Any feedback?
Please rate this page
(enzyme.php)
(0/150)

BRENDA support

BRENDA Home
show all | hide all No of entries

Information on EC 1.5.1.3 - dihydrofolate reductase and Organism(s) Rattus norvegicus and UniProt Accession Q920D2

for references in articles please use BRENDA:EC1.5.1.3
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
     1 Oxidoreductases
         1.5 Acting on the CH-NH group of donors
             1.5.1 With NAD+ or NADP+ as acceptor
                1.5.1.3 dihydrofolate reductase
IUBMB Comments
The enzyme from animals and some micro-organisms also slowly reduces folate to 5,6,7,8-tetrahydrofolate.
Specify your search results
Select one or more organisms in this record: ?
This record set is specific for:
Rattus norvegicus
UNIPROT: Q920D2
Show additional data
Do not include text mining results
Include (text mining) results
Include results (AMENDA + additional results, but less precise)
Word Map
hide
The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
Synonyms
dhfr, dihydrofolate reductase, thy-1, dhfr-ts, hdhfr, dihydrofolate reductase-thymidylate synthase, ecdhfr, pcdhfr, r67 dhfr, ts-dhfr, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7,8-dihydrofolate reductase
-
-
-
-
dehydrogenase, tetrahydrofolate
-
-
-
-
DHFR type IIIC
-
-
-
-
dihydrofolate reductase
-
-
dihydrofolate reductase-thymidylate synthase
-
-
-
-
dihydrofolate reductase:thymidylate synthase
-
-
-
-
dihydrofolic acid reductase
-
-
-
-
dihydrofolic reductase
-
-
-
-
folic acid reductase
-
-
-
-
folic reductase
-
-
-
-
NADPH-dihydrofolate reductase
-
-
-
-
pteridine reductase:dihydrofolate reductase
-
-
-
-
reductase, dihydrofolate
-
-
-
-
tetrahydrofolate dehydrogenase
-
-
-
-
thymidylate synthetase-dihydrofolate reductase
-
-
-
-
Trimethoprim resistance protein
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+
show the reaction diagram
inhibitor binding mechanism
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-, -, -, -
SYSTEMATIC NAME
IUBMB Comments
5,6,7,8-tetrahydrofolate:NADP+ oxidoreductase
The enzyme from animals and some micro-organisms also slowly reduces folate to 5,6,7,8-tetrahydrofolate.
CAS REGISTRY NUMBER
COMMENTARY hide
9002-03-3
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
show the reaction diagram
-
-
-
r
7,8-dihydrofolate + NADPH
5,6,7,8-tetrahydrofolate + NADP+
show the reaction diagram
dihydrofolate + NADPH + H+
tetrahydrofolate + NADP+
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
assay method development
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
7,8-dihydrofolate + NADPH + H+
5,6,7,8-tetrahydrofolate + NADP+
show the reaction diagram
-
-
-
r
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
K+
-
stimulation
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2,4-diaminopyrimidin-5-yl)methyl naphthalene-2-sulfonate
-
-
2,4-diamino-5-isopropyl-6-arylthio-7H-pyrrolo[2,3-d]pyrimidine
-
-
2,4-diamino-5-methyl-6-(1-naphthylthio)furo[2,3-d]pyrimidine
-
-
2,4-diamino-5-methyl-6-(2',3',5',6'-tetrafluoro-4'-trifluoromethylphenylsulfanyl)-furo[2,3-d]pyrimidine
-
-
2,4-diamino-5-methyl-6-(2',5'-dimethoxyphenylsulfanyl)-furo[2,3-d]pyrimidine
-
-
2,4-diamino-5-methyl-6-(2',6'-dichlorophenylsulfanyl)-furo[2,3-d]pyrimidine
-
-
2,4-diamino-5-methyl-6-(2',6'-dimethylphenylsulfanyl)-furo[2,3-d]pyrimidine
-
-
2,4-diamino-5-methyl-6-(2'-isopropyl-6'-methylphenylsulfanyl)-furo[2,3-d]pyrimidine
-
-
2,4-diamino-5-methyl-6-(2'-methoxyphenylsulfanyl)-furo[2,3-d]pyrimidine
-
-
2,4-diamino-5-methyl-6-(2-naphthylthio)furo[2,3-d]pyrimidine
-
-
2,4-diamino-5-methyl-6-(3',4'-dimethoxyphenylsulfanyl)-furo[2,3-d]pyrimidine
-
-
2,4-diamino-5-methyl-6-(3'-methoxyphenylsulfanyl)-furo[2,3-d]pyrimidine
-
-
2,4-diamino-5-methyl-6-(4'-methoxyphenylsulfanyl)-furo[2,3-d]pyrimidine
-
-
2,4-diamino-5-propyl-6-arylthio-7H-pyrrolo[2,3-d]pyrimidine
-
-
3-(2,4-diaminophenyl)-1-(3-(4-methylbenzyloxy)phenyl)prop-2-en-1-one
-
-
3-(2,4-diaminopyrimidin-5-yl)-1-(4-methoxyphenyl)-prop-2-en-1-one
-
-
