Curr Genomics. Bahram S. Author information Article notes Copyright and License information Disclaimer. This article has been cited by other articles in PMC. Open in a separate window. Position of the polymorphism is given relative to the transcription or translation initiation site, or refers to the position within indicated intron. The functional human dihydrofolate reductase gene. The 5-untranslated RNA of the human dhfr minor transcript alters transcription pre-initiation complex assembly at the major core promoter.
Repression of the human dihydrofolate reductase gene by a non-coding interfering transcript. The methylenetetrahydrofolate reductase CT mutation induces cell-specific changes in genomic DNA methylation and uracil misincorporation: a possible molecular basis for the site-specific cancer risk modification.
Assaraf YG. Molecular basis of antifolate resistance. Cancer Metastasis Rev. Dihydrofolate reductase amplification and sensitization to methotrexate of methotrexate-resistant colon cancer cells. Cancer Ther. Intrinsic and acquired resistance to methotrexate in acute leukemia. Chromosomal organization of the human dihydrofolate reductase genes: dispersion, selective amplification, and a novel form of polymorphism.
Multiple forms of human dihydrofolate reductase messenger RNA. Cloning and expression in Escherichia coli of their DNA coding sequence. Preventing neural tube defects in Europe: a missed opportunity. The bp deletion polymorphism in intron-1 of dihydrofolate reductase DHFR may decrease rather than increase risk for spina bifida in the Irish population. Botto LD, Yang Q. Neural-tube defects. New 19 bp deletion polymorphism in intron-1 of dihydrofolate reductase DHFR : a risk factor for spina bifida acting in mothers during pregnancy?
Common dihydrofolate reductase base pair deletion allele: a novel risk factor for preterm delivery. Variation and expression of dihydrofolate reductase DHFR in relation to spina bifida. Molecular genetic analysis of the human dihydrofolate reductase gene: relation with plasma total homocysteine, serum and red blood cell folate levels.
A functional base pair deletion polymorphism of dihydrofolate reductase DHFR and risk of breast cancer in multivitamin users. A base pair deletion polymorphism in dihydrofolate reductase is associated with increased unmetabolized folic acid in plasma and decreased red blood cell folate.
DNA variants in region for noncoding interfering transcript of dihydrofolate reductase gene and outcome in childhood acute lymphoblastic leukemia. Kim YI. Nutritional epigenetics: impact of folate deficiency on DNA methylation and colon cancer susceptibility. Schwahn B, Rozen R. Polymorphisms in the methylenetetrahydrofolate reductase gene: clinical consequences. Breast Cancer Res. Germline polymorphisms in the one-carbon metabolism pathway and DNA methylation in colorectal cancer.
Cancer Causes Control. Genetic polymorphisms in one-carbon metabolism: associations with CpG island methylator phenotype CIMP in colon cancer and the modifying effects of diet. A candidate gene study of folate-associated one carbon metabolism genes and colorectal cancer risk.
PMID Identification of a de novo thymidylate biosynthesis pathway in mammalian mitochondria. Dihydrofolate reductase gene variations in susceptibility to disease and treatment outcomes. Identification and characterization of an inborn error of metabolism caused by dihydrofolate reductase deficiency.
The 5'-untranslated RNA of the human dhfr minor transcript alters transcription pre-initiation complex assembly at the major core promoter. Dihydrofolate reductase deficiency due to a homozygous DHFR mutation causes megaloblastic anemia and cerebral folate deficiency leading to severe neurologic disease. Folate pathway enzyme gene polymorphisms and the efficacy and toxicity of methotrexate in psoriatic arthritis.
Assignment of the human dihydrofolate reductase gene to the qq22 region of chromosome 5. A novel single-nucleotide polymorphism in the 3'-untranslated region of the human dihydrofolate reductase gene with enhanced expression.
Common dihydrofolate reductase base pair deletion allele: a novel risk factor for preterm delivery. Atomic structures of human dihydrofolate reductase complexed with NADPH and two lipophilic antifolates at 1.
