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Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 3 (MAGI3)

Target
MAGI3
Molecular classification
Scaffold protein, Membrane-associated guanylate kinase family, PDZ domain-containing protein, Adaptor protein, Other (not a classical receptor, enzyme, or ion channel)
01

Overview

MAGI3 is a multidomain scaffold protein of the membrane-associated guanylate kinase family, notable for its PDZ, WW, and guanylate kinase domains[1][2][3][4][5]. It acts at cell-cell junctions and membrane sites to organize signaling complexes, controlling processes such as cell adhesion, polarity, and signal transduction. MAGI3 interacts with important proteins including PTEN, receptor tyrosine phosphatases (e.g., PTPRB), Frizzled receptors, and lysophosphatidic acid receptor 2, thereby modulating diverse pathways (e.g., Akt, JNK, ERK, RhoA) relevant to cell migration, immune function, and cell proliferation[1][2][3][4][5][6]. Dysregulation of MAGI3—by genetic variation, viral targeting (high-risk HPV E6, influenza NS1), or aberrant mRNA processing—has been linked to multiple disease processes, especially cancer, autoimmune disorders, and epithelial barrier dysfunction[1][2]. It does not have GMP kinase enzymatic activity but is sometimes annotated as such due to domain homology[2][4]. No approved drugs currently target MAGI3 directly, but its expression and functional status influence disease biology and may aid in biomarker research.

Other names
MAGI3MAGI-3Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 3Membrane-associated guanylate kinase inverted 3Membrane-associated guanylate kinase-related 3DJ730K3.2KIAA1634dJ730K3.24732496O19Rik (mouse)6530407C02Rik (mouse)
02

Mechanism of action

null (No direct mechanism of action for drugs targeting MAGI3 is documented in the search results.)

03

Biological functions

Signal transductionRegulation of cell adhesionRegulation of cell junction organizationRecruitment/assembly of multiprotein complexes at the plasma membraneModulation of kinase activity (e.g., Akt, JNK)Trafficking of membrane proteins (e.g., TGFA)Immune function regulation
04

Disease associations

Cancer (including breast, colon, cervical, endometrial, glioma)Autoimmune disease (e.g., autoimmune thyroid disease, rheumatoid arthritis)Inflammatory bowel diseaseInfection (HPV, Influenza A)Neurodevelopmental and synaptic function roles
05

Safety considerations

No documented direct safety concerns for MAGI3 as a therapeutic target (not targeted directly by approved drugs)[1][2].General challenges of targeting scaffolding/adaptor proteins due to widespread, pleiotropic cellular roles.
06

Interacting drugs

null (No direct, clinically documented drugs known to target MAGI3; however, transcriptomics signatures show that various drugs can perturb MAGI3 expression[1].)
07

Biomarkers

Reduced MAGI3 mRNA/protein levels may serve as a prognostic or diagnostic biomarker in some cancers (e.g., glioma, breast cancer)[1].MAGI3 genetic variants associated with autoimmune thyroid disease and rheumatoid arthritis[1].

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