THIC_BACSU
ID THIC_BACSU Reviewed; 590 AA.
AC P45740; P71090;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 16-JUN-2009, sequence version 3.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Phosphomethylpyrimidine synthase {ECO:0000255|HAMAP-Rule:MF_00089};
DE EC=4.1.99.17 {ECO:0000255|HAMAP-Rule:MF_00089};
DE AltName: Full=Hydroxymethylpyrimidine phosphate synthase {ECO:0000255|HAMAP-Rule:MF_00089};
DE Short=HMP-P synthase {ECO:0000255|HAMAP-Rule:MF_00089};
DE Short=HMP-phosphate synthase {ECO:0000255|HAMAP-Rule:MF_00089};
DE Short=HMPP synthase {ECO:0000255|HAMAP-Rule:MF_00089};
DE AltName: Full=Thiamine biosynthesis protein ThiC {ECO:0000255|HAMAP-Rule:MF_00089};
GN Name=thiC {ECO:0000255|HAMAP-Rule:MF_00089}; Synonyms=thiA;
GN OrderedLocusNames=BSU08790;
OS Bacillus subtilis (strain 168).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus.
OX NCBI_TaxID=224308;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, INDUCTION, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=168;
RX PubMed=9370266; DOI=10.1016/s0378-1119(97)00295-3;
RA Zhang Y., Begley T.P.;
RT "Cloning, sequencing and regulation of thiA, a thiamin biosynthesis gene
RT from Bacillus subtilis.";
RL Gene 198:73-82(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=168;
RX PubMed=9202460; DOI=10.1099/00221287-143-6-1855;
RA Cummings N.J., Connerton I.F.;
RT "The Bacillus subtilis 168 chromosome from sspE to katA.";
RL Microbiology 143:1855-1859(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=168;
RX PubMed=9384377; DOI=10.1038/36786;
RA Kunst F., Ogasawara N., Moszer I., Albertini A.M., Alloni G., Azevedo V.,
RA Bertero M.G., Bessieres P., Bolotin A., Borchert S., Borriss R.,
RA Boursier L., Brans A., Braun M., Brignell S.C., Bron S., Brouillet S.,
RA Bruschi C.V., Caldwell B., Capuano V., Carter N.M., Choi S.-K.,
RA Codani J.-J., Connerton I.F., Cummings N.J., Daniel R.A., Denizot F.,
RA Devine K.M., Duesterhoeft A., Ehrlich S.D., Emmerson P.T., Entian K.-D.,
RA Errington J., Fabret C., Ferrari E., Foulger D., Fritz C., Fujita M.,
RA Fujita Y., Fuma S., Galizzi A., Galleron N., Ghim S.-Y., Glaser P.,
RA Goffeau A., Golightly E.J., Grandi G., Guiseppi G., Guy B.J., Haga K.,
RA Haiech J., Harwood C.R., Henaut A., Hilbert H., Holsappel S., Hosono S.,
RA Hullo M.-F., Itaya M., Jones L.-M., Joris B., Karamata D., Kasahara Y.,
RA Klaerr-Blanchard M., Klein C., Kobayashi Y., Koetter P., Koningstein G.,
RA Krogh S., Kumano M., Kurita K., Lapidus A., Lardinois S., Lauber J.,
RA Lazarevic V., Lee S.-M., Levine A., Liu H., Masuda S., Mauel C.,
RA Medigue C., Medina N., Mellado R.P., Mizuno M., Moestl D., Nakai S.,
RA Noback M., Noone D., O'Reilly M., Ogawa K., Ogiwara A., Oudega B.,
RA Park S.-H., Parro V., Pohl T.M., Portetelle D., Porwollik S.,
RA Prescott A.M., Presecan E., Pujic P., Purnelle B., Rapoport G., Rey M.,
RA Reynolds S., Rieger M., Rivolta C., Rocha E., Roche B., Rose M., Sadaie Y.,
RA Sato T., Scanlan E., Schleich S., Schroeter R., Scoffone F., Sekiguchi J.,
RA Sekowska A., Seror S.J., Serror P., Shin B.-S., Soldo B., Sorokin A.,
RA Tacconi E., Takagi T., Takahashi H., Takemaru K., Takeuchi M.,
RA Tamakoshi A., Tanaka T., Terpstra P., Tognoni A., Tosato V., Uchiyama S.,
RA Vandenbol M., Vannier F., Vassarotti A., Viari A., Wambutt R., Wedler E.,
RA Wedler H., Weitzenegger T., Winters P., Wipat A., Yamamoto H., Yamane K.,
RA Yasumoto K., Yata K., Yoshida K., Yoshikawa H.-F., Zumstein E.,
RA Yoshikawa H., Danchin A.;
RT "The complete genome sequence of the Gram-positive bacterium Bacillus
RT subtilis.";
RL Nature 390:249-256(1997).
