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Protein

Dihydrofolate synthase/folylpolyglutamate synthase

Gene

folC

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Functions in two distinct reactions of the de novo folate biosynthetic pathway. Catalyzes the addition of a glutamate residue to dihydropteroate (7,8-dihydropteroate or H2Pte) to form dihydrofolate (7,8-dihydrofolate monoglutamate or H2Pte-Glu). Also catalyzes successive additions of L-glutamate to tetrahydrofolate or 10-formyltetrahydrofolate or 5,10-methylenetetrahydrofolate, leading to folylpolyglutamate derivatives.3 Publications

Catalytic activityi

ATP + 7,8-dihydropteroate + L-glutamate = ADP + phosphate + 7,8-dihydropteroylglutamate.3 Publications
ATP + tetrahydropteroyl-(gamma-Glu)(n) + L-glutamate = ADP + phosphate + tetrahydropteroyl-(gamma-Glu)(n+1).1 Publication
ATP + 10-formyl-tetrahydropteroyl-(gamma-Glu)(n) + L-glutamate = ADP + phosphate + 10-formyl-tetrahydropteroyl-(gamma-Glu)(n+1).2 Publications
ATP + 5,10-methylene-tetrahydropteroyl-(gamma-Glu)(n) + L-glutamate = ADP + phosphate + 5,10-methylene-tetrahydropteroyl-(gamma-Glu)(n+1).1 Publication

Cofactori

Mg2+1 PublicationNote: Binds 2 Mg2+ ions per subunit.1 Publication

Kineticsi

kcat is 25 min(-1) with 7,8-dihydropteroate as substrate (at 30 degrees Celsius).1 Publication
  1. KM=0.6 µM for 7,8-dihydropteroate1 Publication
  2. KM=6.9 µM for ATP (in the assay for DHFS activity)1 Publication
  3. KM=3.9 mM for glutamate (in the assay for DHFS activity)1 Publication
  4. KM=0.6 µM for (6RS)-10-formyl-tetrahydropteroyl-gamma-Glu1 Publication
  5. KM=66.5 µM for ATP (in the assay for FPGS activity)1 Publication
  6. KM=333 µM for glutamate (in the assay for FPGS activity)1 Publication
  7. KM=0.9 µM for 7,8-dihydropteroate1 Publication
  8. KM=10 µM for ATP (in the assay for DHFS activity)1 Publication
  9. KM=2.8 mM for glutamate (in the assay for DHFS activity)1 Publication
  10. KM=17 µM for 10-formyl-tetrahydropteroyl-gamma-Glu1 Publication
  11. KM=54 µM for ATP (in the assay for FPGS activity)1 Publication
  12. KM=300 µM for glutamate (in the assay for FPGS activity)1 Publication
  13. KM=6.3 µM for 7,8-dihydropteroate1 Publication
  14. KM=50 µM for 5,10-methylenetetrahydrofolate1 Publication
  15. KM=50 µM for tetrahydrofolate1 Publication
  16. KM=1.4 µM for tetrahydrofolate diglutamate1 Publication
  1. Vmax=1.1 µmol/h/mg enzyme for DHFS activity1 Publication
  2. Vmax=4.1 µmol/h/mg enzyme for FPGS activity with 10-formyl-tetrahydropteroyl-gamma-Glu as substrate1 Publication
  3. Vmax=415 µmol/h/mg enzyme for FPGS activity with tetrahydrofolate as substrate1 Publication
  4. Vmax=380 µmol/h/mg enzyme for FPGS activity with tetrahydrofolate diglutamate as substrate1 Publication
  5. Vmax=13 µmol/h/mg enzyme for DHFS activity1 Publication

Pathwayi: tetrahydrofolate biosynthesis

This protein is involved in step 2 of the subpathway that synthesizes 7,8-dihydrofolate from 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine diphosphate and 4-aminobenzoate.1 Publication
Proteins known to be involved in the 2 steps of the subpathway in this organism are:
  1. Dihydropteroate synthase (folP)
  2. Dihydrofolate synthase/folylpolyglutamate synthase (folC)
This subpathway is part of the pathway tetrahydrofolate biosynthesis, which is itself part of Cofactor biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes 7,8-dihydrofolate from 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine diphosphate and 4-aminobenzoate, the pathway tetrahydrofolate biosynthesis and in Cofactor biosynthesis.

