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:regulation of postsynapse organization (GO:0099175)
Synapse type(s):hippocampus, glutamatergic
Annotated paper:Grabrucker AM, et al. "Concerted action of zinc and ProSAP/Shank in synaptogenesis and synapse maturation" EMBO J. 2011 Feb 2;30(3):569-81 PMID:21217644
Figure(s):Fig. 1, 2, 3, 4
Annotation description:Fig. 1, in young neurons, overexpressed ProSAP1/Shank2 and ProSAP2/Shank3 increase synapse density, while knockdown by RNAi of ProSAP1/Shank2 and ProSAP2/Shank3 causes a reduction of synapse density.

Literal:
"When neurons were transfected at DIV 6 and examined at DIV 9 GFP-tagged ProSAP1/Shank2 and ProSAP2/Shank3 efficiently colocalize with the synaptic markers Bassoon and Homer (Figure 1A), while GFP-tagged Shank1 exhibited a limited synaptic localization (Figure 1A). An analysis of synaptic density/unit length of dendrite revealed that GFPtagged ProSAP1/Shank2 and ProSAP2/Shank3 overexpression caused a significant increase in the number of synapses, while GFP-Shank1 overexpression had little effect (Figure 1B). Consistent with a role of these PSD proteins in synapse formation, knockdown of ProSAP/Shank proteins causes a significant reduction in synapse density (Figure 1B; ...)."

23/11/2017 Pim
- Shank's is a is a multidomain protein localized to the PSD that is regarded at a scaffold/structural organized of the PSD.
- This paper shows that:
1] Shank2 and Shank2 influence synapse formation (Fig.1)
2] Shank2 and Shank2 bind Zn2+. The effect on synapse formation of Shank2 and Shank2 is abolished with overexpression of Zn2+ insensitive mutants (Fig.2).
3] Removal of Zn2+ from neurons caused translocation of Shank2 and Shank2 from PSD to the cytosol. This resulted an increase of the number of synapses that lacked a PSD (Fig.3).
4] Zn2+ depletion causes complete loss of Homer1 (marker protein of PSD) from a subset of synapses (Fig.4).
Evidence tracking, Biological System:Intact tissue
Cultured neurons
Evidence tracking, Protein Targeting:RNAi / shRNA
Over-expression
Evidence tracking, Experiment Assay:Electron Microscopy
Confocal
Annotator(s):Chiara Verpelli (ORCID:0000-0003-2949-9725)
Carlo Sala (ORCID:0000-0003-0662-9523)
Lab:CNR Neuroscience Institute Milan and Dept. of Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy
SynGO annotation ID:1963
Dataset release (version):20231201
View annotation as GO-CAM model:Gene Ontology