FunShift

FunShift identifies and analyzes function shifts within protein domain families to improve functional annotation accuracy using evolutionary substitution rates and conservation shifts.

Key Features:

• Subfamily Classification: Built on Pfam 12, FunShift covers 151,934 subfamilies derived from 7,300 protein families.
• Function Shift Analysis: Performs pairwise comparisons between subfamilies using two complementary methods on families with up to 500 members; of 179,210 analyzed subfamily pairs, 62,384 were predicted to exhibit functional shifts across 2,881 families.
• Functional Specificity-Determining Sites: Marks probable specificity-determining sites for each pair of subfamilies predicted to be functionally shifted.

Scientific Applications:

• Functional annotation refinement: Enables more precise functional annotations of proteins by identifying subfamily-specific biochemical function shifts.
• Experimental mutagenesis targeting: Provides candidate specificity-determining sites to inform experimental mutation studies probing functional changes.
• Evolutionary analysis: Supports studies of protein functional diversification and evolutionary biology by quantifying conservation and substitution rate shifts.
• Enzyme function and therapeutic target investigation: Helps investigate enzyme activity differences and identify potential therapeutic targets arising from subfamily-specific functional shifts.

Methodology:

Pairwise comparisons between subfamilies analyzed evolutionary substitution rates and conservation patterns using two complementary methods applied to families with up to 500 members.