RN [4]
RP SEQUENCE REVISION TO 84.
RX PubMed=19383706; DOI=10.1099/mic.0.027839-0;
RA Barbe V., Cruveiller S., Kunst F., Lenoble P., Meurice G., Sekowska A.,
RA Vallenet D., Wang T., Moszer I., Medigue C., Danchin A.;
RT "From a consortium sequence to a unified sequence: the Bacillus subtilis
RT 168 reference genome a decade later.";
RL Microbiology 155:1758-1775(2009).
RN [5]
RP FUNCTION IN THIAMINE METABOLISM.
RX PubMed=15292217; DOI=10.1074/jbc.m404284200;
RA Lawhorn B.G., Gerdes S.Y., Begley T.P.;
RT "A genetic screen for the identification of thiamin metabolic genes.";
RL J. Biol. Chem. 279:43555-43559(2004).
CC -!- FUNCTION: Catalyzes the synthesis of the hydroxymethylpyrimidine
CC phosphate (HMP-P) moiety of thiamine from aminoimidazole ribotide (AIR)
CC in a radical S-adenosyl-L-methionine (SAM)-dependent reaction.
CC {ECO:0000305|PubMed:15292217, ECO:0000305|PubMed:9370266}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-amino-1-(5-phospho-beta-D-ribosyl)imidazole + S-adenosyl-L-
CC methionine = 4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine + 5'-
CC deoxyadenosine + CO + formate + 3 H(+) + L-methionine;
CC Xref=Rhea:RHEA:24840, ChEBI:CHEBI:15378, ChEBI:CHEBI:15740,
CC ChEBI:CHEBI:17245, ChEBI:CHEBI:17319, ChEBI:CHEBI:57844,
CC ChEBI:CHEBI:58354, ChEBI:CHEBI:59789, ChEBI:CHEBI:137981;
CC EC=4.1.99.17; Evidence={ECO:0000255|HAMAP-Rule:MF_00089};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00089};
CC Note=Binds 1 [4Fe-4S] cluster per subunit. The cluster is coordinated
CC with 3 cysteines and an exchangeable S-adenosyl-L-methionine.
CC {ECO:0000255|HAMAP-Rule:MF_00089};
CC -!- PATHWAY: Cofactor biosynthesis; thiamine diphosphate biosynthesis.
CC {ECO:0000255|HAMAP-Rule:MF_00089}.
CC -!- INDUCTION: Repressed by thiamine and 2-methyl-4-amino-5-
CC hydroxymethylpyrimidine. {ECO:0000269|PubMed:9370266}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene do not grow on minimal
CC medium or on 4-methyl-5-(2-hydroxyethyl) thiazole, a thiamine precursor
CC molecule. They do not synthesize 2-methyl-4-amino-5-
CC hydroxymethylpyrimidine. {ECO:0000269|PubMed:9370266}.
CC -!- SIMILARITY: Belongs to the ThiC family. {ECO:0000255|HAMAP-
CC Rule:MF_00089}.
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DR EMBL; U26178; AAA68243.1; -; Genomic_DNA.
DR EMBL; Z82044; CAB04805.1; -; Genomic_DNA.
DR EMBL; AL009126; CAB12707.2; -; Genomic_DNA.
DR PIR; D69722; D69722.
DR RefSeq; NP_388759.2; NC_000964.3.
DR RefSeq; WP_003233473.1; NZ_JNCM01000035.1.
DR AlphaFoldDB; P45740; -.
DR SMR; P45740; -.
DR STRING; 224308.BSU08790; -.
DR PaxDb; P45740; -.
DR PRIDE; P45740; -.
DR EnsemblBacteria; CAB12707; CAB12707; BSU_08790.
DR GeneID; 939745; -.
DR KEGG; bsu:BSU08790; -.