5-((10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)methyl)-pyrimidine-2,4-diamine
-
-
5-((4-methoxyphenylamino)methyl)pyrimidine-2,4-diamine
-
-
5-((5H-dibenzo[b,f]azepin-5-yl)methyl)pyrimidine-2,4-diamine
-
-
5-((benzo[d]oxazol-2-ylthio)methyl)pyrimidine-2,4-diamine
-
-
5-((methyl(naphthalen-1-yl)amino)methyl)pyrimidine-2,4-diamine
-
-
5-((naphthalen-1-ylamino)methyl)pyrimidine-2,4-diamine
-
-
6-((10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)methyl)-1,3,5-triazine-2,4-diamine
-
-
6-((10H-phenothiazin-10-yl)methyl)-1,3,5-triazine-2,4-diamine
-
-
6-((2-chloro-10H-phenothiazin-10-yl)methyl)-1,3,5-triazine-2,4-diamine
-
-
6-(2-(5H-dibenzo[b,f]azepin-5-yl)ethoxy)pyrimidine-2,4-diamine
-
-
6-(3,4,5-trimethoxybenzyloxy)pyrimidine-2,4-diamine
-
-
aminopterin
-
-
chaotrophes
-
e.g. guanidine-HCl
-
Guanidine-HCl
-
above 0.25 M
methotrexate
-
-
N-[4-[(2,4-diamino-5-methyl-furo[2,3-d]pyrimidin-6-yl)-thio]-benzoyl]-L-glutamic acid
-
-
N10-formylaminopterin
-
-
Triazinate
-
-
trimetrexate
-
-
additional information
-
overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Urea
-
slight activation
additional information
-
no activation by NaCl, Na2SO4, MgCl2, Li2SO4, CaCl2, MgSO4
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.022
7,8-dihydrofolate
-
-
0.029
NADPH
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.124
(2,4-diaminopyrimidin-5-yl)methyl naphthalene-2-sulfonate
Rattus norvegicus
-
37°C, pH not specified in the publication
0.000186
2,4-diamino-5-isopropyl-6-arylthio-7H-pyrrolo[2,3-d]pyrimidine
Rattus norvegicus
-
37°C
0.083
2,4-diamino-5-methyl-6-(1-naphthylthio)furo[2,3-d]pyrimidine
Rattus norvegicus
-
37°C, pH not specified in the publication, value above
0.039
2,4-diamino-5-methyl-6-(2',3',5',6'-tetrafluoro-4'-trifluoromethylphenylsulfanyl)-furo[2,3-d]pyrimidine
Rattus norvegicus
-
37°C, pH not specified in the publication
0.042
2,4-diamino-5-methyl-6-(2',5'-dimethoxyphenylsulfanyl)-furo[2,3-d]pyrimidine
Rattus norvegicus
-
37°C, pH not specified in the publication
0.0144
2,4-diamino-5-methyl-6-(2',6'-dichlorophenylsulfanyl)-furo[2,3-d]pyrimidine
Rattus norvegicus
-
37°C, pH not specified in the publication
0.196
2,4-diamino-5-methyl-6-(2',6'-dimethylphenylsulfanyl)-furo[2,3-d]pyrimidine
Rattus norvegicus
-
37°C, pH not specified in the publication
0.024
2,4-diamino-5-methyl-6-(2'-isopropyl-6'-methylphenylsulfanyl)-furo[2,3-d]pyrimidine
Rattus norvegicus
-
37°C, pH not specified in the publication
0.055
2,4-diamino-5-methyl-6-(2'-methoxyphenylsulfanyl)-furo[2,3-d]pyrimidine
Rattus norvegicus
-
37°C, pH not specified in the publication
0.012
2,4-diamino-5-methyl-6-(2-naphthylthio)furo[2,3-d]pyrimidine
Rattus norvegicus
-
37°C, pH not specified in the publication, value above
0.066
2,4-diamino-5-methyl-6-(3',4'-dimethoxyphenylsulfanyl)-furo[2,3-d]pyrimidine
Rattus norvegicus
-
37°C, pH not specified in the publication
0.051
2,4-diamino-5-methyl-6-(3'-methoxyphenylsulfanyl)-furo[2,3-d]pyrimidine
Rattus norvegicus
-
37°C, pH not specified in the publication
0.061
2,4-diamino-5-methyl-6-(4'-methoxyphenylsulfanyl)-furo[2,3-d]pyrimidine
Rattus norvegicus
-
37°C, pH not specified in the publication
0.00006
2,4-diamino-5-propyl-6-arylthio-7H-pyrrolo[2,3-d]pyrimidine
Rattus norvegicus
-
37°C
0.178
3-(2,4-diaminophenyl)-1-(3-(4-methylbenzyloxy)phenyl)prop-2-en-1-one
Rattus norvegicus
-
37°C, pH not specified in the publication
0.127
3-(2,4-diaminopyrimidin-5-yl)-1-(4-methoxyphenyl)-prop-2-en-1-one
Rattus norvegicus
-
37°C, pH not specified in the publication
0.0016
5-((10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)methyl)-pyrimidine-2,4-diamine
Rattus norvegicus
-
37°C, pH not specified in the publication
0.044
5-((4-methoxyphenylamino)methyl)pyrimidine-2,4-diamine
Rattus norvegicus
-
37°C, pH not specified in the publication
0.13
5-((5H-dibenzo[b,f]azepin-5-yl)methyl)pyrimidine-2,4-diamine
Rattus norvegicus
-
37°C, pH not specified in the publication
0.52
5-((benzo[d]oxazol-2-ylthio)methyl)pyrimidine-2,4-diamine
