ITPK1

This gene encodes an enzyme that belongs to the inositol 1,3,4-trisphosphate 5/6-kinase family. This enzyme regulates the synthesis of inositol tetraphosphate, and downstream products, inositol pentakisphosphate and inositol hexakisphosphate. Inositol metabolism plays a role in the development of the neural tube. Disruptions in this gene are thought to be associated with neural tube defects. A pseudogene of this gene has been identified on chromosome X. [provided by RefSeq, Jul 2016]
Diseases associated with ITPK1 include Cerebral Falx Meningioma and Anterior Cranial Fossa Meningioma. Among its related pathways are Inositol phosphate metabolism and superpathway of D-myo-inositol (1,4,5)-trisphosphate metabolism. Gene Ontology (GO) annotations related to this gene include magnesium ion binding and inositol-3,4,5,6-tetrakisphosphate 1-kinase activity.
Kinase that can phosphorylate various inositol polyphosphate such as Ins(3,4,5,6)P4 or Ins(1,3,4)P3 (PubMed:11042108, 8662638).
Phosphorylates Ins(3,4,5,6)P4 at position 1 to form Ins(1,3,4,5,6)P5 (PubMed:11042108).
This reaction is thought to have regulatory importance, since Ins(3,4,5,6)P4 is an inhibitor of plasma membrane Ca(2+)-activated Cl(-) channels, while Ins(1,3,4,5,6)P5 is not.
Also phosphorylates Ins(1,3,4)P3 on O-5 and O-6 to form Ins(1,3,4,6)P4, an essential molecule in the hexakisphosphate (InsP6) pathway (PubMed:11042108, 8662638).
Also acts as an inositol polyphosphate phosphatase that dephosphorylates Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 to Ins(1,3,4)P3, and Ins(1,3,4,5,6)P5 to Ins(3,4,5,6)P4 (PubMed:11909533, 17616525).
May also act as an isomerase that interconverts the inositol tetrakisphosphate isomers Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 in the presence of ADP and magnesium (PubMed:11909533).
Probably acts as the rate-limiting enzyme of the InsP6 pathway.
Modifies TNF-alpha-induced apoptosis by interfering with the activation of TNFRSF1A-associated death domain (PubMed:11909533, 12925536, 17616525).
Plays an important role in MLKL-mediated necroptosis.
Produces highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which bind to MLKL mediating the release of an N-terminal auto-inhibitory region leading to its activation.
Essential for activated phospho-MLKL to oligomerize and localize to the cell membrane during necroptosis (PubMed:17616525).
cytosol 5
Quaternary structure:
Monomer.
Interacts with GPS1/COPS1.