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Literature summary for 6.3.4.2 extracted from

  • Higgins, M.J.; Graves, P.R.; Graves, L.M.
    Regulation of human cytidine triphosphate synthetase 1 by glycogen synthase kinase 3 (2007), J. Biol. Chem., 282, 29493-29503.
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
a carboxyl-terminal FLAG sequence is introduced after insertion of human CTPS1 into pCDNA 4 myc/his, expression by transient transfection of human embryonic kidney (HEK) 293 cells Homo sapiens

Protein Variants

Protein Variants Comment Organism
E579A HEK 293 cells: no effect on phosphorylation of CTPS1 by glycogen synthase kinase 3 Homo sapiens
S571I Ser-571 is the major site phosphorylated by glycogen synthase kinase 3 in intact human embryonic kidney 293 cells Homo sapiens
S571I/S574A phosphorylation by glycogen synthase kinase 3 does not show altered incorporation of phosphate compared with S571I alone Homo sapiens
S571I/S574A/S575A phosphorylation by glycogen synthase kinase 3 shows a slight decrease in the amount of phosphate incorporated into CTPS1 compared with S571I/S575A, suggesting that Ser-574 may serve as a minor secondary site for glycogen synthase kinase 3 phosphorylation Homo sapiens
S571I/S575A phosphorylation by glycogen synthase kinase 3 shows slightly elevated amounts of phosphate incorporated into CTPS1 compared with S571I, suggesting that without the ability to phosphorylate Ser-571 or Ser-575 in vitro, glycogen synthase kinase 3 may phosphorylate an alternative site, albeit to a much lesser extent Homo sapiens
S574A greatly reduces phosphorylation by glycogen synthase kinase 3 Homo sapiens
S574A/S575A greatly reduces phosphorylation by glycogen synthase kinase 3 Homo sapiens
S575A greatly reduces phosphorylation by glycogen synthase kinase 3. Mutation of Ser-575 prevents the phosphorylation of Ser-571, suggesting that phosphorylation of Ser-575 is necessary for priming the glycogen synthase kinase 3 phosphorylation of Ser-571 Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens Q9NRF8
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-

Posttranslational Modification

Posttranslational Modification Comment Organism
phosphoprotein it is shown that Ser-574 and Ser-575 are phosphorylated residues. Mutation of Ser-571 demonstrates that Ser-571 is the major site phosphorylated by glycogen synthase kinase 3 in intact human embryonic kidney 293 cells by glycogen synthase kinase 3 in vitro. Mutation of Ser-575 prevents phosphorylation of Ser-571, suggesting phosphorylation of Ser-575 is necessary for priming the glycogen synthase kinase 3 phosphorylation of Ser-571 Homo sapiens
phosphoprotein stimulation/inhibition of protein kinase A and protein kinase C does not alter the phosphorylation of endogenous human CTPS1 in human embryonic kidney 293 cells. Low serum conditions increased phosphorylation of endogenous CTPS1 and phosphorylation is inhibited by the glycogen synthase kinase 3 (GSK3) inhibitor indirubin-3’-monoxime and GSK3beta short interfering RNAs, demonstrating the involvement of glycogen synthase kinase 3 in phosphorylation of endogenous human CTPS1 Homo sapiens

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
additional information
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low serum is found to decrease CTPS1 activity, and incubation with the glycogen synthase kinase 3 inhibitor indirubin-3’-monoxime protects against this decrease in activity. Incubation with an alkaline phosphatase increases CTPS1 activity in a time-dependent manner, demonstrating that phosphorylation inhibits CTPS1 activity Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + UTP + Gln + H2O
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Homo sapiens ADP + CTP + Glu + phosphate
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?

Synonyms

Synonyms Comment Organism
CTPS1
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Homo sapiens
cytidine triphosphate synthetase
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Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8.1
-
assay at Homo sapiens