WD repeat and FYVE domain-containing protein 2 (WDFY2)

WD repeat and FYVE domain-containing protein 2 (WDFY2) is an adapter/scaffold protein containing multiple WD repeat motifs and an FYVE zinc finger domain, which enables binding to phosphatidylinositol 3-phosphate on endosomal membranes[2][4][7]. It facilitates key steps in endosomal trafficking and signal transduction, particularly related to protein phosphorylation events for kinases such as PRKCZ and AKT2. WDFY2 is required for proper insulin-stimulated phosphorylation of AKT2 and subsequent glucose uptake, suggesting an important modulatory role in metabolic response and adipocyte differentiation. It may also act as a binding platform for protein–protein interactions in specialized vesicular structures, affecting the spatial organization of signaling cascades[1][2][4][7]. The full disease spectrum and druggability of WDFY2 remain under investigation, but its direct functional roles suggest possible links to metabolic disease.

Other names

WDFY2WD repeat and FYVE domain containing 2WD40 and FYVE domain containing protein 2Protein ProF

Adapter/scaffold facilitating interaction between protein kinase C zeta (PRKCZ) and its substrate VAMP2, increasing phosphorylation - Regulates/increases phosphorylation and inactivation of FOXO1 transcription factor via AKT1 - Required for insulin-stimulated AKT2 phosphorylation and downstream glucose uptake[2][4][7]