Gene Symbol: Shank1
Description: SH3 and multiple ankyrin repeat domains 1
Alias: Shank1a, Spank1, Sstrip, SH3 and multiple ankyrin repeat domains protein 1, GKAP/SAPAP-interacting protein, SAPAP-interacting protein synamon, SH3/ankyrin domain gene 1, SPANK-1, SSTR-interacting protein, somatostatin receptor-interacting protein, synamon
Species: rat
Products:     Shank1

Top Publications

  1. 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
    ..b>Shank1 and CL1 are expressed primarily in brain, and both proteins co-enrich in the postsynaptic density...
  2. 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. ..
  3. 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
    ..These results suggest that binding of RSK2 to PDZ domain proteins and phosphorylation of these proteins or their binding partners regulates excitatory synaptic transmission. ..
  4. Sala C, Piech V, Wilson N, Passafaro M, Liu G, Sheng M. Regulation of dendritic spine morphology and synaptic function by Shank and Homer. Neuron. 2001;31:115-30 pubmed
    ..These data suggest a central role for the Shank scaffold in the structural and functional organization of the dendritic spine and synaptic junction. ..
  5. Lim S, Naisbitt S, Yoon J, Hwang J, Suh P, Sheng M, et al. Characterization of the Shank family of synaptic proteins. Multiple genes, alternative splicing, and differential expression in brain and development. J Biol Chem. 1999;274:29510-8 pubmed
    b>Shank1, Shank2, and Shank3 constitute a family of proteins that may function as molecular scaffolds in the postsynaptic density (PSD)...
  6. 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. ..
  7. Bockers T, Segger Junius M, Iglauer P, Bockmann J, Gundelfinger E, Kreutz M, et al. Differential expression and dendritic transcript localization of Shank family members: identification of a dendritic targeting element in the 3' untranslated region of Shank1 mRNA. Mol Cell Neurosci. 2004;26:182-90 pubmed
    ..In situ hybridization revealed that Shank1/SSTRIP and Shank2/ProSAP1 mRNAs are widely expressed early in postnatal brain development whereas Shank3/ProSAP2 ..
  8. Silverman J, Turner S, Barkan C, Tolu S, Saxena R, Hung A, et al. Sociability and motor functions in Shank1 mutant mice. Brain Res. 2011;1380:120-37 pubmed publisher
    ..relevant to the diagnostic and associated symptoms of autism, comprehensive behavioral phenotyping on a line of Shank1 mutant mice was conducted on multiple measures of social interactions, social olfaction, repetitive behaviors, ..
  9. 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. ..

More Information


  1. Hung A, Futai K, Sala C, Valtschanoff J, Ryu J, Woodworth M, et al. Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1. J Neurosci. 2008;28:1697-708 pubmed publisher
    ..Here, we report the phenotype of Shank1 knock-out mice...
  2. Hayashi M, Tang C, Verpelli C, Narayanan R, Stearns M, Xu R, et al. The postsynaptic density proteins Homer and Shank form a polymeric network structure. Cell. 2009;137:159-71 pubmed publisher
    ..We propose that the Homer-Shank complex serves as a structural framework and as an assembly platform for other PSD proteins. ..
  3. Miletic G, Dumitrascu C, Honstad C, Micic D, Miletic V. Loose ligation of the rat sciatic nerve elicits early accumulation of Shank1 protein in the post-synaptic density of spinal dorsal horn neurons. Pain. 2010;149:152-9 pubmed publisher
    ..In this study we examined the early consequences of the loose ligation of the sciatic nerve on Shank1 protein and message levels in the PSD of spinal dorsal horn neurons...
  4. Falley K, Schütt J, Iglauer P, Menke K, Maas C, Kneussel M, et al. Shank1 mRNA: dendritic transport by kinesin and translational control by the 5'untranslated region. Traffic. 2009;10:844-57 pubmed publisher
    ..We have analyzed dendritic localization of shank1 mRNAs; shank proteins (shank1-3) are scaffolding molecules of the postsynaptic density (PSD) of excitatory ..
  5. Romorini S, Piccoli G, Jiang M, Grossano P, Tonna N, Passafaro M, et al. A functional role of postsynaptic density-95-guanylate kinase-associated protein complex in regulating Shank assembly and stability to synapses. J Neurosci. 2004;24:9391-404 pubmed
    ..We investigated the molecular mechanisms of Shank1 targeting and synapse assembly by looking at the function of guanylate kinase-associated protein (GKAP) and PSD-95 ..
