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FLASH GENE
Symbol NDEL1 contributors: mct/npt/pgu - updated : 12-03-2015
HGNC name nudE nuclear distribution gene E homolog (A. nidulans)-like 1
HGNC id 17620
Location 17p13.1      Physical location : 8.339.178 - 8.371.471
Synonym name
  • nudE nuclear distribution gene E homolog like 1 (A. nidulans)
  • NUDE-like protein
  • LIS1-interacting protein NUDEL
  • NUDEL-oligopeptidase
  • endooligopeptidase A
  • mitosin-associated protein MITAP1
  • Synonym symbol(s) NUDEL, MITAP1, EOPA, DKFZp451M0318
    DNA
    TYPE virus associated
    STRUCTURE 32.30 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 2420 - 328 - 2009 19198602
    9 - 2385 - 345 - 2009 19198602
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineadrenal gland   highly
    Nervousbrain   highly
    Respiratoryrespiratory tractlarynx  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    Connectivebonesubchondral  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal region forms a coiled-coil structure, which is involved in homodimerisation
  • several potential phosphorylation sites for casein kinase II, protein kinase C, or CDK5
  • an additional helical region near the C-terminus (amino acids 246277), and C-terminal domain, required for interaction
  • with key protein partners dynein and DISC1 (disrupted-in-schizophrenia 1), includes a predicted disordered region that allows a bent back structure
    HOMOLOGY
    intraspecies paralog to NDE1
    Homologene
    FAMILY
  • nudE family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus
    text
  • associated to centrosome (connected to its role in neuronal migration, since the centrosome is believed to aid nuclear movement (nucleokinesis) as neurons move to its final destination in the cortex)
  • abundant in synaptosomes)
  • basic FUNCTION
  • participating with LIS1 in the regulation of cytoplasmic dynein through phosphorylation by CDK5, complex essential for neuronal migration
  • cysteine peptidase, involved in the conversion and inactivation of a number of bioactive peptides
  • playing an essential role for mitotic cell division and neuronal migration not only via regulation of cytoplasmic dynein function but also by modulation of KATNA1 localization and function
  • facilitates cell migration by sequestering ARHGAP1 at the leading edge to stabilize active CDC42 in response to extracellular stimuli
  • acting with PAFAH1B1, and NDE1 in a common pathway to regulate dynein but each has distinct roles in the regulation of microtubule organization and neuronal migration
  • crucial role of NDEL1, together with DISC1 in cortical layer formation
  • releases the blocking effect of PAFAH1B1 on cytoplasmic dynein
  • essential for mitotic cell division and neuronal migration not only via regulation of cytoplasmic dynein function but also by modulation of KATNB1 localization and function
  • having a critical role for neuronal migration
  • cytoplasmic dynein regulator, that competes with CDC42 for binding ARHGAP1
  • substrate of PPP4C, and PPP4C selectively dephosphorylates NDEL1 at CDK1 sites
  • regulates microtubule organization during spindle assembly independently of its function at kinetochores
  • regulates microtubule organization in part by facilitating assembly of the lamin B spindle matrix in a dynein-dependent manner
  • promotes assembly of the spindle matrix and MT organization
  • antagonistic effect of PAFAH1B2, PAFAH1B3 and NDEL1 for PAFAH1B1 binding, probably to modulate dynein functions
  • NDEL1-dependent microtubule self-organization requires an interaction between NDEL1 and dynein, which is mediated by the dimerization fragment of the coiled-coil
  • in axons, unphosphorylated NDEL1 inhibits the capacity of dynein to transport acidic organelles
  • is important for the early steps of the WAVE regulatory complex (WRC) assembly in vivo by antagonizing the instability of certain WRC subunits and subcomplexes
  • NDE1 (nuclear distribution element 1) and NDEL1 (NDE-like 1) are essential for mitosis and neurodevelopment
  • NDEL1, NUDCD3, PAFAH1B1 are critical components of cytoplasmic dynein complex
  • novel roles of PAFAH1B1, NDEL1 and NUDCD3 in the transport of mitochondria in axons
  • NDEL/NDE1 and PAFAH1B1 promote dynein and dynactin interaction in the context of spindle morphogenesis
  • NDE1, NDEL1 are essential for mitosis and neurodevelopment that have been implicated in psychiatric and neurodevelopmental disorders
  • NDEL1 enzyme activity is a complex trait influenced by many different genetic variants that may contribute to schizophrenia (SCZ) physiopathology
  • CDK5, YWHAE, and CDK5 cofactor C2CD5 together promote NDEL1 phosphorylation and are essential for force adaptation
  • CELLULAR PROCESS cell cycle, division
    cell cycle, progression
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • with PAFAH1B1, YWHAE (maintaining phosphorylation of NDEL1)
  • interacts with neuronal proteins and is essential for brain development and cortical organization during embryogenesis
  • binding to a regulatory subunit of the PP2A phosphatase and to YWHAE
  • interaction between DISC1 and nuclear distribution element-like (NDEL1/NUDEL) is required for neurite outgrowth)
  • interaction with PAFAH1B1 (PAFAH1B1 suppresses motility of MTs (microtubules) by cytoplasmic dynein in a reversible manner, whereas NDEL1 counteracts this suppressive effect)
  • major function of CENPF, is to link the NDEL1/NDE1/PAFAH1B1/Dynein pathway to kinetochores (NDEL1 and NDE1 play distinct roles to ensure chromosome alignment and segregation)
  • interacts directly with LMNB1, LMNB2 to facilitate the accumulation and assembly of lamin-B-containing matrix on microtubules in a dynein-dependent manner
  • interact with dynein and regulate a diverse array of cellular functions, such as axonal transport and membrane trafficking that require dynein
  • can inhibit ARHGAP1-mediated inactivation of CDC42 in a dose-dependent manner
  • PAFAH1B3 and PAFAH1B2, were able to compete against NDEL1 and dynein for PAFAH1B1 binding in a dose-dependent manner
  • DISC1 forms octamers via dimers as building blocks and directly interacts with tetramers of NDEL1
  • UBR4 interacts directly with the neurogenic protein NDEL1
  • NDEL1 enzyme activity was found to be associated with CAMK1D, MAGI2, CCDC25, and GABGR3
  • cell & other
    REGULATION
    Phosphorylated by CDK5 (phosphorylation of NDEL1 not only reduces its inhibition but also allows PAFAH1B1 to further stimulate the cargo transport capacity of dynein)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in the brain tissue from schizophrenia
    constitutional     --other  
    defects in a PAFAH1B1/NdDEL1 regulatory switch could contribute to neurodegenerative diseases linked to axonal pathology in adults
    Susceptibility to schizophrenia,in relation with its partners DISC1 and NDE1
    Variant & Polymorphism other haplotype significantly associated with an increased risk of schizophrenia
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS