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FLASH GENE
Symbol GPM6A contributors: shn - updated : 17-12-2013
HGNC name glycoprotein M6A
HGNC id 4460
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • possesses putative phosphorylation sites for protein kinase C
  • EC2 domain
  • cysteines 162 and 202 are essential for the efficient cell surface expression of the M6a protein
  • conjugated GlycoP
    HOMOLOGY
    interspecies ortholog to Gpm6, mus musculus
    ortholog to Gpm6a, Rattus norvegicus
    intraspecies homolog to PLP,strongly
    Homologene
    FAMILY myelin proteolipid protein family
    CATEGORY structural protein
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text
  • abundant in all hippocampal subregions, and subcellular analysis in primary hippocampal neurons revealed its presence in membrane protrusions (filopodia/spines)
  • localized in membrane microdomains compatible with lipid rafts in cultured rat hippocampal neurons
  • basic FUNCTION
  • stress-responsive gene in the hippocampal formation
  • playing an important role in neurite/filopodium outgrowth and synapse formation
  • implicates in neuronal differentiation as a novel Ca(2+) channel gated selectively by phosphorylation with PKC in the downstream of nerve growth factor signaling pathway
  • associated with the differentiation of neurons derived from undifferentiated ES cells
  • regulates the serotonin uptake by affecting cellular trafficking of the serotonin transporter
  • may play a role in retinal development by regulating neurites, and it may also function to modulate synaptic activities in the adult retina
  • expression level of GPM6A is associated with the differentiation and neuronal migration of neurons derived from undifferentiated human ES cells
  • association of M6a with lipid rafts is important for its role in filopodia formation
  • CELLULAR PROCESS cell organization/biogenesis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule other, lipid rafts
    protein
  • micro-opioid receptor, MOPr
  • serotonin transporter, SERT
  • HIV-1 Nef protein
  • GPM6A, and the Sprouty domain-containing proteins SPRED1 and SPRED3, are indeed palmitoylated by ZDHHC17
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    inducing neurite formation and increasing filopodia density in hippocampal neurons
    Susceptibility
  • schizophrenia
  • a genetic risk for claustrophobia
  • Variant & Polymorphism
    Candidate gene for stress-related disorders such as depression
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • M6a knockdown with small interference RNA methodology showed that M6a low-expressing neurons display decreased filopodia number and a lower density of synaptophysin clusters
  • decrease in both the number of neuronal markers and the number of differentiating neuronal cells (cholinergic, catecholaminergic, and GABAergic neurons) from neural stem cells in knockdown mouse ES cell lines (D3m-shM6A)
  • suppression of GPM6A expression using shRNA in human ES cells led to a decrease in both the expression of neuroectodermal-associated genes and the number of NSCs derived from B2h-shM6A cells
  • increase of the expression of neuroectodermal-associated genes and the number of differentiated neuronal cells (cholinergic, catecholaminergic, and GABAergic neurons) from Human neural stem cells derived from B2h-oeM6A cells which overexpress GPM6A
  • Src-deficient SYF cells over-expressing M6a fail to promote filopodia formation
  • reduced M6 levels in Drosophilia triggered a mild rough-eye phenotype, and a defective response to light
  • Gpm6a-deficient mice develop normally and lack obvious behavioral abnormalities but when mildly stressed by single-housing, tthey develop a striking claustrophobia-like phenotype