Overexpression of thymidylate synthetase confers an independent prognostic indicator in nasopharyngeal carcinoma. A candidate gene study of folate-associated one carbon metabolism genes and colorectal cancer risk. Repression of the human dihydrofolate reductase gene by a non-coding interfering transcript. The former annotated human pseudogene dihydrofolate reductase-like 1 DHFRL1 is expressed and functional. Dihydrofolate reductase amplification and sensitization to methotrexate of methotrexate-resistant colon cancer cells.
Gene polymorphisms in folate metabolizing enzymes in adult acute lymphoblastic leukemia: effects on methotrexate-related toxicity and survival. Risk of retinoblastoma is associated with a maternal polymorphism in dihydrofolatereductase DHFR and prenatal folic acid intake. The bp deletion polymorphism in intron-1 of dihydrofolate reductase DHFR may decrease rather than increase risk for spina bifida in the Irish population.
The bp deletion polymorphism of dihydrofolate reductase DHFR and nonsyndromic cleft lip with or without cleft palate: evidence for a protective role. Polymorphisms in genes involved in the mechanism of action of methotrexate: are they associated with outcome in rheumatoid arthritis patients? Purine biosynthetic pathway genes and methotrexate response in rheumatoid arthritis patients among north Indians. Methotrexate-induced subacute neurotoxicity in a child with acute lymphoblastic leukemia carrying genetic polymorphisms related to folate homeostasis.
It has a long groove that binds to folate at one end, shown here in purple, and to NADPH at the other end, shown here in green. As you can see, the protein wraps sidechains around the two molecules, positioning them tightly next to one another. Then, the enzyme transfers hydrogen atoms from NADPH to the folate, converting folate to a useful reduced form. Enzymes with essential roles are sensitive targets for drug therapy.
Dihydrofolate reductase was the first enzyme to be targeted for cancer chemotherapy. The first drug used for cancer chemotherapy was aminopterin.
It binds to dihydrofolate reductase a thousand times more tightly than folate, blocking the action of the enzyme. Today, methotrexate and other variations on aminopterin are used, because of their tighter binding and better clinical characteristics.
Since these drugs attack a key step in the production of DNA, they tend to kill cells that are actively growing rather than cells that are not growing. Since cancer cells are often the most rapidly reproducing cells in a patient, the drug will have the strongest effect on the cancer cells.
See the description of this reaction in Rhea. Show » « Hide. This subpathway is part of the pathway tetrahydrofolate biosynthesis, which is itself part of Cofactor biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate , the pathway tetrahydrofolate biosynthesis and in Cofactor biosynthesis. Name: DHFR. 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.
Kinetics, crystallography, and potential as selectable markers. SwissPalm i P By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'. Expression is higher in the adult brain than in the fetal brain.
Belongs to the dihydrofolate reductase family. The information is filed in different subsections. Additionally, this section gives relevant information on each alternative protein isoform. Align Add to basket Added to basket This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.
Length: Mass Da : 21, It is useful for tracking sequence updates. The algorithm is described in the ISO standard. Mass Da : 15, Full view. These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary citable accession number'.
See complete history. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Do not show this banner again. Priority is given to the annotation of physiological ligands. Substrate 1 Publication Manual assertion inferred by curator from i Ref.
It always involves more than one amino acid and includes all residues involved in nucleotide-binding. Oxidoreductase , RNA-binding. Methotrexate resistance , One-carbon metabolism. BioCyc i. Pathway Commons web resource for biological pathway data More PathwayCommons i. Reactome - a knowledgebase of biological pathways and processes More Reactome i. UniPathway: a resource for the exploration and annotation of metabolic pathways More UniPathway i.
MoonProt database of moonlighting proteins More MoonProt i. Recommended name: Dihydrofolate reductase EC: 1. Search reactions for this EC number in Rhea.
Homo sapiens Human. This is known as the 'taxonomic identifier' or 'taxid'. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first. Human Gene Nomenclature Database More HGNC i.
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