SHANK2
Identifiers
Aliases	SHANK2, AUTS17, CORTBP1, CTTNBP1, ProSAP1, SHANK, SPANK-3, SH3 and multiple ankyrin repeat domains 2
External IDs	OMIM: 603290; MGI: 2671987; HomoloGene: 105965; GeneCards: SHANK2; OMA: SHANK2 - orthologs
Gene location ( Human) Chr. Chromosome 11 (human) [1] Band 11q13.3-q13.4 Start 70,467,854 bp [1] End 71,252,577 bp [1]
Gene location ( Mouse) Chr. Chromosome 7 (mouse) [2] Band 7|7 F5 Start 143,555,665 bp [2] End 143,978,231 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Brodmann area 23 bronchial epithelial cell middle temporal gyrus Region I of hippocampus proper entorhinal cortex corpus epididymis Epithelium of choroid plexus endothelial cell retinal pigment epithelium primary visual cortex Top expressed in primary visual cortex superior frontal gyrus dentate gyrus of hippocampal formation granule cell otolith organ utricle cerebellar cortex lobe of cerebellum zygote substantia nigra neural layer of retina More reference expression data BioGPS More reference expression data
Gene ontology Molecular function SH3 domain binding protein binding synaptic receptor adaptor activity ionotropic glutamate receptor binding signaling receptor complex adaptor activity Cellular component cytoplasm postsynaptic membrane cell projection membrane postsynaptic density neurofilament photoreceptor inner segment growth cone plasma membrane dendritic spine photoreceptor outer segment synapse brush border membrane cell junction neuronal cell body apical plasma membrane ciliary membrane neuron projection ionotropic glutamate receptor complex cytosol cellular component dendrite neuron spine Biological process learning vocalization behavior adult behavior long-term depression social behavior synapse assembly long-term potentiation brain morphogenesis synaptic assembly at neuromuscular junction positive regulation of synaptic transmission, glutamatergic dendritic spine morphogenesis positive regulation of dendritic spine development postsynaptic density assembly regulation of AMPA receptor activity positive regulation of excitatory postsynaptic potential Sources: Amigo / QuickGO
Orthologs Species Human Mouse Entrez 22941 210274 Ensembl ENSG00000162105 ENSMUSG00000037541 UniProt Q9UPX8 Q80Z38 RefSeq (mRNA) NM_012309 NM_133266 NM_001379226 NM_001081370 NM_001113373 RefSeq (protein) NP_036441 NP_573573 NP_001366155 NP_001074839 NP_001106844 Location (UCSC) Chr 11: 70.47 – 71.25 Mb Chr 7: 143.56 – 143.98 Mb PubMed search [3] [4]
Wikidata
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SH3 and multiple ankyrin repeat domains protein 2 is a protein that in humans is encoded by the SHANK2 gene. ^{[5] [6]} Two alternative splice variants, encoding distinct isoforms, are reported. Additional splice variants exist but their full- length nature has not been determined. ^[6]

Function

This gene encodes a protein that is a member of the Shank family of synaptic proteins that may function as molecular scaffolds in the postsynaptic density (PSD). Shank proteins contain multiple domains for protein-protein interaction, including ankyrin repeats, an SH3 domain, a PSD-95/Dlg/ZO-1 domain, a sterile alpha motif domain, and a proline-rich region. This particular family member contains a PDZ domain, a consensus sequence for cortactin SH3 domain-binding peptides and a sterile alpha motif. The alternative splicing demonstrated in Shank genes has been suggested as a mechanism for regulating the molecular structure of Shank and the spectrum of Shank-interacting proteins in the PSDs of adult and developing brain. ^[6]

It is thought that SHANK2 might play a role in synaptogenesis by attaching metabotropic glutamate receptors (mGluRs) to an existing pool of NMDA receptors (NMDA-R), bylinking to the NMDA-R through PSD-95, and the mGluRs through HOMER1. ^[7] An alternative hypothesis is that the Homer/Shank/GKAP/PSD-95 assembly mediates physical association of the NMDAR with IP3R/RYR and intracellular Ca2+ stores.

Interactions

SHANK2 has been shown to interact with:

• ARHGEF7, ^[8]
• Cortactin, ^[9]
• DLG4, ^{[10] [11]}
• DLGAP1, ^{[10] [11]} and
• DNM2. ^[12]

Associations with neuropsychiatric disease

Mutations in SHANK2 have been associated with autism spectrum disorder (ASD) and schizophrenia. ^[13] In particular, heterozygous loss-of-function mutations have a near-complete penetrance in ASD. ^[14] Neurons generated from people with ASD and SHANK2 mutations develop larger dendritic trees and more synaptic connections than those from healthy controls. ^[15] In addition, common mutations in SHANK2 have been linked to bipolar disorder. ^[16]

References

Further reading

External links

• The SHANK2 Foundation - non-profit supporting families and research into SHANK2 disorders

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