Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Shank3. (This text reflects annotations as of Wednesday, January 23, 2013.)

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a member of the Shank gene family. Shank proteins are multidomain scaffold proteins of the postsynaptic density that connect neurotransmitter receptors, ion channels, and other membrane proteins to the actin cytoskeleton and G-protein-coupled signaling pathways. Shank proteins also play a role in synapse formation and dendritic spine maturation. Mutations in this gene are a cause of autism spectrum disorder (ASD), which is characterized by impairments in social interaction and communication, and restricted behavioral patterns and interests. Mutations in this gene also cause schizophrenia type 15, and are a major causative factor in the neurological symptoms of 22q13.3 deletion syndrome, which is also known as Phelan-McDermid syndrome. Additional isoforms have been described for this gene but they have not yet been experimentally verified. [provided by RefSeq, Mar 2012]

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Shank3
  • participates in the following biological processes:
    • negative regulation of actin filament bundle assembly ^[3]
  • is located in the following cellular components:
    • neuron projection ^[7]
    • neuron spine ^[5]
    • plasma membrane ^[5]
• The gene product of Shank3 has been shown to bind to the gene products of Grb2, Ret. ^[4] Researchers have inferred, based on physical interactions, that the gene product of Shank3
  • performs the following molecular functions:
    • ionotropic glutamate receptor binding ^{[5, 6]}
    • protein C-terminus binding ^[5]
    • scaffold protein binding ^[5]
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Shank3
  • participates in the following biological processes:
    • alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor clustering ^{[7, 8]}
    • brain morphogenesis ^[2]
    • dendritic spine morphogenesis ^{[1, 2, 8]}
    • guanylate kinase-associated protein clustering ^[8]
    • learning ^[8]
    • locomotory exploration behavior ^{[2, 8]}
    • memory ^[8]
    • N-methyl-D-aspartate receptor clustering ^[8]
    • negative regulation of cell volume ^[2]
    • neuromuscular process controlling balance ^[8]
    • positive regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activity ^[2]
    • positive regulation of dendritic spine development ^[7]
    • positive regulation of excitatory postsynaptic membrane potential ^{[1, 2, 7]}
    • positive regulation of glutamate receptor signaling pathway ^[7]
    • positive regulation of long-term neuronal synaptic plasticity ^[1]
    • positive regulation of synapse structural plasticity ^[1]
    • positive regulation of synaptic transmission, glutamatergic ^{[1, 2, 7]}
    • postsynaptic density assembly ^[2]
    • regulation of behavioral fear response ^[2]
    • regulation of dendritic spine morphogenesis ^[7]
    • regulation of grooming behavior ^{[2, 8]}
    • regulation of long term synaptic depression ^[7]
    • regulation of long-term synaptic potentiation ^[8]
    • social behavior ^{[1, 2, 8]}
    • striatal medium spiny neuron differentiation ^[2]
    • synapse assembly ^[2]
    • vocalization behavior ^{[1, 8]}
• Researchers have inferred, based on genetic interactions, that the gene product of Shank3
  • participates in the following biological processes:
    • embryonic epithelial tube formation based on interactions with Ret ^[4]
    • MAPK cascade based on interactions with Grb2, Ret ^[4]
• Based on the experimental annotations above, MGI curators have inferred, that the gene product of Shank3
  • is located in the following cellular components:
    • excitatory synapse ^[2]

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Shank3:
  • participates in the following biological processes:
    • protein oligomerization
  • performs the following molecular functions:
    • GKAP/Homer scaffold activity
    • identical protein binding
    • protein C-terminus binding
    • protein self-association
    • scaffold protein binding
    • SH3 domain binding
    • zinc ion binding
  • is located in the following cellular components:
    • cilium membrane
    • postsynaptic density
    • synapse

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Shank3 indicates that it:
  • is located in the following cellular components:
    • cell junction
    • cytoplasm
    • membrane
    • postsynaptic membrane

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References

1. Bozdagi O et al. (2010) Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication. Mol Autism, 1:15. (PubMed:21167025)
2. Peca J et al. (2011) Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature, 472:437-42. (PubMed:21423165)
3. Sawallisch C et al. (2009) The insulin receptor substrate of 53 kDa (IRSp53) limits hippocampal synaptic plasticity. J Biol Chem, 284:9225-36. (PubMed:19208628)
4. Schuetz G et al. (2004) The neuronal scaffold protein Shank3 mediates signaling and biological function of the receptor tyrosine kinase Ret in epithelial cells. J Cell Biol, 167:945-52. (PubMed:15569713)
5. Uchino S et al. (2006) Direct interaction of post-synaptic density-95/Dlg/ZO-1 domain-containing synaptic molecule Shank3 with GluR1 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor. J Neurochem, 97:1203-14. (PubMed:16606358)
6. Uemura T et al. (2004) Direct interaction of GluRdelta2 with Shank scaffold proteins in cerebellar Purkinje cells. Mol Cell Neurosci, 26:330-41. (PubMed:15207857)
7. Verpelli C et al. (2011) Importance of Shank3 protein in regulating metabotropic glutamate receptor 5 (mGluR5) expression and signaling at synapses. J Biol Chem, 286:34839-50. (PubMed:21795692)
8. Wang X et al. (2011) Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3. Hum Mol Genet, 20:3093-108. (PubMed:21558424)

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Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

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