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P04753 (DYR_MESAU) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 81. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Dihydrofolate reductase

EC=1.5.1.3
Gene names
Name:DHFR
OrganismMesocricetus auratus (Golden hamster)
Taxonomic identifier10036 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaCricetidaeCricetinaeMesocricetus

Protein attributes

Sequence length187 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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.

Catalytic activity

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

Pathway

Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate: step 1/1.

Subunit structure

Homodimer By similarity.

Polymorphism

The sequence shown is that of A3-35. The two clones A3-35 and MQ19-97 represent allelic forms. They differ in their drug sensitivities, possibly because of the difference at position 22.

Miscellaneous

Overexpression of the dihydrofolate gene (generally involving gene amplification) results in resistance to the antitumor antifolate drugs methotrexate (MTX) and methasquin.

Cell line DC-3F/A3 produces 90% of its dihydrofolate reductase in the 21k pI 6.5 form.

Cell line DC-3F/MQ19 produces 90% of its dihydrofolate reductase in the 20k pI 6.7 form (DHFR97).

Sequence similarities

Belongs to the dihydrofolate reductase family.

Contains 1 DHFR (dihydrofolate reductase) domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 187186Dihydrofolate reductase
PRO_0000186363

Regions

Domain4 – 185182DHFR
Nucleotide binding16 – 227NADP By similarity
Nucleotide binding55 – 573NADP By similarity
Nucleotide binding77 – 793NADP By similarity
Nucleotide binding117 – 1248NADP By similarity
Region8 – 3730Involved in methotrexate binding Probable
Region31 – 366Substrate binding By similarity
Region60 – 7011Involved in methotrexate binding Probable

Sites

Binding site101NADP; via amide nitrogen and carbonyl oxygen By similarity
Binding site711Substrate By similarity
Binding site1371Methotrexate Probable

Amino acid modifications

Modified residue331N6-acetyllysine; alternate By similarity
Modified residue331N6-succinyllysine; alternate By similarity

Natural variations

Natural variant231F → L in MQ19-97.
Natural variant961D → N in MQ19-97.

Sequences

Sequence LengthMass (Da)Tools
P04753 [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: A91F85A74658C6F3

FASTA18721,660
        10         20         30         40         50         60 
MVRPLNCIVA VSQNMGIGKN GDFPWPMLRN EFKYFQRMTT TSSVEGKQNL VIMGRKTWFS 

        70         80         90        100        110        120 
IPEKNRPLKD RINIVLSREL KEPPQGAHFL AKSLDDALKL IEQPELADKV DMVWIVGGSS 

       130        140        150        160        170        180 
VYKEAMNQPG HLRLFVTRIM QEFESDTFFP EIDLEKYKLL PEYPGVLSEV QEEKGIKYKF 


EVYEKKG 

« Hide

References

[1]"Antifolate-resistant Chinese hamster cells. Molecular basis for the biochemical and structural heterogeneity among dihydrofolate reductases produced by drug-sensitive and drug-resistant cell lines."
Melera P.W., Davide J.P., Oen H.
J. Biol. Chem. 263:1978-1990(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Phenotypic expression in Escherichia coli and nucleotide sequence of two Chinese hamster lung cell cDNAs encoding different dihydrofolate reductases."
Melera P.W., Davide J.P., Hession C.A., Scotto K.W.
Mol. Cell. Biol. 4:38-48(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Lung fibroblast.
[3]Erratum
Melera P.W., Davide J.P., Hession C.A., Scotto K.W.
Mol. Cell. Biol. 4:1001-1001(1984)

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
K01164 mRNA. Translation: AAA36974.1.
K01165 mRNA. Translation: AAA36976.1.
M19869 mRNA. Translation: AAA36970.1.
PIRS42445.

3D structure databases

ProteinModelPortalP04753.
SMRP04753. Positions 2-186.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Phylogenomic databases

HOVERGENHBG000773.

Enzyme and pathway databases

UniPathwayUPA00077; UER00158.

Family and domain databases

Gene3D3.40.430.10. 1 hit.
InterProIPR012259. DHFR.
IPR024072. DHFR-like_dom.
IPR017925. DHFR_CS.
IPR001796. DHFR_dom.
[Graphical view]
PfamPF00186. DHFR_1. 1 hit.
[Graphical view]
PRINTSPR00070. DHFR.
SUPFAMSSF53597. SSF53597. 1 hit.
PROSITEPS00075. DHFR_1. 1 hit.
PS51330. DHFR_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameDYR_MESAU
AccessionPrimary (citable) accession number: P04753
Entry history
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: January 23, 2007
Last modified: March 19, 2014
This is version 81 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways