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FLASH GENE
Symbol NGFR contributors: mct/shn/ - updated : 11-10-2015
HGNC name nerve growth factor receptor
HGNC id 7809
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveliver     Homo sapiens
Nervousbrain   highly Homo sapiens
 nerve   predominantly
Reproductivefemale systemovary  highly
Respiratorylung   highly Homo sapiens
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectiveadiposewhite   Homo sapiens
Muscularstriatum    Homo sapiens
Nervousperipherous   
cells
SystemCellPubmedSpeciesStageRna symbol
Nervousoptic nerve
NervousSchwann cell
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal region containing the leucine-rich repeats along with the transmembrane and cytoplasmic domains of LINGO1 are not required for self-interaction or interaction with APP
  • an extracellular domain containing four 40-amino acid repeats with 6 cysteine residues at conserved positions
  • a serine/threonine-rich region containing the nerve growth factor binding domain
  • a single transmembrane domain
  • a 155-amino acid cytoplasmic domain
  • a cytoplasmic death domain, with unique intracellular structure and downstream signaling partners
  • mono polymer homomer , dimer
    HOMOLOGY
    interspecies ortholog to Ngfr, Mus musculus
    ortholog to Ngfr, Rattus norvegicus
    Homologene
    FAMILY
  • tumor necrosis factor receptor (TNFR) superfamily
  • CATEGORY enzyme , signaling cytokine growth factor , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytoskeleton,microtubule
    text
  • type I transmembrane protein (TM1)
  • localized along with the SSTR3 receptor to the primary cilia of the granule cells of the murine dentate gyrus, a center of adult neurogenesis
  • NGFR and NTRK1 are localized in the mitochondrial compartment of undifferentiated human podocytes and in all tissues analyzed including rat central nervous system
  • basic FUNCTION
  • important role in the development and function of sensory neurons
  • mediates neurotrophin-dependent apoptosis
  • involved in light-mediated photoreceptor apoptosis in vivo
  • is the signal transducing element for Myelin-associated glycoprotein
  • initiates intracellular signaling leading either to cell survival or to apoptosis
  • an essential role for p75(NTR)-related signalling in early embryonic morphogenesis
  • role in activity-dependent synaptic plasticity
  • receptor tyrosine kinase, class VI, regulating the myelination process in peripheral nervous system
  • a negative growth regulator within the context of myelin inhibition 5
  • may play a positive role in nerve regeneration
  • involved in the control of neuronal survival versus death and axonal regeneration and growth cone collapse
  • regulator of liver repair
  • binds pro and mature neurotrophins and affects the growth, differentiation and death of the nervous system
  • maintains the specificity of neural connectivity
  • regulator of glucose uptake and insulin resistance
  • unanticipated function of NGFR as a unique regulator of glucose metabolism and insulin sensitivity
  • transcriptional activation of NGFR is under circadian regulation in the nervous system and peripheral tissues, and plays an important role in the maintenance of clock and metabolic gene oscillation
  • influences the proliferation, survival, and differentiation of neuronal precursors and its expression is induced in injured brain, where it regulates cell survival
  • can modulate cell-fate decisions through its highly ramified signaling pathways
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • extracellular signal-regulated protein kinases 1 and 2
  • Fas-associated phosphatase-1, FAP-1
  • SC-1
  • the six tumor necrosis factor receptor-associated factors, TRAF1-6
  • caveolin 1, cav1
  • zinc finger protein NRIF
  • trkA, trkB and trkC
  • neurotrophin receptor-interacting MAGE homolog, NRAGE and TrkA, TRKA
  • p75NTR-associated cell death executor, NADE
  • ganglioside GT1b
  • necdin and MAGE-H1
  • neurotrophin receptor-interacting MAGE homolog, NRAGE
  • interleukin 1 receptor-associated kinase, IRAK
  • tumor necrosis factor receptor-associated death domain protein, TRADD, upon nerve growth factor stimulation
  • beta catalytic subunit of cAMP-dependent protein kinase, PKACbeta
  • nerve growth factor, NGF
  • necdin and MAGE-G1
  • Nogo receptor and LINGO-1
  • brain-expressed X-linked 1, Bex1
  • par-3 partitioning defective 3 homolog (C. elegans), PARD3
  • MAGED1 (NGFR adaptor protein, required for developmental apoptosis)
  • SALL2 (SALL2 is a novel NGFR-interacting protein that links NGF signalling to cell cycle progression and neurite outgrowth)
  • serves as a receptor for the pro-forms of theneurotrophins
  • NPHS1 and NGFR share a partial overlapping expression pattern in the epicardium and subepicardial coronary vessels
  • interactions of RTN4R with its co-receptors LINGO1, NGFR and the myelin inhibitor RTN4 is facilitated by gangliosides
  • is required for the signal transduction of PILRB, which interacted with NGFR upon ligand binding
  • on oligodendroglial cells, LINGO1 interacts with NGFR to constitutively inhibit multiple aspects of oligodendrocyte differentiation
  • RAB5A and RAB31 directly interact with NGFR primarily via helix 4 of the NGFR death domain
  • NTRK1 and NGFR collaborate with each other at the plasma membrane to bind NGF
  • NGFRAP1 interacts with the death domain of NGFR and mediates apoptosis in neural cells in response to nerve growth factor
  • NGFR and NTRK1 interact to enhance neurotrophic signaling
  • NGFR associated predominantly with natively expressed LINGO1 containing immature N-glycans, characteristic of protein that has not completed trans-Golgi-mediated processing
  • cell & other
    REGULATION
    repressed by MYCN (acts directly to repress NTRK1 and NGFR gene transcription)
    Other phosphorylated by PKACbeta
    regulated by the helix-loop-helix transcription factors CLOCK and ARNTL
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    expressed in melanomas
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    diabetetype 2 
    unanticipated function of NGFR as a unique regulator of glucose metabolism and insulin sensitivity
    ANIMAL & CELL MODELS
  • mice with NGF receptor p75 mutation are viable and fertile display markedly decreased sensory innervation, loss of heat sensitivity associated with ulcers in the distal extremities
  • light-induced photoreceptor apoptosis in p75NTR knockout mice is significantly reduced
  • impairment of hippocampal long-term potentiation in p75NTR-deficient mouse
  • mice depleted for p75NTR exacerbate liver pathology and inhibited hepatocyte proliferation in vivo