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Search results 301 to 349 out of 349 for Dhfr

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Type Details Score
Genotype
Symbol: Agtpbp1/Agtpbp1
Background: involves: C57BL/6J * CD-1 * DBA/2J
Zygosity: hm
Has Mutant Allele: true
GO Term
Allele
Name: double C2, beta; endonuclease-mediated mutation 1, Channabasavaiah Gurumurthy
Allele Type: Endonuclease-mediated
Attribute String: Inducible, Recombinase
Allele
Name: intergenic site 2; endonuclease-mediated mutation 18, Shanghai Model Organisms Center
Allele Type: Endonuclease-mediated
Attribute String: Inducible, Recombinase
Genotype
Symbol: Dhfr/Dhfr<+>
Background: involves: C57BL/6JAnu
Zygosity: ht
Has Mutant Allele: true
Genotype
Symbol: Dhfr/Dhfr
Background: involves: C57BL/6JAnu
Zygosity: hm
Has Mutant Allele: true
Publication
First Author: Narayana N
Year: 1995
Journal: Nat Struct Biol
Title: A plasmid-encoded dihydrofolate reductase from trimethoprim-resistant bacteria has a novel D2-symmetric active site.
Volume: 2
Issue: 11
Pages: 1018-25
Publication
First Author: Matthews DA
Year: 1985
Journal: J Biol Chem
Title: Dihydrofolate reductase. The stereochemistry of inhibitor selectivity.
Volume: 260
Issue: 1
Pages: 392-9
Protein Domain
Type: Family
Description: Dihydrofolate reductase (DHFR) () catalyses the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate, an essential step in de novosynthesis both of glycine and of purines and deoxythymidine phosphate (the precursors of DNA synthesis) [], and important also in the conversion of deoxyuridine monophosphate to deoxythymidine monophosphate. Although DHFR is found ubiquitously in prokaryotes and eukaryotes, and is found in all dividing cells, maintaining levels of fully reduced folate coenzymes, the catabolic steps are still not well understood [].Bacterial species possesses distinct DHFR enzymes (based on their pattern of binding diaminoheterocyclic molecules), but mammalian DHFRs are highly similar []. The active site is situated in the N-terminal half of the sequence, which includes a conserved Pro-Trp dipeptide; the tryptophan has been shown []to be involved in the binding of substrate by the enzyme. Its central role in DNA precursor synthesis, coupled with its inhibition by antagonists such as trimethoprim and methotrexate, which are used as anti-bacterial or anti-cancer agents, has made DHFR a target of anticancer chemotherapy. However, resistance has developed against some drugs, as a result of changes in DHFR itself [].This entry represents a plasmid-encoded DHFR which shows a high level of resistance to the antibiotic trimethoprim. It is a homotetramer with an unusual pore, which contains the active site, passing through the middle of the molecule []. Its structure is unrelated to that of chromosomal DHFRs.
Protein Domain
Type: Conserved_site
Description: Dihydrofolate reductase (DHFR) () catalyses the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate, an essential step in de novosynthesis both of glycine and of purines and deoxythymidine phosphate (the precursors of DNA synthesis) [], and important also in the conversion of deoxyuridine monophosphate to deoxythymidine monophosphate. Although DHFR is found ubiquitously in prokaryotes and eukaryotes, and is found in all dividing cells, maintaining levels of fully reduced folate coenzymes, the catabolic steps are still not well understood [].Bacterial species possesses distinct DHFR enzymes (based on their pattern of binding diaminoheterocyclic molecules), but mammalian DHFRs are highly similar []. The active site is situated in the N-terminal half of the sequence, which includes a conserved Pro-Trp dipeptide; the tryptophan has been shown []to be involved in the binding of substrate by the enzyme. Its central role in DNA precursor synthesis, coupled with its inhibition by antagonists such as trimethoprim and methotrexate, which are used as anti-bacterial or anti-cancer agents, has made DHFR a target of anticancer chemotherapy. However, resistance has developed against some drugs, as a result of changes in DHFR itself [].This entry covers the region in the N-terminal part of the DHFR domain, which includes a conserved Pro-Trp dipeptide; the tryptophan has been shown to be involved in the binding of substrate by the enzyme [].
