The entire PIP4K2A gene is about 179.7 Kb (start: 22534837 and end: 22714574 bp; orientation: Minus strand) and contains 10 exons. The PIP4K2A cDNA contains 3.8 Kb.

PIP4K2A protein consists of 406 aminoacids with a molecular weight of 53 kDa and has a conserved phosphatidylinositol phosphate kinase (PIPK) domain in the C-terminal region. The schematic representation of PIP4K2A protein is illustrated in Figure 1.

Ubiquitous.

PIP4K2A is predominantly located in the cytoplasm. However, in some cell types PIP4K2A was found in both nucleus and cytoplasm (Figure 2).

PIP4K2A belongs to the class II of the phosphatidylinositol-5-phosphate 4-kinase family, and major function of these proteins is to recognize the phosphatidylinositol (PtdIns) phosphorylated at position five (PtdIns5P) and phosphorylate inositol ring in position four, to generate a new lipid messenger, the phosphatidylinositol-4,5-bisphosphate (PtdIns4,5P2) (Figure 3). The PtdIns4,5P2 plays an important role in phosphoinositide signaling, participating in several cell processes, including vesicle transport, cell proliferation, adhesion, apoptosis and nuclear events (revised in McCrea and De Camilli, 2009). The acknowledgment about the functions of PIP4K proteins in cellular mechanism is still under construction and recent findings suggest that this protein family is strongly involved in oxidative stress and cellular senescence (revised in Fiume, et al., 2015). In contrast, the specific functions of PIP4K2A are poorly elucidated, and seems to vary according to cell type and stimulus. For instance, PIP4K2A silencing reduces cell survival in THP1 cells (an acute myeloid leukemia cells) (Jude, et al., 2015), but not in K562 cells (a chronic myeloid leukemia cell line) (Peretti de Albuquerque Wobeto, et al., 2014), whereas its overexpression reduces clonogenicity and sensibility to oxidative stress in O2OS cells (Jones, et al., 2013). PIP4K2A was initially identified in erythrocytes (Ling, et al., 1989) and its expression was found to be upregulated during erythroid differentiation (Peretti de Albuquerque Wobeto, et al., 2014, Zaccariotto, et al., 2012), suggesting a potential participation in cell differentiation. Of note, among the PIP4K proteins, which include PIP4K2A, PIP4K2B and PIP4KC, PIP4K2A has been reported as having the highest kinase activity (Bultsma, et al., 2010). PIP4K2A might also form heterodimer with PIP4K2B and result in PIP4K2A nuclear translocation (Bultsma, et al., 2010, Wang, et al., 2010).

PIP4K2A shares high homology with the other members of the PIP4K protein family, including PIP4K2B and PIP4K2C. PIP4K2A also shares high homology among different species (Table 1).
Table 1. Comparative identity of human PIP4K2A with other species

% Identity for: Homo sapiens PIP4K2A	Symbol	Protein	DNA
vs. P. troglodytes	PIP4K2A	100	99.9
vs. M. mulatta	PIP4K2A	100	98.7
vs. C. lupus	PIP4K2A	100	91.8
vs. B. taurus	PIP4K2A	99.3	92.6
vs. M. musculus	Pip4k2a	98.3	89.5
vs. R. norvegicus	Pip4k2a	97.5	87.9
vs. G. gallus	PIP4K2A	93.6	84.5
vs. X. tropicalis	pip4k2b	93.2	80.9
vs. D. rerio	pip4k2aa	87.6	76.8

(Source: http://www.ncbi.nlm.nih.gov/homologene)

Recurrent mutations in the PIP4K2A gene are rare, 68 substitution missense, 1 substitution nonsense, 19 substitution synonymous, 2 insertion frameshift and 4 deletion frameshift mutations are reported in COSMIC (Catalogue of somatic mutations in cancer; http://cancer.sanger.ac.uk/cancergenome/projects/cosmic).