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Protein

Dihydrofolate reductase

Gene

folA

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

Functioni

Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.

Catalytic activityi

5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH.PROSITE-ProRule annotation1 Publication

Pathwayi: tetrahydrofolate biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate.
Proteins known to be involved in this subpathway in this organism are:
  1. Dihydrofolate reductase (folA)
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 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate, the pathway tetrahydrofolate biosynthesis and in Cofactor biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei5Substrate; via carbonyl oxygen1 Publication1
Binding sitei7NADP; via amide nitrogen and carbonyl oxygen1 Publication1
Binding sitei27Substrate1 Publication1
Binding sitei52Substrate1 Publication1
Binding sitei57Substrate1 Publication1
Binding sitei76NADP; via carbonyl oxygen1 Publication1
Binding sitei113Substrate1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi13 – 19NADP1 Publication7
Nucleotide bindingi45 – 46NADP1 Publication2
Nucleotide bindingi63 – 64NADP1 Publication2
Nucleotide bindingi95 – 102NADP1 Publication8

GO - Molecular functioni

  • dihydrofolate reductase activity Source: EcoCyc
  • NADP binding Source: InterPro

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Antibiotic resistance, Methotrexate resistance, One-carbon metabolism, Trimethoprim resistance

Keywords - Ligandi

NADP

Enzyme and pathway databases

BioCyciEcoCyc:DIHYDROFOLATEREDUCT-MONOMER.
ECOL316407:JW0047-MONOMER.
MetaCyc:DIHYDROFOLATEREDUCT-MONOMER.
BRENDAi1.5.1.3. 2026.
SABIO-RKP0ABQ4.
UniPathwayiUPA00077; UER00158.

Names & Taxonomyi

Protein namesi
Recommended name:
Dihydrofolate reductase (EC:1.5.1.3)
Gene namesi
Name:folA
Synonyms:tmrA
Ordered Locus Names:b0048, JW0047
OrganismiEscherichia coli (strain K12)
Taxonomic identifieri83333 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeEscherichia
Proteomesi
  • UP000000318 Componenti: Chromosome
  • UP000000625 Componenti: Chromosome

Organism-specific databases

EcoGeneiEG10326. folA.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: EcoCyc
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi16M → F or S: Increases catalytic rate about 2-fold. 1 Publication1
Mutagenesisi16M → N: Increases catalytic rate about 2-fold. Increases catalytic rate about 7-fold; when associated with L-20; Y-42; F-92; A-85 and S-152. 1 Publication1
Mutagenesisi20M → I or V: Increases catalytic rate 2-fold. 1 Publication1
Mutagenesisi20M → L: Increases catalytic rate 2.5-fold. Increases catalytic rate about 7-fold; when associated with N-16; Y-42; F-92; A-85 and S-152. 1 Publication1
Mutagenesisi42M → V: Increases catalytic rate almost 2-fold. 1 Publication1
Mutagenesisi42M → Y: Increases catalytic rate almost 2-fold. Increases catalytic rate about 7-fold; when associated with N-16; L-20; A-85; F-92 and S-152. 1 Publication1
Mutagenesisi85C → A: Decreases catalytic rate by one third. Increases catalytic rate about 7-fold; when associated with N-16; L-20; Y-42; F-92 and S-152. 1 Publication1
Mutagenesisi92M → F: No effect. Increases catalytic rate about 7-fold; when associated with N-16; L-20; Y-42; A-85 and S-152. 1 Publication1
Mutagenesisi92M → L: No effect. 1 Publication1
Mutagenesisi152C → S: Increases catalytic rate 1.5-fold. Increases catalytic rate about 7-fold; when associated with N-16; L-20; Y-42; A-85 and F-92. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL1809.
DrugBankiDB03904. Urea.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001863871 – 159Dihydrofolate reductaseAdd BLAST159

Proteomic databases

EPDiP0ABQ4.
PaxDbiP0ABQ4.
PRIDEiP0ABQ4.

2D gel databases

SWISS-2DPAGEP0ABQ4.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
flxAP776094EBI-550404,EBI-553024

Protein-protein interaction databases

BioGridi4262199. 282 interactors.
DIPiDIP-35824N.
IntActiP0ABQ4. 16 interactors.
MINTiMINT-1239602.
STRINGi511145.b0048.

Chemistry databases

BindingDBiP0ABQ4.

