Recombinant Human Dihydrofolate reductase (DHFR)

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

Subcellular Location

Mitochondrion; Cytoplasm; Nucleus

Disease Association

Megaloblastic anemia due to dihydrofolate reductase deficiency (DHFRD) : 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. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Widely expressed in fetal and adult tissues, including throughout the fetal and adult brains and whole blood. Expression is higher in the adult brain than in the fetal brain

Subunit

Homodimer. Part of the de novo thymidylate synthesis complex composed at least by SHMT1, DHFR and TYMS (PubMed:22235121). Interacts with SHMT1; this interaction is DNA-dependent and mediates DHFR co-localization with LMNB1 (PubMed:22235121)

Pathway

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

• Chen M.-J. et al. The functional human dihydrofolate reductase gene. — J. Biol. Chem. (1984)
• Masters J.N. et al. The nucleotide sequence of the cDNA coding for the human dihydrofolic acid reductase. — Gene (1983)
• Yang J.K. et al. Human dihydrofolate reductase gene organization. Extensive conservation of the G + C-rich 5' non-coding sequence and strong intron size divergence from homologous mammalian genes. — J. Mol. Biol. (1984)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Schmutz J. et al. The DNA sequence and comparative analysis of human chromosome 5. — Nature (2004)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Anderson D.D. et al. Small ubiquitin-like modifier-1 (SUMO-1) modification of thymidylate synthase and dihydrofolate reductase. — Clin. Chem. Lab. Med. (2007)
• Banka S. et al. Identification and characterization of an inborn error of metabolism caused by dihydrofolate reductase deficiency. — Am. J. Hum. Genet. (2011)