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Literature summary for 1.5.1.3 extracted from
- 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 .
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| 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 |
| 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 |
| phylogenetic analysis and tree, quantitative RT-PCR enzyme expression analysis | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| 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
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cytoplasm | - |
Homo sapiens | 5737 | - |
| cytoplasm | - |
Mus musculus | 5737 | - |
| cytoplasm | - |
Rattus norvegicus | 5737 | - |
| mitochondrion | - |
Homo sapiens | 5739 | - |
| mitochondrion | the source of mitochondrial DHFR activity is parental DHFR in mouse | Mus musculus | 5739 | - |
| mitochondrion | the source of mitochondrial DHFR activity is parental DHFR in rat | Rattus norvegicus | 5739 | - |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 7,8-dihydrofolate + NADPH + H+ | Homo sapiens | - |
5,6,7,8-tetrahydrofolate + NADP+ | - |
r |  |
| 7,8-dihydrofolate + NADPH + H+ | Mus musculus | - |
5,6,7,8-tetrahydrofolate + NADP+ | - |
r | |
| 7,8-dihydrofolate + NADPH + H+ | Rattus norvegicus | - |
5,6,7,8-tetrahydrofolate + NADP+ | - |
r | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | P00374 | - |
- |
| Homo sapiens | Q86XF0 | - |
- |
| Mus musculus | P00375 | - |
- |
| Rattus norvegicus | Q920D2 | - |
- |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| native enzyme partially by purification of mitochondria | Mus musculus |
| native enzyme partially by purification of mitochondria | Rattus norvegicus |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| 4T1 cell | enzyme activity is highly increased in the cancer cell line | Mus musculus | - |
| kidney | - |
Rattus norvegicus | - |
| liver | - |
Homo sapiens | - |
| liver | - |
Mus musculus | - |
| liver | - |
Rattus norvegicus | - |
| NRK cell | - |
Rattus norvegicus | - |
Specific Activity [micromol/min/mg]
| Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
|---|---|---|---|
| 0.005 | - |
liver cell mitochondria, pH 7.5, temperature not specified in the publication | Mus musculus |
| 0.006 | - |
liver cell mitochondria, pH 7.5, temperature not specified in the publication | Rattus norvegicus |
| 0.009 | - |
kidney cell mitochondria, pH 7.5, temperature not specified in the publication | Rattus norvegicus |
| 0.044 | - |
mitochondria of cancer cell line 4T1, pH 7.5, temperature not specified in the publication | Mus musculus |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 7,8-dihydrofolate + NADPH + H+ | - |
Homo sapiens | 5,6,7,8-tetrahydrofolate + NADP+ | - |
r | |
| 7,8-dihydrofolate + NADPH + H+ | - |
Mus musculus | 5,6,7,8-tetrahydrofolate + NADP+ | - |
r | |
| 7,8-dihydrofolate + NADPH + H+ | - |
Rattus norvegicus | 5,6,7,8-tetrahydrofolate + NADP+ | - |
r | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| ? | x * 21000, SDS-PAGE | Mus musculus |
| ? | x * 21000, SDS-PAGE | Rattus norvegicus |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| DHFR | - |
Mus musculus |
| DHFR | - |
Rattus norvegicus |
| DHFR | - |
Homo sapiens |
| DHFR2 | - |
Homo sapiens |
| DHFRL1 | - |
Homo sapiens |
| DHFRLS | - |
Mus musculus |
| dihydrofolate reductase-like | - |
Homo sapiens |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7.5 | - |
assay at | Homo sapiens |
| 7.5 | - |
assay at | Mus musculus |
| 7.5 | - |
assay at | Rattus norvegicus |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| NADP+ | - |
Homo sapiens | |
| NADP+ | - |
Mus musculus | |
| NADP+ | - |
Rattus norvegicus | |
| NADPH | - |
Homo sapiens | |
| NADPH | - |
Mus musculus | |
| NADPH | - |
Rattus norvegicus | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
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