  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
    ..We used the N-terminal ankyrin repeats of Shank1 and -3 to search for interacting proteins by yeast two-hybrid screening and by affinity chromatography...
  7. Francke F, Richter D, Bächner D. Immunohistochemical distribution of MIZIP and its co-expression with the Melanin-concentrating hormone receptor 1 in the adult rodent brain. Brain Res Mol Brain Res. 2005;139:31-41 pubmed
    ..These data support the notion that MIZIP might interact with MCHR1 in a cell type specific manner in vivo, suggesting a role in the regulation of MCH signalling in distinct regions of the mammalian brain. ..
  8. Im Y, Kang G, Lee J, Park K, Song H, Kim E, et al. Structural basis for asymmetric association of the betaPIX coiled coil and shank PDZ. J Mol Biol. 2010;397:457-66 pubmed publisher
    ..This structural study provides a clear picture of the molecular recognition of the PDZ ligand and the asymmetric association of betaPIX CC and Shank PDZ. ..
  9. 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. ..
  10. Yoshida T, Yasumura M, Uemura T, Lee S, Ra M, Taguchi R, et al. IL-1 receptor accessory protein-like 1 associated with mental retardation and autism mediates synapse formation by trans-synaptic interaction with protein tyrosine phosphatase ?. J Neurosci. 2011;31:13485-99 pubmed publisher
    ..Our findings raise an intriguing possibility that the impairment of synapse formation may underlie certain forms of MR and autism as a common pathogenic pathway shared by these mental disorders. ..
  11. Arstikaitis P, Gauthier Campbell C, Carolina Gutierrez Herrera R, Huang K, Levinson J, Murphy T, et al. Paralemmin-1, a modulator of filopodia induction is required for spine maturation. Mol Biol Cell. 2008;19:2026-38 pubmed publisher
    ..Our study identifies a key role for paralemmin-1 in spine maturation through modulation of filopodia induction. ..
  12. Roselli F, Hutzler P, Wegerich Y, Livrea P, Almeida O. Disassembly of shank and homer synaptic clusters is driven by soluble beta-amyloid(1-40) through divergent NMDAR-dependent signalling pathways. PLoS ONE. 2009;4:e6011 pubmed publisher
    ..glutamate receptor trafficking, we now show that Abeta also disrupts two other scaffold proteins, Homer1b and Shank1, that couple PSD-95 with ionotropic and metabotropic glutamate receptors...
  13. Epstein I, Tushev G, Will T, Vlatkovic I, Cajigas I, Schuman E. Alternative polyadenylation and differential expression of Shank mRNAs in the synaptic neuropil. Philos Trans R Soc Lond B Biol Sci. 2014;369:20130137 pubmed publisher
    ..Shank proteins, encoded by the three genes Shank1, Shank2 and Shank3 are scaffold molecules in the postsynaptic density of excitatory neurons that contribute to ..
  14. 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
    ..Here, we show that SHANK1 and SHANK3 act as integrin activation inhibitors by sequestering active Rap1 and R-Ras via the SPN domain and thus ..
  15. 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
    ..Taken together with the biochemical interaction of Shank3 with the GluR1 subunit, these results suggest that Shank3 is an important molecule that interacts with GluR1 AMPA receptor at synaptic sites of developing neurons. ..
  16. Im Y, Lee J, Park S, Park S, Rho S, Kang G, et al. Crystal structure of the Shank PDZ-ligand complex reveals a class I PDZ interaction and a novel PDZ-PDZ dimerization. J Biol Chem. 2003;278:48099-104 pubmed
    ..Here we describe the crystal structures of Shank1 PDZ in its peptide free form and in complex with the C-terminal hexapeptide (EAQTRL) of guanylate kinase-..
  17. Dani A, Huang B, BERGAN J, Dulac C, Zhuang X. Superresolution imaging of chemical synapses in the brain. Neuron. 2010;68:843-56 pubmed publisher
    ..Combination with optogenetics further allowed molecular events associated with synaptic plasticity to be resolved at the single-synapse level. ..
  18. Lee J, Park H, Park S, Kim H, Eom S. The structural flexibility of the shank1 PDZ domain is important for its binding to different ligands. Biochem Biophys Res Commun. 2011;407:207-12 pubmed publisher
    ..Here, we have determined the crystal structure of the shank1 PDZ in complex with the ?PIX C-terminal pentapeptide (642-646, DETNL) at 2...
