THI5_YEAST
ID THI5_YEAST Reviewed; 340 AA.
AC P43534; D6VTH2;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase THI5 {ECO:0000303|PubMed:23048037};
DE Short=HMP-P synthase {ECO:0000303|PubMed:23048037};
DE Short=Hydroxymethylpyrimidine phosphate synthase {ECO:0000305};
DE EC=2.-.-.- {ECO:0000269|PubMed:23048037};
DE AltName: Full=Thiamine biosynthesis protein 5 {ECO:0000303|Ref.1};
DE AltName: Full=Thiamine pyrimidine synthase {ECO:0000250|UniProtKB:C4YMW2};
GN Name=THI5 {ECO:0000303|Ref.1}; Synonyms=MOL2 {ECO:0000303|PubMed:12777485};
GN OrderedLocusNames=YFL058W {ECO:0000312|SGD:S000001836};
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RA Hather R.J., Praekelt U., Meacock P.A.;
RT "Characterisation of a new thiamine regulated Saccharomyces cerevisiae
RT gene, THI5.";
RL Submitted (FEB-1995) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7670463; DOI=10.1038/ng0795-261;
RA Murakami Y., Naitou M., Hagiwara H., Shibata T., Ozawa M., Sasanuma S.,
RA Sasanuma M., Tsuchiya Y., Soeda E., Yokoyama K., Yamazaki M., Tashiro H.,
RA Eki T.;
RT "Analysis of the nucleotide sequence of chromosome VI from Saccharomyces
RT cerevisiae.";
RL Nat. Genet. 10:261-268(1995).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP THIAMINE BIOSYNTHESIS IN YEAST.
RX PubMed=8528151;
RA Tazuya K., Azumi C., Yamada K., Kumaoka H.;
RT "Pyrimidine moiety of thiamin is biosynthesized from pyridoxine and
RT histidine in Saccharomyces cerevisiae.";
RL Biochem. Mol. Biol. Int. 36:883-888(1995).
RN [5]
RP PATHWAY.
RX PubMed=12777485; DOI=10.1099/mic.0.26194-0;
RA Wightman R., Meacock P.A.;
RT "The THI5 gene family of Saccharomyces cerevisiae: distribution of
RT homologues among the hemiascomycetes and functional redundancy in the
RT aerobic biosynthesis of thiamin from pyridoxine.";
RL Microbiology 149:1447-1460(2003).
RN [6]
RP THIAMINE BIOSYNTHESIS IN YEAST.
RX PubMed=18388401; DOI=10.3177/jnsv.54.7;
RA Ishida S., Tazuya-Murayama K., Kijima Y., Yamada K.;
RT "The direct precursor of the pyrimidine moiety of thiamin is not urocanic
RT acid but histidine in Saccharomyces cerevisiae.";
RL J. Nutr. Sci. Vitaminol. 54:7-10(2008).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) IN COMPLEX WITH PYRIDOXAL PHOSPHATE,
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, COFACTOR, MASS SPECTROMETRY, AND
RP MUTAGENESIS OF ASN-11; TRP-12; LYS-62 AND HIS-66.
RX PubMed=23048037; DOI=10.1074/jbc.m112.397240;
RA Coquille S., Roux C., Fitzpatrick T.B., Thore S.;
RT "The last piece in the vitamin B1 biosynthesis puzzle: structural and
RT functional insight into yeast 4-amino-5-hydroxymethyl-2-methylpyrimidine
RT phosphate (HMP-P) synthase.";
RL J. Biol. Chem. 287:42333-42343(2012).
CC -!- FUNCTION: Responsible for the formation of the pyrimidine heterocycle
CC in the thiamine biosynthesis pathway. Catalyzes the formation of
CC hydroxymethylpyrimidine phosphate (HMP-P) from histidine and pyridoxal
CC phosphate (PLP). The protein uses PLP and the active site histidine to
CC form HMP-P, generating an inactive enzyme. The enzyme can only undergo
CC a single turnover, which suggests it is a suicide enzyme.
CC {ECO:0000269|PubMed:23048037}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 Fe(3+) + 4 H2O + L-histidyl-[4-amino-5-hydroxymethyl-2-
CC methylpyrimidine phosphate synthase] + N(6)-(pyridoxal phosphate)-L-
CC lysyl-[4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase]
CC = (2S)-2-amino-5-hydroxy-4-oxopentanoyl-[4-amino-5-hydroxymethyl-2-
CC methylpyrimidine phosphate synthase] + 3-oxopropanoate + 4-amino-2-
CC methyl-5-(phosphooxymethyl)pyrimidine + 2 Fe(2+) + 2 H(+) + L-lysyl-
CC [4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase];
CC Xref=Rhea:RHEA:65756, Rhea:RHEA-COMP:16892, Rhea:RHEA-COMP:16893,
CC Rhea:RHEA-COMP:16894, Rhea:RHEA-COMP:16895, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034,
CC ChEBI:CHEBI:29969, ChEBI:CHEBI:29979, ChEBI:CHEBI:33190,
CC ChEBI:CHEBI:58354, ChEBI:CHEBI:143915, ChEBI:CHEBI:157692;
CC Evidence={ECO:0000269|PubMed:23048037};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65757;
CC Evidence={ECO:0000269|PubMed:23048037};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000269|PubMed:23048037};
CC -!- PATHWAY: Cofactor biosynthesis; thiamine diphosphate biosynthesis.
