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SHANK3 is a major scaffold postsynaptic density protein which interacts with multiple proteins and complexes to orchestrate the dendritic spine and synapse formation, maturation and maintenance. It interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors via complexes with GKAP/PSD-95 and HOMER, respectively, and the actin-based cytoskeleton. SHANK3 plays a role in the structural and functional organization of the dendritic spine and synaptic junction through the interaction with Arp2/3 and WAVE1 complex as well as the promotion of the F-actin clusters. By way of this control of actin dynamics, SHANK3 participates in the regulation of developing neurons growth cone motility and the NMDA receptor-signaling. It also modulates GRIA1 exocytosis and GRM5/MGLUR5 expression and signaling to control the AMPA and metabotropic glutamate receptor-mediated synaptic transmission and plasticity. SHANK3 may be required at an early stage of synapse formation and be inhibited by IGF1 to promote synapse maturation. (Uniprot)
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Protein Aliases: proline rich synapse associated protein 2; Proline-rich synapse-associated protein 2; ProSAP2; SH3 and multiple ankyrin repeat domains protein 3; SH3 and multiple ankyrin repeat domains protein 3 variant c-3; SH3 and multiple ankyrin repeat domains protein 3 variant c-4; SH3 and multiple ankyrin repeat domains-like protein 3 variant 1; SH3 and multiple ankyrin repeat domains-like protein 3 variant 2; SH3 and multiple ankyrin repeat domains-like protein 3 variant 3; SH3 and multiple ankyrin repeat domains-like protein 3 variant c-1; SH3 and multiple ankyrin repeat domains-like protein 3 variant c-2; SH3 and multiple ankyrin repeat domains-like protein 3 variant d-1; SH3 and multiple ankyrin repeat domains-like protein 3 variant d-2; SH3 and multiple ankyrin repeat domains-like protein 3 variant d-3; SH3 and multiple ankyrin repeat domains-like protein 3 variant e-1; SH3 and multiple ankyrin repeat domains-like protein 3 variant e-2; SH3/ankyrin domain gene 3; shank postsynaptic density protein; Shank postsynaptic density protein 3a; Shank3; shank3 splice variant II; shank3 splice variant III; shank3 splice variant IV; shank3e splice variant III; shank3e splice variant IV; SPANK 2; SPANK-2; SPANK2
Gene Aliases: AI841104; DEL22q13.3; Kiaa1650; PROSAP2; PSAP2; SCZD15; Shank3; Shank3b; SHANK3c-3; SHANK3c-4; SPANK-2
UniProt ID: (Mouse) Q4ACU6, (Rat) Q9JLU4
Entrez Gene ID: (Human) 85358, (Mouse) 58234, (Rat) 59312
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