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FLASH GENE
Symbol SHANK2 contributors: mct/npt - updated : 20-05-2015
HGNC name SH3 and multiple ankyrin repeat domains 2
HGNC id 14295
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • one SH3 domain
  • ankyrin repeats
  • one PSD -95/DLG/ZO1 domain (PDZ domain)
  • one sterile alpha motif (SAM) domain
  • a proline rich region
  • HOMOLOGY
    interspecies homolog to rattus cortactin binding protein 1
    Homologene
    FAMILY
  • shank family of synaptic protein
  • CATEGORY chaperone/stress
    SUBCELLULAR LOCALIZATION     plasma membrane,junction
        intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule
    text
  • excitatory synpases
  • colocalized with neurofilament at the dendritic region of cells (Kim 2009)
  • basic FUNCTION
  • molecular scaffold in the postsynaptic density
  • regulate the size and shape of dendritic spines because of their capacity to directly interact with many different PSD components and represent master scaffold proteins of the PSD (Schutt 2009)
  • could play a critical role in the neuronal differentiation of the developing retina (Kim 2009)
  • scaffolding molecule of the postsynaptic density (PSD) of excitatory synapses, which is crucial for postsynaptic density (PSD) assembly and the formation of dendritic spines
  • concerted action of SHANK2 and Zn(2+) is essential for the structural integrity of postsynaptic density (PSD) and moreover that it is an important element of synapse formation, maturation and structural plasticity
  • is likely involved in the initial steps of postsynaptic density (PSD) assembly, and may have a function in the signal-dependent recruitment and cross-linking of the other Shank paralogs
  • FMR1 and SHANK2 are central regulators of synaptic organization and function and genetic defects of these genes have effects on spine morphology and synaptic function
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • SLC9A3, SHANK2, and ARHGEF7 form a macromolecular complex when expressed heterologously in mammalian cells (Lee 2010)
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • SHANK proteins are targeted to synapses depending on binding to zinc, which is a prerequisite for the assembly of the SHANK scaffold
  • protein
  • cortactin (rat)
  • sharpin
  • novel SLC9A3 interacting protein that is involved in the fine regulation of transepithelial salt and water transport through affecting SLC9A3 expression and activity (Han 2006)
  • interacting with SLC9A3 (regulate the membrane expression and activity of SLC9A3) (Lee 2010)
  • SHANK2 is a distinctive PDZ domain protein that binds SLC34A1
  • direct, SH3 domain-mediated associations and functional interactions of PACSIN1 with SHANK2
  • SGK1 phosphorylates SHANK2 as well as a peptide containing the first SGK1 consensus motif of SHANK2
  • glucocorticoid-induced increase in CFTR abundance requires phosphorylation of SHANK2 at an SGK1 consensus site
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) AUTS17
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification    
    coamplified with CCND1 in oral squamous cell carcinoma
    tumoral     --over  
    in the differentiated retinoblastoma cells, which was mediated by ERK 1/2 activation (Kim 2009)
    Susceptibility to autism-spectrum disorder (ASD) and mental retardation
    Variant & Polymorphism other nonsense mutation associated to autism-spectrum disorder (ASD) and mental retardation (Berkel 2010)
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • the postnatal expression of the SHANK2-R462X in mice can lead to impaired cognitive functions
  • reduced Nmdar function may contribute to the development of ASD-like phenotypes in Shank2(-/-) mice, and Grm8 modulation of Nmdars offers a potential strategy to treat Autism spectrum disorder (ASD)