Gene Symbol: Shank3
Description: SH3 and multiple ankyrin repeat domains 3
Alias: Prosap2, SH3 and multiple ankyrin repeat domains protein 3, SH3/ankyrin domain gene 3, SPANK-2, Shank postsynaptic density protein 3a, proline-rich synapse-associated protein 2
Species: rat
Products:     Shank3

Top Publications

  1. Peca J, Feliciano C, Ting J, Wang W, Wells M, Venkatraman T, et al. Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature. 2011;472:437-42 pubmed publisher
    ..The neurological basis and circuitry mechanisms underlying these abnormal behaviours are poorly understood. SHANK3 is a postsynaptic protein, whose disruption at the genetic level is thought to be responsible for the development ..
  2. Petralia R, Sans N, Wang Y, Wenthold R. Ontogeny of postsynaptic density proteins at glutamatergic synapses. Mol Cell Neurosci. 2005;29:436-52 pubmed
    ..Development was marked by substantial decreases in NR2B and SAP102 and increases in NR2A, PSD-95, AMPA receptors, and CaMKII. Other components showed more moderate changes. ..
  3. Naisbitt S, Kim E, Tu J, Xiao B, Sala C, Valtschanoff J, et al. Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin. Neuron. 1999;23:569-82 pubmed
    ..Shank may function as a scaffold protein in the PSD, potentially cross-linking NMDA receptor/PSD-95 complexes and coupling them to regulators of the actin cytoskeleton. ..
  4. Boeckers T, Winter C, Smalla K, Kreutz M, Bockmann J, Seidenbecher C, et al. Proline-rich synapse-associated proteins ProSAP1 and ProSAP2 interact with synaptic proteins of the SAPAP/GKAP family. Biochem Biophys Res Commun. 1999;264:247-52 pubmed
    ..A closely related multidomain protein, ProSAP2, shares a highly conserved PDZ (PSD-95/discs-large/ZO-1) domain (80% identity), a ppI domain that mediates the ..
  5. Sheng M, Kim E. The Shank family of scaffold proteins. J Cell Sci. 2000;113 ( Pt 11):1851-6 pubmed
    ..The specific localization of Shank proteins at postsynaptic sites of brain excitatory synapses suggests a role for this family of proteins in the organization of cytoskeletal/ signaling complexes at specialized cell junctions. ..
  6. Bockers T, Mameza M, Kreutz M, Bockmann J, Weise C, Buck F, et al. Synaptic scaffolding proteins in rat brain. Ankyrin repeats of the multidomain Shank protein family interact with the cytoskeletal protein alpha-fodrin. J Biol Chem. 2001;276:40104-12 pubmed
    ..Our data indicate that the Shank1 and -3 family members provide multiple independent connections between synaptic glutamate receptor complexes and the cytoskeleton. ..
  7. Bozdagi O, Sakurai T, Papapetrou D, Wang X, Dickstein D, Takahashi N, et al. Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication. Mol Autism. 2010;1:15 pubmed publisher
    b>SHANK3 is a protein in the core of the postsynaptic density (PSD) and has a critical role in recruiting many key functional elements to the PSD and to the synapse, including components of ?-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic ..
  8. Durand C, Betancur C, Boeckers T, Bockmann J, Chaste P, Fauchereau F, et al. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genet. 2007;39:25-7 pubmed
    SHANK3 (also known as ProSAP2) regulates the structural organization of dendritic spines and is a binding partner of neuroligins; genes encoding neuroligins are mutated in autism and Asperger syndrome...
  9. Proepper C, Johannsen S, Liebau S, Dahl J, Vaida B, Bockmann J, et al. Abelson interacting protein 1 (Abi-1) is essential for dendrite morphogenesis and synapse formation. EMBO J. 2007;26:1397-409 pubmed
    ..assembly, abelson interacting protein-1 (Abi-1), as a binding partner for the postsynaptic density (PSD) protein ProSAP2/Shank3...

More Information


  1. Wang X, MCCOY P, Rodriguiz R, Pan Y, Je H, Roberts A, et al. Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3. Hum Mol Genet. 2011;20:3093-108 pubmed publisher
    b>SHANK3 is a synaptic scaffolding protein enriched in the postsynaptic density (PSD) of excitatory synapses...
