Names & Taxonomy

Uniprot ID:
P00374
Entry Name:
DYR_HUMAN
Status:
reviewed
Protein Names:
Dihydrofolate reductase (EC 1.5.1.3)
Gene Names:
DHFR
Gene Names Primary:
DHFR
Organism:
Homo sapiens (Human)

Structure

Length:
187
Sequence:
MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQRMTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLSRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWIVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND
Proteomes:
UP000005640

Function

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.
Pathway:
Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate: step 1/1.
Catalytic Activity:
5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + NADPH.
Kinetics:
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=2.7 uM for dihydrofolate
Cross Reference Drug Bank:
DB00798 DB00563 DB00642 DB06813 DB01131 DB00205 DB00440 DB01157
Gene Ontology Go:
cytosol
nucleoplasm
dihydrofolate reductase activity
drug binding
folic acid binding
methotrexate binding
mRNA binding
NADPH binding
axon regeneration
dihydrofolate metabolic process
folic acid metabolic process
G1/S transition of mitotic cell cycle
glycine biosynthetic process
mitotic cell cycle
nitric oxide metabolic process
nucleotide biosynthetic process
one-carbon metabolic process
oxidation-reduction process
positive regulation of nitric-oxide synthase activity
regulation of nitric-oxide synthase activity
regulation of removal of superoxide radicals
regulation of transcription involved in G1/S transition of mitotic cell cycle
response to methotrexate
small molecule metabolic process
tetrahydrobiopterin biosynthetic process
tetrahydrofolate biosynthetic process
tetrahydrofolate metabolic process
vitamin metabolic process
water-soluble vitamin metabolic process
Gene Ontology Biological Process:
axon regeneration
dihydrofolate metabolic process
folic acid metabolic process
G1/S transition of mitotic cell cycle
glycine biosynthetic process
mitotic cell cycle
nitric oxide metabolic process
nucleotide biosynthetic process
one-carbon metabolic process
oxidation-reduction process
positive regulation of nitric-oxide synthase activity
regulation of nitric-oxide synthase activity
regulation of removal of superoxide radicals
regulation of transcription involved in G1/S transition of mitotic cell cycle
response to methotrexate
small molecule metabolic process
tetrahydrobiopterin biosynthetic process
tetrahydrofolate biosynthetic process
tetrahydrofolate metabolic process
vitamin metabolic process
water-soluble vitamin metabolic process
Gene Ontology Molecular Function:
dihydrofolate reductase activity
drug binding
folic acid binding
methotrexate binding
mRNA binding
NADPH binding
Gene Ontology Cellular Component:
cytosol
nucleoplasm
Keywords:
3D-structure
Alternative splicing
Complete proteome
Disease mutation
Methotrexate resistance
NADP
One-carbon metabolism
Oxidoreductase
RNA-binding
Reference proteome

Publication

PubMed ID:
6323448 6687716 6235374 14702039 15372022 15489334 21310276 21269460 21876184 21876188 3383852 2248959 1731871 7890613 9374868 9719595 12096917 12657784 12925791 15039552 15681865 16222560 17569517 19196009 19478082 19719239 21310277