THI6_YEAST
ID THI6_YEAST Reviewed; 540 AA.
AC P41835; D6W3F6;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=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=THI6; OrderedLocusNames=YPL214C;
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=ND5-5A;
RX PubMed=7982968; DOI=10.1016/s0021-9258(18)43843-4;
RA Nosaka K., Nishimura H., Kawasaki Y., Tsujihara T., Iwashima A.;
RT "Isolation and characterization of the THI6 gene encoding a bifunctional
RT thiamin-phosphate pyrophosphorylase/hydroxyethylthiazole kinase from
RT Saccharomyces cerevisiae.";
RL J. Biol. Chem. 269:30510-30516(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169875;
RA Bussey H., Storms R.K., Ahmed A., Albermann K., Allen E., Ansorge W.,
RA Araujo R., Aparicio A., Barrell B.G., Badcock K., Benes V., Botstein D.,
RA Bowman S., Brueckner M., Carpenter J., Cherry J.M., Chung E.,
RA Churcher C.M., Coster F., Davis K., Davis R.W., Dietrich F.S., Delius H.,
RA DiPaolo T., Dubois E., Duesterhoeft A., Duncan M., Floeth M., Fortin N.,
RA Friesen J.D., Fritz C., Goffeau A., Hall J., Hebling U., Heumann K.,
RA Hilbert H., Hillier L.W., Hunicke-Smith S., Hyman R.W., Johnston M.,
RA Kalman S., Kleine K., Komp C., Kurdi O., Lashkari D., Lew H., Lin A.,
RA Lin D., Louis E.J., Marathe R., Messenguy F., Mewes H.-W., Mirtipati S.,
RA Moestl D., Mueller-Auer S., Namath A., Nentwich U., Oefner P., Pearson D.,
RA Petel F.X., Pohl T.M., Purnelle B., Rajandream M.A., Rechmann S.,
RA Rieger M., Riles L., Roberts D., Schaefer M., Scharfe M., Scherens B.,
RA Schramm S., Schroeder M., Sdicu A.-M., Tettelin H., Urrestarazu L.A.,
RA Ushinsky S., Vierendeels F., Vissers S., Voss H., Walsh S.V., Wambutt R.,
RA Wang Y., Wedler E., Wedler H., Winnett E., Zhong W.-W., Zollner A.,
RA Vo D.H., Hani J.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XVI.";
RL Nature 387:103-105(1997).
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).
CC -!- FUNCTION: Essential for thiamine biosynthesis. The kinase activity is
CC involved in the salvage synthesis of TH-P from the thiazole.
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 -!- SUBUNIT: Homooctamer.
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}.
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DR EMBL; D31908; BAA06703.1; -; Genomic_DNA.
DR EMBL; Z73570; CAA97929.1; -; Genomic_DNA.
DR EMBL; BK006949; DAA11222.1; -; Genomic_DNA.
DR PIR; A55145; A55145.
DR RefSeq; NP_015110.1; NM_001184028.1.
DR AlphaFoldDB; P41835; -.
DR SMR; P41835; -.
DR BioGRID; 35971; 115.
DR DIP; DIP-1666N; -.
DR IntAct; P41835; 1.
DR MINT; P41835; -.
DR STRING; 4932.YPL214C; -.
DR MaxQB; P41835; -.
DR PaxDb; P41835; -.
DR PRIDE; P41835; -.
DR EnsemblFungi; YPL214C_mRNA; YPL214C; YPL214C.
DR GeneID; 855887; -.
DR KEGG; sce:YPL214C; -.
DR SGD; S000006135; THI6.
DR VEuPathDB; FungiDB:YPL214C; -.
DR eggNOG; ENOG502QS2M; Eukaryota.
DR HOGENOM; CLU_019943_1_1_1; -.
DR InParanoid; P41835; -.
DR OMA; HQNFGAN; -.
DR BioCyc; MetaCyc:YPL214C-MON; -.
DR BioCyc; YEAST:YPL214C-MON; -.
DR UniPathway; UPA00060; UER00139.
