SHANK3

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SH3 and multiple ankyrin repeat domains 3
Protein SHANK3 PDB 2f3n.png
PDB rendering based on 2f3n.
Identifiers
Symbols SHANK3 ; DEL22q13.3; PROSAP2; PSAP2; SCZD15; SPANK-2
External IDs OMIM606230 MGI1930016 HomoloGene75163 GeneCards: SHANK3 Gene
RNA expression pattern
PBB GE SHANK3 gnf1h01748 s at tn.png
PBB GE SHANK3 gnf1h02526 x at tn.png
PBB GE SHANK3 gnf1h02529 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 85358 58234
Ensembl ENSG00000251322 ENSMUSG00000022623
UniProt Q9BYB0 Q4ACU6
RefSeq (mRNA) NM_001080420 NM_021423
RefSeq (protein) NP_277052 NP_067398
Location (UCSC) Chr 22:
51.11 – 51.17 Mb
Chr 15:
89.5 – 89.56 Mb
PubMed search [1] [2]

SH3 and multiple ankyrin repeat domains 3 (Shank3), also known as proline-rich synapse-associated protein 2 (ProSAP2), is a protein that in humans is encoded by the SHANK3 gene on chromosome 22.[1] Additional isoforms have been described for this gene but they have not yet been experimentally verified.

Function[edit]

This gene is a member of the Shank gene family. Shank proteins are multidomain scaffold proteins of the postsynaptic density that connect neurotransmitter receptors, ion channels, and other membrane proteins to the actin cytoskeleton and G-protein-coupled signaling pathways. Shank proteins also play a role in synapse formation and dendritic spine maturation.[2]

Clinical significance[edit]

Mutations in this gene are associated with autism spectrum disorder. This gene is often missing in patients with 22q13.3 deletion syndrome,[3] although not in all cases.[4]

Interactions[edit]

SHANK3 has been shown to interact with ARHGEF7.[5]

Mouse Models[edit]

Mouse models of Shank3 include N-terminal knock-outs[6][7] and a PDZ domain knock-out[8] all of which also show social interaction deficits and variable other phenotypes. Most of the these mice are homozygous knock-outs whereas all the human Shank3 mutations have been heterozygous.

References[edit]

  1. ^ "Entrez Gene: SHANK3 SH3 and multiple ankyrin repeat domains 3". 
  2. ^ Boeckers TM et al. (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. 
  3. ^ Sarasua SM et al. (2011). "Association between deletion size and important phenotypes expands the genomic region of interest in Phelan-McDermid syndrome (22q13 deletion syndrome).". J Med Genet. 48 (11): 761–6. doi:10.1136/jmedgenet-2011-100225. PMID 21984749. 
  4. ^ Simenson K et al. (2013). "A patient with the classic features of Phelan-McDermid syndrome and a high immunoglobulin E level caused by a cryptic interstitial 0.72-Mb deletion in the 22q13.2 region.". Am J Med Genet A. Epub ahead of print. doi:10.1002/ajmg.a.36358. PMID 24375995. 
  5. ^ 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. 
  6. ^ Wang X, McCoy PA, Rodriguiz RM, Pan Y, Je HS, Roberts AC, Kim CJ, Berrios J, Colvin JS, Bousquet-Moore D, Lorenzo I, Wu G, Weinberg RJ, Ehlers MD, Philpot BD, Beaudet AL, Wetsel WC, Jiang YH (August 2011). "Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3". Hum. Mol. Genet. 20 (15): 3093–108. doi:10.1093/hmg/ddr212. PMC 3131048. PMID 21558424. 
  7. ^ Bozdagi O, Sakurai T, Papapetrou D, Wang X, Dickstein DL, Takahashi N, Kajiwara Y, Yang M, Katz AM, Scattoni ML, Harris MJ, Saxena R, Silverman JL, Crawley JN, Zhou Q, Hof PR, Buxbaum JD (2010). "Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication". Mol Autism 1 (1): 15. doi:10.1186/2040-2392-1-15. PMC 3019144. PMID 21167025. 
  8. ^ Peça J, Feliciano C, Ting JT, Wang W, Wells MF, Venkatraman TN, Lascola CD, Fu Z, Feng G (April 2011). "Shank3 mutant mice display autistic-like behaviours and striatal dysfunction". Nature 472 (7344): 437–42. doi:10.1038/nature09965. PMC 3090611. PMID 21423165. 

Further reading[edit]

External links[edit]