membrane-associated guanylate kinase, WW & PDZ domain-containing protein 3 (membrane-associated guanylate kinase inverted 3, MAGI-3, MAGI3, KIAA1634)
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Function
- scaffolding protein at cell-cell junctions, thereby regulating various cellular & signaling processes
- cooperates with PTEN to modulate the kinase activity of AKT1
- interaction with PTPRB & 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 ability of EDG4 to activate ERK & RhoA pathways
- regulates JNK signaling cascade via its interaction with FZD4 & VANGL2
- interacts with ADRB1, FZD4, FZD7, PTPRB, TGFA & VANGL2
- interacts with unidentified tyrosine phosphorylated proteins
- interacts with BAI1, EDG4, GRIN2B & PTEN
Structure
- belongs to the MAGUK family
- contains 1 guanylate kinase-like domain
- contains 6 PDZ domains (DHR domains) (MAGI3 PDZ domains are used to design peptide ligands that bind & inhibit PDZ domains)
- contains 2 WW domains
Compartment
- cell membrane, cell junction, tight junction
- nucleus (putative)
- concentrates in specific sites at the plasma membrane & in the nucleus
- in epithelial cells, localizes at tight junctions (putative)
Alternative splicing
named isoforms=4
Expression
widely expressed
Pathology
- in case of infection, interacts with HTLV TAX1 protein, possibly affecting transformation ability of TAX1
- does not interact with HTLV TAX2 or TAX3 proteins
- in case of infection, interacts with HPV type 16 & HPV type 18 E6 protein
- ubiquitinated following interaction with HPV E6 protein, leading to its degradation by the proteasome
- degradation is independent of E6AP ubiquitin ligase complex