Structurei

Secondary structure

1159
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi2 – 9Combined sources8
Helixi10 – 12Combined sources3
Beta strandi13 – 16Combined sources4
Helixi17 – 19Combined sources3
Helixi25 – 35Combined sources11
Beta strandi40 – 43Combined sources4
Helixi44 – 50Combined sources7
Beta strandi55 – 57Combined sources3
Beta strandi59 – 62Combined sources4
Beta strandi72 – 77Combined sources6
Helixi78 – 85Combined sources8
Beta strandi91 – 93Combined sources3
Helixi97 – 103Combined sources7
Helixi104 – 106Combined sources3
Beta strandi108 – 115Combined sources8
Beta strandi122 – 124Combined sources3
Helixi130 – 132Combined sources3
Beta strandi133 – 141Combined sources9
Beta strandi147 – 149Combined sources3
Beta strandi151 – 158Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DDRX-ray2.45A/B1-159[»]
1DDSX-ray2.20A/B1-159[»]
1DHIX-ray1.90A/B1-159[»]
1DHJX-ray1.80A/B1-159[»]
1DRAX-ray1.90A/B1-159[»]
1DRBX-ray1.96A/B1-159[»]
1DREX-ray2.60A1-159[»]
1DRHX-ray2.30A1-159[»]
1DYHX-ray1.90A/B1-159[»]
1DYIX-ray1.90A/B1-159[»]
1DYJX-ray1.85A/B1-159[»]
1JOLX-ray1.96A/B1-159[»]
1JOMX-ray1.90A1-159[»]
1RA1X-ray1.90A1-159[»]
1RA2X-ray1.60A1-159[»]
1RA3X-ray1.80A1-159[»]
1RA8X-ray1.80A1-159[»]
1RA9X-ray1.55A1-159[»]
1RB2X-ray2.10A/B1-159[»]
1RB3X-ray2.30A/B1-159[»]
1RC4X-ray1.90A1-159[»]
1RD7X-ray2.60A/B1-159[»]
1RE7X-ray2.60A/B1-159[»]
1RF7X-ray1.80A1-159[»]
1RG7X-ray2.00A1-159[»]
1RH3X-ray2.40A1-159[»]
1RX1X-ray2.00A1-159[»]
1RX2X-ray1.80A1-159[»]
1RX3X-ray2.20A1-159[»]
1RX4X-ray2.20A1-159[»]
1RX5X-ray2.30A1-159[»]
1RX6X-ray2.00A1-159[»]
1RX7X-ray2.30A1-159[»]
1RX8X-ray2.80A1-159[»]
1RX9X-ray1.90A1-159[»]
1TDRX-ray2.50A/B1-159[»]
2ANOX-ray2.68A1-159[»]
2ANQX-ray2.13A1-159[»]
2D0KX-ray1.90A/B2-159[»]
2DRCX-ray1.90A/B1-159[»]
2INQneutron diffraction2.20A/B1-159[»]
3DAUX-ray1.50A1-159[»]
3DRCX-ray1.90A/B1-159[»]
3K74X-ray1.95A1-159[»]
3KFYX-ray2.08A1-159[»]
3OCHX-ray1.79A/B1-159[»]
3QL3X-ray1.80A1-159[»]
3QYLX-ray1.79A1-159[»]
3QYOX-ray2.09A1-159[»]
3R33X-ray2.09A1-159[»]
4DFRX-ray1.70A/B1-159[»]
4EIGX-ray2.50A1-159[»]
4EIZX-ray2.20A/B1-159[»]
4EJ1X-ray1.75A/B1-159[»]
4FHBX-ray2.80A1-159[»]
4GH8X-ray1.85A/B1-158[»]
4I13X-ray1.60A1-159[»]
4I1NX-ray1.89A1-159[»]
4KJJX-ray1.15A1-159[»]
4KJKX-ray1.35A1-159[»]
4KJLX-ray1.38A1-159[»]
4NX6X-ray1.35A1-159[»]
4NX7X-ray1.15A1-159[»]
4PDJOther1.60A1-159[»]
4X5FX-ray1.70A/B1-159[»]
4X5GX-ray1.90A/B1-159[»]
4X5HX-ray1.90A1-159[»]
4X5IX-ray1.80A1-159[»]
4X5JX-ray1.85A1-159[»]
5CC9X-ray1.20A1-159[»]
5CCCX-ray1.50A1-159[»]
5DFRX-ray2.30A1-159[»]
5E8QX-ray1.80A/B1-159[»]
5EAJX-ray1.70A/B1-159[»]
6DFRX-ray2.40A1-159[»]
7DFRX-ray2.50A1-159[»]
DisProtiDP00301.
ProteinModelPortaliP0ABQ4.
SMRiP0ABQ4.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP0ABQ4.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 158DHFRPROSITE-ProRule annotationAdd BLAST158

Sequence similaritiesi

Belongs to the dihydrofolate reductase family.Curated
Contains 1 DHFR (dihydrofolate reductase) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG4108YYV. Bacteria.
COG0262. LUCA.
HOGENOMiHOG000040233.
InParanoidiP0ABQ4.
KOiK00287.
OMAiMCITHVE.
PhylomeDBiP0ABQ4.

