Cloned (Comment) | Organism |
---|---|
gene FPGS, DNA and amino acid sequence determination and analysis of splicing variants, quantitative RT- and real-time-PCR analyses of FPGS enzyme expression and splicing patterns. FPGS splicing alterations are abundant in blasts of acute lymphoblastic leukemia (ALL) patients, overview | Homo sapiens |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | required | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate | Homo sapiens | - |
ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1 | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
B-lymphocyte | - |
Homo sapiens | - |
bone marrow cell | - |
Homo sapiens | - |
CCRF-CEM cell | - |
Homo sapiens | - |
CEM cell | - |
Homo sapiens | - |
culture condition:CD34+ cell | - |
Homo sapiens | - |
leukemia cell | - |
Homo sapiens | - |
monocyte | - |
Homo sapiens | - |
peripheral blood cell | - |
Homo sapiens | - |
T-lymphocyte | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate | - |
Homo sapiens | ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1 | - |
? |
Synonyms | Comment | Organism |
---|---|---|
Folylpolyglutamate synthetase | - |
Homo sapiens |
FPGS | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
8.8 | 8.9 | assay at | Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
malfunction | a spectrum of FPGS splicing alterations occur in humans, including exon skipping and intron retention, all of which prove to frequently emerge in both pediatric and adult leukemia patient specimens. These splicing alterations result in loss of FPGS function. Pulse-exposure of leukemia cells to antifolates and other chemotherapeutics markedly enhance the prevalence of several FPGS splicing alterations in antifolate-resistant cells, but not in their parental antifolate-sensitive counterparts. An assortment of deleterious FPGS splicing alterations may constitute a mechanism of antifolate resistance in childhood acute lymphoblastic leukemia (ALL) | Homo sapiens |
additional information | structural and functional consequences of splicing alterations on FPGS protein, the relationship between FPGS splicing alterations and MTX resistance, overview | Homo sapiens |
physiological function | the cytotoxic activity of various antifolates is largely dependent on the activity of folylpolyglutamate synthetase (FPGS). The latter enzyme catalyzes the addition of multiple glutamate residues (i.e. polyglutamylation) to both folates and antifolates upon their entry into the cell. This unique metabolic conversion dramatically enhances the intracellular retention of antifolates including methotreaxate (MTX) as the polyglutamate forms of antifolates are no longer substrates of various efflux transporters. Polyglutamylation also decreases the Ki of MTX and other antifolates like pemetrexed to their target enzymes including dihydrofolate reductase and thymidylate synthase | Homo sapiens |