  2. Grabrucker A, Knight M, Proepper C, Bockmann J, Joubert M, ROWAN M, et al. Concerted action of zinc and ProSAP/Shank in synaptogenesis and synapse maturation. EMBO J. 2011;30:569-81 pubmed publisher
    ..shRNA-mediated knockdown, we could demonstrate that only the overexpression of zinc-sensitive ProSAP1/Shank2 or ProSAP2/Shank3 leads to increased synapse density, although all of them cause a decrease upon knockdown...
  3. Boeckers T, Kreutz M, Winter C, Zuschratter W, Smalla K, Sanmarti Vila L, et al. Proline-rich synapse-associated protein-1/cortactin binding protein 1 (ProSAP1/CortBP1) is a PDZ-domain protein highly enriched in the postsynaptic density. J Neurosci. 1999;19:6506-18 pubmed
    ..Homology screening identified a related protein, ProSAP2. Specific antisera raised against a C-terminal fusion construct and a central part of ProSAP1 detect a cluster of ..
  4. Uchino S, Wada H, Honda S, Nakamura Y, Ondo Y, Uchiyama T, et al. 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. 2006;97:1203-14 pubmed
    ..the cytoplasmic tail of the GluR1 subunit of AMPA receptor as a bait and identified a synaptic molecule, Shank3/ProSAP2, as a GluR1 subunit-interacting molecule...
  5. Tu J, Xiao B, Naisbitt S, Yuan J, Petralia R, Brakeman P, et al. Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins. Neuron. 1999;23:583-92 pubmed
    ..Thus, Shank may cross-link Homer and PSD-95 complexes in the PSD and play a role in the signaling mechanisms of both mGluRs and NMDA receptors. ..
  6. Wilson H, Wong A, Shaw S, Tse W, Stapleton G, Phelan M, et al. Molecular characterisation of the 22q13 deletion syndrome supports the role of haploinsufficiency of SHANK3/PROSAP2 in the major neurological symptoms. J Med Genet. 2003;40:575-84 pubmed
    ..130 kb to over 9 Mb; however all 45 cases that could be specifically tested for the terminal region at the site of SHANK3 were deleted for this gene. The molecular structure of SHANK3 was further characterised...
  7. Baron M, Boeckers T, Vaida B, Faham S, Gingery M, Sawaya M, et al. An architectural framework that may lie at the core of the postsynaptic density. Science. 2006;311:531-5 pubmed
    ..Here we show that the sterile alpha motif domain of rat Shank3/ProSAP2, a master scaffolding protein located deep within the PSD, can form large sheets composed of helical fibers ..
  8. Park E, Na M, Choi J, Kim S, Lee J, Yoon J, et al. 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. 2003;278:19220-9 pubmed
    ..Considering the involvement of Rac1 and PAK in spine dynamics, these results suggest that Shank recruits beta PIX and PAK to spines for the regulation of postsynaptic structure. ..
  9. Bockmann J, Kreutz M, Gundelfinger E, Bockers T. ProSAP/Shank postsynaptic density proteins interact with insulin receptor tyrosine kinase substrate IRSp53. J Neurochem. 2002;83:1013-7 pubmed
    ..The specificity of this interaction was confirmed in transfected COS cells. Co-immunoprecipitation of IRSp53 and ProSAP2 solubilized from rat brain membranes indicates that the interaction occurs in vivo...
  10. Qualmann B, Boeckers T, Jeromin M, Gundelfinger E, Kessels M. Linkage of the actin cytoskeleton to the postsynaptic density via direct interactions of Abp1 with the ProSAP/Shank family. J Neurosci. 2004;24:2481-95 pubmed
    ..that is conserved within the C-terminal parts of ProSAP1(proline-rich synapse-associated protein 1)/Shank2 and ProSAP2/Shank3...
  11. Thomas G, Rumbaugh G, Harrar D, Huganir R. Ribosomal S6 kinase 2 interacts with and phosphorylates PDZ domain-containing proteins and regulates AMPA receptor transmission. Proc Natl Acad Sci U S A. 2005;102:15006-11 pubmed
    ..receptor (NMDA-R) activation leads to ERK and RSK2 activation and RSK-dependent phosphorylation of transfected Shank3. RSK2-PDZ domain interactions are functionally important for synaptic transmission because neurons expressing ..
