membrane-associated guanylate kinase, WW & PDZ domain-containing protein 3 (membrane-associated guanylate kinase inverted 3, MAGI-3, MAGI3, KIAA1634)

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

General

phosphoprotein scaffold protein

Properties

SIZE: entity length = 1506 aa MW = 166 kD COMPARTMENT: cell nucleus MOTIF: lysine-rich region {6-9} MOTIF: lysine residue (SEVERAL) PDZ domain NAME: PDZ domain SITE: 18-106 MOTIF: ADRB1 & TGFA interaction {18-106} domain {114-288} MOTIF: ATP-binding site NAME: ATP-binding site SITE: 121-128 glutamate-rich region {238-243} MOTIF: glutamate residue (SEVERAL) HOMOLOGY: guanylate kinase WW domain (W/rsp5/WWP domain) {293-326} WW domain (W/rsp5/WWP domain) {339-372} proline-rich region SITE: 378-381 MOTIF: proline residue (SEVERAL) PDZ domain NAME: PDZ domain SITE: 435-517 MOTIF: PTEN interaction {435-517} PDZ domain NAME: PDZ domain SITE: 603-679 Ser phosphorylation site {S722} Ser phosphorylation site {S724} PDZ domain NAME: PDZ domain SITE: 751-833 MOTIF: BAI1 interaction {751-833} PDZ domain NAME: PDZ domain SITE: 876-963 MOTIF: EDG4 & GRIN2B interaction {876-963} PDZ domain NAME: PDZ domain SITE: 1046-1128

Database Correlations

UniProt Q5TCQ9 PFAM correlations

References

UniProt :accession Q5TCQ9