Acts as a scaffolding protein at cell-cell junctions, thereby regulating various cellular and signaling processes. Cooperates with PTEN to modulate the kinase activity of AKT1. Its interaction with PTPRB and tyrosine phosphorylated proteins suggests that it may link receptor tyrosine phosphatase with its substrates at the plasma membrane. In polarized epithelial cells, involved in efficient trafficking of TGFA to the cell surface. Regulates the ability of LPAR2 to activate ERK and RhoA pathways. Regulates the JNK signaling cascade via its interaction with FZD4 and VANGL2. Interacts with ADRB1, FZD4, FZD7, PTPRB, TGFA and VANGL2. Interacts with unidentified tyrosine phosphorylated proteins (By similarity). Interacts with ADGRB1, LPAR2/EDG4, GRIN2B and PTEN. Does not interact with HTLV TAX2 or TAX3 proteins. Interacts with DLL1 (By similarity). Interacts with PRRG4 (via cytoplasmic domain) (PubMed:23873930). (Microbial infection) Interacts with HTLV1 Tax protein, possibly affecting the transformation ability of Tax. (Microbial infection) Interacts with human papillomavirus/HPV type 16 and 18 E6 proteins. Concentrates in specific sites at the plasma membrane and in the nucleus. In epithelial cells, it localizes at tight junctions (By similarity). Widely expressed. Ubiquitinated following interaction with HPV E6 protein, leading to its degradation by the proteasome. Degradation is independent of E6AP ubiquitin ligase complex. MAGI3 PDZ domains are used to design peptide ligands that bind and inhibit PDZ domains. Belongs to the MAGUK family. Truncated N-terminus.