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Protein

Dihydrofolate reductase

Gene

folA

Organism
Lactobacillus casei
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 annotation

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), Dihydrofolate reductase (AAW28_04550), Dihydrofolate reductase (IJ11_0204865)
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
Sitei22May be important for enzyme function1
Binding sitei27Methotrexate1 Publication1
Binding sitei27Substrate1 Publication1
Binding sitei32Methotrexate1 Publication1
Binding sitei32Substrate1 Publication1
Binding sitei58Methotrexate1 Publication1
Binding sitei58Substrate1 Publication1
Binding sitei80NADP; via amide nitrogen1 Publication1
Binding sitei117Substrate1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi6 – 7NADP1 Publication2
Nucleotide bindingi14 – 19NADP1 Publication6
Nucleotide bindingi43 – 46NADP1 Publication4
Nucleotide bindingi63 – 66NADP1 Publication4
Nucleotide bindingi98 – 103NADP1 Publication6

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Antibiotic resistance, Methotrexate resistance, One-carbon metabolism

Keywords - Ligandi

NADP

Enzyme and pathway databases

BRENDAi1.5.1.3. 2854.
SABIO-RKP00381.
UniPathwayiUPA00077; UER00158.

Names & Taxonomyi

Protein namesi
Recommended name:
Dihydrofolate reductase (EC:1.5.1.3)
Gene namesi
Name:folA
Synonyms:dhfR
OrganismiLactobacillus casei
Taxonomic identifieri1582 [NCBI]
Taxonomic lineageiBacteriaFirmicutesBacilliLactobacillalesLactobacillaceaeLactobacillus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2902.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved2 Publications
ChainiPRO_00001863932 – 163Dihydrofolate reductaseAdd BLAST162

Interactioni

Subunit structurei

Monomer.1 Publication

Chemistry databases

BindingDBiP00381.

Structurei

Secondary structure

1163
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi3 – 8Combined sources6
Turni10 – 12Combined sources3
Beta strandi13 – 16Combined sources4
Helixi25 – 33Combined sources9
Turni34 – 37Combined sources4
Beta strandi38 – 43Combined sources6
Helixi44 – 49Combined sources6
Beta strandi50 – 54Combined sources5
Beta strandi58 – 63Combined sources6
Beta strandi67 – 69Combined sources3
Beta strandi74 – 79Combined sources6
Helixi80 – 89Combined sources10
Beta strandi91 – 93Combined sources3
Beta strandi95 – 97Combined sources3
Helixi101 – 106Combined sources6
Helixi108 – 110Combined sources3
Beta strandi113 – 121Combined sources9
Beta strandi126 – 128Combined sources3
Helixi134 – 136Combined sources3
Beta strandi137 – 145Combined sources9
Helixi150 – 152Combined sources3
Beta strandi154 – 161Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AO8NMR-A2-163[»]
1BZFNMR-A2-163[»]
1DISNMR-A2-163[»]
1DIUNMR-A2-163[»]
1LUDNMR-A2-163[»]
2HM9NMR-A2-163[»]
2HQPNMR-A2-163[»]
2L28NMR-A2-163[»]
2LF1NMR-A2-163[»]
3DFRX-ray1.70A2-163[»]
ProteinModelPortaliP00381.
SMRiP00381.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP00381.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 161DHFRPROSITE-ProRule annotationAdd BLAST160

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni5 – 7Substrate binding1 Publication3

Sequence similaritiesi

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

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.

Sequence processingi: The displayed sequence is further processed into a mature form.

P00381-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTAFLWAQDR DGLIGKDGHL PWHLPDDLHY FRAQTVGKIM VVGRRTYESF
60 70 80 90 100
PKRPLPERTN VVLTHQEDYQ AQGAVVVHDV AAVFAYAKQH PDQELVIAGG
110 120 130 140 150
AQIFTAFKDD VDTLLVTRLA GSFEGDTKMI PLNWDDFTKV SSRTVEDTNP
160
ALTHTYEVWQ KKA
Length:163
Mass (Da):18,439
Last modified:January 23, 2007 - v3
Checksum:i1E4B556ED7A750D1
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti9D → N AA sequence (PubMed:98527).Curated1
Sequence conflicti91P → L AA sequence (PubMed:98527).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M10922 Genomic DNA. Translation: AAA25237.1.
PIRiA24036. RDLBD.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M10922 Genomic DNA. Translation: AAA25237.1.
PIRiA24036. RDLBD.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AO8NMR-A2-163[»]
1BZFNMR-A2-163[»]
1DISNMR-A2-163[»]
1DIUNMR-A2-163[»]
1LUDNMR-A2-163[»]
2HM9NMR-A2-163[»]
2HQPNMR-A2-163[»]
2L28NMR-A2-163[»]
2LF1NMR-A2-163[»]
3DFRX-ray1.70A2-163[»]
ProteinModelPortaliP00381.
SMRiP00381.
ModBaseiSearch...
MobiDBiSearch...

Chemistry databases

BindingDBiP00381.
ChEMBLiCHEMBL2902.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Enzyme and pathway databases

UniPathwayiUPA00077; UER00158.
BRENDAi1.5.1.3. 2854.
SABIO-RKP00381.

Miscellaneous databases

EvolutionaryTraceiP00381.

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_LACCA
AccessioniPrimary (citable) accession number: P00381
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: January 23, 2007
Last modified: November 2, 2016
This is version 112 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

This bacterial strain is resistant to the folic acid analog methotrexate (amethopterin).

Keywords - Technical termi

3D-structure, Direct protein sequencing

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.