HGNC Approved Gene Symbol: PIK3C2B
Cytogenetic location: 1q32.1 Genomic coordinates (GRCh38): 1:204,422,633-204,494,805 (from NCBI)
Phosphoinositides (PIs) are lipid molecules that play crucial roles in diverse cellular functions. PIs produced in response to specific stimuli recruit their binding proteins to particular intracellular sites where these proteins exert their function. PIs are interconverted through phosphorylation and dephosphorylation by PI kinases and PI phosphatases, respectively. PIK3C2B, the beta isoform of class II PI 3-kinase (PI3K), is thought to produce phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) (summary by Maehama et al., 2013).
Using RT-PCR of breast RNA with degenerate primers derived from conserved motifs within the lipid kinase domain of PI3Ks, Brown et al. (1997) isolated cDNAs encoding a protein that they designated HsC2-PI3K. Sequence analysis revealed that the predicted 1,634-amino acid protein is a PI3K that is most closely related to the class II PI3Ks. Class II PI3Ks are defined by the presence of a C-terminal C2 domain. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes and have also been shown to mediate interactions between proteins. The C2 domain of HsC2-PI3K lacks 3 of 4 conserved aspartate residues implicated in calcium binding, and therefore the authors considered it likely that this C2 domain functions in a calcium-independent manner. Brown et al. (1997) found by Northern blot analysis that HsC2-PI3K is expressed as an 8.5-kb transcript in various tissues, with the highest level of expression in thymus and placenta.
By stimulating human and other mammalian cells with lysophosphatidic acid (LPA), Maffucci et al. (2005) demonstrated production of PtdIns(3)P through activation of PIK3C2B. Confocal microscopy revealed that PtdIns(3)P was generated at the plasma membrane. Time-lapse microscopy indicated that the LPA-dependent pool of PtdIns(3)P and LPA-induced cell migration were sensitive to PI3K inhibitors. Maffucci et al. (2005) concluded that generation of PtdIns(3)P through activation of PIK3C2B is crucial for LPA-dependent migration.
Using short hairpin RNA-mediated gene silencing, Maehama et al. (2013) found that PIK3C2B, but not PIK3C2A (603601) or PIK3C2G (609001), was indispensable for propagation of hepatitis C virus (HCV; see 609532) in cells and that PIK3C2B played a role in HCV genome replication. Immunoblot analysis showed that HCV core protein bound to PtdIns(3,4)P2. Maehama et al. (2013) proposed that the PI generated by PIK3C2B plays an indispensable role in the HCV replication cycle through binding to HCV core protein.
By fluorescence in situ hybridization, Brown et al. (1997) mapped the PIK3C2B gene to chromosome 1q32.
Brown, R. A., Ho, L. K. F., Weber-Hall, S. J., Shipley, J. M., Fry, M. J. Identification and cDNA cloning of a novel mammalian C2 domain-containing phosphoinositide 3-kinase, HsC2-PI3K. Biochem. Biophys. Res. Commun. 233: 537-544, 1997. [PubMed: 9144573] [Full Text: https://doi.org/10.1006/bbrc.1997.6495]
Maehama, T., Fukasawa, M., Date, T., Wakita, T., Hanada, K. A class II phosphoinositide 3-kinase plays an indispensable role in hepatitis C virus replication. Biochem. Biophys. Res. Commun. 440: 150-156, 2013. [PubMed: 24055031] [Full Text: https://doi.org/10.1016/j.bbrc.2013.09.048]
Maffucci, T., Cooke, F. T., Foster, F. M., Traer, C. J., Fry, M. J., Falasca, M. Class II phosphoinositide 3-kinase defines a novel signaling pathway in cell migration. J. Cell Biol. 169: 789-799, 2005. [PubMed: 15928202] [Full Text: https://doi.org/10.1083/jcb.200408005]