Pathwayi: tetrahydrofolylpolyglutamate biosynthesis

This protein is involved in the pathway tetrahydrofolylpolyglutamate biosynthesis, which is part of Cofactor biosynthesis.1 Publication
View all proteins of this organism that are known to be involved in the pathway tetrahydrofolylpolyglutamate biosynthesis and in Cofactor biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi83Magnesium 11 Publication1
Metal bindingi146Magnesium 11 Publication1
Metal bindingi173Magnesium 21 Publication1
Binding sitei257ATPCombined sources1 Publication1
Binding sitei289ATPCombined sources1 Publication1
Binding sitei302ATPCombined sources1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi59 – 62ATPCombined sources1 Publication4

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • dihydrofolate synthase activity Source: EcoCyc
  • metal ion binding Source: UniProtKB-KW
  • tetrahydrofolylpolyglutamate synthase activity Source: EcoCyc

GO - Biological processi

Keywordsi

Molecular functionLigase
Biological processFolate biosynthesis, One-carbon metabolism
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciEcoCyc:FOLC-MONOMER.
MetaCyc:FOLC-MONOMER.
BRENDAi6.3.2.17. 2026.
UniPathwayiUPA00077; UER00157.
UPA00850.

Names & Taxonomyi

Protein namesi
Recommended name:
Dihydrofolate synthase/folylpolyglutamate synthaseCurated (EC:6.3.2.123 Publications, EC:6.3.2.171 Publication)
Short name:
DHFS / FPGS1 Publication
Alternative name(s):
Folylpoly-gamma-glutamate synthetase-dihydrofolate synthetase1 Publication
Folylpolyglutamate synthetase1 Publication
Tetrahydrofolylpolyglutamate synthase
Gene namesi
Name:folC1 Publication
Synonyms:dedC
Ordered Locus Names:b2315, JW2312
OrganismiEscherichia coli (strain K12)
Taxonomic identifieri83333 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeEscherichia
Proteomesi
  • UP000000318 Componenti: Chromosome
  • UP000000625 Componenti: Chromosome

Organism-specific databases

EcoGeneiEG10327. folC.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: EcoCyc

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi122T → H or W: Causes large decrease in affinity for both THF and DHP. 1 Publication1
Mutagenesisi154D → A: Severely impairs activity with THF as substrate, even more so than with DHP. Both substrates show a reduced affinity, but the catalytic rate with THF is 23-fold lower than wild-type, whereas that with DHP is 2.5-fold lower. The catalytic rate with THF diglutamate is 10-fold higher than with monoglutamate and close to that of the wild-type enzyme. 1 Publication1
Mutagenesisi155A → H: Causes large decrease in affinity for both THF and DHP. 1 Publication1

Chemistry databases

DrugBankiDB02437. (5r)-5-Amino-6-Hydroxyhexylcarbamic Acid.
DB03830. Phosphorylated Dihydropteroate.
DB01015. Sulfamethoxazole.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001683031 – 422Dihydrofolate synthase/folylpolyglutamate synthaseAdd BLAST422

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei188N6-carboxylysine1 Publication1

Proteomic databases

PaxDbiP08192.
PRIDEiP08192.

Interactioni

Subunit structurei

Monomer.1 Publication

Protein-protein interaction databases

BioGridi4261362. 387 interactors.
DIPiDIP-9674N.
IntActiP08192. 9 interactors.
MINTiMINT-1301447.
STRINGi511145.b2315.

