Study of the Evolutionary History of FBXO41

F-box proteins are a part of SCF (SKP1-Cullin1-RBX1-F-box-protein) ubiquitin ligase complexes that ubiquitinate cellular proteins. They are essential for normal functioning of several important cellular processes, including cellular signaling, cell cycle progression, stress response and cell death pathways. Deregulation of F-box proteins results in multiple disorders, however their role often remains elusive. FBXO41 has emerged as a key regulator in many cellular processes, notably in neurobiology and cancer. FBXO41 gene is mapped to human chromosome 2p13.2, which is located in PARK3 gene locus (2p13). FBXO41 is shown to disrupt neuronal primary cilia and affects the hedgehog signaling, which is crucial for brain development and function (King et al., 2019). It also plays a role in synaptic transmission and hippocampal network maturation; its loss leading to behavioral defects and impaired brain development (Quadros et al., 2022). Additionally, FBXO41 contributes to cancer biology, particularly in arsenic trioxide (ATO)-mediated autophagic cell death, highlighting its potential as a therapeutic target (Agrawal et al., 2022). Our study aims to construct a comprehensive phylogenetic tree of FBXO41 across species, identifying the conserved protein domains and motifs. By analyzing evolutionary relationships and the conserved and divergent regions, we aim to better understand the functions and implications of FBXO41 in neurodegenerative diseases. We have identified two undocumented conserved motifs and are working on understanding their potential roles. This could provide new insights into FBXO41 activity and pave the way for further research into FBXO41's molecular mechanisms and involvement in cellular development.