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Literature summary for 2.7.4.21 extracted from

  • Chakraborty, A.; Koldobskiy, M.A.; Sixt, K.M.; Juluri, K.M.; Mustafa, A.K.; Snowman, A.M.; van Rossum, D.B.; Patterson, R.L.; Snyder, S.H.
    HSP90 regulates cell survival via inositol hexakisphosphate kinase-2 (2008), Proc. Natl. Acad. Sci. USA, 105, 1134-1139.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.7.4.21

Activating Compound

Activating Compound Comment Organism Structure
additional information drugs and selective mutations that abolish HSP90–IP6K2 binding elicit activation of IP6K2, leading to cell death Mus musculus

Application

Application Comment Organism
medicine selectively blocking HSP90-IP6K2 binding could provide effective and safer modes of chemotherapy to block apoptosis Mus musculus

Cloned(Commentary)

Cloned (Comment) Organism
expression of the wild-type enzyme in Saccharomyces cerevisiae mutant strains, overexpression of the GST-tagged or Myc-tagged enzyme in HEK-293, HeLa, and HCT116 cells, expression of wild-type and mutant enzymes in HEK-293 cells Mus musculus

Protein Variants

Protein Variants Comment Organism
additional information depletion of IP6K2 in HEK-293 cells by RNAi leads to 40-50% reduced cell death, overview. Deletion mapping of IP6K2 to identify HSP90-binding motif, overview. The yeast Saccharomyces cerevisiae possesses constitutive and inducible homologues of HSP90, designated HSC82 and HSP82, respectively. In HSC82 KO yeast, IP6K activity is 2.5fold higher than murine wild-type, in yeast HSP82 null mutant, IP6K catalytic activity is increased but to a lesser extent. Overexpression of HSP90 markedly reduces IP6K catalytic activity in HEK-293 cells Mus musculus
R133A mutation of IP6K2 in its putative HSP90-binding motif, mutation of Arg133 abolishes IP6K2-HSP90 binding Mus musculus
R136A mutation of IP6K2 in its putative HSP90-binding motif, mutation of Arg136 abolishes IP6K2-HSP90 binding Mus musculus
W131A mutation of IP6K2 in its putative HSP90-binding motif, mutation of Trp131 modestly diminishes IP6K2-HSP90 binding, the catalytically impaired IP6K2-W131A does not induce cell death Mus musculus

Inhibitors

Inhibitors Comment Organism Structure
heat shock protein Hsp90 binding of HSP90 inhibits IP6K2 catalytic activity, IP6K2 binds to HSP90's C terminus. Depletion of HSP90 by RNAi in HEK-293 cells increases IP6K catalytic activity about 2.5fold, specificity of IP6K2-HSP90 interaction, overview. Drugs and selective mutations that abolish HSP90–IP6K2 binding elicit activation of IP6K2, leading to cell death. Overexpression of HSP90 markedly and specifically reduces IP6K catalytic activity in HEK-293 cells, overexpression of HSP90 does not influence catalytic activity of IP6K1 Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Mus musculus IP6K2 belongs to a family of enzymes generating the inositol pyrophosphate IP7 [diphosphoinositol pentakisphosphate (5-PP-IP5)], it mediates apoptosis, increased IP6K2 activity sensitizes cancer cells to stressors, whereas its depletion blocks cell death ?
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Organism

Organism UniProt Comment Textmining
Mus musculus
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Source Tissue

Source Tissue Comment Organism Textmining
brain coexpression with Hsp90 Mus musculus
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kidney coexpression with Hsp90 Mus musculus
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information IP6K2 belongs to a family of enzymes generating the inositol pyrophosphate IP7 [diphosphoinositol pentakisphosphate (5-PP-IP5)], it mediates apoptosis, increased IP6K2 activity sensitizes cancer cells to stressors, whereas its depletion blocks cell death Mus musculus ?
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Synonyms

Synonyms Comment Organism
inositol hexakisphosphate kinase-2
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 Mus musculus
IP6K2
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 Mus musculus