HGNC Approved Gene Symbol: ITPKB
Cytogenetic location: 1q42.12 Genomic coordinates (GRCh38): 1:226,631,690-226,739,282 (from NCBI)
Inositol 1,4,5-trisphosphate 3-kinase (ITPK) catalyzes the phosphorylation of Ins(1,4,5)P3 to Ins(1,3,4,5)P4, both of which are modulators of calcium homeostasis. ITPK isoforms include ITPKA (147521), ITPKB, and ITPKC (606476), all of which contain a conserved catalytic unit in their C termini, but have unique N-terminal sequences and tissue distributions.
Takazawa et al. (1991) isolated an ITPKB cDNA from a human hippocampus cDNA library. Sequencing yielded an open reading frame encoding a 472-amino acid protein with a calculated relative mass of 53,451. The C-terminal part of ITPKB, namely residues 187 to 462, was 68% identical to ITPKA in amino acid sequence.
By in situ hybridization, Erneux et al. (1992) mapped the ITPKB gene to 1q41-q43.
Pouillon et al. (2003) generated Itpkb-deficient mice by homologous recombination. They observed 50% mortality in these mice within the first 3 months of age and no survival beyond 6 months of age. The mice had dilated stomachs and intestines accompanied by Giardia infection, suggesting a defect in T-cell development or function. Immunohistochemical and flow cytometric analyses demonstrated an absence of CD4 (186940)- and CD8 (see 186910)-positive T lymphocytes, but no lack of B cells, in spleen and lymph nodes, as well as an absence of thymic medulla epithelial cells. T-cell-dependent immunoglobulin isotype production was also reduced in mutant mice. The authors identified a developmental block between double-positive (CD4 and CD8) and single-positive thymocytes, whose numbers were reduced in Itpkb -/- mice and intermediate in heterozygotes. Mitogenic stimulation of thymocytes resulted in decreased Ins(1,3,4,5)P4, but not Ins(3,4,5)P3, production. Experiments with Itpkc-deficient mice showed no T-lymphocyte defects, and Itpkb/Itpkc double-knockout mice had no additional alterations beyond those of Itpkb-deficient mice. Pouillon et al. (2003) concluded that Ins(1,3,4,5)P4 is an essential messenger during T-cell selection and differentiation in the thymus.
Erneux, C., Roeckel, N., Takazawa, K., Mailleux, P., Vassart, G., Mattei, M. G. 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: 546-547, 1992. [PubMed: 1330886] [Full Text: https://doi.org/10.1016/s0888-7543(05)80265-4]
Pouillon, V., Hascakova-Bartova, R., Pajak, B., Adam, E., Bex, F., Dewaste, V., Van Lint, C., Leo, O., Erneux, C., Schurmans, S. Inositol 1,3,4,5-tetrakisphosphate is essential for T lymphocyte development. Nature Immun. 4: 1136-1143, 2003. [PubMed: 14517551] [Full Text: https://doi.org/10.1038/ni980]
Takazawa, K., Perret, J., Dumont, J. E., Erneux, C. Molecular cloning and expression of a new putative inositol 1,4,5-trisphosphate 3-kinase isoenzyme. Biochem. J. 278: 883-886, 1991. [PubMed: 1654894] [Full Text: https://doi.org/10.1042/bj2780883]