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Gene Review

Magi2  -  membrane associated guanylate kinase, WW...

Rattus norvegicus

Synonyms: AIP-1, Acvrinp1, Acvrip1, Aip1, Atrophin-1-interacting protein 1, ...
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Disease relevance of Magi2

  • These results suggest that the PSD-95 family proteins and S-SCAM have a novel function as KIF1Balpha receptors, linking KIF1Balpha to its specific cargos, and are involved in peripheral neuropathies [1].

High impact information on Magi2

  • Cell junction-associated proteins IQGAP1, MAGI-2, CASK, spectrins, and alpha-actinin are components of the nephrin multiprotein complex [2].
  • During glomerular development, IQGAP1 is expressed in the junctional complexes between the earliest identifiable podocytes, MAGI-2/S-SCAM is first detected in junctional complexes in podocytes after their migration to the base of the cells [2].
  • The ability of Dasm1 to regulate synaptic AMPA-Rs requires its intracellular C-terminal PDZ domain-binding motif, which interacts with two synaptic PDZ domain-containing proteins involved in spine/synapse maturation, Shank and S-SCAM [3].
  • Therefore, S-SCAM, PSD-95/SAP90, and SAPAP may form a complex in vivo [4].
  • The region containing both of PDZ-4 and -5 is sufficient for the clustering of NMDA receptors and forms a dimer in gel filtration, suggesting that S-SCAM forms multimers via the interaction between the C-terminal PDZ domains and assembles NMDA receptors into clusters [4].

Biological context of Magi2


Anatomical context of Magi2


Associations of Magi2 with chemical compounds

  • The guanylate kinase domain of S-SCAM directly bound to the GSK3beta-binding region of Axin [5].
  • We have identified here shorter isoforms of S-SCAM that start at the 164th or 224th methionine, and we renamed the original one, S-SCAMalpha, the middle one, S-SCAMbeta, and the shortest one, S-SCAM-gamma [4].
  • SAPAP is a protein highly enriched in the PSD fraction and may link PSD-95/SAP90 and S-SCAM to Triton X-100-insoluble structures [12].
  • PKC regulates the delta2 glutamate receptor interaction with S-SCAM/MAGI-2 protein [8].
  • In this investigation, we report that HCN2 forms a protein assembly with tamalin, S-SCAM and Mint2 scaffold proteins, using several different approaches including immunoprecipitation of rat brain and heterologously expressing cell extracts and glutathione S-transferase pull-down assays [13].

Physical interactions of Magi2


Other interactions of Magi2

  • Postsynaptic density (PSD)-95/Synapse-associated protein (SAP) 90 and synaptic scaffolding molecule (S-SCAM) are neuronal membrane-associated guanylate kinases [16].
  • Synaptic scaffolding molecule is involved in the synaptic clustering of neuroligin [15].
  • SAPAP1 also interacts with various proteins, including neurofilaments, synaptic scaffolding molecule (S-SCAM), nArgBP2, dynein light chain and Shank through different regions [17].
  • The PDZ domain of tamalin interacts with HCN2 at both the PDZ-binding motif and the internal carboxy-terminal tail of HCN2, whereas binding of the PDZ domain of S-SCAM occurs at the cyclic nucleotide-binding domain (CNBD) and the CNBD-downstream sequence of the carboxy-terminal tail of HCN2 [13].


