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Protein

Dihydrofolate reductase

Gene

Dhfr

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1 (By similarity).By similarity

Catalytic activityi

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

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei10 – 101NADP; via amide nitrogen and carbonyl oxygenBy similarity
Binding sitei71 – 711SubstrateBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi16 – 227NADPBy similarity
Nucleotide bindingi55 – 573NADPBy similarity
Nucleotide bindingi77 – 793NADPBy similarity
Nucleotide bindingi117 – 1248NADPBy similarity

GO - Molecular functioni

  1. dihydrofolate reductase activity Source: UniProtKB
  2. dihydrofolic acid binding Source: RGD
  3. drug binding Source: UniProtKB
  4. mRNA binding Source: UniProtKB
  5. NADP binding Source: RGD

GO - Biological processi

  1. dihydrofolate metabolic process Source: RGD
  2. glycine biosynthetic process Source: InterPro
  3. nucleotide biosynthetic process Source: InterPro
  4. one-carbon metabolic process Source: UniProtKB-KW
  5. response to methotrexate Source: UniProtKB-KW
  6. response to nicotine Source: RGD
  7. tetrahydrofolate biosynthetic process Source: RGD
  8. tetrahydrofolate metabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Methotrexate resistance, One-carbon metabolism

Keywords - Ligandi

NADP, RNA-binding

Enzyme and pathway databases

ReactomeiREACT_196414. G1/S-Specific Transcription.
REACT_199128. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
REACT_246418. Metabolism of folate and pterines.
REACT_249225. E2F mediated regulation of DNA replication.
SABIO-RKQ920D2.
UniPathwayiUPA00077; UER00158.

Names & Taxonomyi

Protein namesi
Recommended name:
Dihydrofolate reductase (EC:1.5.1.3)
Gene namesi
Name:Dhfr
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 2

Organism-specific databases

RGDi2500. Dhfr.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 187186Dihydrofolate reductasePRO_0000186366Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei33 – 331N6-acetyllysine; alternateBy similarity
Modified residuei33 – 331N6-succinyllysine; alternateBy similarity

Keywords - PTMi

Acetylation

Proteomic databases

PaxDbiQ920D2.
PRIDEiQ920D2.

PTM databases

PhosphoSiteiQ920D2.

Expressioni

Gene expression databases

ExpressionAtlasiQ920D2. baseline and differential.
GenevestigatoriQ920D2.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

MINTiMINT-4580348.

Structurei

3D structure databases

ProteinModelPortaliQ920D2.
SMRiQ920D2. Positions 2-187.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini4 – 185182DHFRPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni31 – 366Substrate bindingBy similarity

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiCOG0262.
GeneTreeiENSGT00390000010283.
HOGENOMiHOG000040235.
HOVERGENiHBG000773.
InParanoidiQ920D2.
KOiK00287.
OMAiDQVWVIG.
OrthoDBiEOG7V1FS3.
PhylomeDBiQ920D2.
TreeFamiTF317636.

Family and domain databases

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.

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

Q920D2-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MVRPLNCIVA VSQNMGIGKN GDLPWPLLRN EFKYFQRMTT TSSVEGKQNL
60 70 80 90 100
VIMGRKTWFS IPEKNRPLKD RINIVLSREL KEPPQGAHFL AKSLDDALKL
110 120 130 140 150
IEQPELASKV DMVWVVGGSS VYQEAMNQPG HLRLFVTRIM QEFESDTFFP
160 170 180
EIDLEKYKLL PEYPGVLSEI QEEKGIKYKF EVYEKKD
Length:187
Mass (Da):21,638
Last modified:January 23, 2007 - v3
Checksum:iFE1DB4F3515F8B26
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF318150 mRNA. Translation: AAL11500.1.
RefSeqiNP_569084.1. NM_130400.2.
UniGeneiRn.233753.
Rn.24681.

Genome annotation databases

EnsembliENSRNOT00000018259; ENSRNOP00000018259; ENSRNOG00000013521.
GeneIDi24312.
KEGGirno:24312.
UCSCiRGD:2500. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF318150 mRNA. Translation: AAL11500.1.
RefSeqiNP_569084.1. NM_130400.2.
UniGeneiRn.233753.
Rn.24681.

3D structure databases

ProteinModelPortaliQ920D2.
SMRiQ920D2. Positions 2-187.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-4580348.

Chemistry

BindingDBiQ920D2.
ChEMBLiCHEMBL2097173.

PTM databases

PhosphoSiteiQ920D2.

Proteomic databases

PaxDbiQ920D2.
PRIDEiQ920D2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000018259; ENSRNOP00000018259; ENSRNOG00000013521.
GeneIDi24312.
KEGGirno:24312.
UCSCiRGD:2500. rat.

Organism-specific databases

CTDi1719.
RGDi2500. Dhfr.

Phylogenomic databases

eggNOGiCOG0262.
GeneTreeiENSGT00390000010283.
HOGENOMiHOG000040235.
HOVERGENiHBG000773.
InParanoidiQ920D2.
KOiK00287.
OMAiDQVWVIG.
OrthoDBiEOG7V1FS3.
PhylomeDBiQ920D2.
TreeFamiTF317636.

Enzyme and pathway databases

UniPathwayiUPA00077; UER00158.
ReactomeiREACT_196414. G1/S-Specific Transcription.
REACT_199128. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
REACT_246418. Metabolism of folate and pterines.
REACT_249225. E2F mediated regulation of DNA replication.
SABIO-RKQ920D2.

Miscellaneous databases

NextBioi602953.
PROiQ920D2.

Gene expression databases

ExpressionAtlasiQ920D2. baseline and differential.
GenevestigatoriQ920D2.

Family and domain databases

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...

Publicationsi

  1. "Isolation of rat dihydrofolate reductase gene and characterization of recombinant enzyme."
    Wang Y., Bruenn J.A., Queener S.F., Cody V.
    Antimicrob. Agents Chemother. 45:2517-2523(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Sprague-Dawley.
    Tissue: Liver.

Entry informationi

Entry nameiDYR_RAT
AccessioniPrimary (citable) accession number: Q920D2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 20, 2005
Last sequence update: January 23, 2007
Last modified: January 7, 2015
This is version 97 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.