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FLASH GENE
Symbol SHANK3 contributors: mct/npt - updated : 06-12-2015
HGNC name SH3 and multiple ankyrin repeat domains 3
HGNC id 14294
Corresponding disease
AUTS20 autism spectrum disorder, 20
DEL22Q13 chromosome 22q13 subtelomeric deletion syndrome
Location 22q13.33      Physical location : 51.113.069 - 51.171.641
Synonym name
  • shank postsynaptic density protein
  • proline-rich synapse-associated protein 2
  • likely ortholog of rat proline rich synapse associated protein 2
  • Synonym symbol(s) PSAP2, KIAA1650, PROSAP2, SPANK-2
    DNA
    TYPE functioning gene
    STRUCTURE 58.57 kb     23 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    KIAA0685 22q13.3 similar to RPL23AP7 protein SBF1 22q13.33 SET binding factor 1 FLJ21135 ALDRL6 22q13.3 aldehyde reductase (aldose reductase) like 6 BC002942 22q13.33 hypothetical protein BC002942 384D8-2 22q13.33 hypothetical protein 384D8_6 SCO2 22q13.33 SCO cytochrome oxidase deficient homolog 2 (yeast) ECGF1 22q13.3 endothelial cell growth factor 1 (platelet-derived) LOC391341 22 similar to MGC52679 protein LOC113730 22q13.33 hypothetical protein BC009980 LOC388918 22 LOC388918 CHKL-CPT1B 22q13.33 choline kinase-like, carnitine palmitoyltransferase 1B (muscle) transcription unit CPT1B 22q13.3 carnitine palmitoyltransferase 1B (muscle) CHKL 22q13.33 choline kinase-like MAPK8IP2 22q13.2-q13.33 mitogen-activated protein kinase 8 interacting protein 2 ARSA 22q13.33 arylsulfatase A SHANK3 22q13-3 SH3 and multiple ankyrin repeat domains 3 ACR 22q13.33 acrosin LOC150417 22q13.33 u2 small nuclear ribonucleoprotein A' pseudogene RABL2B 22q13.33 RAB, member of RAS oncogene family-like 2B LOC284942 22q13.33 similar to RPL23AP7 protein
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    23 - 7145 - 1747 only in brain Bonaglia, Durand (2007)
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrainforebraincerebral cortex highly
     brainhindbraincerebellum highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text developing brain
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a SHANK/ProSAP N-terminal (SPN) domain regulates accessibility of the ankyrin repeats through an intramolecular interaction, and is involved in an intramolecular, inhibitory interaction with the ankyrin repeat region (ARR)
  • five ankyrin repeats
  • PDZ domain
  • SH3 domain (proline rich SRC homology 3)
  • C terminal SAM domain (steril alpha motif)
  • HOMOLOGY
    interspecies ortholog to rattus proline rich synapse associated protein
    Homologene
    FAMILY
  • shank family
  • CATEGORY chaperone/stress , structural protein
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic,ribosome
    text
  • near the synapses
  • uncoupling of SHANK3 nuclear shuttling from synaptic activity may represent a molecular mechanism that contributes to the pathology of schizophrenia in patients with mutations in SHANK3
  • basic FUNCTION
  • molecular scaffold in neuronal postsynaptic densities
  • protein of the postsynaptic density (PSD) of excitatory synapses, where it may function as a master scaffolder forming large sheets that may represent the platform for the construction of the PSD complex
  • promotes the formation, maturation, and enlargement of dendritic spines
  • 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)
  • scaffolding molecule of the postsynaptic density (PSD) of excitatory synapses, which is crucial for PSD assembly and the formation of dendritic spines
  • scaffolding protein that promotes the formation and maturation of dendritic spines (Gauthier 2010)
  • is a scaffolding protein that connects glutamate receptors to the actin cytoskeleton via a chain of intermediary elements
  • participates in growth cone motility in developing neurons
  • synaptic scaffolding protein enriched in the postsynaptic density of excitatory synapses, and plays important roles in the formation, maturation, and maintenance of synapses
  • scaffolding protein that anchors multiple elements of the postsynaptic density at the synapse
  • SHANK3 isoforms are required for normal synaptic transmission/plasticity in the hippocampus, as well as hippocampus-dependent spatial learning and memory
  • act as major organizing scaffolding elements within the postsynaptic density of excitatory synapses
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    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
  • sharpin
  • binding of SHANK3 C terminus to HOMER1 is critical for its expression at synapses, and HOMER1 stabilizes SHANK3 protein
  • role in regulating metabotropic glutamate receptor 5 (GRM5) expression and signaling at synapses
  • LZTS3 is an interaction partner of the well-known PSD protein SHANK3 and SPAR
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) DEL22Q13 , AUTS20
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    haploinsufficiency of SHANK3 can cause a monogenic form of autism
    Susceptibility
  • to autism spectrum disorder, AUTS20
  • to schizophrenia
  • Variant & Polymorphism other mutation associated with schizophrenia (Gauthier 2010)
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    mental retardationother 
    pharmacological augmentation of GRM5 activity represents a possible new therapeutic approach for patients with SHANK3 mutations
    ANIMAL & CELL MODELS
  • demonstrate a critical role for SHANK3 in the normal development of neuronal connectivity and establish causality between a disruption in the Shank3 gene and the genesis of autistic-like behaviours in mice (
  • a mouse genetic model that mimics a human mutation of Shank3 that deletes the Homer-binding domain at the C terminus (&
  • 916;C) and is associated with autism
  • Shank3(+/&
  • 916;C) mice exhibit behavioral phenotypes that parallel symptoms of ASD
  • Shank3 mutant mice exhibit autistic-like behaviors, including impaired social interaction and repetitive behaviors