CC {ECO:0000305|PubMed:12777485}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:23048037}.
CC -!- INTERACTION:
CC P43534; P39940: RSP5; NbExp=2; IntAct=EBI-19221, EBI-16219;
CC -!- MASS SPECTROMETRY: Mass=38513.4; Method=Electrospray; Note=This mass is
CC that of the untagged protein plus the mass of an iron ion.;
CC Evidence={ECO:0000269|PubMed:23048037};
CC -!- SIMILARITY: Belongs to the NMT1/THI5 family. {ECO:0000305}.
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DR EMBL; Z48220; CAA88253.1; -; Genomic_DNA.
DR EMBL; D50617; BAA09183.1; -; Genomic_DNA.
DR EMBL; BK006940; DAA12382.1; -; Genomic_DNA.
DR RefSeq; NP_116597.1; NM_001179909.1.
DR PDB; 4H65; X-ray; 2.60 A; A/B=1-340.
DR PDB; 4H67; X-ray; 2.70 A; A/B/C/D/E/F/G/H=1-340.
DR PDB; 4H6D; X-ray; 2.90 A; A/B/C/D/E/F/G/H=1-340.
DR PDBsum; 4H65; -.
DR PDBsum; 4H67; -.
DR PDBsum; 4H6D; -.
DR AlphaFoldDB; P43534; -.
DR SMR; P43534; -.
DR BioGRID; 31089; 24.
DR DIP; DIP-3951N; -.
DR IntAct; P43534; 2.
DR STRING; 4932.YFL058W; -.
DR PaxDb; P43534; -.
DR EnsemblFungi; YFL058W_mRNA; YFL058W; YFL058W.
DR GeneID; 850486; -.
DR KEGG; sce:YFL058W; -.
DR SGD; S000001836; THI5.
DR VEuPathDB; FungiDB:YFL058W; -.
DR eggNOG; ENOG502QQ87; Eukaryota.
DR GeneTree; ENSGT00940000176330; -.
DR HOGENOM; CLU_028871_6_3_1; -.
DR InParanoid; P43534; -.
DR OMA; CDLESYG; -.
DR BioCyc; MetaCyc:MON3O-3915; -.
DR BioCyc; YEAST:MON3O-3915; -.
DR BRENDA; 4.1.99.17; 984.
DR UniPathway; UPA00060; -.
DR PRO; PR:P43534; -.
DR Proteomes; UP000002311; Chromosome VI.
DR RNAct; P43534; protein.
DR GO; GO:0106344; F:4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase activity from histidine and PLP; IDA:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB.
DR GO; GO:0009228; P:thiamine biosynthetic process; IDA:UniProtKB.
DR GO; GO:0009229; P:thiamine diphosphate biosynthetic process; IEA:UniProtKB-UniPathway.
DR InterPro; IPR027939; NMT1/THI5.
DR InterPro; IPR015168; SsuA/THI5.
DR PANTHER; PTHR31528; PTHR31528; 1.
DR Pfam; PF09084; NMT1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Iron; Metal-binding; Pyridoxal phosphate; Reference proteome;
KW Thiamine biosynthesis; Transferase.
FT CHAIN 1..340
FT /note="4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate
FT synthase THI5"
FT /id="PRO_0000211618"
FT MOTIF 195..199
FT /note="CCCFC; essential for catalytic activity, may be the
FT site of iron coordination"
FT /evidence="ECO:0000305|PubMed:23048037"
FT ACT_SITE 66
FT /evidence="ECO:0000305|PubMed:23048037"
FT BINDING 115..118
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000269|PubMed:23048037"
FT MOD_RES 62
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000269|PubMed:23048037"
FT MUTAGEN 11
FT /note="N->A: Unable to sustain growth in thiamine-free
FT medium."
FT /evidence="ECO:0000269|PubMed:23048037"
FT MUTAGEN 12
FT /note="W->A: Unable to sustain growth in thiamine-free
FT medium."
FT /evidence="ECO:0000269|PubMed:23048037"
FT MUTAGEN 62
FT /note="K->A: Unable to sustain growth in thiamine-free
FT medium."
FT /evidence="ECO:0000269|PubMed:23048037"
FT MUTAGEN 66
FT /note="H->A: Unable to sustain growth in thiamine-free
FT medium."
FT /evidence="ECO:0000269|PubMed:23048037"
FT MUTAGEN 195
FT /note="C->A: Attenuates the coordination of ion and is
FT unable to sustain growth in thiamine-free medium."
