SHANK3 pathway involved in Phelan McDermid syndrome (WP5566)

Homo sapiens

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This pathway shows the molecular pathway around the SHANK3 gene. Mutations in SHANK3 can cause Phelan McDermid syndrome.

For a description of pathway objects, see the WikiPathways Legend.

Authors

SabyaSherpa , Yuanyuan Duan , and Friederike Ehrhart

Activity

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Cited In

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Organisms

Homo sapiens

Communities

Rare Diseases

Annotations

Pathway Ontology

disease pathway

Disease Ontology

Phelan-McDermid syndrome

Participants
Query Drugst.One

Label Type Compact URI Comment
glutamate Metabolite chebi:14321
Zn(2+) Metabolite chebi:29105
MAP3K7 GeneProduct ensembl:ENSG00000135341
LZTS3 GeneProduct ensembl:ENSG00000088899
CDC42 GeneProduct ensembl:ENSG00000070831
GRIN2B GeneProduct ensembl:ENSG00000273079
ACTB GeneProduct ensembl:ENSG00000075624
SPAAR GeneProduct ensembl:ENSG00000235387
ARHGAP44 GeneProduct ensembl:ENSG00000006740
RAC1 GeneProduct ensembl:ENSG00000136238-
BAIAP2 GeneProduct ensembl:ENSG00000175866
CTNND2 GeneProduct ensembl:ENSG00000169862
CAMK2A GeneProduct ensembl:ENSG00000070808
GRIA2 GeneProduct ensembl:ENSG00000120251
SYNGAP1 GeneProduct ensembl:ENSG00000197283
DLGAP1 GeneProduct ensembl:ENSG00000170579 dlgap1
ITGB1 GeneProduct ensembl:ENSG00000150093
GRIA1 GeneProduct ensembl:ENSG00000155511
PSD-95 GeneProduct ensembl:ENSG00000132535 dlg4
GRIN1 GeneProduct ensembl:ENSG00000176884
ABI1 GeneProduct ensembl:ENSG00000136754
SPTAN1 GeneProduct ensembl:ENSG00000197694
SHANK3 GeneProduct ensembl:ENSG00000251322
HOMER1 GeneProduct ensembl:ENSG00000152413
SHARPIN GeneProduct ensembl:ENSG00000179526
ARHGEF7 GeneProduct ensembl:ENSG00000102606
GRM5 GeneProduct ensembl:ENSG00000168959
HRAS GeneProduct ensembl:ENSG00000174775
DBNL GeneProduct ensembl:ENSG00000136279
PAK1 GeneProduct ensembl:ENSG00000149269
TAB2/3 GeneProduct ensembl:ENSG00000055208
RAP1A GeneProduct ensembl:ENSG00000116473
HCN1 GeneProduct ensembl:ENSG00000164588
ADGRL1 GeneProduct ensembl:ENSG00000072071
GRM1 GeneProduct ensembl:ENSG00000152822
CTTN GeneProduct ensembl:ENSG00000085733
ITPR1 GeneProduct ensembl:ENSG00000150995

