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Description

SH3 and multiple ankyrin repeat domains protein 3 (UniProt Q9BYB0, also known as Proline rich synapse associated protein 2, ProSAP2, Shank postsynaptic density protein, Shank3) is encoded by the SHANK3 (also known as DEL22q13.3, PROSAP2, PSAP2, SCZD15, SPANK-2) gene (Gene ID 85358) in human. Shank3/ProSAP2 belongs to the ProSAP/Shank family of scaffolding proteins, which are important dendritic spines postsynaptic density (PSD) complex components that play an important role in linking membrane glutamate receptors to intracellular signaling proteins and actin cytoskeleton. Shank proteins interact with adaptor proteins and assembles glutamate receptors at the postsynaptic membrane via multiple domains, including ankyrin repeat, proline-rich, SH3, PSD95/disc-large/zona occludens-1 (PDZ), and SAM domains. Shanks, together with the adaptor protein Homer and the endocytic vesicle-associated protein dynamin-3, are required for proper localization of the endocytic zone in close proximity to the PSD. Shank-3 induces formation of functional dendritic spines in aspiny cerebellar neurons, whereas Shank-3 knockdown results in reduced spine density and size in cultured hippocampal neurons. SHANK3 gene mutations are known causes of mental retardation and autism spectrum disorders.