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FLASH GENE
Symbol NBEA contributors: mct - updated : 18-10-2017
HGNC name neurobeachin
HGNC id 7648
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a concanavalin A-like lectin domain flanked by armadillo repeats (ACA),
  • an A-kinase anchoring protein domain that can bind to PRKCA,
  • a domain of unknown function (DUF1088)
  • a BEACH domain (beige and Chediak-Higashi domain), preceded by a pleckstrin homology-like domain and followed by C-terminal WD40 repeats (PBW)
  • HOMOLOGY
    interspecies homolog to murine Nbea
    homolog to Drosophila protein kinase A anchoring protein RG
    Homologene
    FAMILY BEACH domain family of proteins
    CATEGORY enzyme , transport
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic,vesicle
    text
  • predominantly in neuronal cell bodies and along neurites within intensely stained punctate structure
  • basic FUNCTION
  • presumptive protein kinase A anchoring function
  • may be involved in membrane trafficking events
  • neuron-specific multidomain protein implicated in membrane trafficking that is predominantly expressed in the brain and during development
  • putative regulator of membrane protein trafficking associated with tubulovesicular endomembranes and postsynaptic plasma membranes
  • function at central synapses that may be based on its presumed role in targeting membrane proteins to synaptic contact
  • role of VPS35 and NBEA in the retrieval and post-Golgi trafficking of synaptic GLYRs and possibly other neurotransmitter receptors
  • potential roles of VPS35 and NBEA in inhibitory receptor trafficking
  • potential role in trafficking important cargo to pre- and postsynaptic compartments
  • regulates neuronal membrane protein trafficking and is required for the development and functioning of central and neuromuscular synapses
  • potential risk gene in human obesity
  • is important also for the functioning of central synapses, where it is suggested to play a role in trafficking membrane proteins to both, the pre- and post-synaptic sites
  • regulates synaptic transmission under basal conditions by targeting neurotransmitter receptors to synapses
  • acts as a critical regulator in the postsynaptic neuron for the coordination of dendritic morphology with synaptogenesis
  • brain specific, and is required for synaptic surface expression of both glutamate and GABA receptors
  • regulates glutamate- and GABA-Receptor targeting to synapses via distinct pathways
  • role for NBEA as transcriptional regulator in the nucleus
  • CELLULAR PROCESS cell life, antiapoptosis
    PHYSIOLOGICAL PROCESS cellular trafficking transport
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • GLRB binds the trafficking proteins VPS35 and Neurobeachin (NBEA)
  • interacts with the GLRB loop but not with gephyrin (GPHN)
  • DLG3 binds the C-terminal part of the scaffolding protein neurobeachin (NBEA)
  • physical interaction of NBEA with NOTCH1 is most relevant for autism spectrum disorders (ASD) pathogenesis because NOTCH signaling is essential for neural development
  • cell & other
  • peripherally associated with several membrane compartments including trans-Golgi network and endosome-like structures
  • REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    expression are frequently disrupted in multiple myeloma
    Susceptibility
    Variant & Polymorphism
    Candidate gene for AUTS3
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • deletion of Nbea leads to reduced numbers of spinous synapses in cultured neurons from complete knockouts and in cortical tissue from heterozygous mice, accompanied by altered miniature postsynaptic currents
  • Nbea-null mice have severe defects in neuromuscular synaptic transmission resulting in lethal paralysis of the newborns