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Literature summary extracted from

  • 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 (2015), FEBS Lett., 589, 1855-1862 .
    View publication on PubMed

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.5.1.3 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 Rattus norvegicus
1.5.1.3 a dihydrofolate reductase-like sequence, DHFRLS, is encoded on chromosome 9, orf 31567433:31568480, phylogenetic analysis and tree, quantitative RT-PCR enzyme expression analysis Mus musculus
1.5.1.3 phylogenetic analysis and tree, quantitative RT-PCR enzyme expression analysis Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
1.5.1.3 additional information DHFRLS in wild black rat has an intact open reading frame due to a 2 bp deletion compared to the brown rat or the Brown Norway rat Rattus norvegicus

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
1.5.1.3 cytoplasm
-
 Homo sapiens 5737
-
1.5.1.3 cytoplasm
-
 Mus musculus 5737
-
1.5.1.3 cytoplasm
-
 Rattus norvegicus 5737
-
1.5.1.3 mitochondrion
-
 Homo sapiens 5739
-
1.5.1.3 mitochondrion the source of mitochondrial DHFR activity is parental DHFR in mouse Mus musculus 5739
-
1.5.1.3 mitochondrion the source of mitochondrial DHFR activity is parental DHFR in rat Rattus norvegicus 5739
-

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.5.1.3 7,8-dihydrofolate + NADPH + H+ Homo sapiens
-
 5,6,7,8-tetrahydrofolate + NADP+
-
 r
1.5.1.3 7,8-dihydrofolate + NADPH + H+ Mus musculus
-
 5,6,7,8-tetrahydrofolate + NADP+
-
 r
1.5.1.3 7,8-dihydrofolate + NADPH + H+ Rattus norvegicus
-
 5,6,7,8-tetrahydrofolate + NADP+
-
 r

Organism

EC Number Organism UniProt Comment Textmining
1.5.1.3 Homo sapiens P00374
-
-
1.5.1.3 Homo sapiens Q86XF0
-
-
1.5.1.3 Mus musculus P00375
-
-
1.5.1.3 Rattus norvegicus Q920D2
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.5.1.3 native enzyme partially by purification of mitochondria Mus musculus
1.5.1.3 native enzyme partially by purification of mitochondria Rattus norvegicus

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.5.1.3 4T1 cell enzyme activity is highly increased in the cancer cell line Mus musculus
-
1.5.1.3 kidney
-
 Rattus norvegicus
-
1.5.1.3 liver
-
 Homo sapiens
-
1.5.1.3 liver
-
 Mus musculus
-
1.5.1.3 liver
-
 Rattus norvegicus
-
1.5.1.3 NRK cell
-
 Rattus norvegicus
-

Specific Activity [micromol/min/mg]

EC Number Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
1.5.1.3 0.005
-
 liver cell mitochondria, pH 7.5, temperature not specified in the publication Mus musculus
1.5.1.3 0.006
-
 liver cell mitochondria, pH 7.5, temperature not specified in the publication Rattus norvegicus
1.5.1.3 0.009
-
 kidney cell mitochondria, pH 7.5, temperature not specified in the publication Rattus norvegicus
1.5.1.3 0.044
-
 mitochondria of cancer cell line 4T1, pH 7.5, temperature not specified in the publication Mus musculus

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.5.1.3 7,8-dihydrofolate + NADPH + H+
-
 Homo sapiens 5,6,7,8-tetrahydrofolate + NADP+
-
 r
1.5.1.3 7,8-dihydrofolate + NADPH + H+
-
 Mus musculus 5,6,7,8-tetrahydrofolate + NADP+
-
 r
1.5.1.3 7,8-dihydrofolate + NADPH + H+
-
 Rattus norvegicus 5,6,7,8-tetrahydrofolate + NADP+
-
 r

Subunits

EC Number Subunits Comment Organism
1.5.1.3 ? x * 21000, SDS-PAGE Mus musculus
1.5.1.3 ? x * 21000, SDS-PAGE Rattus norvegicus

Synonyms

EC Number Synonyms Comment Organism
1.5.1.3 DHFR
-
 Mus musculus
1.5.1.3 DHFR
-
 Rattus norvegicus
1.5.1.3 DHFR
-
 Homo sapiens
1.5.1.3 DHFR2
-
 Homo sapiens
1.5.1.3 DHFRL1
-
 Homo sapiens
1.5.1.3 DHFRLS
-
 Mus musculus
1.5.1.3 dihydrofolate reductase-like
-
 Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.5.1.3 7.5
-
 assay at Homo sapiens
1.5.1.3 7.5
-
 assay at Mus musculus
1.5.1.3 7.5
-
 assay at Rattus norvegicus

Cofactor

EC Number Cofactor Comment Organism Structure
1.5.1.3 NADP+
-
 Homo sapiens
1.5.1.3 NADP+
-
 Mus musculus
1.5.1.3 NADP+
-
 Rattus norvegicus
1.5.1.3 NADPH
-
 Homo sapiens
1.5.1.3 NADPH
-
 Mus musculus
1.5.1.3 NADPH
-
 Rattus norvegicus

General Information

EC Number General Information Comment Organism
1.5.1.3 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 Homo sapiens
1.5.1.3 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 Mus musculus
1.5.1.3 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 Rattus norvegicus
1.5.1.3 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 Homo sapiens
1.5.1.3 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 Mus musculus
1.5.1.3 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 Rattus norvegicus