  1. Association of the kinesin superfamily motor protein KIF1Balpha with postsynaptic density-95 (PSD-95), synapse-associated protein-97, and synaptic scaffolding molecule PSD-95/discs large/zona occludens-1 proteins. Mok, H., Shin, H., Kim, S., Lee, J.R., Yoon, J., Kim, E. J. Neurosci. (2002) [Pubmed]
  2. Cell junction-associated proteins IQGAP1, MAGI-2, CASK, spectrins, and alpha-actinin are components of the nephrin multiprotein complex. Lehtonen, S., Ryan, J.J., Kudlicka, K., Iino, N., Zhou, H., Farquhar, M.G. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  3. The immunoglobulin family member dendrite arborization and synapse maturation 1 (Dasm1) controls excitatory synapse maturation. Shi, S.H., Cheng, T., Jan, L.Y., Jan, Y.N. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  4. Three isoforms of synaptic scaffolding molecule and their characterization. Multimerization between the isoforms and their interaction with N-methyl-D-aspartate receptors and SAP90/PSD-95-associated protein. Hirao, K., Hata, Y., Yao, I., Deguchi, M., Kawabe, H., Mizoguchi, A., Takai, Y. J. Biol. Chem. (2000) [Pubmed]
  5. Synaptic scaffolding molecule interacts with axin. Hirabayashi, S., Nishimura, W., Iida, J., Kansaku, A., Kishida, S., Kikuchi, A., Tanaka, N., Hata, Y. J. Neurochem. (2004) [Pubmed]
  6. Synaptic localization of membrane-associated guanylate kinase-interacting protein mediated by the pleckstrin homology domain. Iida, J., Nishimura, W., Yao, I., Hata, Y. Eur. J. Neurosci. (2002) [Pubmed]
  7. Association of membrane-associated guanylate kinase-interacting protein-1 with Raf-1. Yao, I., Ohtsuka, T., Kawabe, H., Matsuura, Y., Takai, Y., Hata, Y. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  8. PKC regulates the delta2 glutamate receptor interaction with S-SCAM/MAGI-2 protein. Yap, C.C., Muto, Y., Kishida, H., Hashikawa, T., Yano, R. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  9. Interaction of synaptic scaffolding molecule and Beta -catenin. Nishimura, W., Yao, I., Iida, J., Tanaka, N., Hata, Y. J. Neurosci. (2002) [Pubmed]
  10. Human T-cell leukemia virus type 1 Tax oncoprotein induces and interacts with a multi-PDZ domain protein, MAGI-3. Ohashi, M., Sakurai, M., Higuchi, M., Mori, N., Fukushi, M., Oie, M., Coffey, R.J., Yoshiura, K., Tanaka, Y., Uchiyama, M., Hatanaka, M., Fujii, M. Virology (2004) [Pubmed]
  11. CIN85 is localized at synapses and forms a complex with S-SCAM via dendrin. Kawata, A., Iida, J., Ikeda, M., Sato, Y., Mori, H., Kansaku, A., Sumita, K., Fujiwara, N., Rokukawa, C., Hamano, M., Hirabayashi, S., Hata, Y. J. Biochem. (2006) [Pubmed]
  12. nArgBP2, a novel neural member of ponsin/ArgBP2/vinexin family that interacts with synapse-associated protein 90/postsynaptic density-95-associated protein (SAPAP). Kawabe, H., Hata, Y., Takeuchi, M., Ide, N., Mizoguchi, A., Takai, Y. J. Biol. Chem. (1999) [Pubmed]
  13. Hyperpolarization-activated, cyclic nucleotide-gated HCN2 cation channel forms a protein assembly with multiple neuronal scaffold proteins in distinct modes of protein-protein interaction. Kimura, K., Kitano, J., Nakajima, Y., Nakanishi, S. Genes Cells (2004) [Pubmed]
  14. nRap GEP: a novel neural GDP/GTP exchange protein for rap1 small G protein that interacts with synaptic scaffolding molecule (S-SCAM). Ohtsuka, T., Hata, Y., Ide, N., Yasuda, T., Inoue, E., Inoue, T., Mizoguchi, A., Takai, Y. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  15. Synaptic scaffolding molecule is involved in the synaptic clustering of neuroligin. Iida, J., Hirabayashi, S., Sato, Y., Hata, Y. Mol. Cell. Neurosci. (2004) [Pubmed]
  16. MAGUIN, a novel neuronal membrane-associated guanylate kinase-interacting protein. Yao, I., Hata, Y., Ide, N., Hirao, K., Deguchi, M., Nishioka, H., Mizoguchi, A., Takai, Y. J. Biol. Chem. (1999) [Pubmed]
  17. Synaptic localization of SAPAP1, a synaptic membrane-associated protein. Yao, I., Iida, J., Nishimura, W., Hata, Y. Genes Cells (2003) [Pubmed]
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