DHFR
entrez
1719
canonical
uniprot
P00374
canonical
ensembl
ENSG00000228716
resolver
ensp
ENSP00000396308
resolver
ensp
ENSP00000421334
resolver
ensp
ENSP00000422732
resolver
enst
ENST00000511032
resolver
genesymbol
DHFR
resolver
hgnc
HGNC:2861
resolver
uniprot
B0YJ76
resolver
uniprot
B4DDD2
resolver
uniprot
B4DM58
resolver
uniprot
F6V442
resolver
uniprot
Q14130
resolver
uniprot
Q6IRW8
resolver
uniprot_entry
B0YJ76_HUMAN
resolver
uniprot_entry
B4DM58_HUMAN
resolver
uniprot_entry
DYR_HUMAN
resolver
uniprot_entry
F6V442_HUMAN
resolver
uniprot_sec
B4DDD2
resolver
uniprot_sec
Q14130
resolver
uniprot_sec
Q6IRW8
resolver
amino_acid_sequence
MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQRMTTTSSVEGKQNLVIMGKKTWFSIPEKNRPLKGRINLVLSRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWIVGGSSVYKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLLPEYPGVLSDVQEEKGIKYKFEVYEKND
uniprot
proteins
disease_involvement
DISEASE: Megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD) [MIM:613839]: An inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency. Clinical features include variable neurologic symptoms, ranging from severe developmental delay and generalized seizures in infancy, to childhood absence epilepsy with learning difficulties, to lack of symptoms. {ECO:0000269|PubMed:21310276, ECO:0000269|PubMed:21310277}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
1.5.1.3
uniprot
proteins
function
FUNCTION: Catalyzes the reduction of 7,8-dihydrofolate (DHF) to 5,6,7,8-tetrahydrofolate in a NADPH-dependent manner (PubMed:12096917, PubMed:15039552, PubMed:17569517, PubMed:19196009, PubMed:19478082, PubMed:21876184, PubMed:9719595). Key enzyme in folate metabolism. Contributes to the nuclear and mitochondrial de novo thymidylate biosynthesis pathway (PubMed:21876188, PubMed:22235121). Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFR2. {ECO:0000269|PubMed:12096917, ECO:0000269|PubMed:15039552, ECO:0000269|PubMed:17569517, ECO:0000269|PubMed:19196009, ECO:0000269|PubMed:19478082, ECO:0000269|PubMed:21876184, ECO:0000269|PubMed:21876188, ECO:0000269|PubMed:22235121, ECO:0000269|PubMed:9719595}.
uniprot
proteins
mass_dalton
21453
uniprot
proteins
mutagenesis
MUTAGEN 23; /note="L->F,W,Y: Decreases affinity for NADP and dihydrofolate over 10-fold."; /evidence="ECO:0000269|PubMed:15681865, ECO:0000269|PubMed:7890613"; MUTAGEN 23; /note="L->R: Strongly decreased affinity for methotrexate. Decreases catalytic rate constant 200-fold. Decreases affinity for NADP and dihydrofolate over 10-fold."; /evidence="ECO:0000269|PubMed:15681865, ECO:0000269|PubMed:7890613"; MUTAGEN 32; /note="F->R: Reduces catalytic rate 5-fold. Reduces affinity for dihydrofolate 9-fold; when associated with E-36."; /evidence="ECO:0000269|PubMed:19478082"; MUTAGEN 36; /note="Q->E: Reduces catalytic rate 2-fold. Reduces affinity for dihydrofolate 9-fold; when associated with R-32."; /evidence="ECO:0000269|PubMed:15039552, ECO:0000269|PubMed:19196009, ECO:0000269|PubMed:19478082"; MUTAGEN 36; /note="Q->K: Increases affinity for dihydrofolate about 3-fold. Reduces affinity for NADPH about 3-fold."; /evidence="ECO:0000269|PubMed:15039552, ECO:0000269|PubMed:19196009, ECO:0000269|PubMed:19478082"; MUTAGEN 36; /note="Q->S: Increases affinity for dihydrofolate about 2-fold. No effect on affinity for NADPH."; /evidence="ECO:0000269|PubMed:15039552, ECO:0000269|PubMed:19196009, ECO:0000269|PubMed:19478082"; MUTAGEN 65; /note="N->F: Increases affinity for dihydrofolate about 3-fold. No effect on affinity for NADPH."; /evidence="ECO:0000269|PubMed:15039552, ECO:0000269|PubMed:19196009"; MUTAGEN 65; /note="N->S: Increases affinity for dihydrofolate about 15-fold. No effect on affinity for NADPH."; /evidence="ECO:0000269|PubMed:15039552, ECO:0000269|PubMed:19196009
uniprot
proteins
pathway_participation
PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate: step 1/1. {ECO:0000269|PubMed:21876184}.
uniprot
proteins
post_translational_modification
PTM: Sumoylated by UBE2I/UBC9. {ECO:0000269|PubMed:18067453}.
uniprot
proteins
protein_family
Dihydrofolate reductase family
uniprot
proteins
pubmed
12096917
uniprot
proteins
pubmed
12657784
uniprot
proteins
pubmed
12925791
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15039552
uniprot
proteins
pubmed
15372022
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15681865
uniprot
proteins
pubmed
16222560
uniprot
proteins
pubmed
1731871
uniprot
proteins
pubmed
17569517
uniprot
proteins
pubmed
18067453
uniprot
proteins
pubmed
19196009
uniprot
proteins
pubmed
19478082
uniprot
proteins
pubmed
19719239
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21310276
uniprot
proteins
pubmed
21310277
uniprot
proteins
pubmed
21876184
uniprot
proteins
pubmed
21876188
uniprot
proteins
pubmed
22235121
uniprot
proteins
pubmed
2248959
uniprot
proteins
pubmed
3383852
uniprot
proteins
pubmed
6235374
uniprot
proteins
pubmed
6323448
uniprot
proteins
pubmed
6687716
uniprot
proteins
pubmed
7890613
uniprot
proteins
pubmed
9374868
uniprot
proteins
pubmed
9719595
uniprot
proteins
sequence_length
187
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:P00375}. Cytoplasm {ECO:0000250|UniProtKB:P00375}. Nucleus {ECO:0000269|PubMed:22235121}. Note=Localized to the nucleus during S and G2/M phases of the cell cycle. As a component of the de novo thymidylate synthesis complex, localizes specifically to replication forks during DNA synthesis (PubMed:22235121). {ECO:0000269|PubMed:22235121}.
uniprot
proteins