DR UniPathway; UPA00060; UER00141.
DR PRO; PR:P41835; -.
DR Proteomes; UP000002311; Chromosome XVI.
DR RNAct; P41835; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0005829; C:cytosol; IDA:SGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004417; F:hydroxyethylthiazole kinase activity; IMP:SGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004789; F:thiamine-phosphate diphosphorylase activity; IMP:SGD.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0009228; P:thiamine biosynthetic process; IMP:SGD.
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_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 3: Inferred from homology;
KW ATP-binding; Kinase; Magnesium; Metal-binding; Multifunctional enzyme;
KW Nucleotide-binding; Reference proteome; Thiamine biosynthesis; Transferase.
FT CHAIN 1..540
FT /note="Thiamine biosynthetic bifunctional enzyme"
FT /id="PRO_0000157090"
FT REGION 1..238
FT /note="Thiamine-phosphate synthase"
FT REGION 239..540
FT /note="Hydroxyethylthiazole kinase"
FT ACT_SITE 465
FT /note="Proton acceptor; for hydroxyethylthiazole kinase
FT activity"
FT /evidence="ECO:0000250"
FT BINDING 43..47
FT /ligand="4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine"
FT /ligand_id="ChEBI:CHEBI:57841"
FT /evidence="ECO:0000250"
FT BINDING 75
FT /ligand="4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine"
FT /ligand_id="ChEBI:CHEBI:57841"
FT /evidence="ECO:0000250"
FT BINDING 76
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 95
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 114
FT /ligand="4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine"
FT /ligand_id="ChEBI:CHEBI:57841"
FT /evidence="ECO:0000250"
FT BINDING 143..145
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 146
FT /ligand="4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine"
FT /ligand_id="ChEBI:CHEBI:57841"
FT /evidence="ECO:0000250"
FT BINDING 181
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 209..210
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 290
FT /ligand="5-(2-hydroxyethyl)-4-methylthiazole"
FT /ligand_id="ChEBI:CHEBI:17957"
FT /evidence="ECO:0000250"
FT BINDING 365
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 415
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 462
FT /ligand="5-(2-hydroxyethyl)-4-methylthiazole"
FT /ligand_id="ChEBI:CHEBI:17957"
FT /evidence="ECO:0000250"
FT VARIANT 370
FT /note="E -> K (in THI6-3; possesses TMP-PPASE activity
FT only)"
FT VARIANT 476
FT /note="G -> D (in THI6-2; both enzyme activities greatly
FT decreased)"
FT VARIANT 510
FT /note="G -> D (in THI6-1; both enzyme activities greatly
FT decreased)"
SQ SEQUENCE 540 AA; 58059 MW; F34FA1E0B76E3930 CRC64;
MVFTKEEVDY SLYLVTDSTM LPPGTTLCSQ VEAGLKNGVT LVQIREKDIE TKNFVAEALE
VQKICKKYNV PLIINDRIDV AMAIDADGVH VGQDDMPIPM VRKLLGPSKI LGWSVGKPSE
VETLAKWGPD MVDYIGVGTL FPTSTKKNPK KSPMGPQGAI AILDALEEFK ATWCRTVGIG
GLHPDNIQRV LCQCVASNGK RSLDGISLVS DIMAAPDACA ATKRLRGLLD ATRYQFVECE
LNNTFPTTTS IQNVISQVSN NRPLVQHITN KVHQNFGANV TLALGSSPIM SEIESEVSEL
ARIPNASLLL NTGSVAPIEM LKAAINAYNE VNRPITFDPV GYSATETRLC LNNTLLTYGQ
FACIKGNCSE ILSLAKLNNH KMKGVDSSSG KTNIDTLVRA TQIVAFQYRT VAVCTGEFDC
VADGTFGGEY KLSSGTEGIT AEDLPCVIIE DGPIPIMGDI TASGCSLGST IASFIGGLDS
TGKLFDAVVG AVLLYKSAGK LASTRCQGSG SFHVELIDAL YQLFHENKPE KWSASLKKFK
