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Protein

Dihydrofolate reductase

Gene

folA

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: -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.

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.

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
  • dihydrofolic acid binding Source: CAFA
  • folic acid binding Source: CAFA
  • methotrexate binding Source: CAFA
  • NADP+ binding Source: CAFA
  • NADPH binding Source: CAFA

GO - Biological processi

Keywordsi

Molecular functionOxidoreductase
Biological processAntibiotic resistance, Methotrexate resistance, One-carbon metabolism, Trimethoprim resistance
LigandNADP

Enzyme and pathway databases

BioCyciEcoCyc:DIHYDROFOLATEREDUCT-MONOMER
MetaCyc:DIHYDROFOLATEREDUCT-MONOMER
BRENDAi1.5.1.3 2026
SABIO-RKiP0ABQ4
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

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
DrugBankiDB07262 1-{[N-(1-IMINO-GUANIDINO-METHYL)]SULFANYLMETHYL}-3-TRIFLUOROMETHYL-BENZENE
DB03461 2'-Monophosphoadenosine 5'-Diphosphoribose
DB02363 2'-Monophosphoadenosine-5'-Diphosphate
DB02718 5-Formyl-6-Hydrofolic Acid
DB02015 Dihydrofolic Acid
DB03904 Urea

PTM / Processingi

Molecule processing

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

Proteomic databases

EPDiP0ABQ4
PaxDbiP0ABQ4
PRIDEiP0ABQ4

2D gel databases

SWISS-2DPAGEiP0ABQ4

Interactioni

Binary interactionsi

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

Protein-protein interaction databases

BioGridi4262199, 297 interactors
DIPiDIP-35824N
IntActiP0ABQ4, 16 interactors
STRINGi316385.ECDH10B_0049

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
Turni20 – 23Combined sources4
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[»]
5UIHX-ray1.65A1-159[»]
5UIIX-ray1.35A2-159[»]
5UIOX-ray1.93A/B/C/D/E1-159[»]
5UIPX-ray1.90A/B2-159[»]
5UJXX-ray1.80A/B1-159[»]
5W3QX-ray1.40A1-159[»]
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

Phylogenomic databases

eggNOGiENOG4108YYV Bacteria
COG0262 LUCA
HOGENOMiHOG000040233
InParanoidiP0ABQ4
KOiK00287
OMAiRDNQLPW
PhylomeDBiP0ABQ4

Family and domain databases

CDDicd00209 DHFR, 1 hit
Gene3Di3.40.430.10, 2 hits
InterProiView protein in InterPro
IPR012259 DHFR
IPR024072 DHFR-like_dom_sf
IPR017925 DHFR_CS
IPR001796 DHFR_dom
PANTHERiPTHR22778:SF16 PTHR22778:SF16, 1 hit
PfamiView protein in Pfam
PF00186 DHFR_1, 1 hit
PIRSFiPIRSF000194 DHFR, 1 hit
SUPFAMiSSF53597 SSF53597, 1 hit
PROSITEiView protein in PROSITE
PS00075 DHFR_1, 1 hit
PS51330 DHFR_2, 1 hit

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
PATRICifig|511145.12.peg.49

Similar proteinsi

Entry informationi

Entry nameiDYR_ECOLI
AccessioniPrimary (citable) accession number: P0ABQ4
Secondary accession number(s): P00379
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: June 20, 2018
This is version 123 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

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

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