FT /evidence="ECO:0000269|PubMed:23048037"
FT MUTAGEN 196
FT /note="C->A: Attenuates the coordination of ion and is
FT unable to sustain growth in thiamine-free medium."
FT /evidence="ECO:0000269|PubMed:23048037"
FT MUTAGEN 197
FT /note="C->A: Attenuates the coordination of ion and is
FT unable to sustain growth in thiamine-free medium."
FT /evidence="ECO:0000269|PubMed:23048037"
FT MUTAGEN 199
FT /note="C->A: Attenuates the coordination of ion and is
FT unable to sustain growth in thiamine-free medium."
FT /evidence="ECO:0000269|PubMed:23048037"
FT STRAND 6..9
FT /evidence="ECO:0007829|PDB:4H65"
FT STRAND 11..13
FT /evidence="ECO:0007829|PDB:4H65"
FT HELIX 16..18
FT /evidence="ECO:0007829|PDB:4H65"
FT HELIX 19..26
FT /evidence="ECO:0007829|PDB:4H65"
FT HELIX 29..32
FT /evidence="ECO:0007829|PDB:4H65"
FT STRAND 37..44
FT /evidence="ECO:0007829|PDB:4H65"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:4H65"
FT HELIX 48..54
FT /evidence="ECO:0007829|PDB:4H65"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:4H65"
FT STRAND 59..63
FT /evidence="ECO:0007829|PDB:4H65"
FT HELIX 64..71
FT /evidence="ECO:0007829|PDB:4H65"
FT TURN 72..74
FT /evidence="ECO:0007829|PDB:4H65"
FT STRAND 77..84
FT /evidence="ECO:0007829|PDB:4H65"
FT STRAND 89..94
FT /evidence="ECO:0007829|PDB:4H65"
FT TURN 95..98
FT /evidence="ECO:0007829|PDB:4H65"
FT HELIX 103..106
FT /evidence="ECO:0007829|PDB:4H65"
FT STRAND 110..113
FT /evidence="ECO:0007829|PDB:4H65"
FT HELIX 117..127
FT /evidence="ECO:0007829|PDB:4H67"
FT TURN 128..130
FT /evidence="ECO:0007829|PDB:4H67"
FT STRAND 135..140
FT /evidence="ECO:0007829|PDB:4H65"
FT HELIX 142..144
FT /evidence="ECO:0007829|PDB:4H65"
FT HELIX 145..150
FT /evidence="ECO:0007829|PDB:4H65"
FT STRAND 153..160
FT /evidence="ECO:0007829|PDB:4H65"
FT TURN 161..163
FT /evidence="ECO:0007829|PDB:4H65"
FT HELIX 164..174
FT /evidence="ECO:0007829|PDB:4H65"
FT HELIX 179..181
FT /evidence="ECO:0007829|PDB:4H65"
FT STRAND 182..186
FT /evidence="ECO:0007829|PDB:4H65"
FT STRAND 192..194
FT /evidence="ECO:0007829|PDB:4H6D"
FT HELIX 196..199
FT /evidence="ECO:0007829|PDB:4H6D"
FT STRAND 201..206
FT /evidence="ECO:0007829|PDB:4H65"
FT HELIX 207..212
FT /evidence="ECO:0007829|PDB:4H65"
FT HELIX 214..233
FT /evidence="ECO:0007829|PDB:4H65"
FT HELIX 235..245
FT /evidence="ECO:0007829|PDB:4H65"
FT HELIX 247..249
FT /evidence="ECO:0007829|PDB:4H65"
FT HELIX 252..261
FT /evidence="ECO:0007829|PDB:4H65"
FT TURN 262..264
FT /evidence="ECO:0007829|PDB:4H65"
FT HELIX 273..285
FT /evidence="ECO:0007829|PDB:4H65"
FT HELIX 315..330
FT /evidence="ECO:0007829|PDB:4H65"
SQ SEQUENCE 340 AA; 38592 MW; D810C5D5A86FA6C0 CRC64;
MSTDKITFLL NWQPTPYHIP IFLAQTKGYF KEQGLDMAIL EPTNPSDVTE LIGSGKVDMG
LKAMIHTLAA KARGFPVTSV ASLLDEPFTG VLYLKGSGIT EDFQSLKGKK IGYVGEFGKI
QIDELTKHYG MKPEDYTAVR CGMNVAKYII EGKIDAGIGI ECMQQVELEE YLAKQGRPAS
DAKMLRIDKL ACLGCCCFCT VLYICNDEFL KKNPEKVRKF LKAIKKATDY VLADPVKAWK
EYIDFKPQLN NDLSYKQYQR CYAYFSSSLY NVHRDWKKVT GYGKRLAILP PDYVSNYTNE
YLSWPEPEEV SDPLEAQRLM AIHQEKCRQE GTFKRLALPA