Family and domain databases

CDDicd00209. DHFR. 1 hit.
Gene3Di3.40.430.10. 1 hit.
InterProiIPR012259. DHFR.
IPR024072. DHFR-like_dom.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
[Graphical view]
PfamiPF00186. DHFR_1. 1 hit.
[Graphical view]
PIRSFiPIRSF000194. DHFR. 1 hit.
PRINTSiPR00070. DHFR.
SUPFAMiSSF53597. SSF53597. 1 hit.
PROSITEiPS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P0ABQ4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MISLIAALAV DRVIGMENAM PWNLPADLAW FKRNTLNKPV IMGRHTWESI
60 70 80 90 100
GRPLPGRKNI ILSSQPGTDD RVTWVKSVDE AIAACGDVPE IMVIGGGRVY
110 120 130 140 150
EQFLPKAQKL YLTHIDAEVE GDTHFPDYEP DDWESVFSEF HDADAQNSHS

YCFEILERR
Length:159
Mass (Da):17,999
Last modified:July 21, 1986 - v1
Checksum:i6A03CDCD7F5F8562
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti28L → R in strain: B[RT500] isozyme 2. 1
Natural varianti30W → G in strain: 1810. 1
Natural varianti154E → K in strain: B[MB1428]. 1
Natural varianti154E → Q in strain: 1810. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J01609 Genomic DNA. Translation: AAA87976.1.
X05108 Genomic DNA. Translation: CAA28755.1.
U00096 Genomic DNA. Translation: AAC73159.1.
AP009048 Genomic DNA. Translation: BAB96616.1.
PIRiA93704. RDECD.
RefSeqiNP_414590.1. NC_000913.3.
WP_000624375.1. NZ_LN832404.1.

Genome annotation databases

EnsemblBacteriaiAAC73159; AAC73159; b0048.
BAB96616; BAB96616; BAB96616.
GeneIDi944790.
KEGGiecj:JW0047.
eco:b0048.
PATRICi32115195. VBIEscCol129921_0049.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J01609 Genomic DNA. Translation: AAA87976.1.
X05108 Genomic DNA. Translation: CAA28755.1.
U00096 Genomic DNA. Translation: AAC73159.1.
AP009048 Genomic DNA. Translation: BAB96616.1.
PIRiA93704. RDECD.
RefSeqiNP_414590.1. NC_000913.3.
WP_000624375.1. NZ_LN832404.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DDRX-ray2.45A/B1-159[»]
1DDSX-ray2.20A/B1-159[»]
1DHIX-ray1.90A/B1-159[»]
1DHJX-ray1.80A/B1-159[»]
1DRAX-ray1.90A/B1-159[»]
1DRBX-ray1.96A/B1-159[»]
1DREX-ray2.60A1-159[»]
1DRHX-ray2.30A1-159[»]
1DYHX-ray1.90A/B1-159[»]
1DYIX-ray1.90A/B1-159[»]
1DYJX-ray1.85A/B1-159[»]
1JOLX-ray1.96A/B1-159[»]
1JOMX-ray1.90A1-159[»]
1RA1X-ray1.90A1-159[»]
1RA2X-ray1.60A1-159[»]
1RA3X-ray1.80A1-159[»]
1RA8X-ray1.80A1-159[»]
1RA9X-ray1.55A1-159[»]
1RB2X-ray2.10A/B1-159[»]
1RB3X-ray2.30A/B1-159[»]
1RC4X-ray1.90A1-159[»]
1RD7X-ray2.60A/B1-159[»]
1RE7X-ray2.60A/B1-159[»]
1RF7X-ray1.80A1-159[»]
1RG7X-ray2.00A1-159[»]
1RH3X-ray2.40A1-159[»]
1RX1X-ray2.00A1-159[»]
1RX2X-ray1.80A1-159[»]
1RX3X-ray2.20A1-159[»]
1RX4X-ray2.20A1-159[»]
1RX5X-ray2.30A1-159[»]
1RX6X-ray2.00A1-159[»]
1RX7X-ray2.30A1-159[»]
1RX8X-ray2.80A1-159[»]
1RX9X-ray1.90A1-159[»]
1TDRX-ray2.50A/B1-159[»]
2ANOX-ray2.68A1-159[»]
2ANQX-ray2.13A1-159[»]
2D0KX-ray1.90A/B2-159[»]
2DRCX-ray1.90A/B1-159[»]
2INQneutron diffraction2.20A/B1-159[»]
3DAUX-ray1.50A1-159[»]
3DRCX-ray1.90A/B1-159[»]
3K74X-ray1.95A1-159[»]
3KFYX-ray2.08A1-159[»]
3OCHX-ray1.79A/B1-159[»]
3QL3X-ray1.80A1-159[»]
3QYLX-ray1.79A1-159[»]
3QYOX-ray2.09A1-159[»]
3R33X-ray2.09A1-159[»]
4DFRX-ray1.70A/B1-159[»]
4EIGX-ray2.50A1-159[»]
4EIZX-ray2.20A/B1-159[»]
4EJ1X-ray1.75A/B1-159[»]
4FHBX-ray2.80A1-159[»]
4GH8X-ray1.85A/B1-158[»]
4I13X-ray1.60A1-159[»]
4I1NX-ray1.89A1-159[»]
4KJJX-ray1.15A1-159[»]
4KJKX-ray1.35A1-159[»]
4KJLX-ray1.38A1-159[»]
4NX6X-ray1.35A1-159[»]
4NX7X-ray1.15A1-159[»]
4PDJOther1.60A1-159[»]
4X5FX-ray1.70A/B1-159[»]
4X5GX-ray1.90A/B1-159[»]
4X5HX-ray1.90A1-159[»]
4X5IX-ray1.80A1-159[»]
4X5JX-ray1.85A1-159[»]
5CC9X-ray1.20A1-159[»]
5CCCX-ray1.50A1-159[»]
5DFRX-ray2.30A1-159[»]
5E8QX-ray1.80A/B1-159[»]
5EAJX-ray1.70A/B1-159[»]
6DFRX-ray2.40A1-159[»]
7DFRX-ray2.50A1-159[»]
DisProtiDP00301.
ProteinModelPortaliP0ABQ4.
SMRiP0ABQ4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi4262199. 282 interactors.
DIPiDIP-35824N.
IntActiP0ABQ4. 16 interactors.
MINTiMINT-1239602.
STRINGi511145.b0048.

