The spleen tyrosine kinase (Syk) is a key regulator in immune cell signaling and is linked to various mechanisms in cancer and neurodegenerative diseases. Although most computational research on Syk focuses on novel drug design, the molecular-level regulatory dynamics remain unexplored. In this study, we utilized 5 × 1 μs all-atom molecular dynamics simulations of the Syk kinase domain, examining it in combinations of activation segment phosphorylated/unphosphorylated (at Tyr525, Tyr526) and the "DFG"-Asp protonated/deprotonated (at Asp512) states to investigate conformational variations and regulatory dynamics of various loops and motifs within the kinase domain. Our findings revealed that the formation and disruption of several electrostatic interactions among residues within and near the activation segment likely influenced its dynamics. The protein structure network analysis indicated that the N-terminal and C-terminal anchors were stabilized by connections with the nearby stable helical regions. The P-loop showed conformational variation characterized by movements toward and away from the conserved "HRD"-motif. Additionally, there was a significant correlation between the movement of the β3-αC loop and the P-loop, which controls the dimensions of the adenine-binding cavity of the C-spine region. Overall, understanding these significant motions of the Syk kinase domain enhances our knowledge of its functional regulatory mechanism and can guide future research.