Annotated protein:SH3 and multiple ankyrin repeat domains protein 3 (Shank3) (Proline-rich synapse-associated protein 2) (ProSAP2) (SPANK-2). Gene symbol: SHANK3. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: Q9JLU4
antibody wiki:
SynGO gene info:SynGO data @ SHANK3
Ontology domain:Biological Process
SynGO term:structural constituent of postsynaptic density (GO:0098919)
Synapse type(s):brain, glutamatergic
Annotated paper:Tu JC, et al. "Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins" Neuron. 1999 Jul;23(3):583-92 PMID:10433269
Figure(s):Fig1, Fig 2c, Fig 3a, Fig 6a, Fig 7a,b,c
Annotation description:This work was published in the same issue as Naisbitt et al., 1999, which reports the interaction of Shanks with GKAP/PSD95, known to interact with NMDA receptors. In this work, authors describe the interaction of Shank3 (also Shank1) with Homer, which in turns bind to mGluR1a/5, using Y2H, pull-down assays with GST proteins and coimmunoprecipitation assays from cortex and cerebellum extracts using an antibody against Shank3. Pull-down from heterologous cell expression and also cerebellar and cortex extracts also show that Shank3 can interact directly with mGluR1/5 (and also indirectly with Homer1). Altogether, these publications showing the interaction with PSD95/GKAP and Homer/mGluR1/5 point to Shanks being a postsynaptic scaffold protein, which also couples NMDAR and mGluR signaling.
Evidence tracking, Biological System:Intact tissue
Evidence tracking, Protein Targeting:Antibody (detection)
Evidence tracking, Experiment Assay:Western blot
Y2H
Protein-protein interaction (generic)
Annotator(s):Maria Andres-Alonso (ORCID:0000-0002-1585-539X)
Michael Kreutz (ORCID:0000-0003-0575-6950)
Lab:RG Neuroplasticity, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany and Leibniz Group 'Dendritic Organelles and Synaptic Function', Center for Molecular Neurobiology, ZMNH, University MC, Hamburg-Eppendorf, Hamburg, 20251, Germany
Additional literature:In this study, which was published in the same issue together with Tu et al., 1999, researchers described the Shank family of proteins localized in the postsynaptic part of glutamatergic synapses and they report the existence of a ternary complex made out of Shank/GKAP/PSD-95 using heterologous expression but also coIP from rat brain. Experiments in this publication are done with Shank1 and Shank3 antisera, and authors suggest that different combinations of GKAPs and Shanks can "generate a heterogeneity of associations in vivo". @ PMID:10433268
SynGO annotation ID:1139
Dataset release (version):20231201
View annotation as GO-CAM model:Gene Ontology