Chemistry databases

BindingDBiP0ABQ4.
ChEMBLiCHEMBL1809.
DrugBankiDB03904. Urea.

2D gel databases

SWISS-2DPAGEP0ABQ4.

Proteomic databases

EPDiP0ABQ4.
PaxDbiP0ABQ4.
PRIDEiP0ABQ4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAC73159; AAC73159; b0048.
BAB96616; BAB96616; BAB96616.
GeneIDi944790.
KEGGiecj:JW0047.
eco:b0048.
PATRICi32115195. VBIEscCol129921_0049.

Organism-specific databases

EchoBASEiEB0322.
EcoGeneiEG10326. folA.

Phylogenomic databases

eggNOGiENOG4108YYV. Bacteria.
COG0262. LUCA.
HOGENOMiHOG000040233.
InParanoidiP0ABQ4.
KOiK00287.
OMAiMCITHVE.
PhylomeDBiP0ABQ4.

Enzyme and pathway databases

UniPathwayiUPA00077; UER00158.
BioCyciEcoCyc:DIHYDROFOLATEREDUCT-MONOMER.
ECOL316407:JW0047-MONOMER.
MetaCyc:DIHYDROFOLATEREDUCT-MONOMER.
BRENDAi1.5.1.3. 2026.
SABIO-RKP0ABQ4.

Miscellaneous databases

EvolutionaryTraceiP0ABQ4.
PROiP0ABQ4.

Family and domain databases

CDDicd00209. DHFR. 1 hit.
Gene3Di3.40.430.10. 1 hit.
InterProiIPR012259. DHFR.
IPR024072. DHFR-like_dom.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
[Graphical view]
PfamiPF00186. DHFR_1. 1 hit.
[Graphical view]
PIRSFiPIRSF000194. DHFR. 1 hit.
PRINTSiPR00070. DHFR.
SUPFAMiSSF53597. SSF53597. 1 hit.
PROSITEiPS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDYR_ECOLI
AccessioniPrimary (citable) accession number: P0ABQ4
Secondary accession number(s): P00379
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: November 30, 2016
This is version 111 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

The strain K12 sequence is shown.
Strain B [RT500] is resistant to 500 micrograms per milliliter of trimethoprim.
Strain B [MB1428] is methotrexate-resistant.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, 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.