THI6_SCHPO
ID THI6_SCHPO Reviewed; 518 AA.
AC P40386;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Probable thiamine biosynthetic bifunctional enzyme;
DE Includes:
DE RecName: Full=Thiamine-phosphate synthase;
DE Short=TP synthase;
DE Short=TPS;
DE EC=2.5.1.3;
DE AltName: Full=Thiamine-phosphate pyrophosphorylase;
DE Short=TMP pyrophosphorylase;
DE Short=TMP-PPase;
DE Includes:
DE RecName: Full=Hydroxyethylthiazole kinase;
DE EC=2.7.1.50;
DE AltName: Full=4-methyl-5-beta-hydroxyethylthiazole kinase;
DE Short=TH kinase;
DE Short=THZ kinase;
GN Name=thi4; ORFNames=SPAC23H4.10c;
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=7961415; DOI=10.1128/jb.176.21.6631-6635.1994;
RA Zurlinden A., Schweingruber M.E.;
RT "Cloning, nucleotide sequence, and regulation of Schizosaccharomyces pombe
RT thi4, a thiamine biosynthetic gene.";
RL J. Bacteriol. 176:6631-6635(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
CC -!- FUNCTION: Condenses 4-methyl-5-(beta-hydroxyethyl)thiazole
CC monophosphate (THZ-P) and 2-methyl-4-amino-5-hydroxymethyl pyrimidine
CC pyrophosphate (HMP-PP) to form thiamine monophosphate (TMP).
CC {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-ylidene]ethyl
CC phosphate + 4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + 2
CC H(+) = CO2 + diphosphate + thiamine phosphate; Xref=Rhea:RHEA:47844,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:37575, ChEBI:CHEBI:57841, ChEBI:CHEBI:62899; EC=2.5.1.3;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-(2-carboxy-4-methylthiazol-5-yl)ethyl phosphate + 4-amino-2-
CC methyl-5-(diphosphooxymethyl)pyrimidine + 2 H(+) = CO2 + diphosphate
CC + thiamine phosphate; Xref=Rhea:RHEA:47848, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:33019, ChEBI:CHEBI:37575,
CC ChEBI:CHEBI:57841, ChEBI:CHEBI:62890; EC=2.5.1.3;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine + 4-methyl-
CC 5-(2-phosphooxyethyl)-thiazole + H(+) = diphosphate + thiamine
CC phosphate; Xref=Rhea:RHEA:22328, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:37575, ChEBI:CHEBI:57841,
CC ChEBI:CHEBI:58296; EC=2.5.1.3;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-(2-hydroxyethyl)-4-methylthiazole + ATP = 4-methyl-5-(2-
CC phosphooxyethyl)-thiazole + ADP + H(+); Xref=Rhea:RHEA:24212,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17957, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:58296, ChEBI:CHEBI:456216; EC=2.7.1.50;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000250};
CC -!- PATHWAY: Cofactor biosynthesis; thiamine diphosphate biosynthesis; 4-
CC methyl-5-(2-phosphoethyl)-thiazole from 5-(2-hydroxyethyl)-4-
CC methylthiazole: step 1/1.
CC -!- PATHWAY: Cofactor biosynthesis; thiamine diphosphate biosynthesis;
CC thiamine phosphate from 4-amino-2-methyl-5-diphosphomethylpyrimidine
CC and 4-methyl-5-(2-phosphoethyl)-thiazole: step 1/1.
CC -!- INDUCTION: Repressed by thiamine and 5-(2-hydroxyethyl)-4-
CC methylthiazole.
CC -!- SIMILARITY: In the N-terminal section; belongs to the thiamine-
CC phosphate synthase family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the Thz kinase
CC 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; X78824; CAA55402.1; -; Genomic_DNA.
DR EMBL; CU329670; CAB11664.1; -; Genomic_DNA.
DR PIR; S44183; S44183.
DR RefSeq; NP_593396.1; NM_001018828.2.
DR AlphaFoldDB; P40386; -.
DR SMR; P40386; -.
DR BioGRID; 278362; 15.
DR STRING; 4896.SPAC23H4.10c.1; -.
DR iPTMnet; P40386; -.
DR MaxQB; P40386; -.
DR PaxDb; P40386; -.
DR PRIDE; P40386; -.
DR EnsemblFungi; SPAC23H4.10c.1; SPAC23H4.10c.1:pep; SPAC23H4.10c.
DR GeneID; 2541872; -.
DR KEGG; spo:SPAC23H4.10c; -.
DR PomBase; SPAC23H4.10c; thi4.
DR VEuPathDB; FungiDB:SPAC23H4.10c; -.
DR eggNOG; ENOG502QS2M; Eukaryota.
DR HOGENOM; CLU_019943_1_1_1; -.
DR InParanoid; P40386; -.
DR OMA; HQNFGAN; -.
DR PhylomeDB; P40386; -.
DR UniPathway; UPA00060; UER00139.
DR UniPathway; UPA00060; UER00141.
DR PRO; PR:P40386; -.
DR Proteomes; UP000002485; Chromosome I.
DR GO; GO:0005737; C:cytoplasm; HDA:PomBase.