Protein Domain
Type: Domain
Description: Dihydrofolate reductase (DHFR) () catalyses the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate, which can be used in de novosynthesis both certain amino acids, purines and deoxythymidine phosphate (the precursors of DNA synthesis) [], and important also in the conversion of deoxyuridine monophosphate to deoxythymidine monophosphate. Although DHFR is found ubiquitously in prokaryotes and eukaryotes, and is found in all dividing cells, maintaining levels of fully reduced folate coenzymes, the catabolic steps are still not well understood [].Bacterial species possesses distinct DHFR enzymes (based on their pattern of binding diaminoheterocyclic molecules), but mammalian DHFRs are highly similar []. The active site is situated in the N-terminal half of the sequence, which includes a conserved Pro-Trp dipeptide; the tryptophan has been shown []to be involved in the binding of substrate by the enzyme. Its central role in DNA precursor synthesis, coupled with its inhibition by antagonists such as trimethoprim and methotrexate, which are used as anti-bacterial or anti-cancer agents, has made DHFR a target of anticancer chemotherapy. However, resistance has developed against some drugs, as a result of changes in DHFR itself [].
Publication  
First Author: Neumann P
Year: 1989
Journal: Mouse News Lett
Title: Insertional mutation at the pcd locus in transgenic mice
Volume: 83
Pages: 156
Allele
Name: gene trap ROSA 26, Philippe Soriano; endonuclease-mediated mutation 2, Zhiyong Liu
Allele Type: Endonuclease-mediated
Attribute String: Conditional ready, Epitope tag, Inserted expressed sequence, Reporter
Strain
Attribute String: coisogenic, mutant strain, targeted mutation
Publication
First Author: Taylor C
Year: 1998
Journal: Cancer Detect Prev
Title: c-Myc-associated genomic instability of the dihydrofolate reductase locus in vivo.
Volume: 22
Issue: 4
Pages: 350-6
Strain
Attribute String: endonuclease-mediated mutation, mutant stock
Genotype
Symbol: Doc2b/Doc2b<+> Gt(ROSA)26Sor/Gt(ROSA)26Sor<+>
Background: involves: 129S6/SvEvTac * C57BL/6J * C57BL/6NCrl
Zygosity: cn
Has Mutant Allele: true
Publication
First Author: Graziani I
Year: 2009
Journal: Biochem Biophys Res Commun
Title: Protein folding does not prevent the nonclassical export of FGF1 and S100A13.
Volume: 381
Issue: 3
Pages: 350-4
Publication
First Author: Dong YJ
Year: 1993
Journal: Exp Hematol
Title: Evidence for an accessory component that increases the affinity of the erythropoietin receptor.
Volume: 21
Issue: 3
Pages: 483-6
Publication
First Author: Stolzenburg F
Year: 1994
Journal: Chromosoma
Title: Structural homologies and functional similarities between mammalian origins of replication and amplification promoting sequences.
Volume: 103
Issue: 3
Pages: 209-14
Publication
First Author: Skierka K
Year: 2019
Journal: Biochem Biophys Res Commun
Title: Human dihydrofolate reductase is a substrate of protein kinase CK2α.
Volume: 513
Issue: 2
Pages: 368-373
Publication
First Author: Yuvaniyama J
Year: 2003
Journal: Nat Struct Biol
Title: Insights into antifolate resistance from malarial DHFR-TS structures.
