The Cys-His-Gly triplet within the WNT motif is essential for Wnt16 function in vivo

2025/07/04 by Emily G. Ramirez, Maria F. Rojas, Jyoti Rai +3
Biochemistry, Genetics and Molecular Biology · Medicine · #Cancer-related gene regulation #Pancreatic function and diabetes #Wnt/β-catenin signaling in development and cancer

paper · doi:10.17912/micropub.biology.001736

openalex publication_date 2025/07/04 · openalex created_date 2025/09/04 · openalex updated_date 2026/07/28

Abstract

WNTs are critical to many developmental and disease processes. They are post-translationally acylated at a serine within a highly conserved sequence termed the "WNT motif". Changes in individual amino acids in the WNT motif reduce but do not eliminate WNT function. However, the role of a highly conserved triplet of residues (Cys-His-Gly) upstream of the serine has yet to be examined. We show that an in-frame deletion of the Cys-His-Gly triplet in zebrafish Wnt16 likely functions as a null mutation. These findings highlight the utility of using small in-frame indels that target conserved amino acid regions to modulate protein function.

Citations

• WNT1 Mutations in Early-Onset Osteoporosis and Osteogenesis Imperfecta
• Accurate prediction of protein structures and interactions using a three-track neural network

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