Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1 (MAGI1)

MAGI1 is a large scaffolding protein belonging to the membrane-associated guanylate kinase (MAGUK) family, containing multiple protein–protein interaction domains such as WW and PDZ motifs. It localizes primarily at tight and adherens junctions, where it organizes multiprotein complexes regulating cell–cell contact, cytoskeletal dynamics, and signal transduction. MAGI1 is crucial for tissue architecture in epithelia, endothelium, and kidneys, and regulates pathways like Rap1/Notch. It acts as a tumor suppressor, with reduced expression linked to enhanced cancer invasiveness and genomic instability. MAGI1 is a target for viral oncoproteins (HPV E6, adenovirus), which degrade or antagonize it to promote viral persistence and tumorigenesis. MAGI1 genetic variants are linked to several diseases including scoliosis, nephropathy, and colitis, reflecting its broad structural and immunological functions.

Other names

MAGI-1TNRC19WWP3MAGI1DAIP3AIP-3BAIAP1BAP-1BAP1MAGI-1bMagi1dAtrophin-1-interacting protein 3BAI1-associated protein 1Membrane-associated guanylate kinase inverted 1Trinucleotide repeat-containing gene 19 proteinWW domain-containing protein 3

For viral oncoproteins (HPV E6), the mechanism involves binding MAGI1's PDZ domains resulting in proteasomal degradation and disruption of cell junction integrity. Some experimental interventions block MAGI1-virus interactions to alter infection tropism.