ZFYVE26

ZFYVE26 (Zinc Finger FYVE-Type Containing 26) is a human gene encoding a protein also known as WDFY2. The ZFYVE26 protein is implicated in several cellular processes, most notably endosomal trafficking and autophagy. It belongs to the WDFY protein family, characterized by the presence of a WD40 repeat and a FYVE domain.

Function:

ZFYVE26 plays a crucial role in regulating endosomal maturation and trafficking, particularly in the context of autophagy. It acts as a phosphatidylinositol-3-phosphate (PI3P) effector protein, binding to PI3P-enriched membranes of early endosomes and autophagosomes through its FYVE domain. This interaction facilitates the recruitment of other proteins involved in autophagy and endosomal sorting. ZFYVE26 is required for the proper formation and trafficking of autophagosomes, and defects in ZFYVE26 function can disrupt autophagic flux.

Structure:

The ZFYVE26 protein contains several functional domains including WD40 repeats, a FYVE domain, and a coiled-coil domain. The WD40 repeats mediate protein-protein interactions, forming a scaffold for the assembly of multiprotein complexes. The FYVE domain is responsible for binding to PI3P, a lipid signaling molecule. The coiled-coil domain may be involved in protein oligomerization or interactions with other proteins.

Clinical Significance:

Mutations in the ZFYVE26 gene have been linked to neurodevelopmental disorders, including intellectual disability, autism spectrum disorder, and epilepsy. These mutations often disrupt the function of the ZFYVE26 protein, leading to impaired autophagy and endosomal trafficking in neuronal cells. The resulting cellular dysfunction is thought to contribute to the pathogenesis of these neurological conditions. Studies have also indicated a potential role for ZFYVE26 in the development and progression of certain cancers. Further research is necessary to fully understand the clinical implications of ZFYVE26 dysfunction.

Interactions:

ZFYVE26 interacts with a variety of other proteins involved in autophagy and endosomal trafficking, including:

• PIK3C3/VPS34: a phosphatidylinositol 3-kinase that produces PI3P.
• RUFY1/Beclin 1-associated autophagy regulator 1: involved in autophagy initiation and autophagosome formation.
• Other proteins involved in endosomal sorting and trafficking.

These interactions are critical for the proper function of ZFYVE26 in regulating cellular processes.