EC Number   |
General Information |
Reference |
|---|
   2.7.1.151 | evolution |
IPMK is a member of the so-called IP-kinase family that includes IP3Ks and IP6Ks, evolutionary relationships and structure comparisons, overview. There has been co-evolution of Ins(1,4,5)P3 and PtdIns(4,5)P2 3-kinase activities |
761469 |
| 2.7.1.151 | malfunction |
immediate early gene induction by electroconvulsive stimulation is virtually abolished in the brains of IPMK-deleted mice, which also display deficits in spatial memory. Dominant-negative constructs, which prevent IPMK-CBP binding, substantially decrease immediate early gene induction |
739531 |
| 2.7.1.151 | malfunction |
IPMK depletion or catalytic inactivation selectively decreases RAD51 protein abundance and the nuclear export of RAD51 mRNA, thereby impairing homologous recombination. Depletion or catalytic inactivation of IPMK selectively inhibits the nuclear export of the poly(A)+ mRNAs that encode essential homologous recombination factors such as RAD51, CHK1, or FANCD2, decreasing protein abundance, whereas, in contrast, several genes involved in NHEJ are unaffected. IPMK inactivation inhibits RAD51 recombinase assembly, provokes sensitivity to genotoxic lesions repaired by homologous recombination, and causes structural chromosome aberrations typical of defective homologous recombination. Overexpression of catalytically inactive IPMK mutants is sufficient to reduce RAD51 foci formation |
739065 |
| 2.7.1.151 | 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 |
739703 |
| 2.7.1.151 | malfunction |
severe loss of IPMK in the striatum of Huntington's disease patients, the depletion reflects mHtt-induced impairment of COUP-TF-interacting protein 2 (Ctip2), a striatal-enriched transcription factor for IPMK, as well as alterations in IPMK protein stability. IPMK overexpression reverses the metabolic activity deficit in a cell model of Huntington's disease. IPMK depletion appears to mediate neural dysfunction, because intrastriatal delivery of IPMK abates the progression of motor abnormalities and rescues striatal pathology in transgenic murine models of Huntington's disease |
739553 |
| 2.7.1.151 | metabolism |
IPMK expression rescues mHtt-induced deficits in mitochondrial metabolic activity. Delivery of IPMK in a transgenic Huntington's disease model improves pathological changes and motor performance. The Ctip2-IPMK-Akt signaling pathway provides a previously unidentified therapeutic target for Huntington's disease |
739553 |
| 2.7.1.151 | metabolism |
the enzyme IPMK is involved in a transcript-selective mRNA export pathway controlled by phosphoinositide turnover that preserves genome integrity in humans |
739065 |
| 2.7.1.151 | more |
HsIPMK owns a catalytic pocket that is more constrained than those of the plant and yeast orthologues. Also unique to mammalian IPMK is a catalytically important proline-loop, and a preponderance of Gln residues in the active site. Description of two versions of Ins(1,4,5)P3 within the active site, first as a free inositol phosphate, and second as the headgroup of a soluble analogue of PtdIns(4,5)P2. The structure of the IPMK apoenzyme is determined by a molecular replacement approach using a model constructed from the template of yeast ScIPMK (PDB accession code 2IF8), and this apo-structure is used for further elucidation of the structures of crystal complexes with ADP plus either Ins(1,4,5)P3 or diC4-PtdIns(4,5)P2. Domains that are similar to the so-called N- and C-lobes that comprise the ATP-binding site. The C-terminal lobe comprising residues 136-149 and 175-416, which is an alphabeta-fold with five, central antiparallel beta-strands including beta4-6, beta8, and beta9, a pair of small antiparallel beta-strands (beta7 and beta10), and three alpha-helices (alpha5-alpha7). Also in the C-lobe of HsIPMK, a 310 helix is observed between the beta6 strand and alpha5 helix. His388 is at the catalytic center. Structure comparisons, overview |
761469 |
| 2.7.1.151 | physiological function |
human inositol phosphate multikinase (HsIPMK) critically contributes to intracellular signaling through its inositol-1,4,5-trisphosphate (Ins(1,4,5)P3) 3-kinase and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) 3-kinase activities. HsIPMK is both an inositol phosphate kinase and a PtdIns(4,5)P2 kinase |
761469 |
| 2.7.1.151 | physiological function |
inositol phosphate multikinase regulates transcript-selective nuclear mRNA export to preserve genome integrity. The transcript-selective nuclear export mechanism affecting certain human transcripts, enriched for functions in genome duplication and repair, is controlled by inositol polyphosphate multikinase, an enzyme catalyzing inositol polyphosphate and phosphoinositide turnover. Function for human IPMK in RAD51 assembly and DNA repair by homologous recombination, overview |
739065 |
