SHANK3
SHANK3 (SH3 and multiple ankyrin repeat domains 3, also known as SPANK-2, PROSAP2, PSAP2 and KIAA1650) is a major scaffold protein of the postsynaptic density. It organises dendritic spine and synapse formation, maturation and maintenance. Browse Assay Genie's current range of SHANK3 research reagents below, or read on for the biology behind the target.
SHANK3 is a multidomain scaffold protein that sits in the postsynaptic density and interacts with many proteins and complexes to orchestrate dendritic spine and synapse formation, maturation and maintenance. It interconnects receptors of the postsynaptic membrane, including NMDA-type and metabotropic glutamate receptors, with the actin-based cytoskeleton. These links are made through complexes with GKAP/PSD-95 and HOMER, respectively.
Through its interaction with the Arp2/3 and WAVE1 complex, and by promoting F-actin clusters, SHANK3 contributes to the structural and functional organisation of the dendritic spine and synaptic junction. By controlling actin dynamics, it takes part in regulating growth cone motility in developing neurons and NMDA receptor signalling. It also modulates GRIA1 exocytosis and GRM5/mGluR5 expression and signalling, which shapes AMPA and metabotropic glutamate receptor-mediated synaptic transmission and plasticity. SHANK3 may be required at an early stage of synapse formation and may be inhibited by IGF1 to promote synapse maturation.
The human SHANK3 gene belongs to the Shank gene family and encodes a protein that localises to the cytoplasm, the postsynaptic density and dendritic spines. It is classed in the ankyrin repeat, sterile alpha motif, PDZ and SH3 domain-containing groups. Mutations in the gene are a cause of autism spectrum disorder and of schizophrenia type 15. They are also a major causative factor in the neurological symptoms of 22q13.3 deletion syndrome, also known as Phelan-McDermid syndrome. Additional isoforms have been described but are not yet experimentally verified. Mouse and rat both have a Shank3 ortholog.
SHANK3 orchestrates dendritic spine and synapse formation, maturation and maintenance, making it a central target for studying how excitatory synapses are built.
Mutations in SHANK3 are a cause of autism spectrum disorder, which is characterised by impaired social interaction and communication.
SHANK3 is a major causative factor in the neurological symptoms of 22q13.3 deletion syndrome, also called Phelan-McDermid syndrome.
SHANK3 links NMDA and metabotropic glutamate receptors to actin and modulates GRIA1 and mGluR5, affecting synaptic transmission and plasticity.
SHANK3 is a scaffold protein of the postsynaptic density. It connects NMDA-type and metabotropic glutamate receptors to the actin cytoskeleton via GKAP/PSD-95 and HOMER complexes, and so supports dendritic spine and synapse formation, maturation and maintenance. It also influences AMPA and metabotropic receptor-mediated transmission and plasticity.
SHANK3 is also known as SPANK-2, PROSAP2, PSAP2 and KIAA1650, and its full name is SH3 and multiple ankyrin repeat domains 3. It is one member of the Shank family. Additional isoforms have been described but have not yet been experimentally verified.
Yes. SHANK3 mutations are a cause of autism spectrum disorder and schizophrenia type 15, and contribute to Phelan-McDermid syndrome. Mouse and rat each have a Shank3 ortholog; check the datasheet of any product for its validated reactivity.
Other Shank family scaffold proteins of the postsynaptic density with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q9BYB0; product specifications from Assay Genie datasheets.