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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
DNA
TYPE functioning gene
STRUCTURE 193.91 kb     10 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked   status provisional
RNA
TRANSCRIPTS type messenger
text several (?4)
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
10 splicing 10641 220 1849 specifically expressed in the brain 2012 21994763
  • contains an SH3 domain followed by a PDZ domain, a long proline-rich region and a C-terminal SAM domain
  • 8 splicing 8850 - 1261 - 2012 21994763
    truncated
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbraindiencephalonhypothalamus  
    Visualeyeretina   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connective    
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
     fibroblast
    Nervousneuron
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text
  • growth cones and developing neurons
  • expressed in the neurons of the developing retina (Kim 2009)
  • 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)