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IPMK

Function

Inositol phosphate kinase with a broad substrate specificity (PubMed:12027805, PubMed:12223481, PubMed:28882892, PubMed:30420721, PubMed:30624931). Phosphorylates inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) first to inositol 1,3,4,5-tetrakisphosphate and then to inositol 1,3,4,5,6-pentakisphosphate (Ins(1,3,4,5,6)P5) (PubMed:12027805, PubMed:12223481, PubMed:28882892, PubMed:30624931). Phosphorylates inositol 1,3,4,6-tetrakisphosphate (Ins(1,3,4,6)P4) (PubMed:12223481). Phosphorylates inositol 1,4,5,6-tetrakisphosphate (Ins(1,4,5,6)P4) (By similarity). Phosphorylates glycero-3-phospho-1D-myo-inositol 4,5-bisphosphate to glycero-3-phospho-1D-myo-inositol 3,4,5-trisphosphate (PubMed:28882892, PubMed:30420721). Plays an important role in MLKL-mediated necroptosis via its role in the biosynthesis of inositol pentakisphosphate (InsP5) and inositol hexakisphosphate (InsP6). Binding of these highly phosphorylated inositol phosphates to MLKL mediates the release of an N-terminal auto-inhibitory region, leading to activation of the kinase. Essential for activated phospho-MLKL to oligomerize and localize to the cell membrane during necroptosis (PubMed:29883610). Required for normal embryonic development, probably via its role in the biosynthesis of inositol 1,3,4,5,6-pentakisphosphate (Ins(1,3,4,5,6)P5) and inositol hexakisphosphate (InsP6) (By similarity).

Pathway

Phospholipid metabolism; phosphatidylinositol metabolism.

Sequence Similarities

Belongs to the inositol phosphokinase (IPK) family.

Tissue Specificity

Ubiquitous, with the highest expression in skeletal muscle, liver, placenta, lung, peripheral blood leukocytes, kidney, spleen and colon.

Cellular localization

Alternative names

IMPK, IPMK, Inositol polyphosphate multikinase

swissprot:Q8NFU5 omim:609851 entrezGene:253430