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FLASH GENE
Symbol NEO1 contributors: mct/pgu - updated : 15-01-2018
HGNC name neogenin 1
HGNC id 7754
Location 15q24.1      Physical location : 73.344.824 - 73.597.547
Synonym name
  • neogenin homolog 1 (chicken)
  • immunoglobulin superfamily, DCC subclass, member 2
  • Synonym symbol(s) NGN, HsT17534, IGDCC2, DKFZp547A066, DKFZp547B146, NTN1R2
    DNA
    TYPE functioning gene
    STRUCTURE 253.49 kb     29 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    text structure
  • a functional Gli-binding site in the first intron of the human NEO1 gene
  • MAPPING cloned Y linked   status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    29 splicing 7088 160 1461 - 1997 9121761
    28 splicing 6929 - 1408 - 1997 9121761
    28 - 7055 - 1450 - 1997 9121761
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrainforebraincerebral cortex moderately Homo sapiens
     brainlimbic systemhippocampus predominantly Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, pregnancy
    Text nervous system, visual axons, gastrointestinal and other tissues
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a putative signal peptide
  • ectodomain composed of four immunoglobulin-like (Ig) domains
  • six fibronectin type III-like (FNIII) domains
  • a single transmembrane region
  • a cytoplasmic tail
  • HOMOLOGY
    Homologene
    FAMILY
  • immunoglobulin superfamily
  • DCC family
  • N-Cam family
  • CATEGORY adhesion , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • regulation if tissue growth, transition from cell proliferation to differentiation
  • neuron guiding activity
  • may play a role in mammary carcinogenesis as well as morphogenesis, and the expression may be inversely correlated with mammary carcinogenicity
  • multifunctional receptor implicated in axon navigation, neuronal differentiation, morphogenesis, and cell death
  • required for the establishment of the pseudostratified epithelium of the neural tube, probably by promoting cell adhesion
  • netrin-neogenin signaling is an important extracellular cue in regulation of myogenic differentiation and myofiber size
  • plays a critical role in iron homeostasis by regulation of HFE2 secretion and bone morphogenetic protein (BMP) signaling
  • regulates iron homeostasis via inhibiting secretion of HFE2, an inhibitor of BMP signaling, to enhance BMP signaling and hepcidin expression
  • receptor for netrins and proteins of the repulsive guidance molecule family, is a receptor for BMPs and modulates SMAD signal transduction
  • negatively regulates the functions of BMP and that this effect of neogenin is mediated by the activation of RHOA
  • acts as a receptor for BMPs and activates RhoA in a ligand-dependent manner
  • regulates SHH signaling in the limb bud to achieve proper digit patterning
  • guidance receptor neogenin holds crucial importance for the propagation of an acute inflammatory response
  • neogenin is required for the rapid turnover of TMPRSS6 through facilitating its internalization
  • novel role for NEO1 as a regulator of the neuroblast cell cycle
  • is a key component of the actin nucleation machinery governing junctional stability
  • is a pivotal component of the adherens junctions (AJs), where it influences both cadherin dynamics and junctional tension
  • NEO1 acts as a scaffold to facilitate assembly of the HFE2·BMP·BMP receptor complex to induce hepcidin expression
  • CELLULAR PROCESS cell life, proliferation/growth
    cell communication
    cell migration & motility
    PHYSIOLOGICAL PROCESS development , nervous system , visual cycle
    text development of nervous visual system
    PATHWAY
    metabolism
    signaling
    a component
  • part of a multiprotein complex at the hepatocyte membrane involving BMP, its receptors, and hemojuvelin (HFE2)
  • may form a receptor complex with UNC5B for signal transduction between BMPs to RHOA
  • NEO1 likely forms a ternary complex with both TMPRSS6 and HFE2 at the plasma membrane
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • receptor for RGMA and RGMB (RGM/neogenin regulates cell fate by controlling the DAPK1 activity)
  • interaction with NTN4 and UNC5B (NTN4 acts as an antiangiogenic factor through binding to neogenin and recruitment of UNC5B)
  • binds to cleaved and noncleaved HFE2 (the hemojuvelin binding site on neogenin is to the membrane-proximal fifth and sixth FNIII domains)
  • receptor for the neuronal axon guidance cues netrins and repulsive guidance molecules repulsive guidance molecules (RGMA and RGMB)
  • may stabilize HFE2, a glycosylphosphatidylinositol-anchored protein that interacts with neogenin and suppresses its secretion (Lee 2010)
  • interacts with DAPK and reduces DAPK autophosphorylation
  • bind directly with BMP2, BMP4, BMP6, and BMP7
  • DCC and NEO1, a family of immunoglobin-domain-containing transmembrane receptors for netrins, interact with MYO10
  • NEO1 interacted with TMPRSS6 as well as with HFE2 and facilitated the cleavage of HFE2 by TMPRSS6
  • death dependence receptor, that is a new direct SHH downstream regulator in neural precursor proliferation
  • NEO1 enhances TMPRSS6 degradation by facilitating cell surface TMPRSS6 internalization in a dynamin-dependent manner
  • acts to synchronize neuroblast migration and terminal differentiation through the regulation of neuroblast cell cycle kinetics within the neurogenic microenvironment of the rostral migratory stream (RMS)
  • HFE2 can simultaneously bind to both BMP2 and the ubiquitously expressed cell surface receptor NEO1
  • RGMB-NEO1-mediated cell-cell interactions between newly born neurons and progenitor cells control the ratio of glia and neurons produced in the olfactory epithelium (OE)
  • NEO1 is implicated in the maintenance of neural stem cells in the hippocampus by enhancing PCNA expressions
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    in colorectal cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    osteoarticularboneothers
    in addition to the ROCK inhibitors, may be a promising molecular target for promoting osteogenesis
    cancerbrain 
    is a novel downstream effector of the SHH pathway in medulloblastoma (MB) and a possible therapeutic target
    ANIMAL & CELL MODELS
  • defects of iron homeostasis in neogenin mutant mice appear to result from the blunted BMP signaling