Jump to navigation Jump to search
External IDsGeneCards: [1]
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)n/an/a
PubMed searchn/an/a
View/Edit Human

SH3 and multiple ankyrin repeat domains protein 2 is a protein that in humans is encoded by the SHANK2 gene.[1][2] Two alternative splice variants, encoding distinct isoforms, are reported. Additional splice variants exist but their full-length nature has not been determined.[2]


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.[2]

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.[3] 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.


SHANK2 has been shown to interact with:


  1. Lim S, Naisbitt S, Yoon J, Hwang JI, Suh PG, Sheng M, Kim E (November 1999). "Characterization of the Shank family of synaptic proteins. Multiple genes, alternative splicing, and differential expression in brain and development". J Biol Chem. 274 (41): 29510–8. doi:10.1074/jbc.274.41.29510. PMID 10506216.
  2. 2.0 2.1 2.2 "Entrez Gene: SHANK2 SH3 and multiple ankyrin repeat domains 2".
  3. Boeckers TM, Bockmann J, Kreutz MR, Gundelfinger ED (June 2002). "ProSAP/Shank proteins - a family of higher order organizing molecules of the postsynaptic density with an emerging role in human neurological disease". J. Neurochem. 81 (5): 903–10. doi:10.1046/j.1471-4159.2002.00931.x. PMID 12065602.
  4. Park E, Na M, Choi J, Kim S, Lee JR, Yoon J, Park D, Sheng M, Kim E (May 2003). "The Shank family of postsynaptic density proteins interacts with and promotes synaptic accumulation of the beta PIX guanine nucleotide exchange factor for Rac1 and Cdc42". J. Biol. Chem. 278 (21): 19220–9. doi:10.1074/jbc.M301052200. PMID 12626503.
  5. Du Y, Weed SA, Xiong WC, Marshall TD, Parsons JT (October 1998). "Identification of a novel cortactin SH3 domain-binding protein and its localization to growth cones of cultured neurons". Mol. Cell. Biol. 18 (10): 5838–51. PMC 109170. PMID 9742101.
  6. 6.0 6.1 Naisbitt S, Valtschanoff J, Allison DW, Sala C, Kim E, Craig AM, Weinberg RJ, Sheng M (June 2000). "Interaction of the postsynaptic density-95/guanylate kinase domain-associated protein complex with a light chain of myosin-V and dynein". J. Neurosci. 20 (12): 4524–34. PMID 10844022.
  7. 7.0 7.1 Boeckers TM, Winter C, Smalla KH, Kreutz MR, Bockmann J, Seidenbecher C, Garner CC, Gundelfinger ED (October 1999). "Proline-rich synapse-associated proteins ProSAP1 and ProSAP2 interact with synaptic proteins of the SAPAP/GKAP family". Biochem. Biophys. Res. Commun. 264 (1): 247–52. doi:10.1006/bbrc.1999.1489. PMID 10527873.
  8. Okamoto PM, Gamby C, Wells D, Fallon J, Vallee RB (Dec 2001). "Dynamin isoform-specific interaction with the shank/ProSAP scaffolding proteins of the postsynaptic density and actin cytoskeleton". J. Biol. Chem. 276 (51): 48458–65. doi:10.1074/jbc.M104927200. PMC 2715172. PMID 11583995.

Further reading