Helper component proteinase (HC-Pro) is a multifunctional protein responsible for multiple molecular events in viral cycle. Here, we demonstrate that functional correlation of sequence motifs of HC-Pro is an important source to predict its role in deubiqutinylation pathway and rescuing viral proteins from degradation. The sequence of papaya ringspot viral HC-Pro was compared with respect to both inter and intea-species across different potyviruses. This study suggested that highly conserved domains involved in post transcriptional gene silencing (PTGS) suppression and proteolytic activity are essential functions in plant-virus cycle. In contrast, mechanisms primed for differentiation such as host specificity and virus replication are less conserved. Also, they contribute substantially to the differences among HC-Pro, derived from different potyviruses. The results obtained from this study provide a framework for new hypothesis and research directions in the area of differential role of potyviral HC-Pro.