Structurei

Secondary structure

1422
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi13 – 20Combined sources8
Beta strandi23 – 27Combined sources5
Helixi33 – 42Combined sources10
Beta strandi48 – 55Combined sources8
Helixi60 – 73Combined sources14
Beta strandi78 – 81Combined sources4
Helixi89 – 92Combined sources4
Beta strandi93 – 95Combined sources3
Helixi102 – 115Combined sources14
Turni116 – 118Combined sources3
Helixi123 – 138Combined sources16
Beta strandi141 – 146Combined sources6
Beta strandi148 – 151Combined sources4
Helixi155 – 158Combined sources4
Beta strandi162 – 166Combined sources5
Helixi174 – 177Combined sources4
Helixi181 – 188Combined sources8
Helixi189 – 191Combined sources3
Beta strandi196 – 200Combined sources5
Helixi207 – 216Combined sources10
Beta strandi219 – 223Combined sources5
Turni224 – 226Combined sources3
Beta strandi227 – 231Combined sources5
Beta strandi236 – 240Combined sources5
Beta strandi243 – 248Combined sources6
Helixi255 – 268Combined sources14
Helixi274 – 283Combined sources10
Beta strandi289 – 294Combined sources6
Turni295 – 297Combined sources3
Beta strandi298 – 302Combined sources5
Helixi307 – 319Combined sources13
Beta strandi326 – 330Combined sources5
Helixi338 – 346Combined sources9
Beta strandi350 – 354Combined sources5
Beta strandi359 – 362Combined sources4
Helixi365 – 372Combined sources8
Helixi381 – 391Combined sources11
Beta strandi397 – 403Combined sources7
Helixi404 – 417Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1W78X-ray1.82A1-422[»]
1W7KX-ray2.10A1-422[»]
ProteinModelPortaliP08192.
SMRiP08192.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP08192.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni29 – 317,8-dihydropteroate bindingCombined sources1 Publication3
Regioni122 – 1257,8-dihydropteroate bindingCombined sources1 Publication4
Regioni153 – 1557,8-dihydropteroate bindingCombined sources1 Publication3

Domaini

The N-terminal domain alone (residues 1-287) is sufficient to bind both tetrahydrofolate and dihydropteroate with the same affinity as the intact enzyme, but is not able to bind ATP and has no enzymatic activity.1 Publication

Sequence similaritiesi

Belongs to the folylpolyglutamate synthase family.Curated

Phylogenomic databases

eggNOGiENOG4105DPM. Bacteria.
COG0285. LUCA.
HOGENOMiHOG000019982.
InParanoidiP08192.
KOiK11754.
OMAiFHALENI.
PhylomeDBiP08192.

Family and domain databases

Gene3Di3.40.1190.10. 1 hit.
3.90.190.20. 1 hit.
InterProiView protein in InterPro
IPR001645. Folylpolyglutamate_synth.
IPR018109. Folylpolyglutamate_synth_CS.
IPR004101. Mur_ligase_C.
IPR013221. Mur_ligase_cen.
PANTHERiPTHR11136. PTHR11136. 1 hit.
PfamiView protein in Pfam
PF02875. Mur_ligase_C. 1 hit.
PF08245. Mur_ligase_M. 1 hit.
PIRSFiPIRSF001563. Folylpolyglu_synth. 1 hit.
SUPFAMiSSF53244. SSF53244. 1 hit.
SSF53623. SSF53623. 1 hit.
TIGRFAMsiTIGR01499. folC. 1 hit.
PROSITEiView protein in PROSITE
PS01011. FOLYLPOLYGLU_SYNT_1. 1 hit.
PS01012. FOLYLPOLYGLU_SYNT_2. 1 hit.

Sequencei

Sequence statusi: Complete.

P08192-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MIIKRTPQAA SPLASWLSYL ENLHSKTIDL GLERVSLVAA RLGVLKPAPF
60 70 80 90 100
VFTVAGTNGK GTTCRTLESI LMAAGYKVGV YSSPHLVRYT ERVRVQGQEL
110 120 130 140 150
PESAHTASFA EIESARGDIS LTYFEYGTLS ALWLFKQAQL DVVILEVGLG
160 170 180 190 200
GRLDATNIVD ADVAVVTSIA LDHTDWLGPD RESIGREKAG IFRSEKPAIV
210 220 230 240 250
GEPEMPSTIA DVAQEKGALL QRRGVEWNYS VTDHDWAFSD AHGTLENLPL
260 270 280 290 300
PLVPQPNAAT ALAALRASGL EVSENAIRDG IASAILPGRF QIVSESPRVI
310 320 330 340 350
FDVAHNPHAA EYLTGRMKAL PKNGRVLAVI GMLHDKDIAG TLAWLKSVVD
360 370 380 390 400
DWYCAPLEGP RGATAEQLLE HLGNGKSFDS VAQAWDAAMA DAKAEDTVLV
410 420
CGSFHTVAHV MEVIDARRSG GK
Length:422
Mass (Da):45,406
Last modified:November 1, 1997 - v2
Checksum:i0C0F33D3CFB77705
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti326V → M in AAA23808 (PubMed:3040739).Curated1
Sequence conflicti326V → M in AAA23802 (PubMed:3040739).Curated1
Sequence conflicti328A → AA in AAA23966 (PubMed:3040734).Curated1
Sequence conflicti391 – 392DA → EP in AAA23966 (PubMed:3040734).Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M32445 Genomic DNA. Translation: AAA23808.1.
J02808 Genomic DNA. Translation: AAA23802.1.
M68934 Genomic DNA. Translation: AAA23966.1.
U00096 Genomic DNA. Translation: AAC75375.1.
AP009048 Genomic DNA. Translation: BAA16164.1.
PIRiA65004. SYECFG.
RefSeqiNP_416818.1. NC_000913.3.
WP_000584546.1. NZ_LN832404.1.