References

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  4. Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors. Tu JC, Xiao B, Yuan JP, Lanahan AA, Leoffert K, Li M, et al. Neuron. 1998 Oct;21(4):717–26. PubMed Europe PMC Scholia
  5. Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin. Naisbitt S, Kim E, Tu JC, Xiao B, Sala C, Valtschanoff J, et al. Neuron. 1999 Jul;23(3):569–82. PubMed Europe PMC Scholia
  6. Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins. Tu JC, Xiao B, Naisbitt S, Yuan JP, Petralia RS, Brakeman P, et al. Neuron. 1999 Jul;23(3):583–92. PubMed Europe PMC Scholia
  7. Proline-rich synapse-associated proteins ProSAP1 and ProSAP2 interact with synaptic proteins of the SAPAP/GKAP family. Boeckers TM, Winter C, Smalla KH, Kreutz MR, Bockmann J, Seidenbecher C, et al. Biochem Biophys Res Commun. 1999 Oct 14;264(1):247–52. PubMed Europe PMC Scholia
  8. The calcium-independent receptor for alpha-latrotoxin from human and rodent brains interacts with members of the ProSAP/SSTRIP/Shank family of multidomain proteins. Kreienkamp HJ, Zitzer H, Gundelfinger ED, Richter D, Bockers TM. J Biol Chem. 2000 Oct 20;275(42):32387–90. PubMed Europe PMC Scholia
  9. Sharpin, a novel postsynaptic density protein that directly interacts with the shank family of proteins. Lim S, Sala C, Yoon J, Park S, Kuroda S, Sheng M, et al. Mol Cell Neurosci. 2001 Feb;17(2):385–97. PubMed Europe PMC Scholia
  10. Interaction with the NMDA receptor locks CaMKII in an active conformation. Bayer KU, De Koninck P, Leonard AS, Hell JW, Schulman H. Nature. 2001 Jun 14;411(6839):801–5. PubMed Europe PMC Scholia
  11. Synaptic scaffolding proteins in rat brain. Ankyrin repeats of the multidomain Shank protein family interact with the cytoskeletal protein alpha-fodrin. Böckers TM, Mameza MG, Kreutz MR, Bockmann J, Weise C, Buck F, et al. J Biol Chem. 2001 Oct 26;276(43):40104–12. PubMed Europe PMC Scholia
  12. 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. Park E, Na M, Choi J, Kim S, Lee JR, Yoon J, et al. J Biol Chem. 2003 May 23;278(21):19220–9. PubMed Europe PMC Scholia
  13. Cortactin binding to F-actin revealed by electron microscopy and 3D reconstruction. Pant K, Chereau D, Hatch V, Dominguez R, Lehman W. J Mol Biol. 2006 Jun 16;359(4):840–7. PubMed Europe PMC Scholia
  14. Abelson interacting protein 1 (Abi-1) is essential for dendrite morphogenesis and synapse formation. Proepper C, Johannsen S, Liebau S, Dahl J, Vaida B, Bockmann J, et al. EMBO J. 2007 Mar 7;26(5):1397–409. PubMed Europe PMC Scholia
  15. The actin-binding protein Abp1 controls dendritic spine morphology and is important for spine head and synapse formation. Haeckel A, Ahuja R, Gundelfinger ED, Qualmann B, Kessels MM. J Neurosci. 2008 Oct 1;28(40):10031–44. PubMed Europe PMC Scholia
  16. SHARPIN is a key regulator of immune and inflammatory responses. Wang Z, Potter CS, Sundberg JP, Hogenesch H. J Cell Mol Med. 2012 Oct;16(10):2271–9. PubMed Europe PMC Scholia
  17. Shank3-Rich2 interaction regulates AMPA receptor recycling and synaptic long-term potentiation. Raynaud F, Janossy A, Dahl J, Bertaso F, Perroy J, Varrault A, et al. J Neurosci. 2013 Jun 5;33(23):9699–715. PubMed Europe PMC Scholia
  18. Active calcium/calmodulin-dependent protein kinase II (CaMKII) regulates NMDA receptor mediated postischemic long-term potentiation (i-LTP) by promoting the interaction between CaMKII and NMDA receptors in ischemia. Wang N, Chen L, Cheng N, Zhang J, Tian T, Lu W. Neural Plast. 2014;2014:827161. PubMed Europe PMC Scholia
  19. The Shank3 Interaction Partner ProSAPiP1 Regulates Postsynaptic SPAR Levels and the Maturation of Dendritic Spines in Hippocampal Neurons. Reim D, Weis TM, Halbedl S, Delling JP, Grabrucker AM, Boeckers TM, et al. Front Synaptic Neurosci. 2016 May 24;8:13. PubMed Europe PMC Scholia
  20. Shank3 Is Part of a Zinc-Sensitive Signaling System That Regulates Excitatory Synaptic Strength. Arons MH, Lee K, Thynne CJ, Kim SA, Schob C, Kindler S, et al. J Neurosci. 2016 Aug 31;36(35):9124–34. PubMed Europe PMC Scholia
  21. Shank3 mutations and HCN channelopathy: one size does not fit all. Monteiro P. J Physiol. 2018 Apr 1;596(7):1123. PubMed Europe PMC Scholia
  22. Glutamate and Glycine Binding to the NMDA Receptor. Yu A, Lau AY. Structure. 2018 Jul 3;26(7):1035-1043.e2. PubMed Europe PMC Scholia
  23. Shank3 Binds to and Stabilizes the Active Form of Rap1 and HRas GTPases via Its NTD-ANK Tandem with Distinct Mechanisms. Cai Q, Hosokawa T, Zeng M, Hayashi Y, Zhang M. Structure. 2020 Mar 3;28(3):290-300.e4. PubMed Europe PMC Scholia
  24. How CBP/Shank3 Guards Rap and H-Ras. Chowdhury D, Hell JW. Structure. 2020 Mar 3;28(3):274–6. PubMed Europe PMC Scholia
  25. CaMKIIα-driven, phosphatase-checked postsynaptic plasticity via phase separation. Cai Q, Zeng M, Wu X, Wu H, Zhan Y, Tian R, et al. Cell Res. 2021 Jan;31(1):37–51. PubMed Europe PMC Scholia
  26. Restoring glutamate receptosome dynamics at synapses rescues autism-like deficits in Shank3-deficient mice. Moutin E, Sakkaki S, Compan V, Bouquier N, Giona F, Areias J, et al. Mol Psychiatry. 2021 Dec;26(12):7596–609. PubMed Europe PMC Scholia
  27. Homer1a regulates Shank3 expression and underlies behavioral vulnerability to stress in a model of Phelan-McDermid syndrome. Lin R, Learman LN, Bangash MA, Melnikova T, Leyder E, Reddy SC, et al. Cell Rep. 2021 Nov 16;37(7):110014. PubMed Europe PMC Scholia
  28. IRSp53 promotes postsynaptic density formation and actin filament bundling. Feng Z, Lee S, Jia B, Jian T, Kim E, Zhang M. J Cell Biol. 2022 Aug 1;221(8):e202105035. PubMed Europe PMC Scholia
  29. GluA1-Shank3 interaction decreases in response to chronic neuronal depolarization. Ross MM, Aizenman E. Neurosci Lett. 2023 Jul 13;809:137305. PubMed Europe PMC Scholia