SH3 and multiple ankyrin repeat domains protein 2 is a protein that in humans is encoded by the SHANK2gene.[1][2] Two alternative splice variants, encoding distinct isoforms, are reported. Additional splice variants exist but their full-length nature has not been determined.[2]
This gene encodes a protein that is a member of the Shank family of synaptic proteins that may function as molecular scaffolds in the postsynaptic density (PSD). Shank proteins contain multiple domains for protein-protein interaction, including ankyrin repeats, an SH3 domain, a PSD-95/Dlg/ZO-1 domain, a sterile alpha motif domain, and a proline-rich region. This particular family member contains a PDZ domain, a consensus sequence for cortactin SH3 domain-binding peptides and a sterile alpha motif. The alternative splicing demonstrated in Shank genes has been suggested as a mechanism for regulating the molecular structure of Shank and the spectrum of Shank-interacting proteins in the PSDs of adult and developing brain.[2]
It is thought that SHANK2 might play a role in synaptogenesis by attaching metabotropic glutamate receptors (mGluRs) to an existing pool of NMDA receptors (NMDA-R), bylinking to the NMDA-R through PSD-95, and the mGluRs through HOMER1.[3] An alternative hypothesis is that the Homer/Shank/GKAP/PSD-95 assembly mediates physical association of the NMDAR with IP3R/RYR and intracellular Ca2+ stores.
↑Lim S, Naisbitt S, Yoon J, Hwang JI, Suh PG, Sheng M, Kim E (November 1999). "Characterization of the Shank family of synaptic proteins. Multiple genes, alternative splicing, and differential expression in brain and development". J Biol Chem. 274 (41): 29510–8. doi:10.1074/jbc.274.41.29510. PMID10506216.
↑Boeckers TM, Bockmann J, Kreutz MR, Gundelfinger ED (June 2002). "ProSAP/Shank proteins - a family of higher order organizing molecules of the postsynaptic density with an emerging role in human neurological disease". J. Neurochem. 81 (5): 903–10. doi:10.1046/j.1471-4159.2002.00931.x. PMID12065602.
↑Park E, Na M, Choi J, Kim S, Lee JR, Yoon J, Park D, Sheng M, Kim E (May 2003). "The Shank family of postsynaptic density proteins interacts with and promotes synaptic accumulation of the beta PIX guanine nucleotide exchange factor for Rac1 and Cdc42". J. Biol. Chem. 278 (21): 19220–9. doi:10.1074/jbc.M301052200. PMID12626503.
↑ 6.06.1Naisbitt S, Valtschanoff J, Allison DW, Sala C, Kim E, Craig AM, Weinberg RJ, Sheng M (June 2000). "Interaction of the postsynaptic density-95/guanylate kinase domain-associated protein complex with a light chain of myosin-V and dynein". J. Neurosci. 20 (12): 4524–34. PMID10844022.
↑ 7.07.1Boeckers TM, Winter C, Smalla KH, Kreutz MR, Bockmann J, Seidenbecher C, Garner CC, Gundelfinger ED (October 1999). "Proline-rich synapse-associated proteins ProSAP1 and ProSAP2 interact with synaptic proteins of the SAPAP/GKAP family". Biochem. Biophys. Res. Commun. 264 (1): 247–52. doi:10.1006/bbrc.1999.1489. PMID10527873.
Zitzer H, Richter D, Kreienkamp HJ (1999). "Agonist-dependent interaction of the rat somatostatin receptor subtype 2 with cortactin-binding protein 1". J. Biol. Chem. 274 (26): 18153–6. doi:10.1074/jbc.274.26.18153. PMID10373412.
Tu JC, Xiao B, Naisbitt S, Yuan JP, Petralia RS, Brakeman P, Doan A, Aakalu VK, Lanahan AA, Sheng M, Worley PF (1999). "Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins". Neuron. 23 (3): 583–92. doi:10.1016/S0896-6273(00)80810-7. PMID10433269.
Kikuno R, Nagase T, Ishikawa K, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (1999). "Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 6 (3): 197–205. doi:10.1093/dnares/6.3.197. PMID10470851.
Boeckers TM, Winter C, Smalla KH, Kreutz MR, Bockmann J, Seidenbecher C, Garner CC, Gundelfinger ED (1999). "Proline-rich synapse-associated proteins ProSAP1 and ProSAP2 interact with synaptic proteins of the SAPAP/GKAP family". Biochem. Biophys. Res. Commun. 264 (1): 247–52. doi:10.1006/bbrc.1999.1489. PMID10527873.
Kreienkamp HJ, Zitzer H, Gundelfinger ED, Richter D, Bockers TM (2000). "The calcium-independent receptor for alpha-latrotoxin from human and rodent brains interacts with members of the ProSAP/SSTRIP/Shank family of multidomain proteins". J. Biol. Chem. 275 (42): 32387–90. doi:10.1074/jbc.C000490200. PMID10964907.
Kreienkamp HJ, Zitzer H, Richter D (2001). "Identification of proteins interacting with the rat somatostatin receptor subtype 2". J. Physiol. Paris. 94 (3–4): 193–8. doi:10.1016/S0928-4257(00)00204-7. PMID11087996.
Soltau M, Richter D, Kreienkamp HJ (2003). "The insulin receptor substrate IRSp53 links postsynaptic shank1 to the small G-protein cdc42". Mol. Cell. Neurosci. 21 (4): 575–83. doi:10.1006/mcne.2002.1201. PMID12504591.
Park E, Na M, Choi J, Kim S, Lee JR, Yoon J, Park D, Sheng M, Kim E (2003). "The Shank family of postsynaptic density proteins interacts with and promotes synaptic accumulation of the beta PIX guanine nucleotide exchange factor for Rac1 and Cdc42". J. Biol. Chem. 278 (21): 19220–9. doi:10.1074/jbc.M301052200. PMID12626503.
Han W, Kim KH, Jo MJ, Lee JH, Yang J, Doctor RB, Moe OW, Lee J, Kim E, Lee MG (2006). "Shank2 associates with and regulates Na+/H+ exchanger 3". J. Biol. Chem. 281 (3): 1461–9. doi:10.1074/jbc.M509786200. PMID16293618.
Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T, Kim DW, She X, Barlow KF, Bloom T, Bruford E, Chang JL, Cuomo CA, Eichler E, FitzGerald MG, Jaffe DB, LaButti K, Nicol R, Park HS, Seaman C, Sougnez C, Yang X, Zimmer AR, Zody MC, Birren BW, Nusbaum C, Fujiyama A, Hattori M, Rogers J, Lander ES, Sakaki Y (2006). "Human chromosome 11 DNA sequence and analysis including novel gene identification". Nature. 440 (7083): 497–500. doi:10.1038/nature04632. PMID16554811.
