FOLC_BACSU
ID FOLC_BACSU Reviewed; 430 AA.
AC Q05865;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1994, sequence version 2.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Dihydrofolate synthase/folylpolyglutamate synthase;
DE Short=DHFS / FPGS;
DE EC=6.3.2.12;
DE EC=6.3.2.17;
DE AltName: Full=Folylpoly-gamma-glutamate synthetase-dihydrofolate synthetase;
DE AltName: Full=Folylpolyglutamate synthetase;
DE AltName: Full=Tetrahydrofolylpolyglutamate synthase;
GN Name=folC; OrderedLocusNames=BSU28080;
OS Bacillus subtilis (strain 168).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus.
OX NCBI_TaxID=224308;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=168 / PY79;
RX PubMed=8419299; DOI=10.1128/jb.175.2.528-540.1993;
RA Margolis P.S., Driks A., Losick R.;
RT "Sporulation gene spoIIB from Bacillus subtilis.";
RL J. Bacteriol. 175:528-540(1993).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 294-429.
RX PubMed=2553669; DOI=10.1128/jb.171.11.6043-6051.1989;
RA Mohan S., Aghion J., Guillen N., Dubnau D.A.;
RT "Molecular cloning and characterization of comC, a late competence gene of
RT Bacillus subtilis.";
RL J. Bacteriol. 171:6043-6051(1989).
CC -!- FUNCTION: Functions in two distinct reactions of the de novo folate
CC biosynthetic pathway. Catalyzes the addition of a glutamate residue to
CC dihydropteroate (7,8-dihydropteroate or H2Pte) to form dihydrofolate
CC (7,8-dihydrofolate monoglutamate or H2Pte-Glu). Also catalyzes
CC successive additions of L-glutamate to tetrahydrofolate, leading to
CC folylpolyglutamate derivatives. {ECO:0000250|UniProtKB:P08192}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7,8-dihydropteroate + ATP + L-glutamate = 7,8-dihydrofolate +
CC ADP + H(+) + phosphate; Xref=Rhea:RHEA:23584, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17839, ChEBI:CHEBI:29985, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57451, ChEBI:CHEBI:456216;
CC EC=6.3.2.12; Evidence={ECO:0000250|UniProtKB:P08192};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-5,6,7,8-tetrahydrofolyl-(gamma-L-Glu)(n) + ATP + L-
CC glutamate = (6S)-5,6,7,8-tetrahydrofolyl-(gamma-L-Glu)(n+1) + ADP +
CC H(+) + phosphate; Xref=Rhea:RHEA:10580, Rhea:RHEA-COMP:14738,
CC Rhea:RHEA-COMP:14740, ChEBI:CHEBI:15378, ChEBI:CHEBI:29985,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:141005,
CC ChEBI:CHEBI:456216; EC=6.3.2.17;
CC Evidence={ECO:0000250|UniProtKB:P08192};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P08192};
CC Note=Binds 2 Mg(2+) ions per subunit. {ECO:0000250|UniProtKB:P08192};
CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 7,8-
CC dihydrofolate from 2-amino-4-hydroxy-6-hydroxymethyl-7,8-
CC dihydropteridine diphosphate and 4-aminobenzoate: step 2/2.
CC {ECO:0000250|UniProtKB:P08192}.
CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolylpolyglutamate
CC biosynthesis. {ECO:0000250|UniProtKB:P08192}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P08192}.
CC -!- SIMILARITY: Belongs to the folylpolyglutamate synthase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA83364.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; L04520; AAB59021.1; -; Genomic_DNA.
DR EMBL; AL009126; CAB14768.1; -; Genomic_DNA.
DR EMBL; M30805; AAA83364.1; ALT_INIT; Genomic_DNA.
DR PIR; B40646; B40646.
DR RefSeq; NP_390686.1; NC_000964.3.
DR RefSeq; WP_003229640.1; NZ_JNCM01000036.1.
DR AlphaFoldDB; Q05865; -.
DR SMR; Q05865; -.
DR STRING; 224308.BSU28080; -.
