Undergraduate student College of William and Mary Williamsburg, Virginia, United States
Yi Qi (College of William and Mary)| Di "Silas" Kuang (Washington University)| Kylan Kelley (College of William and Mary)| William Buchser (Washington University)| Shantá D. Hinton (College of William and Mary)
MK-STYX [MAPK (mitogen-activated protein kinase) phosphoserine/threonine/tyrosine-binding protein] is an atypical member of the dual-specificity family subfamily of protein tyrosine phosphatases. It is catalytically inactive due to mutations at critical histidine and cysteine residues within its signature active motif (HCX5R). Therefore, MK-STYX is a pseudophosphatase. Nonetheless, MK-STYX has significant roles in cell signaling such as stress granule formation, neurite formation, and apoptosis. MK-STYX also has been implicated in diseases such as Ewing sarcoma, oncogenic glioblastoma, and hepatocarcinoma. Our study seeks to analyze the significance of MK-STYX throughout evolutionary conservation. We collected data on proteins that have either (the dual-specificity or the rhodanese-like) or both domains of MK-STYX. We utilized the protein sequences, coding sequences (CDS), and official gene (STYXL1; serine/threonine/tyrosine interacting like 1) names to compare its evolution. Evolutionary trees of MK-STYX were constructed to analyze any deviation from the species evolutionary paths. In addition, the calculation of MK-STYX’s distance with its protein sequences and Ka/Ks ratio with its CDS were determined and ranked among all proteins. A higher protein distance and Ka/Ks ratio of MK-STYX compared to other proteins indicate that MK-STYX is more mutable and potentially more pathogenic and/or oncogenic. However, a lower distance and Ka/Ks ratio suggest that MK-STYX is more conserved and potentially has more important roles in the cellular environment. The statistical coupling analysis (SCA) algorithm was employed to identify MK-STYX’s co-evoling, cross-domain amino acids, which are defined as its independent components (ICs). Each IC is assumed to evolve independently and be functionally organized with other ICs. Our study reveals MK-STYX’s evolutionary conservation and shed light on its general functional significance. Furthermore, this study could also identify highly correlated amino acids of MK-STYX and provide computational evidence to further explore MK-STYX’s properties.
Support or Funding Information
This work was supported by the National Science Foundation Grant MCB1909316 to S.D.H., William & Mary Honors Fellowship to Y.Q., and Charles Center Summer Research Grant to K.K.