THIME_SYMTH
ID THIME_SYMTH Reviewed; 480 AA.
AC Q67T51;
DT 22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Thiamine biosynthesis bifunctional protein ThiM/ThiE;
DE Includes:
DE RecName: Full=Hydroxyethylthiazole kinase;
DE EC=2.7.1.50 {ECO:0000250|UniProtKB:P39593};
DE AltName: Full=4-methyl-5-beta-hydroxyethylthiazole kinase;
DE Short=TH kinase;
DE Short=Thz kinase;
DE Includes:
DE RecName: Full=Thiamine-phosphate synthase;
DE Short=TMP-PPase;
DE Short=TP synthase;
DE Short=TPS;
DE EC=2.5.1.3 {ECO:0000250|UniProtKB:P39594};
DE AltName: Full=Thiamine-phosphate pyrophosphorylase;
DE Short=TMP pyrophosphorylase;
GN Name=thiM/thiE; OrderedLocusNames=STH157;
OS Symbiobacterium thermophilum (strain T / IAM 14863).
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Symbiobacteriaceae;
OC Symbiobacterium.
OX NCBI_TaxID=292459;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=T / IAM 14863;
RX PubMed=15383646; DOI=10.1093/nar/gkh830;
RA Ueda K., Yamashita A., Ishikawa J., Shimada M., Watsuji T., Morimura K.,
RA Ikeda H., Hattori M., Beppu T.;
RT "Genome sequence of Symbiobacterium thermophilum, an uncultivable bacterium
RT that depends on microbial commensalism.";
RL Nucleic Acids Res. 32:4937-4944(2004).
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=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 Evidence={ECO:0000250|UniProtKB:P39593};
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 Evidence={ECO:0000250|UniProtKB:P39594};
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 Evidence={ECO:0000250|UniProtKB:P39594};
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 Evidence={ECO:0000250|UniProtKB:P39594};
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 -!- SIMILARITY: In the N-terminal section; belongs to the Thz kinase
CC family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the thiamine-
CC phosphate synthase family. {ECO:0000305}.
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DR EMBL; AP006840; BAD39142.1; -; Genomic_DNA.
DR AlphaFoldDB; Q67T51; -.
DR SMR; Q67T51; -.
DR STRING; 292459.STH157; -.
DR PRIDE; Q67T51; -.
DR EnsemblBacteria; BAD39142; BAD39142; STH157.
DR KEGG; sth:STH157; -.
DR eggNOG; COG0352; Bacteria.
DR eggNOG; COG2145; Bacteria.
DR HOGENOM; CLU_568500_0_0_9; -.
DR OMA; RRRMFLN; -.
DR UniPathway; UPA00060; UER00139.
DR UniPathway; UPA00060; UER00141.
DR Proteomes; UP000000417; Chromosome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004417; F:hydroxyethylthiazole kinase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004789; F:thiamine-phosphate diphosphorylase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0009228; P:thiamine biosynthetic process; IEA:UniProtKB-UniRule.
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.
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..480
FT /note="Thiamine biosynthesis bifunctional protein
FT ThiM/ThiE"
FT /id="PRO_0000383912"
FT REGION 1..287
FT /note="Hydroxyethylthiazole kinase"
FT REGION 288..480
FT /note="Thiamine-phosphate synthase"
FT BINDING 40
FT /ligand="5-(2-hydroxyethyl)-4-methylthiazole"
FT /ligand_id="ChEBI:CHEBI:17957"
FT /evidence="ECO:0000250"
FT BINDING 116
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 164
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 191
FT /ligand="5-(2-hydroxyethyl)-4-methylthiazole"
FT /ligand_id="ChEBI:CHEBI:17957"
FT /evidence="ECO:0000250"
FT BINDING 303..307
FT /ligand="4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine"
FT /ligand_id="ChEBI:CHEBI:57841"
FT /evidence="ECO:0000250"
FT BINDING 335
FT /ligand="4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine"
FT /ligand_id="ChEBI:CHEBI:57841"
FT /evidence="ECO:0000250"
FT BINDING 336
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 355
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 374
FT /ligand="4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine"
FT /ligand_id="ChEBI:CHEBI:57841"
FT /evidence="ECO:0000250"
FT BINDING 400..402
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 403
FT /ligand="4-amino-2-methyl-5-(diphosphooxymethyl)pyrimidine"
FT /ligand_id="ChEBI:CHEBI:57841"
FT /evidence="ECO:0000250"
FT BINDING 431
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 451..452
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"
SQ SEQUENCE 480 AA; 48683 MW; 0FEC441B02894F29 CRC64;
MSTLPERVRE RRPLVHAITN CVTMEWVARG LLAAGARPVM ARDAAEAPVV AAAADALVLN
LGTWSPGLQQ AMLEAGQVAA RRGIPVVLDP VGAGGTETRT RAALELLERV RVTAVRGNAG
EILALAGRDG LVRGVDGPDG RPGPQTERAA RAVARRFGCL VAVTGATDLV TDGRRTLAVR
AGHPLMSQVP GTGCLATALV AAALAAGTGA GPAGRDRPME DVDVVAEALL WAGWAGEQAA
SAASGPGTFA AAFLDRLALR GPLPPGRIAP PLSERLSLYV LVSGATPPDV LEAVLQAGCR
MIQFREKRLP LPAQLEAAAR VREACRRHGA LLVVNDRVDL ALAVGADGVH LGQEDLPVAA
ARRILGPDAV IGATCETAGE ARAARDAGAD YIGAGPVYVT PSKPDAGEPY GPDVVRRVSE
AADLPVVGIG GIGPGRAAPV IAAGAAGVAV ISAVLGAPDP GAAARAILDE VRRAKGEVSA