Volume: 10
Issue: 5
Pages: 357-65
Protein Domain
Type: Family
Description: This group represents a bifunctional dihydrofolate reductase/thymidylate synthase found in some plant species and protozoal parasites including malarial species and trypanosomes. In other species dihydrofolate reductase and thymidilate synthase are encoded on separate polypeptides.Thymidylate synthase () []catalyzes the reductive methylation of dUMP to dTMP with concomitant conversion of 5,10-methylenetetrahydrofolate to dihydrofolate:5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMPThis provides the sole de novopathway for production of dTMP and is the only enzyme in folate metabolism in which the 5,10-methylenetetrahydrofolate is oxidised during one-carbon transfer []. The enzyme is important for regulating the balanced supply of the 4 DNA precursors in normal DNA replication: defects in the enzyme activity affecting the regulation process can cause various biological and genetic abnormalities. A cysteine residue is involved in the catalytic mechanism (it covalently binds the 5,6-dihydro-dUMP intermediate). The sequence around the active site of this enzyme is conserved from phages to vertebrates.Dihydrofolate reductase (DHFR) () catalyses the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate:5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+This is an essential step in de novosynthesis both of glycine and of purines and deoxythymidine phosphate (the precursors of DNA synthesis) [], and important also in the conversion of deoxyuridine monophosphate to deoxythymidine monophosphate.Although DHFR is found ubiquitously in prokaryotes and eukaryotes, and is found in all dividing cells, maintaining levels of fully reduced folate coenzymes, the catabolic steps are still not well understood [].As this enzyme is essential in both nucleic acid and amino acid biosynthesis, it is an important target of antiparasitic drugs. Resistance to antimalarial drugs that target this enzyme is often due to mutations that prevent drug binding but maintain enzyme activity. The structure of the wild-type and drug resistant malarial enzymes provides insights into the development of resistance and suggests approaches for the design of new drugs against this target [].
Publication
First Author: Li Y
Year: 1994
Journal: Mol Cell Biol
Title: Cloning, chromosomal location, and characterization of mouse E2F1.
Volume: 14
Issue: 3
Pages: 1861-9
Publication
First Author: Siu KL
Year: 2014
Journal: PLoS One
Title: Recoupling of eNOS with folic acid prevents abdominal aortic aneurysm formation in angiotensin II-infused apolipoprotein E null mice.
Volume: 9
Issue: 2
Pages: e88899
Publication
First Author: Zhang Z
Year: 2019
Journal: Br J Pharmacol
Title: PPARδ agonist prevents endothelial dysfunction via induction of dihydrofolate reductase gene and activation of tetrahydrobiopterin salvage pathway.
Volume: 176
Issue: 16
Pages: 2945-2961
Publication
First Author: Chen H
Year: 2006
Journal: Cancer Res
Title: Hypoxic stress induces dimethylated histone H3 lysine 9 through histone methyltransferase G9a in mammalian cells.
Volume: 66
Issue: 18
Pages: 9009-16
Publication
First Author: Smith ML
Year: 2000
Journal: Mol Cell Biol
Title: p53-mediated DNA repair responses to UV radiation: studies of mouse cells lacking p53, p21, and/or gadd45 genes.
Volume: 20
Issue: 10
Pages: 3705-14
Publication
First Author: Anagnou NP
Year: 1988
Journal: Am J Hum Genet
Title: Chromosomal localization and racial distribution of the polymorphic human dihydrofolate reductase pseudogene (DHFRP1).
Volume: 42
Issue: 2
Pages: 345-52
Publication
First Author: Wani MA
Year: 1997
Journal: Somat Cell Mol Genet
Title: Expression of Rap 1 suppresses genomic instability of H-ras transformed mouse fibroblasts.
Volume: 23
Issue: 2
Pages: 123-33
Publication
First Author: Nevaldine BH
Year: 1999
Journal: Mutat Res
Title: Differential sensitivity of double minute chromosomes to hydroxyurea treatment in cultured methotrexate-resistant mouse cells.
Volume: 406
Issue: 2-4
Pages: 55-62
Publication
First Author: Datta A
Year: 2005
Journal: Mol Cell Biol
Title: ARF directly binds DP1: interaction with DP1 coincides with the G1 arrest function of ARF.
Volume: 25
Issue: 18
Pages: 8024-36
Publication
First Author: Maguire M
Year: 2008
Journal: Cancer Res
Title: MDM2 regulates dihydrofolate reductase activity through monoubiquitination.
