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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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei5 – 51Substrate; via carbonyl oxygen1 Publication
Binding sitei7 – 71NADP; via amide nitrogen and carbonyl oxygen1 Publication
Binding sitei27 – 271Substrate1 Publication
Binding sitei52 – 521Substrate1 Publication
Binding sitei57 – 571Substrate1 Publication
Binding sitei76 – 761NADP; via carbonyl oxygen1 Publication
Binding sitei113 – 1131Substrate1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi13 – 197NADP1 Publication
Nucleotide bindingi45 – 462NADP1 Publication
Nucleotide bindingi63 – 642NADP1 Publication
Nucleotide bindingi95 – 1028NADP1 Publication

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 lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi16 – 161M → F or S: Increases catalytic rate about 2-fold. 1 Publication
Mutagenesisi16 – 161M → 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 Publication
Mutagenesisi20 – 201M → I or V: Increases catalytic rate 2-fold. 1 Publication
Mutagenesisi20 – 201M → 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 Publication
Mutagenesisi42 – 421M → V: Increases catalytic rate almost 2-fold. 1 Publication
Mutagenesisi42 – 421M → 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 Publication
Mutagenesisi85 – 851C → 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 Publication
Mutagenesisi92 – 921M → F: No effect. Increases catalytic rate about 7-fold; when associated with N-16; L-20; Y-42; A-85 and S-152. 1 Publication
Mutagenesisi92 – 921M → L: No effect. 1 Publication
Mutagenesisi152 – 1521C → 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 Publication

Chemistry

ChEMBLiCHEMBL2364669.
DrugBankiDB03904. Urea.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 159159Dihydrofolate reductasePRO_0000186387Add
BLAST

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 interactions.
DIPiDIP-35824N.
IntActiP0ABQ4. 16 interactions.
MINTiMINT-1239602.
STRINGi511145.b0048.

Chemistry

BindingDBiP0ABQ4.

Structurei

Secondary structure

1
159
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi2 – 98Combined sources
Helixi10 – 123Combined sources
Beta strandi13 – 164Combined sources
Helixi17 – 193Combined sources
Helixi25 – 3511Combined sources
Beta strandi40 – 434Combined sources
Helixi44 – 507Combined sources
Beta strandi55 – 573Combined sources
Beta strandi59 – 624Combined sources
Beta strandi72 – 776Combined sources
Helixi78 – 858Combined sources
Beta strandi91 – 933Combined sources
Helixi97 – 1037Combined sources
Helixi104 – 1063Combined sources
Beta strandi108 – 1158Combined sources
Beta strandi122 – 1243Combined sources
Helixi130 – 1323Combined sources
Beta strandi133 – 1419Combined sources
Beta strandi147 – 1493Combined sources
Beta strandi151 – 1588Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
6DFRX-ray2.40A1-159[»]
7DFRX-ray2.50A1-159[»]
DisProtiDP00301.
ProteinModelPortaliP0ABQ4.
SMRiP0ABQ4. Positions 1-159.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP0ABQ4.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 158158DHFRPROSITE-ProRule annotationAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti28 – 281L → R in strain: B[RT500] isozyme 2.
Natural varianti30 – 301W → G in strain: 1810.
Natural varianti154 – 1541E → K in strain: B[MB1428].
Natural varianti154 – 1541E → Q in strain: 1810.

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
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[»]
6DFRX-ray2.40A1-159[»]
7DFRX-ray2.50A1-159[»]
DisProtiDP00301.
ProteinModelPortaliP0ABQ4.
SMRiP0ABQ4. Positions 1-159.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Chemistry

BindingDBiP0ABQ4.
ChEMBLiCHEMBL2364669.
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: September 7, 2016
This is version 109 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.