Genome annotation databases

EnsemblBacteriaiAAC75375; AAC75375; b2315.
BAA16164; BAA16164; BAA16164.
GeneIDi945451.
KEGGiecj:JW2312.
eco:b2315.
PATRICi32120001. VBIEscCol129921_2410.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M32445 Genomic DNA. Translation: AAA23808.1.
J02808 Genomic DNA. Translation: AAA23802.1.
M68934 Genomic DNA. Translation: AAA23966.1.
U00096 Genomic DNA. Translation: AAC75375.1.
AP009048 Genomic DNA. Translation: BAA16164.1.
PIRiA65004. SYECFG.
RefSeqiNP_416818.1. NC_000913.3.
WP_000584546.1. NZ_LN832404.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1W78X-ray1.82A1-422[»]
1W7KX-ray2.10A1-422[»]
ProteinModelPortaliP08192.
SMRiP08192.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi4261362. 387 interactors.
DIPiDIP-9674N.
IntActiP08192. 9 interactors.
MINTiMINT-1301447.
STRINGi511145.b2315.

Chemistry databases

DrugBankiDB02437. (5r)-5-Amino-6-Hydroxyhexylcarbamic Acid.
DB03830. Phosphorylated Dihydropteroate.
DB01015. Sulfamethoxazole.

Proteomic databases

PaxDbiP08192.
PRIDEiP08192.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAC75375; AAC75375; b2315.
BAA16164; BAA16164; BAA16164.
GeneIDi945451.
KEGGiecj:JW2312.
eco:b2315.
PATRICi32120001. VBIEscCol129921_2410.

Organism-specific databases

EchoBASEiEB0323.
EcoGeneiEG10327. folC.

Phylogenomic databases

eggNOGiENOG4105DPM. Bacteria.
COG0285. LUCA.
HOGENOMiHOG000019982.
InParanoidiP08192.
KOiK11754.
OMAiFHALENI.
PhylomeDBiP08192.

Enzyme and pathway databases

UniPathwayiUPA00077; UER00157.
UPA00850.
BioCyciEcoCyc:FOLC-MONOMER.
MetaCyc:FOLC-MONOMER.
BRENDAi6.3.2.17. 2026.

Miscellaneous databases

EvolutionaryTraceiP08192.
PROiP08192.

Family and domain databases

Gene3Di3.40.1190.10. 1 hit.
3.90.190.20. 1 hit.
InterProiView protein in InterPro
IPR001645. Folylpolyglutamate_synth.
IPR018109. Folylpolyglutamate_synth_CS.
IPR004101. Mur_ligase_C.
IPR013221. Mur_ligase_cen.
PANTHERiPTHR11136. PTHR11136. 1 hit.
PfamiView protein in Pfam
PF02875. Mur_ligase_C. 1 hit.
PF08245. Mur_ligase_M. 1 hit.
PIRSFiPIRSF001563. Folylpolyglu_synth. 1 hit.
SUPFAMiSSF53244. SSF53244. 1 hit.
SSF53623. SSF53623. 1 hit.
TIGRFAMsiTIGR01499. folC. 1 hit.
PROSITEiView protein in PROSITE
PS01011. FOLYLPOLYGLU_SYNT_1. 1 hit.
PS01012. FOLYLPOLYGLU_SYNT_2. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiFOLC_ECOLI
AccessioniPrimary (citable) accession number: P08192
Secondary accession number(s): P78237
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: November 1, 1997
Last modified: March 15, 2017
This is version 152 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

Mutant studies have shown that dihydrofolate synthase and folylpolyglutamate synthetase activities are catalyzed by a single catalytic site.2 Publications

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Escherichia coli
    Escherichia coli (strain K12): entries and cross-references to EcoGene
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.