CTermini

C-termini, or carboxyl termini, refer to the ends of proteins or polypeptide chains that bear a free carboxyl group. They are distinct from N-termini, which have a free amino group. In translation and maturation, the C-terminus is formed by the final peptide bond; the exact length and composition of the C-terminus can influence folding, stability, and interactions. C-termini can be modified or cleaved during maturation, trafficking, and signaling processes, producing mature protein forms with different functions.

Many cells use C-terminal signals to control localization and trafficking. For example, the KDEL motif at the C-terminus of soluble endoplasmic reticulum residents and KKXX motifs in membrane proteins serve as retrieval signals to the ER. In secreted or membrane-anchored proteins, C-terminal signal peptides can direct the attachment of glycosylphosphatidylinositol (GPI) anchors, after which the C-terminal peptide sequence is replaced by the GPI anchor to anchor the protein to the membrane.

Post-translational modification at the C-terminus includes C-terminal amidation, common in peptide hormones and neuropeptides, produced by the enzyme peptidylglycine alpha-amidating monooxygenase after removal of a C-terminal glycine. C-terminal truncation and proteolytic processing create mature peptides from larger precursors. The study of C-termini, together with N-termini, forms terminomics, a proteomics approach to map protein ends and to profile proteolytic events.

Alterations at the C-terminus can affect protein stability, localization, and interactions, with implications for health and disease. C-terminal mutations or abnormal processing can disrupt signaling pathways or trafficking, underscoring the functional importance of the terminal region across diverse proteins.