  19. Wöhr M, Roullet F, Hung A, Sheng M, Crawley J. Communication impairments in mice lacking Shank1: reduced levels of ultrasonic vocalizations and scent marking behavior. PLoS ONE. 2011;6:e20631 pubmed publisher
    ..To test the hypothesis that a mutation in SHANK1 contributes to the symptoms of autism, we evaluated Shank1(-/-) null mutant mice for behavioral phenotypes with ..
  20. Sato D, Lionel A, Leblond C, Prasad A, Pinto D, Walker S, et al. SHANK1 Deletions in Males with Autism Spectrum Disorder. Am J Hum Genet. 2012;90:879-87 pubmed publisher
    ..The SHANK gene family consists of three members (SHANK1, SHANK2, and SHANK3), which encode scaffolding proteins required for the proper formation and function of neuronal ..
  21. Tao Cheng J, Yang Y, Reese T, Dosemeci A. Differential distribution of Shank and GKAP at the postsynaptic density. PLoS ONE. 2015;10:e0118750 pubmed publisher
    ..These observations identify two pools of Shank at the PSD complex, one relatively stable pool, closer to the postsynaptic membrane that can bind to GKAP, and another more dynamic pool at a location too far away to bind to GKAP. ..
  22. Yao I, Hata Y, Hirao K, Deguchi M, Ide N, Takeuchi M, et al. Synamon, a novel neuronal protein interacting with synapse-associated protein 90/postsynaptic density-95-associated protein. J Biol Chem. 1999;274:27463-6 pubmed
    ..We have identified here a novel neuronal GKAP/SAPAP/DAP-binding protein and named it synamon. Synamon has seven ankyrin repeats at the NH(2) terminus followed by one src homology 3 domain and one PSD-95/Dlg-..
  23. 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. ..
  24. 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
    ..b>Shank1 and Shank2 proteins as well as GluRdelta2 proteins were localized in the dendritic spines of cultured Purkinje ..
  25. Miletic G, Miyabe T, Gebhardt K, Miletic V. Increased levels of Homer1b/c and Shank1a in the post-synaptic density of spinal dorsal horn neurons are associated with neuropathic pain in rats. Neurosci Lett. 2005;386:189-93 pubmed
    ..differential weight-bearing behavior 7 days after loose ligation of the sciatic nerve the levels of Homer1b/c and Shank1a were significantly greater than in control, uninjured or sham-operated animals...
  26. Park S, Im Y, Rho S, Lee J, Yang S, Kim E, et al. Crystallization and preliminary X-ray crystallographic studies of the PDZ domain of Shank1 from Rattus norvegicus. Acta Crystallogr D Biol Crystallogr. 2002;58:1353-5 pubmed
    ..The PDZ domain of Shank binds to the C-terminus of guanylate kinase-associated protein (GKAP). The PDZ domain of Shank1 from Rattus norvegicus and its complex with the C-terminal octapeptide of GKAP were crystallized at 294 K using ..
  27. Okamoto P, Gamby C, Wells D, Fallon J, Vallee R. Dynamin isoform-specific interaction with the shank/ProSAP scaffolding proteins of the postsynaptic density and actin cytoskeleton. J Biol Chem. 2001;276:48458-65 pubmed
    ..These data are consistent with a role for this otherwise broadly distributed form of dynamin in glutamate receptor down-regulation and other aspects of postsynaptic membrane turnover. ..
  28. Zitzer H, Hönck H, Bächner D, Richter D, Kreienkamp H. Somatostatin receptor interacting protein defines a novel family of multidomain proteins present in human and rodent brain. J Biol Chem. 1999;274:32997-3001 pubmed
    ..This protein termed somatostatin receptor interacting protein is characterized by a novel domain structure, consisting of six N-terminal ankyrin repeats ..
  29. Lim S, Sala C, Yoon J, Park S, Kuroda S, Sheng M, et al. Sharpin, a novel postsynaptic density protein that directly interacts with the shank family of proteins. Mol Cell Neurosci. 2001;17:385-97 pubmed
    The Shank family of proteins (also termed CortBP, ProSAP, or Synamon) is highly enriched in the postsynaptic density (PSD) of excitatory synapses in brain...