DR PaxDb; Q05865; -.
DR PRIDE; Q05865; -.
DR EnsemblBacteria; CAB14768; CAB14768; BSU_28080.
DR GeneID; 936327; -.
DR KEGG; bsu:BSU28080; -.
DR PATRIC; fig|224308.179.peg.3050; -.
DR eggNOG; COG0285; Bacteria.
DR InParanoid; Q05865; -.
DR OMA; KCDYAVI; -.
DR PhylomeDB; Q05865; -.
DR BioCyc; BSUB:BSU28080-MON; -.
DR UniPathway; UPA00077; UER00157.
DR UniPathway; UPA00850; -.
DR Proteomes; UP000001570; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008841; F:dihydrofolate synthase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004326; F:tetrahydrofolylpolyglutamate synthase activity; IBA:GO_Central.
DR GO; GO:0046656; P:folic acid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0009396; P:folic acid-containing compound biosynthetic process; IBA:GO_Central.
DR GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.40.1190.10; -; 1.
DR Gene3D; 3.90.190.20; -; 1.
DR InterPro; IPR001645; Folylpolyglutamate_synth.
DR InterPro; IPR018109; Folylpolyglutamate_synth_CS.
DR InterPro; IPR036565; Mur-like_cat_sf.
DR InterPro; IPR004101; Mur_ligase_C.
DR InterPro; IPR036615; Mur_ligase_C_dom_sf.
DR InterPro; IPR013221; Mur_ligase_cen.
DR PANTHER; PTHR11136; PTHR11136; 1.
DR Pfam; PF02875; Mur_ligase_C; 1.
DR Pfam; PF08245; Mur_ligase_M; 1.
DR PIRSF; PIRSF001563; Folylpolyglu_synth; 1.
DR SUPFAM; SSF53244; SSF53244; 1.
DR SUPFAM; SSF53623; SSF53623; 1.
DR TIGRFAMs; TIGR01499; folC; 1.
DR PROSITE; PS01011; FOLYLPOLYGLU_SYNT_1; 1.
DR PROSITE; PS01012; FOLYLPOLYGLU_SYNT_2; 1.
PE 3: Inferred from homology;
KW ATP-binding; Folate biosynthesis; Ligase; Magnesium; Metal-binding;
KW Nucleotide-binding; One-carbon metabolism; Reference proteome.
FT CHAIN 1..430
FT /note="Dihydrofolate synthase/folylpolyglutamate synthase"
FT /id="PRO_0000168299"
FT BINDING 51..54
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 75
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 114..117
FT /ligand="7,8-dihydropteroate"
FT /ligand_id="ChEBI:CHEBI:17839"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 145
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 152..154
FT /ligand="7,8-dihydropteroate"
FT /ligand_id="ChEBI:CHEBI:17839"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 172
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 263
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 302
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT BINDING 315
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P08192"
FT CONFLICT 295
FT /note="V -> M (in Ref. 2; AAA83364)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 430 AA; 48165 MW; 8AD1DF9151D51160 CRC64;
MFTAYQDARS WIHGRLKFGV KPGLGRMKQL MARLGHPEKK IRAFHVAGTN GKGSTVAFIR
SMLQEAGYTV GTFTSPYIIT FNERISVNGI PISDEEWTAL VNQMKPHVEA LDQTEYGQPT
EFEIMTACAF LYFAEFHKVD FVIFETGLGG RFDSTNVVEP LLTVITSIGH DHMNILGNTI
EEIAGEKAGI IKEGIPIVTA VTQPEALQVI RHEAERHAAP FQSLHDACVI FNEEALPAGE
QFSFKTEEKC YEDIRTSLIG THQRQNAALS ILAAEWLNKE NIAHISDEAL RSGLVKAAWP
GRLELVQEHP PVYLDGAHNE EGVEKLAETM KQRFANSRIS VVFSALKDKP YQNMIKRLET
IAHAIHFASF DFPRASLAKD LYDASEISNK SWSEDPDDVI KFIESKKGSN EIVLITGSLY
FISDIRKRLK
