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FLASH GENE
Symbol KIDINS220 contributors: mct - updated : 07-07-2015
HGNC name kinase D-interacting substrate, 220kDa
HGNC id 29508
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • 11 ankyrin repeats
  • four transmembrane domains within the N-terminal region
    • HOMOLOGY
    Homologene
    FAMILY
    CATEGORY signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus,nucleoplasm
    text
  • interacts with the microtubule and actin cytoskeleton
    • basic FUNCTION
  • key feature of the neurotrophin signaling, shown to be critical for neuronal survival under pathologic settings
  • plays an important role in NF-kappaB signaling elicited by brain-derived neurotrophic factor (BDNF)
  • important for the growth of dendritic arbors and spine stability during an activity- and BDNF-dependent period of development
  • key modulator of the activity of microtubule-regulating proteins known to actively regulate neuronal morphogenesis and suggest a mechanism by which it contributes to control neuronal development
  • scaffold protein that has important implications in neurotrophin signalling, modulates the development and maturation of axons and dendrites
  • modulation of its levels can regulate basal synaptic strength in a specific manner in hippocampal neurons
  • serves as a unique downstream adaptor protein of Trk receptor tyrosine kinases
  • major factor that links neurotrophin signaling to NF-kappaB
  • interaction with SEPT5 suggests a possible role as a functional link between neurotrophin receptors and septins to mediate neurotrophin-induced intracellular signaling events, such as neurite outgrowth and cytoskeletal remodeling
  • can be potentially regulated by neuronal activity and calpain action to influence synaptic function
  • required for neuronal differentiation and survival, and its expression levels modulate synaptic plasticity
  • is not essential for basal synaptic transmission and various forms of short-term plasticity, but instead plays a novel role in the mechanisms regulating the recovery of synaptic strength in GABAergic synapses
  • is likely a key player in organizing the signaling complex to transduce the extracellular stimuli to cellular responses during dendrite development
  • was required for optimal calcium signaling
  • acts as a major signaling platform in organizing the signaling complex to regulate various cellular responses in the nervous and vascular systems
  • role of ARMS/Kidins220 as a signaling platform to regulate tumor cell proliferation in response to the extracellular stimuli
  • acts as a signaling platform at the plasma membrane and is implicated in a multitude of neuronal functions, including the control of neuronal activity
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • transmembrane substrate of tropomyosin receptor kinase B (TRKB)
  • intreacting with Septin 5 (SEPT5)
  • integral membrane protein that was initially identified as a substrate for protein kinase D, a kinase we have found to regulate its intracellular traffic in neurons
  • is rapidly cleaved by calpain during excitotoxicity, a form of neuronal death associated to phosphatases (PPs) activation
  • downstream target of neurotrophin and ephrin receptors, in dendrite development
  • association of NMDARs with KIDINS220 and the participation of this protein in neuronal survival and death pathways
  • KIDINS220 stability and cleavage by calpain is under the control of GSK3B and PP1 activities
  • is a substrate for GSK3B and is likely phosphorylated by this kinase in AD brain, as it has been demonstrated for MAPT
  • is required for TCR-induced sustained, but not transient, Erk activation
  • is a novel TCR-interacting protein that couples BRAF to the TCR
  • transmembrane protein playing a crucial role in neuronal and cardiovascular development
  • downstream target of neurotrophin receptors and interacts with several signalling and trafficking factors
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    to melanoma formation by preventing stress-induced apoptotic death mediated by the MEK/ERK signaling pathway, especially in acral lentiginous melanoma
    constitutional     --low  
    by excitotoxicity and cerebral ischaemia contributed to neuronal death
    constitutional     --over  
    in necropsies from AD patients where it accumulates with hyperphosphorylated MAPT, and is phosphorylated by GSK3B in AD brain, wich could be protecting KIDINS220 from calpain cleavage, contributing to accumulation of this protein in AD samples
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS