ITPKA is one of three inositol-trisphosphate 3-kinase (ITP3K) genes in humans. ITP3K proteins regulate inositol phosphate metabolism by phosphorylation of the second messenger inositol 1,4,5-trisphosphate to produce Ins(1,3,4,5)P4, which is sometimes abbreviated as IP4. Structurally, ITPKA belongs to the inositol polyphosphate kinase (IPK) family. The activity of the inositol 1,4,5-trisphosphate 3-kinase is responsible for regulating the levels of a large number of inositol polyphosphates that are important in cellular signaling, most notably, inositol trisphosphate, which is the enzyme's only substrate. Both calcium/calmodulin and protein phosphorylation mechanisms control its activity. It is also a substrate for the cyclic AMP-dependent protein kinase, calcium/calmodulin- dependent protein kinase II, and protein kinase C in vitro. ITPKA and ITPKB are 68% identical in the C-terminus region The amino- terminal region of ITPKA binds filamentous actin. This property localizes the ITPKA to dendritic spines in principal neurons.[8][9][10] ITPKA is expressed physiologically in neurons, but it is sometimes expressed in cancer cells and may contribute to processes of metastasis.[11]
Although ITPKA is expressed physiologically in neurons and testis, it sometimes becomes expressed in cancer cells, and the expression usually makes the cancer more aggressive.[11][14]
F-tractin is amino acids 9-52 of rat ITPKA. It was later determined that amino acids 9-40 were sufficient for binding filamentous actin.[15][16] When fused to a reporter, such as green fluorescent protein, It is useful for the visualization of actin dynamics in living cells.[17][18]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Erneux C, Roeckel N, Takazawa K, Mailleux P, Vassart G, Mattei MG (October 1992). "Localization of the genes for human inositol 1,4,5-trisphosphate 3-kinase A (ITPKA) and B (ITPKB) to chromosome regions 15q14-q21 and 1q41-q43, respectively, by in situ hybridization". Genomics. 14 (2): 546–7. doi:10.1016/S0888-7543(05)80265-4. PMID1330886.
^Yamada M, Kakita A, Mizuguchi M, Rhee SG, Kim SU, Ikuta F (March 1993). "Specific expression of inositol 1,4,5-trisphosphate 3-kinase in dendritic spines". Brain Research. 606 (2): 335–40. doi:10.1016/0006-8993(93)91004-C. PMID8387863. S2CID10790958.
Takazawa K, Perret J, Dumont JE, Erneux C (January 1991). "Molecular cloning and expression of a human brain inositol 1,4,5-trisphosphate 3-kinase". Biochemical and Biophysical Research Communications. 174 (2): 529–35. doi:10.1016/0006-291X(91)91449-M. PMID1847047.
Lin AN, Barnes S, Wallace RW (August 1990). "Phosphorylation by protein kinase C inactivates an inositol 1,4,5-trisphosphate 3-kinase purified from human platelets". Biochemical and Biophysical Research Communications. 170 (3): 1371–6. doi:10.1016/0006-291X(90)90546-Y. PMID2167676.
