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Beschreibung

SH3 and multiple ankyrin repeat domains protein 3 (UniProt: Q9JLU4, also known as Shank3, Proline-rich synapse-associated protein 2, ProSAP2, SPANK-2) is encoded by the Shank3 (also known as Prosap2) gene (Gene ID: 59312) in rat. ProSAP2 belongs to SHANK family of proteins that is widely expressed in the brain. It serves as a major scaffold postsynaptic density (PSD) protein that interacts with multiple proteins and complexes to coordinate the dendritic spine and synapse formation, maturation and maintenance. It is reported to interconnect 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. ProSAP2 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. It may be required at an early stage of synapse formation and be inhibited by IGF-1 to promote synapse maturation. ProSAP2 interacts with ankyrin repeats via its N-terminal region (aa 1-75). Its SH3-binding domain is localized to amino acids 1411-1417.