Rattus norvegicus
-
37°C, pH not specified in the publication
0.184
5-((methyl(naphthalen-1-yl)amino)methyl)pyrimidine-2,4-diamine
Rattus norvegicus
-
37°C, pH not specified in the publication
0.127
5-((naphthalen-1-ylamino)methyl)pyrimidine-2,4-diamine
Rattus norvegicus
-
37°C, pH not specified in the publication
0.139
6-((10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)methyl)-1,3,5-triazine-2,4-diamine
Rattus norvegicus
-
37°C, pH not specified in the publication
0.142
6-((10H-phenothiazin-10-yl)methyl)-1,3,5-triazine-2,4-diamine
Rattus norvegicus
-
37°C, pH not specified in the publication
0.117
6-((2-chloro-10H-phenothiazin-10-yl)methyl)-1,3,5-triazine-2,4-diamine
Rattus norvegicus
-
37°C, pH not specified in the publication
0.18
6-(2-(5H-dibenzo[b,f]azepin-5-yl)ethoxy)pyrimidine-2,4-diamine
Rattus norvegicus
-
37°C, pH not specified in the publication
0.119
6-(3,4,5-trimethoxybenzyloxy)pyrimidine-2,4-diamine
Rattus norvegicus
-
37°C, pH not specified in the publication
0.0205
N-[4-[(2,4-diamino-5-methyl-furo[2,3-d]pyrimidin-6-yl)-thio]-benzoyl]-L-glutamic acid
Rattus norvegicus
-
37°C, pH not specified in the publication
0.000003
trimetrexate
Rattus norvegicus
-
37°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.006
liver cell mitochondria, pH 7.5, temperature not specified in the publication
0.009
kidney cell mitochondria, pH 7.5, temperature not specified in the publication
additional information
-
enzyme assay
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
the source of mitochondrial DHFR activity is parental DHFR in rat
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
identification of a second functional dihydrofolate reductase enzyme in humans, DHFRL1. RNA-mediated DHFR duplication events occur across the mammal tree. Dihydrofolate reductase activity is also a feature of the mitochondria in both rat and mouse but this is not due to a second enzyme. Humans have evolved the need for two separate enzymes, while laboratory rats and mice have just one. RNA-mediated DHFR duplicates in brown rat and mouse are likely to be processed pseudogenes
physiological function
dihydrofolate reductase (DHFR) is an enzyme from the folate one-carbon metabolism pathway that plays a role in drug resistance and in reducing the synthetic supplement folic acid and 7,8-dihydrofolate to the active form, tetrahydrofolate
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
DYR_RAT
187
0
21638
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
21500
-
sedimentation equilibrium ultracentrifugation
22500
-
Walker 256 carcinoma cells, meniscus depletion method
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 21000, SDS-PAGE
monomer
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
60
-
half-life: 2 min
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
4°C, without urea, 50% loss of activity
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-65°C, frozen tissue, 4 months
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
native enzyme partially by purification of mitochondria
Walker 256 carcinosarcoma cells
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
a dihydrofolate reductase-like sequence, DHFRLS, is encoded on chromosome 4, orfs 3139757-3140178 and 413244-415704, phylogenetic analysis and tree, quantitative RT-PCR enzyme expression analysis. RT-qPCR analysis shows no evidence of expression of the DHFRLS in rat
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
renal ischemia-reperfusion decreases dihydrofolate reductase mRNA and protein levels, both of which are restored by angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, whereas GTP-cyclohydrolase 1 expression is unaltered. Renal ischemia-reperfusion suppresses endothelial nitric oxide synthase dimer while enhancing the monomer and augments inducible nitric oxide synthase mRNA, total inducible nitric oxide synthase protein and monomer, which are attenuated by angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Baker, B.R.
