Cloned (Comment) | Organism |
---|---|
gene impk, recombinant GST-tagged IMPK overexpression in human colon cancer cell line HCT-116 and the human osteosarcoma cell line U2-OS. Overexpression of kinase-deficient IPMK inhibits cell proliferation in etoposide-treated U2OS cells to a similar extent as does wild-type IPMK | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
K129A/S235A | catalytically inactive mutant | Homo sapiens |
additional information | genetic or RNA interference-mediated, and shRNA-mediated knockdown of enzyme IPMK | 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 + 1D-myo-inositol 1,4,5,6-tetrakisphosphate | Homo sapiens | - |
ADP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate | - |
? | |
ATP + 1D-myo-inositol 1,4,5-trisphosphate | Homo sapiens | - |
ADP + 1D-myo-inositol 1,4,5,6-tetrakisphosphate | - |
? | |
additional information | Homo sapiens | IPMK is a broad-specificity enzyme that converts inositol 1,4,5-trisphosphate into inositol 1,4,5,6-tetrakisphosphate (IP4) and subsequently inositol 1,3,4,5,6-pentakisphosphate | ? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q8NFU5 | gene impk | - |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
HCT-116 cell | - |
Homo sapiens | - |
U2-OS cell | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + 1D-myo-inositol 1,4,5,6-tetrakisphosphate | - |
Homo sapiens | ADP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate | - |
? | |
ATP + 1D-myo-inositol 1,4,5-trisphosphate | - |
Homo sapiens | ADP + 1D-myo-inositol 1,4,5,6-tetrakisphosphate | - |
? | |
additional information | IPMK is a broad-specificity enzyme that converts inositol 1,4,5-trisphosphate into inositol 1,4,5,6-tetrakisphosphate (IP4) and subsequently inositol 1,3,4,5,6-pentakisphosphate | Homo sapiens | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
inositol polyphosphate multikinase | - |
Homo sapiens |
IPMK | - |
Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
malfunction | knockdown of IPMK results in decreased activation of p53, decreased recruitment of p53 and p300 to target gene promoters, abrogated transcription of p53 target genes, and enhanced cell viability. Blocking the IPMK-p53 interaction decreases the extent of p53-mediated transcription. Depletion of IPMK results in decreased PUMA, Bax, and p21 abundance after treatment with etoposide, p53-null HCT116 cells transfected with IPMK shRNA do not exhibit decreased amounts of PUMA, Bax, or p21 mRNAs. In etoposide-treated HCT-116 cells, shRNA-mediated knockdown of IPMK reduces the binding of p300 to p53 | Homo sapiens |
physiological function | the enzyme stimulates tumor suppressor p53-mediated transcription by binding to p53 and enhancing its acetylation by the acetyltransferase p300 independently of its inositol phosphate and lipid kinase activities. IPMK acts as a transcriptional coactivator for p53 and that it is an integral part of the p53 transcriptional complex facilitating cell death. Tumor suppressor p53 is a critical transcriptional factor that senses and modulates cellular responses to injury and stress. Recombinantly expressed enzyme IPMK in the transfected cells binds to endogenous p53 upon treatment with etoposide, a DNA-damaging agent that canonically induces apoptosis by activating p53. IPMK enhances p53 acetylation and histone acetylation via p300, molecular mechanisms responsible for the stimulation of p53 transcriptional activity by IPMK, overview. IPMK does not require catalytic activity to enhance p53-mediated cell death | Homo sapiens |