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FLASH GENE
Symbol NGB contributors: mct/npt - updated : 02-12-2015
HGNC name neuroglobin
HGNC id 14077
Location 14q24.3      Physical location : 77.731.833 - 77.737.655
DNA
TYPE functioning gene
STRUCTURE 5.82 kb     4 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
cytosine-phosphate-guanine/HTF
Binding site   transcription factor
text structure
  • two GC-boxes located at -16 and +30bp relative to the transcription start site which are bound by transcription factor Sp1 and Sp3
  • MAPPING cloned Y linked N status provisional
    Physical map
    ESRRB 14q24.3 estrogen-related receptor beta CYCSP1 14q24.3 cytochrome c, somatic pseudogene 1 LAMR1P3 14 laminin receptor 1 pseudogene 3 LOC388000 14 LOC388000 KIAA1036 14q24.3 LOC388000 KIAA0759 14q24.3 LOC388000 LOC145497 14q24.3 hypothetical protein LOC145497 RPL22P2 14 ribosomal protein L22 pseudogene 2 RPLP1P1 14q23 ribosomal protein, large, P1 pseudogene 1 C14orf4 14q24.3 chromosome 14 open reading frame 4 KIAA1737 14q24.3 KIAA1737 C14orf59 14 chromosome 14 open reading frame 59 C14orf171 14q24.3 chromosome 14 open reading frame 171 NGB 14q24 neuroglobin POMT2 14q24.3 protein-O-mannosyltransferase 2 GSTZ1 14q24.3 glutathione transferase zeta 1 (maleylacetoacetate isomerase) LOC283578 14q24.3 hypothetical protein LOC283578 LOC161394 14q24.3 hypothetical protein LOC161394 LOC122945 14q24.3 hypothetical protein FLJ32809 C14orf133 14q24.3-q31 chromosome 14 open reading frame 133 AHSA1 14q23.3-31 AHA1, activator of heat shock 90kDa protein ATPase homolog 1 (yeast) THSD3 14q24.3 thrombospondin, type I domain-containing 3 SPTLC2 14q24.3-q31 serine palmitoyltransferase, long chain base subunit 2 ALKBH 14q24 alkB, alkylation repair homolog (E. coli) RPL21P10 14 ribosomal protein L21 pseudogene 10 DC50 14q24.3 hypothetical protein DC50 SNW1 14q24.3 hypothetical protein DC50 FLJ25976 14q24.3 hypothetical protein FLJ25976 ADCK1 14q24.3 aarF domain containing kinase 1 FRDAP 14q24.3 Friedreich ataxia pseudogene
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 1885 16.9 151 - 2005 15598495
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Hearing/EquilibriumearinnercochleaCorti  Homo sapiens
    Nervousbrain     Homo sapiens
     brainhindbrainpons   Homo sapiens
     braindiencephalonamygdala highly Homo sapiens
     braindiencephalonhypothalamus highly Homo sapiens
    Visualeyeretina  highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier liningretinal pigment epithelium (RPE)   Homo sapiens
    Epithelialsensoryvisualganglion cell layer  Homo sapiens
    Epithelialsensoryvisualinner nuclear layer  Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousastrocyte Homo sapiens
    Nervousglia
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a globin domain
  • a hexacoordinated heme
  • two surface cysteines (Cys-46 and Cys-55) that form a disulfide bridge upon oxidation
  • mono polymer monomer
    HOMOLOGY
    Homologene
    FAMILY
  • hemoglobin family
  • CATEGORY storage , transport
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus
    text
  • found in cytoplasm, along neurotubuli, in mitochondria and in the nucleus
  • basic FUNCTION
  • increasing the availability of oxygen in brain tissues
  • involved in neuroprotection under oxidative stress conditions such as ischemia and reperfusion (GDI activity is tightly correlated with its neuroprotective activity)
  • playing a role in neuronal oxygen homeostasis and hypoxia protection
  • NGB and CYGB may serve a neuroprotective role as scavengers of reactive oxygen species
  • hexacoordinate globin expressed in the nervous system of vertebrates, where it protects neurons against hypoxia
  • may confer protection against ischemia-reperfusion injury in the brain through its intrinsic antioxidant properties
  • role in nitric oxide signalling for CYGB and involvement in sleep-wake cycling for CYGB and NGB
  • may function as a physiological oxidative stress sensor and a post-translationally redox-regulated nitrite reductase that generates NO under six-to-five-coordinate heme pocket control
  • under hypoxic conditions neuroglobin can inhibit mitochondrial respiration in the presence of nitrite
  • potential role of DNA methylation in regulating NGB tissue-specific expression
  • exerts significant neuroprotective effects after mechanical injury, and thus has important implications for the prognosis and cure of traumatic brain injury
  • may regulate neuronal survival under hypoxia or oxidative stress
  • may modulate retinal ganglion cells susceptibility to glaucomatous neural damage
  • characterized heme globin that is widely expressed in the vertebrate central and peripheral nervous system as well as retina and endocrine tissues
  • globin protein that is highly and specifically expressed in brain neurons
  • neuroprotective molecule against hypoxic/ischemic brain injury and other related neurological disorder
  • pivotal role of neuroglobin in retinal glia involved in neuronal support and/or healing
  • plays an important role in neuronal death upon ischemia and oxidative stress
  • critical role in neuritogenesis or development via interacting with PTEN and AKT1 differentially to activate phosphatidylinositol 3-kinase/AKT1 pathway
  • promotes neuron survival under hypoxic/ischemic conditions
  • NGB signal differentiates the central projections of the inner and outer hair cells
  • NGB can bind to mitochondrial complex III subunit CYC1, leading to suppression of oxygen-glucose deprivation-mediated complex III activity and subsequent ROS production elevation
  • anti-apoptotic property of NGB may play a neuroprotective role against Alzheimer disease
  • displayed a neuron restricted expression pattern in mammalian brains
  • may participate in defense mechanisms in inner ear pathologies where oxidative stress is involved.
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text oxygen transport
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • heme containing 02+
  • protein
  • binds to the alpha-subunits of heterotrimeric G proteins (Galpha(i/o)) and acts as a guanine nucleotide dissociation inhibitor (GDI) for Galpha(i/o)
  • interaction with PRNP
  • functions as a metabolic regulator and enhances cellular anabolism through the inhibition of AMPK signaling
  • CYC1 is an NGB-interacting molecule
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    in astrocytoma
    tumoral     --over  
    hypoxic up-regulation of CYGB/NGB in glioblastoma multiforme cell lines and tumor tissues
    constitutional     --over  
    in early and moderately advanced Alzheimer disease compared to controls, but declined to control levels in severe disease
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurosensorialvisualanterior chamber
    manipulating the expression and bioactivity of NGB may represent a novel therapeutic strategy for glaucoma
    neurosensorialvisual 
    should be considered when developing therapeutic strategies for treatment of hypoxia-related ocular diseases
    neurologyneurodegenerativealzheimer
    may attenuate tau hyperphosphorylation through activating Akt signaling pathway, implying a therapeutic target for AD
    ANIMAL & CELL MODELS