WWC1 Human

The WWC family proteins are highly conserved across different species. The WWC genes originated from a single ancestral gene in bilateral animals, such as insects and vertebrates. In fish, a progenitor-like sequence of mammalian KIBRA/WWC1 and WWC2 is expressed together with WWC3. In tetrapods, including humans, the three family members (WWC1, WWC2, and WWC3) are present, except for a large genomic deletion including WWC3 in mice .

WWC1/KIBRA is involved in the regulation of important intracellular transport processes and the establishment of cell polarity. It is an upstream regulator of the Hippo signaling pathway, which controls cell proliferation and organ size in animals. The Hippo pathway is crucial for maintaining tissue homeostasis and preventing excessive cell growth and cancer .

WWC1/KIBRA interacts with various proteins to regulate cellular processes. For instance, it regulates exocytosis of the transferrin receptor through an interaction with Dynein Light Chain 1 (DLC1) and Sorting Nexin 4 (SNX4). Additionally, it plays a role in synaptic signaling and higher brain functions .

The WWC1 protein consists of 1,113 amino acids and shares a common protein architecture with WWC2 (1,192 amino acids) and WWC3 (1,217 amino acids). The two N-terminal WW domains mediate binding to target proteins harboring L/PPxY motifs, while the internal C2 domain is involved in membrane association. The C-terminal region contains a binding site for aPKC and a PDZ domain interaction motif, which are essential for its scaffolding functions .

Research on WWC1/KIBRA has provided insights into its role in various diseases and conditions. For example, alterations in the Hippo signaling pathway, regulated by WWC1, have been linked to cancer development. Understanding the molecular mechanisms of WWC1 and its interactions with other proteins can help in developing therapeutic strategies for diseases related to cell proliferation and organ size regulation .