  12. Tobaben S, Sudhof T, Stahl B. The G protein-coupled receptor CL1 interacts directly with proteins of the Shank family. J Biol Chem. 2000;275:36204-10 pubmed
    ..Shank1 and CL1 are expressed primarily in brain, and both proteins co-enrich in the postsynaptic density. Furthermore, Shank1 induces a clustering of CL1 in transfected cells, strongly supporting an interaction of both proteins in vivo. ..
  13. Zhang Y, Gao B, Xiong Y, Zheng F, Xu X, Yang Y, et al. Expression of SHANK3 in the Temporal Neocortex of Patients with Intractable Temporal Epilepsy and Epilepsy Rat Models. Cell Mol Neurobiol. 2017;37:857-867 pubmed publisher
    SH3 and multiple ankyrin (ANK) repeat domain 3 (SHANK3) is a synaptic scaffolding protein enriched in the postsynaptic density of excitatory synapses. SHANK3 plays an important role in the formation and maturation of excitatory synapses...
  14. Wendholt D, Spilker C, Schmitt A, Dolnik A, Smalla K, Proepper C, et al. ProSAP-interacting protein 1 (ProSAPiP1), a novel protein of the postsynaptic density that links the spine-associated Rap-Gap (SPAR) to the scaffolding protein ProSAP2/Shank3. J Biol Chem. 2006;281:13805-16 pubmed
    ..ProSAPiP1 is widely expressed in rat brain and co-localizes with ProSAP2/Shank3 in excitatory spines and synapses...
  15. Liebau S, Proepper C, Schmidt T, Schoen M, Bockmann J, Boeckers T. ProSAPiP2, a novel postsynaptic density protein that interacts with ProSAP2/Shank3. Biochem Biophys Res Commun. 2009;385:460-5 pubmed publisher
    ..Here, we characterize a novel interaction partner of ProSAP2/Shank3, named ProSAP interacting protein 2 (ProSAPiP2) that does not show any close homology to other known ..
  16. Ponna S, Myllykoski M, Boeckers T, Kursula P. Structure of an unconventional SH3 domain from the postsynaptic density protein Shank3 at ultrahigh resolution. Biochem Biophys Res Commun. 2017;490:806-812 pubmed publisher
    ..We solved the crystal structure of the SH3 domain from Shank3 at sub-atomic resolution...
  17. Mameza M, Dvoretskova E, Bamann M, Honck H, Güler T, Boeckers T, et al. SHANK3 gene mutations associated with autism facilitate ligand binding to the Shank3 ankyrin repeat region. J Biol Chem. 2013;288:26697-708 pubmed publisher
    Shank/ProSAP proteins are major scaffold proteins of the postsynaptic density; mutations in the human SHANK3 gene are associated with intellectual disability or autism spectrum disorders...
  18. MacGillavry H, Song Y, Raghavachari S, Blanpied T. Nanoscale scaffolding domains within the postsynaptic density concentrate synaptic AMPA receptors. Neuron. 2013;78:615-22 pubmed publisher
  19. Verpelli C, Dvoretskova E, Vicidomini C, Rossi F, Chiappalone M, Schoen M, et al. Importance of Shank3 protein in regulating metabotropic glutamate receptor 5 (mGluR5) expression and signaling at synapses. J Biol Chem. 2011;286:34839-50 pubmed publisher
    Shank3/PROSAP2 gene mutations are associated with cognitive impairment ranging from mental retardation to autism...
  20. Waga C, Okamoto N, Ondo Y, Fukumura Kato R, Goto Y, Kohsaka S, et al. Novel variants of the SHANK3 gene in Japanese autistic patients with severe delayed speech development. Psychiatr Genet. 2011;21:208-11 pubmed publisher
    ..Cumulative evidence has shown that haploinsufficiency of the SHANK3 gene is a major cause of the neurological symptoms of the 22q13.3 deletion syndrome...
  21. Raab M, Boeckers T, Neuhuber W. Proline-rich synapse-associated protein-1 and 2 (ProSAP1/Shank2 and ProSAP2/Shank3)-scaffolding proteins are also present in postsynaptic specializations of the peripheral nervous system. Neuroscience. 2010;171:421-33 pubmed publisher
    Proline-rich synapse-associated protein-1 and 2 (ProSAP1/Shank2 and ProSAP2/Shank3) were originally found as synapse-associated protein 90/postsynaptic density protein-95-associated protein (SAPAP)/guanylate-kinase-associated protein (..
