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Literature summary for 2.7.1.67 extracted from

  • Berger, K.L.; Kelly, S.M.; Jordan, T.X.; Tartell, M.A.; Randall, G.
    Hepatitis C virus stimulates the phosphatidylinositol 4-kinase III alpha-dependent phosphatidylinositol 4-phosphate production that is essential for its replication (2011), J. Virol., 85, 8870-8883.
    View publication on PubMedView publication on EuropePMC

Activating Compound

Activating Compound Comment Organism Structure
NS5A stimulates phosphatidylinositol 4-phosphate production in vivo and enhances PI4KA kinase activity in vitro, but not other viral proteins from hepatitis C virus, overview Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
isozyme PI4KA, DNA and amino acid sequence determination and analysis, expression of GFP-tagged wild-type and mutant enzymes in HEK-293T cells and in U2OS cells Homo sapiens

Protein Variants

Protein Variants Comment Organism
K1792L site-direcetd mutagenesis, inactive isozyme PI4KA Homo sapiens
additional information isozyme PI4KA depletion by siRNA expression in Huh-7.5 cells, transcomplementation, complementation with the siRNA-resistant PI4KA enhances infectious HCV production 110fold compared to the vector alone, overview. In cell lines expressing the HCV polyprotein, PI4KA siRNAs alter the localization of the HCV NS5A protein, while membranous webs are difficult to detect in HCV-infected cells pretreated with PI4KA siRNAs Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
cytoplasm
-
Homo sapiens 5737
-
endoplasmic reticulum
-
Homo sapiens 5783
-
additional information phosphatidylinositol 4-phosphate localization has a distinct pattern in cells infected with hepatitis C virus (extensive cytoplasmic distribution) compared to uninfected cells Homo sapiens
-
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + 1-phosphatidyl-1D-myo-inositol Homo sapiens
-
ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
Huh-7.5 cell
-
Homo sapiens
-
U2-OS cell cell lines with inducible expression of the HCV polyprotein or individual viral proteins Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + 1-phosphatidyl-1D-myo-inositol
-
Homo sapiens ADP + 1-phosphatidyl-1D-myo-inositol 4-phosphate
-
?

Synonyms

Synonyms Comment Organism
phosphatidylinositol 4-kinase III alpha
-
Homo sapiens
PI4KA
-
Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ATP
-
Homo sapiens

General Information

General Information Comment Organism
malfunction siRNAs that reduce PI4KA accumulation appear to perturb membranous web formation. Cell viral polyprotein expression results in enhanced cytoplasmic phosphatidylinositol 4-phosphate production. Increased phosphatidylinositol 4-phosphate accumulation following hepatitis C virus protein expression is precluded by silencing the expression of isozyme PI4KA, but not the related isozyme PI4KB. Silencing PI4KA also results in aberrant agglomeration of viral replicase proteins, including NS5A, NS5B, and NS3. NS5A alone, but not other viral proteins, stimulates phosphatidylinositol 4-phosphate production in vivo and enhanced PI4KA kinase activity in vitro Homo sapiens
additional information hepatitis C virus stimulates the phosphatidylinositol 4-kinase III alpha-dependent phosphatidylinositol 4-phosphate production that is essential for its replication, overview. PI4KA is also implicated in HCV replication complex formation Homo sapiens