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FLASH GENE
Symbol NELL2 contributors: mct/npt - updated : 04-03-2014
HGNC name NEL-like 2 (chicken)
HGNC id 7751
Location 12q12      Physical location : 44.902.057 - 45.307.711
Synonym name
  • neural epidermal growth factor-like 2
  • protein kinase C-binding protein NELL2
  • NEL-like 2 (chicken)
  • Synonym symbol(s) NRP2, NEL
    DNA
    TYPE functioning gene
    STRUCTURE 405.65 kb     21 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure
  • two E2F1 binding sites located in the NELL2 promoter region
  • MAPPING cloned Y linked   status provisional
    Physical map
    DKFZp434B0417 12q12 similar to semaF cytoplasmic domain associated protein 3 LOC283464 12q12 hypothetical protein LOC283464 YAF2 12p11.23 YY1 associated factor 2 LOC283465 12q12 similar to hepatocellular carcinoma autoantigen MADP-1 12q12 MADP-1 protein PPHLN1 12q12 periphilin 1 PRICKLE1 12q12 prickle-like 1 (Drosophila) LOC390308 12 hypothetical gene supported by NM_018464 MRPS36P5 12q12 mitochondrial ribosomal protein S36 pseudogene ADAMTS20 12q12 a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 20 LOC387852 12 similar to 52 kDa repressor of the inhibitor of the protein kinase (p58IPK-interacting protein) (58 kDa interferon-induced protein kinase-interacting protein) (P52rIPK) (Death associated protein 4) (THAP domain protein 0) LOC390309 12 similar to elongation factor 1 alpha DKFZP434G1415 12q12 hypothetical protein DKFZp434G1415 IRAK4 12q12 interleukin-1 receptor-associated kinase 4 PTK9 12q12 PTK9 protein tyrosine kinase 9 DKFZp434K2435 12q12 hypothetical protein DKFZp434K2435 ZNF75B 12q13 zinc finger protein 75b NELL2 12q13.1-q13.12 NEL-like 2 (chicken) FKSG42 12q12 FKSG42 LOC51054 12q putative glycolipid transfer protein DKFZp313M0720 12q12-q13.11 hypothetical protein DKFZp313M0720 DKFZp686G052 SFRS2IP 12q12-q14.3 splicing factor, arginine/serine-rich 2, interacting protein SLC38A1 12p11.21 solute carrier family 38, member 1 SLC38A2 12q solute carrier family 38, member 2 LOC387853 12 hypothetical gene supported by BC014370 SLC38A4 12q12-q13 solute carrier family 38, member 4 LOC390310 12 similar to transient receptor protein 6 AMIGO2 12q13.11 amphoterin induced gene 2 MGC16044 12q13.11 hypothetical protein MGC16044 LOC387854 12 LOC387854 LOC387855 12 LOC387855 FLJ21908 12q13.11 hypothetical protein FLJ21908 P11 12q13.1 26 serine protease EPAC 12q13.1 Rap1 guanine-nucleotide-exchange factor directly activated by cAMP FLJ20489 12q13.11 hypothetical protein FLJ20489 HDAC7A 12q13.1 histone deacetylase 7A VDR 12q13.1 vitamin D (1,25- dihydroxyvitamin D3) receptor MGC5576 12q13.1 hypothetical protein MGC5576
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    21 - 3385 - 866 - 2010 19931511
    20 - 3705 91.3 816 - 2010 19931511
    21 - 3312 91.3 816 - 2010 19931511
    21 - 3271 94.2 839 - 2010 19931511
    20 - 3210 90 815 - 2010 19931511
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrainforebraincerebral cortex highly Homo sapiens
     brainlimbic systemhippocampus highly
     brainhindbraincerebellum predominantly Homo sapiens
    Urinarykidney   highly Homo sapiens
    Visualeyeretina    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervouscentral  predominantly Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Visualganglion cell Homo sapiens
    cell lineage hemopoietic cells (nucleated peripheral blood cells)
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text brain, but not in B cell at an earlier stage of development
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal signal peptide and thrombospondin I-like domain (TSP-N), important for intermolecular binding of NELL2, and for binding to heparin, and N-terminal 29 AAs of NELL2 were important for secretion
  • five von Willebrand factor C domains (VWC)
  • five CR domains
  • six calcium binding EGF-like repeats, that could be involved in the secretion mechanism of NELL2 and three of the six EGF-like domains contain the residues required for Ca2+ binding, suggesting that NELL2 may act as a Ca2+-dependent signaling molecule (Kim 2010)
  • three additional cysteine-rich domains, playing major roles in NELL2-induced growth cone collapse of retinal axons
  • conjugated GlycoP
    mono polymer trimer
    HOMOLOGY
    Homologene
    FAMILY
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic,vesicle
    text
  • secreted
  • found in the cytoplasm of neurons, but not in glial fibrillary acidic protein (GFAP)-positive glial cells (Jeong 2008)
  • basic FUNCTION
  • involved in the growth and differentiation of neural cells
  • playing a potential oncogenic role in neural cells
  • promotes survival of neurons by modulating MAPK activities (Aihara 2003)
  • dual functions in both the cell autonomous differentiation of neural progenitor cells while simultaneously exerting paracrine proliferative activity (Nelson 2004)
  • neural tissue-enriched protein, produced in the embryo, and postembryonically in the mammalian brain, with a broad distribution (Jeong 2008)
  • new component of glutamatergic neurons and provide evidence for its physiological involvement in a major, glutamate-dependent, process of neuroendocrine regulation (Ha 2008)
  • secreted protein that promotes neuronal survival and differentiation (Kim 2010)
  • potential mediator of estrogen-induced neuronal survival in the central nervous system
  • is involved in the maintenance of the normal female reproductive cycle in mammals
  • play crucial roles in development and functioning of the nervous system
  • important regulator of neural development and functions
  • having an alternative splicing form that encodes cytoplasmic protein, may regulate intracellular signaling through its EGF-like repeats
  • novel activity for NELL2 in cancer progression through the regulation of E2F1
  • may affect the cellular activity of cells in a paracrine or autocrine manner
  • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    cell organization/biogenesis
    PHYSIOLOGICAL PROCESS
    text neurogenesis
    PATHWAY
    metabolism
    signaling
    a component
  • associate intermolecularly to form homotrimers through their coiled-coil region or CR domains (Kim 2010)
  • exists as trimers of &
  • 8764;400 kDa in solution
  • NELL2 and and NELL1 can form hetero-oligomer when co-expressed in the same cells (pMID: 22157752)
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Ca2+
  • protein
  • PRKCB1
  • NELL2 is a novel target gene of E2F1, which is a key regulator of cell proliferation
  • cell & other
  • binds to a specific receptor expressed on retinal axons and acts as an inhibitory guidance molecule
  • REGULATION
    Other highly regulated spatially and temporally, being only transiently expressed in discrete regions of the central (CNS) and peripheral nervous systems (PNS) and in a subset of mesoderm derived structures during their peak periods of development (Nelson 2002)
    trans-activated by estrogen (E2)and contributes to mediating the survival promoting effects of E2 via intracellular signaling pathway of ERK
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • involved in the estrogen-dependent organization of a sexually dimorphic nucleus in the preoptic area in rat
  • Nel mutant mice show impairment of spatial learning, further suggesting that Nel plays important roles in regulation of synaptic plasticity in the hippocampus