Phosphoinositide 3-kinase (PI3K) enzyme plays a vital role in the insulin signaling pathway as well as in other pathways that are involved in the growth, migration, and survival of cells. In the insulin signaling pathway, PI3K proteins that include p50 alpha, p85 alpha, p85 beta, p55 gamma, p110 alpha, p110 beta, and p110 gamma are associated with the critical node-2. This study has used bioinformatic tools to understand phylogenetics, conservation patterns, conserved domains, orientation of residues, and interactions among PI3K proteins. The phylogenetic analysis showed p110 alpha and p110 gamma with a common origin while p50 alpha and p85 alpha sharing an evolutionary history. The sequence alignment showed the highest score (97) between p85 alpha and p50 alpha. Several highly conserved amino acid residues were found high in p110 beta (n = 102). Subsequently, the number of highly conserved amino acid restudies was low in p50alpha and p55 gamma (n = 15). The PI3K proteins are evidentially linked to other proteins and pathways as well.