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Protein

Dihydrofolate reductase

Gene

Dhfr

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

By interacting with vestigial (vg), may control genes involved in DNA replication.
Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis (By similarity).By similarity

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 (Dhfr)
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 sitei9NADP; via amide nitrogen and carbonyl oxygenBy similarity1
Binding sitei69SubstrateBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi15 – 21NADPBy similarity7
Nucleotide bindingi53 – 55NADPBy similarity3
Nucleotide bindingi75 – 77NADPBy similarity3
Nucleotide bindingi113 – 120NADPBy similarity8

GO - Molecular functioni

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

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

DNA replication, One-carbon metabolism

Keywords - Ligandi

NADP

Enzyme and pathway databases

BRENDAi1.5.1.3. 1994.
ReactomeiR-DME-113510. E2F mediated regulation of DNA replication.
R-DME-196757. Metabolism of folate and pterines.
R-DME-69205. G1/S-Specific Transcription.
UniPathwayiUPA00077; UER00158.

Names & Taxonomyi

Protein namesi
Recommended name:
Dihydrofolate reductase (EC:1.5.1.3)
Gene namesi
Name:Dhfr
ORF Names:CG14887
OrganismiDrosophila melanogaster (Fruit fly)
Taxonomic identifieri7227 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
Proteomesi
  • UP000000803 Componenti: Chromosome 3R

Organism-specific databases

FlyBaseiFBgn0004087. Dhfr.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001863701 – 182Dihydrofolate reductaseAdd BLAST182

Proteomic databases

PaxDbiP17719.
PRIDEiP17719.

Expressioni

Gene expression databases

BgeeiFBgn0004087.
ExpressionAtlasiP17719. baseline.
GenevisibleiP17719. DM.

Interactioni

Subunit structurei

Monomer. Interacts with vg.1 Publication

Protein-protein interaction databases

BioGridi67048. 3 interactors.
DIPiDIP-20310N.
IntActiP17719. 1 interactor.
MINTiMINT-323567.
STRINGi7227.FBpp0110210.

Structurei

3D structure databases

ProteinModelPortaliP17719.
SMRiP17719.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini3 – 180DHFRPROSITE-ProRule annotationAdd BLAST178

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni29 – 34Substrate bindingBy similarity6

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG1324. Eukaryota.
COG0262. LUCA.
GeneTreeiENSGT00390000010283.
InParanoidiP17719.
KOiK00287.
OMAiNGIKYEY.
OrthoDBiEOG091G0PRK.
PhylomeDBiP17719.

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]
PRINTSiPR00070. DHFR.
SUPFAMiSSF53597. SSF53597. 1 hit.
PROSITEiPS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P17719-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLRFNLIVAV CENFGIGIRG DLPWRIKSEL KYFSRTTKRT SDPTKQNAVV
60 70 80 90 100
MGRKTYFGVP ESKRPLPDRL NIVLSTTLQE SDLPKGVLLC PNLETAMKIL
110 120 130 140 150
EEQNEVENIW IVGGSGVYEE AMASPRCHRL YITKIMQKFD CDTFFPAIPD
160 170 180
SFREVAPDSD MPLGVQEENG IKFEYKILEK HS
Length:182
Mass (Da):20,775
Last modified:June 1, 2001 - v3
Checksum:iD2C9198F1D2CE430
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti3R → T AA sequence (PubMed:2116172).Curated1
Sequence conflicti11C → S AA sequence (PubMed:2116172).Curated1
Sequence conflicti134K → Q in AAA19051 (PubMed:8195153).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U06861 Unassigned DNA. Translation: AAA19051.1.
AE014297 Genomic DNA. Translation: AAF55324.1.
AE014297 Genomic DNA. Translation: ABI31175.1.
PIRiA53803.
S10759. A33105.
RefSeqiNP_001036720.1. NM_001043255.2.
NP_732147.1. NM_169721.2.
UniGeneiDm.8025.

Genome annotation databases

EnsemblMetazoaiFBtr0083295; FBpp0082746; FBgn0004087.
FBtr0110910; FBpp0110210; FBgn0004087.
GeneIDi42003.
KEGGidme:Dmel_CG14887.
UCSCiCG14887-RB. d. melanogaster.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U06861 Unassigned DNA. Translation: AAA19051.1.
AE014297 Genomic DNA. Translation: AAF55324.1.
AE014297 Genomic DNA. Translation: ABI31175.1.
PIRiA53803.
S10759. A33105.
RefSeqiNP_001036720.1. NM_001043255.2.
NP_732147.1. NM_169721.2.
UniGeneiDm.8025.

3D structure databases

ProteinModelPortaliP17719.
SMRiP17719.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi67048. 3 interactors.
DIPiDIP-20310N.
IntActiP17719. 1 interactor.
MINTiMINT-323567.
STRINGi7227.FBpp0110210.

Proteomic databases

PaxDbiP17719.
PRIDEiP17719.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaiFBtr0083295; FBpp0082746; FBgn0004087.
FBtr0110910; FBpp0110210; FBgn0004087.
GeneIDi42003.
KEGGidme:Dmel_CG14887.
UCSCiCG14887-RB. d. melanogaster.

Organism-specific databases

CTDi1719.
FlyBaseiFBgn0004087. Dhfr.

Phylogenomic databases

eggNOGiKOG1324. Eukaryota.
COG0262. LUCA.
GeneTreeiENSGT00390000010283.
InParanoidiP17719.
KOiK00287.
OMAiNGIKYEY.
OrthoDBiEOG091G0PRK.
PhylomeDBiP17719.

Enzyme and pathway databases

UniPathwayiUPA00077; UER00158.
BRENDAi1.5.1.3. 1994.
ReactomeiR-DME-113510. E2F mediated regulation of DNA replication.
R-DME-196757. Metabolism of folate and pterines.
R-DME-69205. G1/S-Specific Transcription.

Miscellaneous databases

GenomeRNAii42003.
PROiP17719.

Gene expression databases

BgeeiFBgn0004087.
ExpressionAtlasiP17719. baseline.
GenevisibleiP17719. DM.

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]
PRINTSiPR00070. DHFR.
SUPFAMiSSF53597. SSF53597. 1 hit.
PROSITEiPS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDYR_DROME
AccessioniPrimary (citable) accession number: P17719
Secondary accession number(s): A4V302, Q9VEU4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: June 1, 2001
Last modified: November 30, 2016
This is version 138 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Drosophila
    Drosophila: entries, gene names and cross-references to FlyBase
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  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.