HGNC Approved Gene Symbol: PIP5K1A
Cytogenetic location: 1q21.3 Genomic coordinates (GRCh38): 1:151,195,419-151,249,531 (from NCBI)
Phosphatidylinositol 4-phosphate 5-kinases (PIP5Ks) synthesize phosphatidylinositol 4,5-bisphosphate by phosphorylating phosphatidylinositol 4-phosphate. See 603261.
By searching sequence databases with peptide sequences obtained from the 68-kD type I PIP5K purified from bovine erythrocytes, Loijens and Anderson (1996) identified a human EST encoding PIP5K1A, which they called PIP5KI-alpha. They screened a human fetal brain cDNA library and isolated full-length PIP5K1A cDNAs. The deduced 549-amino acid protein has the conserved kinase homology domain of PIP5K family members. Within this domain, PIP5K1A shows 83% and 35% amino acid identity with PIP5K1B (602745) and PIP5K2A (603140), respectively. Overall, the PIP5K1A and PIP5K1B proteins are 64% identical. Recombinant PIP5K1A expressed in bacteria had a molecular mass of approximately 66.3 kD by Western blot analysis. The authors isolated additional PIP5K1A cDNAs which they suggested represent splicing isoforms. Northern blot analysis detected a major 4.2-kb PIP5K1A transcript which had a wide tissue distribution.
Using deletion mutant analysis, Ishihara et al. (1998) identified an approximately 380-amino acid minimal core sequence of mouse Pip5k1a that was sufficient for phosphatidylinositol 4-phosphate kinase activity. Overexpression of mouse Pip5k1a in COS-7 cells induced an increase in short actin fibers and a decrease in actin stress fibers.
To determine roles for nuclear phosphatidylinositol 4,5-bisphosphate (PtdIns4,5P(2)), Mellman et al. (2008) set out to identify proteins that interact with the nuclear PIPK, PIPK1A. Mellman et al. (2008) found that PIPK1A colocalizes at nuclear speckles and interacts with a noncanonical poly(A) polymerase, TUT1 (610641), which they termed Star-PAP for 'nuclear speckle-targeted PIPK1A-regulated poly(A) polymerase,' and that the activity of TUT1 can be specifically regulated by PtdIns4,5P(2). TUT1 and PIPK1A function together in a complex to control the expression of select mRNAs, including the transcript encoding the key cytoprotective enzyme heme oxygenase-1 (141250) and other oxidative stress response genes, by regulating the 3-prime-end formation of their mRNAs. Mellman et al. (2008) concluded that, taken together, the data demonstrated a model by which phosphoinositide signaling works in tandem with complement pathways to regulate the activity of TUT1 (Star-PAP) and the subsequent biosynthesis of its target mRNA. Mellman et al. (2008) suggested that their results revealed a mechanism for the integration of nuclear phosphoinositide signals and a method for regulating gene expression.
By screening a human kinase small interfering RNA library, Pan et al. (2008) identified phosphatidylinositol 4-kinase type II-alpha (PI4K2A; 609763) and phosphatidylinositol 4-phosphate 5-kinase type I (PIP5KI) as required for Wnt3a (606359)-induced LRP6 (603507) phosphorylation at ser1490 in mammalian cells and confirmed that these kinases are important for Wnt signaling in Xenopus embryos. Wnt3a stimulates the formation of phosphatidylinositol 4,5-bisphosphates through 'frizzled' (see 603408) and 'dishevelled' (see 601365), the latter of which directly interacted with and activated PIP5KI. In turn, phosphatidylinositol 4,5-bisphosphates regulated phosphorylation of LRP6 at thr1479 and ser1490. Pan et al. (2008) concluded that their study revealed a signaling mechanism for Wnt to regulate LRP6 phosphorylation.
Xie et al. (2000) localized the PIP5K1A gene to chromosome 1q22-q24 by FISH.
Ishihara, H., Shibasaki, Y., Kizuki, N., Wada, T., Yazaki, Y., Asano, T., Oka, Y. Type I phosphatidylinositol-4-phosphate 5-kinases: cloning of the third isoform and deletion/substitution analysis of members of this novel lipid kinase family. J. Biol. Chem. 273: 8741-8748, 1998. [PubMed: 9535851] [Full Text: https://doi.org/10.1074/jbc.273.15.8741]
Loijens, J. C., Anderson, R. A. Type I phosphatidylinositol-4-phosphate 5-kinases are distinct members of this novel lipid kinase family. J. Biol. Chem. 271: 32937-32943, 1996. [PubMed: 8955136] [Full Text: https://doi.org/10.1074/jbc.271.51.32937]
Mellman, D. L., Gonzales, M. L., Song, C., Barlow, C. A., Wang, P., Kendziorski, C., Anderson, R. A. A PtdIns4,5P(2)-regulated nuclear poly(A) polymerase controls expression of select mRNAs. Nature 451: 1013-1017, 2008. [PubMed: 18288197] [Full Text: https://doi.org/10.1038/nature06666]
Pan, W., Choi, S.-C., Wang, H., Qin, Y., Volpicelli-Daley, L., Swan, L., Lucast, L., Khoo, C., Zhang, X., Li, L., Abrams, C. S., Sokol, S. Y., Wu, D. Wnt3a-mediated formation of phosphatidylinositol 4,5-bisphosphate regulates LRP6 phosphorylation. Science 321: 1350-1353, 2008. [PubMed: 18772438] [Full Text: https://doi.org/10.1126/science.1160741]
Xie, Y., Zhu, L., Zhao, G. Assignment of type I phosphatidylinositol-4-phosphate 5-kinase (PIP5K1A) to human chromosome bands 1q22-q24 by in situ hybridization. Cytogenet. Cell Genet. 88: 197-199, 2000. [PubMed: 10828584] [Full Text: https://doi.org/10.1159/000015545]