THI5_CANAL
ID THI5_CANAL Reviewed; 339 AA.
AC Q5A3Y5; A0A1D8PTX4;
DT 07-JAN-2015, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase {ECO:0000250|UniProtKB:P43534};
DE Short=HMP-P synthase {ECO:0000305};
DE Short=Hydroxymethylpyrimidine phosphate synthase {ECO:0000305};
DE EC=2.-.-.- {ECO:0000269|PubMed:22568620};
DE AltName: Full=Thiamine biosynthesis protein 5 {ECO:0000303|PubMed:22568620};
DE AltName: Full=Thiamine pyrimidine synthase {ECO:0000303|PubMed:22568620};
GN Name=THI13; Synonyms=THI5 {ECO:0000303|PubMed:22568620};
GN OrderedLocusNames=CAALFM_CR09290WA; ORFNames=CaO19.7324;
OS Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=237561;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=15123810; DOI=10.1073/pnas.0401648101;
RA Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S., Magee B.B.,
RA Newport G., Thorstenson Y.R., Agabian N., Magee P.T., Davis R.W.,
RA Scherer S.;
RT "The diploid genome sequence of Candida albicans.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=17419877; DOI=10.1186/gb-2007-8-4-r52;
RA van het Hoog M., Rast T.J., Martchenko M., Grindle S., Dignard D.,
RA Hogues H., Cuomo C., Berriman M., Scherer S., Magee B.B., Whiteway M.,
RA Chibana H., Nantel A., Magee P.T.;
RT "Assembly of the Candida albicans genome into sixteen supercontigs aligned
RT on the eight chromosomes.";
RL Genome Biol. 8:RESEARCH52.1-RESEARCH52.12(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=24025428; DOI=10.1186/gb-2013-14-9-r97;
RA Muzzey D., Schwartz K., Weissman J.S., Sherlock G.;
RT "Assembly of a phased diploid Candida albicans genome facilitates allele-
RT specific measurements and provides a simple model for repeat and indel
RT structure.";
RL Genome Biol. 14:RESEARCH97.1-RESEARCH97.14(2013).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBUNIT, AND MUTAGENESIS OF HIS-66.
RX PubMed=22568620; DOI=10.1021/ja302474a;
RA Lai R.Y., Huang S., Fenwick M.K., Hazra A., Zhang Y., Rajashankar K.,
RA Philmus B., Kinsland C., Sanders J.M., Ealick S.E., Begley T.P.;
RT "Thiamin pyrimidine biosynthesis in Candida albicans: a remarkable reaction
RT between histidine and pyridoxal phosphate.";
RL J. Am. Chem. Soc. 134:9157-9159(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:22568620}.
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:22568620};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65757;
CC Evidence={ECO:0000269|PubMed:22568620};
CC -!- COFACTOR:
CC Name=Fe(3+); Xref=ChEBI:CHEBI:29034;
CC Evidence={ECO:0000269|PubMed:22568620};
CC -!- PATHWAY: Cofactor biosynthesis; thiamine diphosphate biosynthesis.
CC {ECO:0000305|PubMed:22568620}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:22568620}.
CC -!- SIMILARITY: Belongs to the NMT1/THI5 family. {ECO:0000305}.
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DR EMBL; CP017630; AOW31591.1; -; Genomic_DNA.
DR RefSeq; XP_716458.1; XM_711365.1.
DR AlphaFoldDB; Q5A3Y5; -.
DR SMR; Q5A3Y5; -.
DR STRING; 237561.Q5A3Y5; -.
DR GeneID; 3641921; -.
DR KEGG; cal:CAALFM_CR09290WA; -.
DR CGD; CAL0000188398; THI13.
DR VEuPathDB; FungiDB:CR_09290W_A; -.
DR eggNOG; ENOG502QQ87; Eukaryota.
DR HOGENOM; CLU_028871_6_3_1; -.
DR InParanoid; Q5A3Y5; -.
DR OMA; DWFVNPD; -.
DR OrthoDB; 1164887at2759; -.
DR UniPathway; UPA00060; -.
DR Proteomes; UP000000559; Chromosome R.
DR GO; GO:0106344; F:4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase activity from histidine and PLP; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0009228; P:thiamine biosynthetic process; IDA:CGD.
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 Iron; Metal-binding; Pyridoxal phosphate; Reference proteome;
KW Thiamine biosynthesis; Transferase.
FT CHAIN 1..339
FT /note="4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate
FT synthase"
FT /id="PRO_0000431580"
FT MOTIF 195..199
FT /note="CCCFC; essential for catalytic activity, may be the
FT site of iron coordination"
FT /evidence="ECO:0000250|UniProtKB:P43534"
FT ACT_SITE 66
FT /evidence="ECO:0000305|PubMed:22568620"
FT BINDING 115..118
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /evidence="ECO:0000250|UniProtKB:C4YMW2"
FT MOD_RES 62
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:C4YMW2"
FT MUTAGEN 66
FT /note="H->N,G: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:22568620"
SQ SEQUENCE 339 AA; 38333 MW; ABE29C9E16F9D59C CRC64;
MSTNKITFLL NWEAAPYHIP VYLANIKGYF KDENLDIAIL EPSNPSDVTE LVGSGKVDMG
LKAMVHTLAA KARGLPVTSI GSLLDEPFTG ICYLEGSGIT SDFQSLKGKR IGYVGEFGKI
QVDELTKHYG MTPDDYVAVR CGMNVAKYIL EGTIDCGIGI ECIQQVELEE ALKEQGKDSN
DAKMLRIDKL AELGCCCFCT ILYIANDKFI AENSQAVKKF LKAIKRATDY MLAHPREAWA
EYGNFKPTMQ TDLNTKKFQR CYAYFSESLY NVHRDWRKVN NYGKRLDILP ENYVPNYTNE
YLSWPEPKEV DDPEKAQDLM LKHQEECKTC GGYKRLVLA