DR PATRIC; fig|224308.179.peg.949; -.
DR eggNOG; COG0422; Bacteria.
DR InParanoid; P45740; -.
DR OMA; TWELFRD; -.
DR PhylomeDB; P45740; -.
DR BioCyc; BSUB:BSU08790-MON; -.
DR BioCyc; MetaCyc:BSU08790-MON; -.
DR UniPathway; UPA00060; -.
DR Proteomes; UP000001570; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0016830; F:carbon-carbon lyase activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0009228; P:thiamine biosynthetic process; IBA:GO_Central.
DR GO; GO:0009229; P:thiamine diphosphate biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.20.20.540; -; 1.
DR HAMAP; MF_00089; ThiC; 1.
DR InterPro; IPR037509; ThiC.
DR InterPro; IPR025747; ThiC-associated_dom.
DR InterPro; IPR038521; ThiC/Bza_core_dom.
DR InterPro; IPR002817; ThiC/BzaA/B.
DR PANTHER; PTHR30557; PTHR30557; 1.
DR Pfam; PF13667; ThiC-associated; 1.
DR Pfam; PF01964; ThiC_Rad_SAM; 1.
DR SFLD; SFLDF00407; phosphomethylpyrimidine_syntha; 1.
DR TIGRFAMs; TIGR00190; thiC; 1.
PE 1: Evidence at protein level;
KW 4Fe-4S; Iron; Iron-sulfur; Lyase; Metal-binding; Reference proteome;
KW S-adenosyl-L-methionine; Thiamine biosynthesis; Zinc.
FT CHAIN 1..590
FT /note="Phosphomethylpyrimidine synthase"
FT /id="PRO_0000152785"
FT BINDING 197
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00089"
FT BINDING 226
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00089"
FT BINDING 255
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00089"
FT BINDING 291
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00089"
FT BINDING 311..313
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00089"
FT BINDING 352..355
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00089"
FT BINDING 391
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00089"
FT BINDING 395
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00089"
FT BINDING 418
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00089"
FT BINDING 459
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00089"
FT BINDING 539
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00089"
FT BINDING 542
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00089"
FT BINDING 547
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00089"
FT CONFLICT 84
FT /note="K -> I (in Ref. 1; AAA68243 and 2; CAB04805)"
FT /evidence="ECO:0000305"
FT CONFLICT 140
FT /note="K -> Q (in Ref. 1; AAA68243)"
FT /evidence="ECO:0000305"
FT CONFLICT 170..174
FT /note="AIIPS -> RLFLP (in Ref. 1; AAA68243)"
FT /evidence="ECO:0000305"
FT CONFLICT 334
FT /note="F -> L (in Ref. 1; AAA68243)"
FT /evidence="ECO:0000305"
FT CONFLICT 547
FT /note="C -> G (in Ref. 1; AAA68243)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 590 AA; 65932 MW; E43A62307AA530E2 CRC64;
MQNNSVQQAN ISIMSSFSGS KKVYVEGSSS DIQVPMREIA LSPTTGSFGE EENAPVRVYD
TSGPYTDPEV TINIQEGLKP LRQKWITERG DVEEYEGRAI KPEDNGYKKA KPNVSYPGLK
RKPLRAKAGQ NVTQMHYAKK GIITPEMEFI AIREHVSPEF VRDEVASGRA IIPSNINHPE
SEPMIIGRNF HVKINANIGN SAVTSSIEEE VEKMTWAIRW GADTMMDLST GKDIHTTREW
IIRNCPVPVG TVPIYQALEK VNGVAEDLTW EIYRDTLIEQ AEQGVDYFTI HAGVLLRYVP
LTAKRTTGIV SRGGAIMAQW CLAHHQESFL YTHFEEICEI MKMYDIAFSL GDGLRPGSIA
DANDEAQFAE LETLGELTQI AWKHDVQVMI EGPGHVPMHK IKENVDKQMD ICKEAPFYTL
GPLTTDIAPG YDHITSAIGA AMIGWYGTAM LCYVTPKEHL GLPNRDDVRE GVITYKIAAH
AADLAKGHPG AQIRDDALSK ARFEFRWRDQ FNLSLDPERA LEYHDETLPA EGAKTAHFCS
MCGPKFCSMR ISQDIRDYAK KNDLSEAEAI NKGLKEKAKE FVDTGSNLYQ
