToxoDB:TGVEG_312480; -. DR OMA; DIANRWV; -. DR BRENDA; 2.4.2.9; 6411. DR SABIO-RK; Q26998; -. DR UniPathway; UPA00574; UER00636. DR EvolutionaryTrace; Q26998; -. DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW. DR GO; GO:0004845; F:uracil phosphoribosyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:0044206; P:UMP salvage; IEA:UniProtKB-UniPathway. DR CDD; cd06223; PRTases_typeI; 1. DR Gene3D; 3.40.50.2020; -; 1. DR InterPro; IPR000836; PRibTrfase_dom. DR InterPro; IPR029057; PRTase-like. DR PANTHER; PTHR10285; URIDINE KINASE; 1. DR PANTHER; PTHR10285:SF70; URIDINE-CYTIDINE KINASE; 1. DR Pfam; PF14681; UPRTase; 1. DR SUPFAM; SSF53271; PRTase-like; 1. PE 1: Evidence at protein level; KW 3D-structure; Allosteric enzyme; Direct protein sequencing; KW Glycosyltransferase; GTP-binding; Nucleotide-binding; Transferase. FT CHAIN 1..244 FT /note="Uracil phosphoribosyltransferase" FT /id="PRO_0000120783" FT BINDING 59 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|PubMed:9628859, FT ECO:0007744|PDB:1BD3, ECO:0007744|PDB:1UPU" FT BINDING 68 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|PubMed:11773618, FT ECO:0007744|PDB:1JLR" FT BINDING 102..105 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|PubMed:11773618, FT ECO:0007744|PDB:1JLR" FT BINDING 112 FT /ligand="5-phospho-alpha-D-ribose 1-diphosphate" FT /ligand_id="ChEBI:CHEBI:58017" FT /evidence="ECO:0000269|PubMed:11773618, FT ECO:0007744|PDB:1JLS" FT BINDING 129 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|PubMed:11773618, FT ECO:0000269|PubMed:9628859, ECO:0007744|PDB:1BD3, FT ECO:0007744|PDB:1BD4, ECO:0007744|PDB:1JLR, FT ECO:0007744|PDB:1JLS, ECO:0007744|PDB:1UPU" FT BINDING 137 FT /ligand="5-phospho-alpha-D-ribose 1-diphosphate" FT /ligand_id="ChEBI:CHEBI:58017" FT /evidence="ECO:0000269|PubMed:11773618, FT ECO:0000269|PubMed:9628859, ECO:0007744|PDB:1BD3, FT ECO:0007744|PDB:1BD4, ECO:0007744|PDB:1JLR, FT ECO:0007744|PDB:1JLS, ECO:0007744|PDB:1UPU" FT BINDING 158 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000269|PubMed:11773618, FT ECO:0000269|PubMed:9628859, ECO:0007744|PDB:1BD3, FT ECO:0007744|PDB:1BD4, ECO:0007744|PDB:1JLR, FT ECO:0007744|PDB:1JLS, ECO:0007744|PDB:1UPU" FT BINDING 164..172 FT /ligand="5-phospho-alpha-D-ribose 1-diphosphate" FT /ligand_id="ChEBI:CHEBI:58017" FT /evidence="ECO:0000269|PubMed:11773618, FT ECO:0000269|PubMed:9628859, ECO:0007744|PDB:1BD3, FT ECO:0007744|PDB:1BD4, ECO:0007744|PDB:1JLR, FT ECO:0007744|PDB:1JLS" FT BINDING 164 FT /ligand="5-phospho-alpha-D-ribose 1-diphosphate" FT /ligand_id="ChEBI:CHEBI:58017" FT /evidence="ECO:0000269|PubMed:11773618, FT ECO:0000269|PubMed:9628859, ECO:0007744|PDB:1JLS, FT ECO:0007744|PDB:1UPU" FT BINDING 229 FT /ligand="uracil" FT /ligand_id="ChEBI:CHEBI:17568" FT /evidence="ECO:0000269|PubMed:9628859, FT ECO:0007744|PDB:1UPU" FT BINDING 234..236 FT /ligand="uracil" FT /ligand_id="ChEBI:CHEBI:17568" FT /evidence="ECO:0000269|PubMed:9628859, FT ECO:0007744|PDB:1UPU" FT BINDING 235 FT /ligand="5-phospho-alpha-D-ribose 1-diphosphate" FT /ligand_id="ChEBI:CHEBI:58017" FT /evidence="ECO:0000269|PubMed:11773618, FT ECO:0007744|PDB:1JLR, ECO:0007744|PDB:1JLS" FT MUTAGEN 59 FT /note="K->A: GTP-induced enzymatic activation is reduced FT 4-fold." FT /evidence="ECO:0000269|PubMed:11773618" FT MUTAGEN 68 FT /note="R->A: GTP-induced enzymatic activation is reduced FT 2-fold." FT /evidence="ECO:0000269|PubMed:11773618" FT MUTAGEN 128 FT /note="C->V: No effect on activity. Far less oxidation FT sensitive than wild-type." FT /evidence="ECO:0000269|PubMed:9628859" FT MUTAGEN 150 FT /note="K->A: GTP-induced enzymatic activation is reduced FT 4-fold." FT /evidence="ECO:0000269|PubMed:11773618" FT MUTAGEN 235 FT /note="D->A,N: No enzymatic activity." FT /evidence="ECO:0000269|PubMed:11773618" FT STRAND 14..16 FT /evidence="ECO:0007829|PDB:1JLR" FT HELIX 22..32 FT /evidence="ECO:0007829|PDB:1BD3" FT STRAND 36..38 FT /evidence="ECO:0007829|PDB:1BD3" FT HELIX 43..53 FT /evidence="ECO:0007829|PDB:1BD3" FT HELIX 59..78 FT /evidence="ECO:0007829|PDB:1BD3" FT STRAND 83..89 FT /evidence="ECO:0007829|PDB:1BD3" FT TURN 91..93 FT /evidence="ECO:0007829|PDB:1JLS" FT STRAND 95..101 FT /evidence="ECO:0007829|PDB:1BD3" FT STRAND 105..111 FT /evidence="ECO:0007829|PDB:1BD3" FT TURN 112..114 FT /evidence="ECO:0007829|PDB:1BD3" FT HELIX 115..124 FT /evidence="ECO:0007829|PDB:1BD3" FT STRAND 130..137 FT /evidence="ECO:0007829|PDB:1BD3" FT STRAND 139..141 FT /evidence="ECO:0007829|PDB:1BD3" FT STRAND 144..150 FT /evidence="ECO:0007829|PDB:1BD3" FT HELIX 155..157 FT /evidence="ECO:0007829|PDB:1BD3" FT STRAND 158..163 FT /evidence="ECO:0007829|PDB:1BD3" FT STRAND 165..169 FT /evidence="ECO:0007829|PDB:1BD3" FT HELIX 171..183 FT /evidence="ECO:0007829|PDB:1BD3" FT HELIX 187..189 FT /evidence="ECO:0007829|PDB:1BD3" FT STRAND 190..197 FT /evidence="ECO:0007829|PDB:1BD3" FT HELIX 199..208 FT /evidence="ECO:0007829|PDB:1BD3" FT STRAND 212..219 FT /evidence="ECO:0007829|PDB:1BD3" FT STRAND 221..223 FT /evidence="ECO:0007829|PDB:1BD3" FT STRAND 229..231 FT /evidence="ECO:0007829|PDB:1BD3" FT HELIX 236..241 FT /evidence="ECO:0007829|PDB:1BD3" SQ SEQUENCE 244 AA; 27646 MW; 1810CC234B2CE60F CRC64; MAQVPASGKL LVDPRYSTND QEESILQDII TRFPNVVLMK QTAQLRAMMT IIRDKETPKE EFVFYADRLI RLLIEEALNE LPFEKKEVTT PLDVSYHGVS FYSKICGVSI VRAGESMESG LRAVCRGCRI GKILIQRDET TAEPKLIYEK LPADIRDRWV MLLDPMCATA GSVCKAIEVL LRLGVKEERI IFVNILAAPQ GIERVFKEYP KVRMVTAAVD ICLNSRYYIV PGIGDFGDRY FGTM //