Tissue-specific irreversible inhibitors of dihydrofolic reductase
Acc. Chem. Res.
2
129-136
1969
Mus musculus, Pigeon, Rattus norvegicus
-
Manually annotated by BRENDA team
Then, R.L.
Purification of guanosine triphosphate cyclohydrolase I and dihydrofolate reductase on a dihydrofolate-Sepharose affinity column
Anal. Biochem.
100
122-128
1979
Escherichia coli, Rattus norvegicus, Escherichia coli B / ATCC 11303, Escherichia coli MB 1428 / B / ATCC 11303
Manually annotated by BRENDA team
Kaufman, B.T.
Methotrexate-agarose in the purification of dihydrofolate reductase
Methods Enzymol.
34
272-281
1974
Tequatrovirus T4, Bos taurus, Saccharomyces cerevisiae, Gallus gallus, Cricetulus sp., Escherichia coli, Lacticaseibacillus casei, Mus musculus, Rattus norvegicus, Salmonella enterica subsp. enterica serovar Typhimurium
Manually annotated by BRENDA team
Stanley, B.G.; Neal, G.E.; Williams, D.C.
Dihydrofolic reductase (5,6,7,8-tetrahydrofolate:NADP oxidoreductase, EC 1.5.1.3)
Methods Enzymol.
18B
775-779
1971
Rattus norvegicus
-
Manually annotated by BRENDA team
Johnson, S.J.; Gupta, S.V.; Stevenson, K.J.; Freisheim, J.H.
Purification and characterization of dihydrofolate reductase from Walker 256 carcinosarcoma
Can. J. Biochem.
60
1132-1142
1982
Rattus norvegicus
Manually annotated by BRENDA team
Delves, C.J.; Ballantine, S.P.; Tansik, R.L.; Baccanari, D.P.; Stammers, D.K.
Refolding of recombinant Pneumocystis carinii dihydrofolate reductase and characterization of the enzyme
Protein Expr. Purif.
4
16-23
1993
Pneumocystis carinii, Rattus norvegicus
Manually annotated by BRENDA team
Seujange, Y.; Eiam-Ong, S.; Tirawatnapong, T.; Eiam-Ong, S.
Role of angiotensin II on dihydrofolate reductase, GTP-cyclohydrolase 1 and nitric oxide synthase expressions in renal ischemia-reperfusion
Am. J. Nephrol.
28
692-700
2008
Rattus norvegicus (Q920D2), Rattus norvegicus
Manually annotated by BRENDA team
Gangjee, A.; Jain, H.D.; Queener, S.F.; Kisliuk, R.L.
The effect of 5-alkyl modification on the biological activity of pyrrolo[2,3-d]pyrimidine containing classical and nonclassical antifolates as inhibitors of dihydrofolate reductase and as antitumor and/or antiopportunistic infection agents
J. Med. Chem.
51
4589-4600
2008
Pneumocystis carinii, Rattus norvegicus, Toxoplasma gondii, Homo sapiens (P00374), Homo sapiens
Manually annotated by BRENDA team
Bag, S.; Tawari, N.R.; Degani, M.S.; Queener, S.F.
Design, synthesis, biological evaluation and computational investigation of novel inhibitors of dihydrofolate reductase of opportunistic pathogens
Bioorg. Med. Chem.
18
3187-3197
2010
Mycobacterium avium, Rattus norvegicus, Toxoplasma gondii, Pneumocystis carinii (P16184), Pneumocystis carinii
Manually annotated by BRENDA team
Gangjee, A.; Jain, H.D.; Phan, J.; Guo, X.; Queener, S.F.; Kisliuk, R.L.
2,4-Diamino-5-methyl-6-substituted arylthio-furo[2,3-d]pyrimidines as novel classical and nonclassical antifolates as potential dual thymidylate synthase and dihydrofolate reductase inhibitors
Bioorg. Med. Chem.
18
953-961
2010
Mycobacterium avium, Pneumocystis carinii, Rattus norvegicus, Toxoplasma gondii
Manually annotated by BRENDA team
Hughes, L.; Carton, R.; Minguzzi, S.; McEntee, G.; Deinum, E.E.; OConnell, M.J.; Parle-McDermott, A.
An active second dihydrofolate reductase enzyme is not a feature of rat and mouse, but they do have activity in their mitochondria
FEBS Lett.
589
1855-1862
2015
Homo sapiens (P00374), Homo sapiens (Q86XF0), Homo sapiens, Mus musculus (P00375), Mus musculus, Rattus norvegicus (Q920D2), Rattus norvegicus
Manually annotated by BRENDA team