The carboxy-terminus, a key regulator of protein function

Abstract

All proteins end with a carboxyl terminus that has unique biophysical properties and is often disordered. Although there are examples of important C-termini functions, a more global role for the C-terminus is not yet established. In this review, we summarize research on C-termini, a unique region in proteins that cells exploit. Alternative splicing and proteolysis increase the diversity of proteins and peptides in cells with unique C-termini. The C-termini of proteins contain minimotifs, short peptides with an encoded function generally characterized as binding, posttranslational modifications, and trafficking. Many of these activities are specific to minimotifs on the C-terminus. Approximately 13% of C-termini in the human proteome have a known minimotif, and the majority, if not all of the remaining termini have conserved motifs inferring a function that remains to be discovered. C-termini, their predictions, and their functions are collated in the C-terminome, Proteus, and Terminus Oriented Protein Function INferred Database (TopFIND) database/web systems. Many C-termini are well conserved, and some have a known role in health and disease. We envision that this summary of C-termini will guide future investigation of their biochemical and physiological significance.

Keywords:

• C-terminus
• minimotifs
• C-terminome
• short linear motifs
• posttranslational modification
• trafficking
• C-terminal minimotifs

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The National Institutes of Health under grants R15-GM107983-01 and P20-GM121325-01A1; and the Nevada Governor’s Office of Economic Development supported this research.