  22. Grubb D, Iliades P, Cooley N, Yu Y, Luo J, Filtz T, et al. Phospholipase Cbeta1b associates with a Shank3 complex at the cardiac sarcolemma. FASEB J. 2011;25:1040-7 pubmed publisher
    ..but not PLC?1a, coimmunoprecipitated with the high-MW scaffolding protein SH3 and ankyrin repeat protein 3 (Shank3), as well as the known Shank3-interacting protein ?-fodrin...
  23. Tao Cheng J, Toy D, Winters C, Reese T, Dosemeci A. Zinc Stabilizes Shank3 at the Postsynaptic Density of Hippocampal Synapses. PLoS ONE. 2016;11:e0153979 pubmed publisher
    b>Shank3 is a postsynaptic density (PSD) scaffold protein of the Shank family. Here we use pre-embedding immunogold electron microscopy to investigate factors influencing the distribution of Shank3 at the PSD...
  24. Arons M, Lee K, Thynne C, Kim S, Schob C, Kindler S, et al. Shank3 Is Part of a Zinc-Sensitive Signaling System That Regulates Excitatory Synaptic Strength. J Neurosci. 2016;36:9124-34 pubmed publisher
    b>Shank3 is a multidomain scaffold protein localized to the postsynaptic density of excitatory synapses...
  25. Schuetz G, Rosario M, Grimm J, Boeckers T, Gundelfinger E, Birchmeier W. The neuronal scaffold protein Shank3 mediates signaling and biological function of the receptor tyrosine kinase Ret in epithelial cells. J Cell Biol. 2004;167:945-52 pubmed
    ..The PDZ domain-containing Shank3 protein was found to represent a novel interaction partner of the receptor tyrosine kinase Ret, which binds ..
  26. Saavedra M, Smalla K, Thomas U, Sandoval S, Olavarria K, Castillo K, et al. Scaffolding proteins in highly purified rat olfactory cilia membranes. Neuroreport. 2008;19:1123-6 pubmed publisher
    ..Ion channels involved in chemotransduction could be reconstituted into planar lipid bilayers for electrophysiological recordings. Our procedure should allow the identification of further chemotransduction-related proteins. ..
  27. Uemura T, Mori H, Mishina M. Direct interaction of GluRdelta2 with Shank scaffold proteins in cerebellar Purkinje cells. Mol Cell Neurosci. 2004;26:330-41 pubmed
    ..These results suggest that through Shank1 and Shank2, GluRdelta2 interacts with the metabotropic GluR1alpha, the AMPA-type GluR, and the inositol 1,4,5-trisphosphate receptor (IP3R) that are essential for cerebellar LTD. ..
  28. Proepper C, Pütz S, Russell R, Boeckers T, Liebau S. The Kv?2 subunit of voltage-gated potassium channels is interacting with ProSAP2/Shank3 in the PSD. Neuroscience. 2014;261:133-43 pubmed publisher
    ..b>ProSAP2/Shank3 represents a crucial player at postsynaptic sites, assembling large multimeric platforms and anchoring ..
  29. Lilja J, Zacharchenko T, Georgiadou M, Jacquemet G, De Franceschi N, Peuhu E, et al. SHANK proteins limit integrin activation by directly interacting with Rap1 and R-Ras. Nat Cell Biol. 2017;19:292-305 pubmed publisher
    b>SHANK3, a synaptic scaffold protein and actin regulator, is widely expressed outside of the central nervous system with predominantly unknown function...
  30. Zhang H, Maximov A, Fu Y, Xu F, Tang T, Tkatch T, et al. Association of CaV1.3 L-type calcium channels with Shank. J Neurosci. 2005;25:1037-49 pubmed
    ..3 L-type Ca2+ channels in pCREB signaling. ..
  31. Halbedl S, Schoen M, Feiler M, Boeckers T, Schmeisser M. Shank3 is localized in axons and presynaptic specializations of developing hippocampal neurons and involved in the modulation of NMDA receptor levels at axon terminals. J Neurochem. 2016;137:26-32 pubmed publisher
    Autism-related Shank1, Shank2, and Shank3 are major postsynaptic scaffold proteins of excitatory glutamatergic synapses...