ITPK1
ITPK1 (inositol-tetrakisphosphate 1-kinase) is an inositol polyphosphate kinase that phosphorylates Ins(3,4,5,6)P4 and Ins(1,3,4)P3 and is probably the rate-limiting enzyme of the InsP6 pathway. It was previously named inositol 1,3,4-triphosphate 5/6 kinase. Browse Assay Genie's current range of ITPK1 research reagents below, or read on for the biology behind the target.
ITPK1 is a kinase that acts on several inositol polyphosphates. It phosphorylates Ins(3,4,5,6)P4 at position 1 to form Ins(1,3,4,5,6)P5. This step is thought to be regulatory, because Ins(3,4,5,6)P4 inhibits plasma membrane Ca(2+)-activated Cl(-) channels while Ins(1,3,4,5,6)P5 does not. ITPK1 also phosphorylates Ins(1,3,4)P3 on O-5 and O-6 to give Ins(1,3,4,6)P4, an essential molecule in the hexakisphosphate (InsP6) pathway, where it probably acts as the rate-limiting enzyme.
The enzyme is not purely a kinase. It can also act as an inositol polyphosphate phosphatase, dephosphorylating 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. It may also act as an isomerase, interconverting Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 in the presence of ADP and magnesium. ITPK1 belongs to the ITPK1 family and, in HGNC classification, to the inositol phosphate kinases and ATP-grasp fold containing gene groups. The mouse ortholog is Itpk1.
Beyond inositol metabolism, ITPK1 influences cell death. It modifies TNF-induced apoptosis by interfering with activation of the TNFRSF1A-associated death domain. It also plays an important role in MLKL-mediated necroptosis: the highly phosphorylated inositol phosphates it produces, such as InsP6, bind MLKL and release its N-terminal auto-inhibitory region. ITPK1 is essential for activated phospho-MLKL to oligomerize and localise to the cell membrane. According to the NCBI Gene summary, inositol metabolism contributes to neural tube development, and disruptions in the ITPK1 gene are thought to be associated with neural tube defects. A pseudogene has been identified on chromosome X.
ITPK1 regulates synthesis of inositol tetrakisphosphate and the downstream products inositol pentakisphosphate and inositol hexakisphosphate.
ITPK1 is needed for MLKL activation, as its InsP6 products release MLKL auto-inhibition and allow oligomerisation and membrane localisation.
ITPK1 modifies TNF-induced apoptosis by interfering with activation of the TNFRSF1A-associated death domain.
Inositol metabolism contributes to neural tube development, and disruptions in the ITPK1 gene are thought to be associated with neural tube defects.
ITPK1 phosphorylates inositol polyphosphates such as Ins(3,4,5,6)P4 and Ins(1,3,4)P3, and can also dephosphorylate several inositol phosphates. It is probably the rate-limiting enzyme of the InsP6 pathway and supports MLKL-mediated necroptosis through its highly phosphorylated products.
The HGNC full name is inositol-tetrakisphosphate 1-kinase, and the previous name was inositol 1,3,4-triphosphate 5/6 kinase. NCBI describes the enzyme as a member of the inositol 1,3,4-trisphosphate 5/6-kinase family. No alternative gene symbols are listed.
NCBI Gene reports that disruptions in the ITPK1 gene are thought to be associated with neural tube defects. A mouse ortholog, Itpk1, exists. Check the datasheet of any product for its validated reactivity.
Related inositol phosphate kinases with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q13572; product specifications from Assay Genie datasheets.