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FLASH GENE
Symbol NELL1 contributors: mct/npt/pgu - updated : 04-03-2014
HGNC name NEL-like 1 (chicken)
HGNC id 7750
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N terminal signal peptide, with six epidermal growth factor-like motifs, containing signal peptides, and a N-terminal thrombospondin-1 domain involved in multimer formation and heparin- and retinal axon-binding
  • a thrombospondin-1 (TSP-1)-like domain (TSPN)
  • five von Willebrand factor C domains (VWC)
  • six calcium binding EGF-like repeats, lacking the transmembrane domain of chicken nel
  • five cysteine-rich domains
  • C-terminal cysteine-rich region is critical for cell adhesion activity of NELL1
    • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to chicken nel-like 1
    Homologene
    FAMILY
  • laminin G/TSP-N/pentraxin supergene family, the chordin-like cysteine-rich domain family and the EGF-like domain family
    • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm
    intracellular,nuclear envelope
    basic FUNCTION
  • playing a potential oncogenic role in neural cells
  • involved in cell growth regulation and differentiation of neural cells
  • craniosynostosis-related gene
  • modulating calvarial osteoblast differentiation and apoptosis pathways
  • extracellular protein inducing osteogenic differentiation and bone formation of osteoblastic cells
  • plays a key role as a regulator of craniofacial skeletal morphogenesis, especially in committed chondrogenic and osteogenic differentiation
  • NELL1 signaling may inhibit adipogenic differentiation via a Hedgehog dependent mechanism
  • in addition to the well-recognized role of NELL1 in promotion of osteogenic differentiation and bone formation, NELL1 significantly represses adipogenic differentiation
  • osteoinductive molecule associated with premature calvarial suture closure
  • role on osteoblastic differentiation and proliferation are partly through binding to APR3
  • is an important growth factor for regulation of osteochondral differentiation, by regulating both RUNX2 and SOX9 expression within the calvarium
  • is required for normal craniofacial membranous and endochondral skeletal development
  • plays an important role in osteoblast differentiation, bone formation, and bone regeneration
  • does contribute to the enhanced constructive remodeling of skeletal muscle
  • large oligomeric secretory glycoprotein that functions as an osteoinductive factor
    • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    cell organization/biogenesis
    PHYSIOLOGICAL PROCESS
    text neurogenesis
    PATHWAY
    metabolism
    signaling
    a component
  • 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
  • interacting with RUNX2 (RUNX2 directly binds to the OSE2 elements and transactivates the promoter)
  • with PRKCB1
  • transiently activates the MAPK signaling cascade, induces the phosphorylation of RUNX2, and promotes the rapid intracellular accumulation of Tyr-phosphorylated proteins
  • NFATC2 is a primary response gene of NELL1
  • binding to APR3
  • SP7 is a direct transcriptional regulator with repressive effect on NELL1 gene expression, contributing to a delicate balance of regulatory effects on NELL1 transcription with RUNX2, and may play a crucial role in osteoblast differentiation and mineralization
  • interacts with a range of molecules through its different domains and exerts distinct functions
  • increases pre-osteoblast mineralization using both phosphate transporter SLC20A1, SLC20A2
  • NELL1 binds to extracellular ITGB1 and induces cell focal adhesion
    • cell & other
    REGULATION
    activated by upregulated during unilateral premature closure of the coronal suture
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in craniofacial anomalies, premature suture closure
    tumoral     --low  
    by promoter hypermethylation in early-stage esophageal adenocarcinoma, occuring early during Barrett's-associated esophageal neoplastic progression, and is a potential biomarker of poor prognosis in early-stage EAC
    tumoral     --other  
    expressed mainly in tumors in the neuronal cell lineage
    Susceptibility
    Variant & Polymorphism
    Candidate gene
  • candidate growth factor able to induce human perivascular stem cells osteogenesis
    • Marker
    Therapy target
    SystemTypeDisorderPubmed
    osteoarticularbone 
    future therapeutic utility of NELL1 for either skeletal or soft-tissue regenerative medicine
    ANIMAL & CELL MODELS
  • Nell-1 overexpressing mice demonstrate calvarial bone overgrowth and inappropriate cranial suture fusion