Volume: 68
Issue: 9
Pages: 3232-42
Publication
First Author: Shen L
Year: 2012
Journal: Cancer Res
Title: Geminin functions downstream of p53 in K-ras-induced gene amplification of dihydrofolate reductase.
Volume: 72
Issue: 23
Pages: 6153-62
Publication  
First Author: Wang T
Year: 2007
Journal: Brain Res
Title: The Purkinje cell degeneration (pcd) mouse: an unexpected molecular link between neuronal degeneration and regeneration.
Volume: 1140
Pages: 26-40
Publication
First Author: Youn JY
Year: 2012
Journal: Diabetologia
Title: The p47phox- and NADPH oxidase organiser 1 (NOXO1)-dependent activation of NADPH oxidase 1 (NOX1) mediates endothelial nitric oxide synthase (eNOS) uncoupling and endothelial dysfunction in a streptozotocin-induced murine model of diabetes.
Volume: 55
Issue: 7
Pages: 2069-79
Publication
First Author: Tomé S
Year: 2013
Journal: PLoS Genet
Title: MSH3 polymorphisms and protein levels affect CAG repeat instability in Huntington's disease mice.
Volume: 9
Issue: 2
Pages: e1003280
Publication  
First Author: Huang K
Year: 2021
Journal: Redox Biol
Title: Targeting feed-forward signaling of TGFβ/NOX4/DHFR/eNOS uncoupling/TGFβ axis with anti-TGFβ and folic acid attenuates formation of aortic aneurysms: Novel mechanisms and therapeutics.
Volume: 38
Pages: 101757
Publication
First Author: Foureman P
Year: 1998
Journal: Gene
Title: Chromosome breakpoints near CpG islands in double minutes.
Volume: 218
Issue: 1-2
Pages: 121-8
Publication
First Author: Gaub MP
Year: 1992
Journal: Exp Cell Res
Title: Immunodetection of multiple species of retinoic acid receptor alpha: evidence for phosphorylation.
Volume: 201
Issue: 2
Pages: 335-46
Publication
First Author: Ito K
Year: 2014
Journal: Oncogene
Title: Overexpression of Cdk6 and Ccnd1 in chondrocytes inhibited chondrocyte maturation and caused p53-dependent apoptosis without enhancing proliferation.
Volume: 33
Issue: 14
Pages: 1862-71
Publication
First Author: Bi Z
Year: 2022
Journal: Natl Sci Rev
Title: Development and transdifferentiation into inner hair cells require Tbx2.
Volume: 9
Issue: 12
Pages: nwac156
Publication  
First Author: Vanin EF
Year: 1985
Journal: Annu Rev Genet
Title: Processed pseudogenes: characteristics and evolution.
Volume: 19
Pages: 253-72
Publication
First Author: Wu H
Year: 2021
Journal: Nat Commun
Title: Distinct subtypes of proprioceptive dorsal root ganglion neurons regulate adaptive proprioception in mice.
Volume: 12
Issue: 1
Pages: 1026
Publication  
First Author: Benkovic SJ
Year: 1980
Journal: Annu Rev Biochem
Title: On the mechanism of action of folate- and biopterin-requiring enzymes.
Volume: 49
Pages: 227-51
Publication
First Author: Hardy LW
Year: 1987
Journal: Science
Title: Atomic structure of thymidylate synthase: target for rational drug design.
Volume: 235
Issue: 4787
Pages: 448-55
Publication  
First Author: Collin GB
Year: 2020
Journal: Cells
Title: Mouse Models of Inherited Retinal Degeneration with Photoreceptor Cell Loss.
Volume: 9
Issue: 4
Publication      
First Author: European Mouse Mutant Archive
Year: 2003
Journal: Unpublished
Title: Information obtained from the European Mouse Mutant Archive (EMMA)
Publication      
First Author: Shanghai Model Organisms Center
Year: 2017
Journal: MGI Direct Data Submission
Title: Information obtained from the Shanghai Model Organisms Center (SMOC), Shanghai, China