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FLASH GENE
Symbol NGFR contributors: mct/shn/ - updated : 11-10-2017
HGNC name nerve growth factor receptor
HGNC id 7809
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
  • NDN and MAGEH1, are interactors for the intracellular domain of NGFR and the interaction is enhanced by ligand stimulation
  • 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
  • NDN and NSMCE3 target both E2F1 and NGFR to regulate cell viability during brain development
  • 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
  • neuronal NRDC critically regulates cardiac sympathetic innervation and circulatory dynamics via modulation of NGFR
    • 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