DR GO; GO:0005829; C:cytosol; HDA:PomBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004417; F:hydroxyethylthiazole kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004789; F:thiamine-phosphate diphosphorylase activity; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0009228; P:thiamine biosynthetic process; IBA:GO_Central.
DR GO; GO:0009229; P:thiamine diphosphate biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd01170; THZ_kinase; 1.
DR CDD; cd00564; TMP_TenI; 1.
DR Gene3D; 3.20.20.70; -; 1.
DR Gene3D; 3.40.1190.20; -; 1.
DR HAMAP; MF_00228; Thz_kinase; 1.
DR HAMAP; MF_00097; TMP_synthase; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR000417; Hyethyz_kinase.
DR InterPro; IPR029056; Ribokinase-like.
DR InterPro; IPR036206; ThiamineP_synth_sf.
DR InterPro; IPR022998; ThiamineP_synth_TenI.
DR InterPro; IPR034291; TMP_synthase.
DR Pfam; PF02110; HK; 1.
DR Pfam; PF02581; TMP-TENI; 1.
DR PRINTS; PR01099; HYETHTZKNASE.
DR SUPFAM; SSF51391; SSF51391; 1.
DR SUPFAM; SSF53613; SSF53613; 1.
DR TIGRFAMs; TIGR00693; thiE; 1.
DR TIGRFAMs; TIGR00694; thiM; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Kinase; Magnesium; Metal-binding; Multifunctional enzyme;
KW Nucleotide-binding; Reference proteome; Thiamine biosynthesis; Transferase.
FT CHAIN 1..518
FT /note="Probable thiamine biosynthetic bifunctional enzyme"
FT /id="PRO_0000157089"
FT REGION 1..229
FT /note="Thiamine-phosphate synthase"
FT REGION 230..518
FT /note="Hydroxyethylthiazole kinase"
FT ACT_SITE 433
FT /note="Proton acceptor; for hydroxyethylthiazole kinase
FT activity"
FT /evidence="ECO:0000250"
FT BINDING 40..44
FT /ligand="4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine"
FT /ligand_id="ChEBI:CHEBI:57841"
FT /evidence="ECO:0000250"
FT BINDING 72
FT /ligand="4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine"
FT /ligand_id="ChEBI:CHEBI:57841"
FT /evidence="ECO:0000250"
FT BINDING 73
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 92
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 111
FT /ligand="4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine"
FT /ligand_id="ChEBI:CHEBI:57841"
FT /evidence="ECO:0000250"
FT BINDING 137..139
FT /ligand="2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-
FT ylidene]ethyl phosphate"
FT /ligand_id="ChEBI:CHEBI:62899"
FT /evidence="ECO:0000250"
FT BINDING 140
FT /ligand="4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine"
FT /ligand_id="ChEBI:CHEBI:57841"
FT /evidence="ECO:0000250"
FT BINDING 173
FT /ligand="2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-
FT ylidene]ethyl phosphate"
FT /ligand_id="ChEBI:CHEBI:62899"
FT /evidence="ECO:0000250"
FT BINDING 199..200
FT /ligand="2-[(2R,5Z)-2-carboxy-4-methylthiazol-5(2H)-
FT ylidene]ethyl phosphate"
FT /ligand_id="ChEBI:CHEBI:62899"
FT /evidence="ECO:0000250"
FT BINDING 281
FT /ligand="5-(2-hydroxyethyl)-4-methylthiazole"
FT /ligand_id="ChEBI:CHEBI:17957"
FT /evidence="ECO:0000250"
FT BINDING 355
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 403
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 430
FT /ligand="5-(2-hydroxyethyl)-4-methylthiazole"
FT /ligand_id="ChEBI:CHEBI:17957"
FT /evidence="ECO:0000250"
SQ SEQUENCE 518 AA; 55566 MW; B8836D2BD67C79AA CRC64;
MKRQIDYSLY LVTSSSLIAP GSTIERQVEE GILGGVTLVQ HREKDISTKC FVERAKRLSE
ICKKYDVPFL INDRIDVALA VGADGVHIGQ DDMDCALARK ILGDDAIIGV STNNIEEIEK
AAADGADYVG IGSIYETNTK DVKDRLIGIT GLRKILEHVS KMHCQLGTVA IAGLNSSNIQ
RVIYLSEANG KRIDGIALVS AIMCSITPRE TAKELRNLIA TPPCFAQARS SLTTPKDLLN
QIPAALQKLK DFTPLIHHLT NAVAKNFSAN VTLAAYGSPT MGESYDEVAD FAKAPGALVL
NIGILENTKT YIHAAQVNND LARPVILDPV AVGATTARSK VINTLLNYAY YDIIKGNEGE
IMNLAGEQGL MRGVDSISQH TLAARITAVH RLAVERRCVV AMSGAVDVIS DGNSTYVIKN
GNPLLGQITA SGCSLGSVMG VTASICQNDK LLAAITATLL YNIASELAVE AKNSCGDLLV
QGPGTFIPIF VDKLHQLINE TIKGNVDWIE RAKLEKAE
