The GYF domain

GYF domains are small, versatile adaptor domains that recognize proline‐rich sequences (PRS). They are present in most eukaryotic species sequenced so far, but in contrast to other PRS‐recognition domains (PRD), GYF domains have not experienced the same amplification in metazoa during evolution. Mutational and structural analysis has shown the conserved signature W‐X‐Y‐X 6‐11 ‐GPF‐X 4 ‐M‐X 2 ‐W‐X 3 ‐GYF to be the site of interaction with proline‐rich peptides. In contrast, composition and length of the C‐terminal half of GYF domains are not conserved. Similar to other PRD, GYF domains bind to many different PRS that converge on a minimal consensus sequence. All GYF domains analyzed so far selected for the core motif PPG, whereas amino‐acid preferences adjacent to this motif vary. As a result of this analysis, two subfamilies have been identified: CD2BP2‐type and SMY2‐type GYF domains. The latter subfamily comprises most GYF domains and is characterized by a shorter β 1 –β 2 loop and an aspartate instead of the tryptophan found at position 8 in CD2BP2‐type GYF domains. Recent analysis of binding specificities for GYF domains allowed identification of novel interaction partners. Thereby proteomics has contributed to a functional understanding of GYF domain‐containing proteins and sets the stage for a more systematic investigation of their functions in vivo .