ITPK1 Human

Inositol-Tetrakisphosphate 1-Kinase (ITPK1) is an enzyme that plays a crucial role in the metabolism of inositol phosphates. This enzyme is encoded by the ITPK1 gene, which is located on chromosome 14 in humans . ITPK1 is involved in the phosphorylation of various inositol polyphosphates, which are important signaling molecules in cellular processes.

The enzyme activity of ITPK1 was first described in 1987 by two independent research groups . The gene encoding the enzyme was cloned almost a decade later, in 1996 . Initially, the enzyme was referred to as inositol 1,3,4-trisphosphate 5/6-kinase due to its ability to phosphorylate inositol 1,3,4-trisphosphate (Ins(1,3,4)P3) at positions 5 and 6 . Later, it was discovered that ITPK1 could also phosphorylate Ins(3,4,5,6)P4 at position 1, leading to the updated nomenclature .

ITPK1 is a kinase that can phosphorylate various inositol polyphosphates, such as Ins(3,4,5,6)P4 and Ins(1,3,4)P3 . The enzyme’s activity is crucial for the synthesis of inositol tetraphosphate, pentakisphosphate, and hexakisphosphate . These molecules play significant roles in cellular signaling pathways, including the regulation of calcium channels and chloride flux across the plasma membrane .

The enzyme is composed of 12 exons and is ubiquitously expressed in various tissues, with the highest expression levels observed in the brain and heart . Alternative splicing at the 5′ untranslated region of the gene has been noted, although its significance remains unclear .

Inositol metabolism, regulated by ITPK1, is essential for various physiological processes. One of the critical roles of inositol phosphates is in the development of the neural tube . Disruptions in the ITPK1 gene have been associated with neural tube defects, highlighting the enzyme’s importance in embryonic development .

Additionally, the enzyme’s ability to regulate chloride flux across the plasma membrane through the phosphorylation of Ins(3,4,5,6)P4 has implications for various physiological processes . The enzyme’s unique phosphotransferase activity, which involves the ADP-driven removal of the 1-phosphate from Ins(1,3,4,5,6)P5, further underscores its regulatory significance .

Mutations or disruptions in the ITPK1 gene have been linked to several disorders. For instance, alterations in the gene are thought to be associated with Spitzoid melanoma and developmental and epileptic encephalopathy 95 . The enzyme’s role in neural tube development also implicates it in conditions related to neural tube defects .