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FLASH GENE
Symbol NDC80 contributors: mct/npt/pgu/shn - updated : 13-11-2017
HGNC name NDC80 homolog, kinetochore complex component (S. cerevisiae)
HGNC id 16909
Location 18p11.32      Physical location : 2.571.509 - 2.616.633
Synonym name
  • NDC80 homolog, kinetochore complex component
  • kinetochore protein NDC80 homolog
  • highly expressed in cancer protein
  • mitotic regulator, highly expressed in cancer
  • highly expressed in cancer, rich in leucine heptad repeats
  • kinetochore associated 2
  • kinetochore-associated protein 2
  • retinoblastoma-associated protein HEC
  • kinetochore protein Hec1
  • Synonym symbol(s) HEC1, HEC, KNTC2, TID3, hsNDC80
    DNA
    TYPE functioning gene
    STRUCTURE 45.13 kb     17 Exon(s)
    regulatory sequence Promoter
    Binding site   transcription factor
    text structure TATA-less promoter that contains several putative binding sites for different transcription factors
    MAPPING cloned Y linked N status provisional
    Map pter - D18S1146 - D18S476 - NDC80 - D18S1098 - D18S481 - cen
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    17 - 2209 73 642 - 2008 18794333
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen    
     thymus    
    Reproductivefemale systemuteruscervix  
     male systemtestis   
    Urinarybladder    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    cell cycle     cell cycle, S, M
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal tail of the NDC80 protein, is the site of phospho-regulation by AURKB
  • positively charged 80-AA N-terminal tail of the NDC80 protein is required for high-affinity microtubule binding, probably by interaction with the acidic C-terminal tails of tubulin (also known as E-hooks)
  • a serie of typical leucine heptad repeats at the C terminal region
  • a coiled coil myosin heavy chain tail domain
  • a globular domain that binds strongly at the interface between tubulin dimers and weakly at the adjacent intradimer interface along the protofilament axis
  • CH and tail domains generate essential contacts between kinetochores and microtubules in cells (
  • a calponin homology domain (CHD)
  • HOMOLOGY
    interspecies ortholog to NDC80, Pan troglodytes
    ortholog to Ndc80, Mus musculus
    ortholog to Ndc80, Rattus norvegicus
    ortholog to ndc80, Danio rerio
    Homologene
    FAMILY
  • NDC80/HEC1 family
  • CATEGORY signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,chromatin/chromosome,kinetochore
    text
  • localizing to kinetochores (specifically to the outer plate) from late prophase to anaphase
  • with ZWINT, co-localize at kinetochores beginning at prophase and ZW10 joins them later at prometaphase
  • basic FUNCTION
  • required for recruiting MAD1/MAD2 complex to kinetochores
  • play a critical role in modulating chromosomal segregation (
  • core component of the kinetochore outer plate, essential for organizing microtubule attachment sites
  • surveillance mechanism assuring correct segregation of chromosomes by detecting unaligned chromosomes and causing prometaphase arrest until the proper bipolar attachment of chromosomes is achieved
  • plays a crucial role for spindle checkpoint control and faithful chromosome segregation (
  • kinetochore component conserved from yeast to humans, is essential for proper chromosome alignment and segregation during mitosis
  • plays an essential role in chromosome segregation for M phase progression
  • directly connects kinetochores to spindle microtubules
  • NDC80 complex is the key site for kinetochore&
  • 65533;microtubule attachment and a landing pad for the spindle assembly checkpoint
  • NDC80 complex binds the microtubule with a tubulin monomer repeat, recognizing alpha- and beta-tubulin at both intra- and inter-tubulin dimer interfaces in a manner that is sensitive to tubulin conformation
  • in addition to regulating attachment stability, Aurora B controls microtubule dynamics through phosphorylation of the NDC80 complex
  • NDC80 complex is a key site of kinetochore-microtubule attachment during cell division
  • functions of the NDC80/Hec1 subunit of the highly conserved NDC80 kinetochore complex are normally restricted to M phase when it exerts a pivotal kinetochore-based role
  • novel role for AURKB-NDC80-TTK signaling axis in governing accurate chromosome segregation in mitosis
  • molecular target to produce massive chromosome missegregation and cell death in cancer cells
  • the NDC80 complex, which mediates end-on attachment of spindle microtubules, is linked to centromeric chromatin in human cells by two inner kinetochore proteins, CENPT and CENPC1
  • is a crucial regulator of the cell division cycle that has recently been identified as a novel oncoprotein in various solid tumors
  • CELLULAR PROCESS cell cycle, division, mitosis
    cell cycle, checkpoint
    PHYSIOLOGICAL PROCESS
    text spindle checkpoint signaling
    PATHWAY
    metabolism
    signaling
    a component
  • component of the NDC80 complex, forming a direct link between kinetochore core components and spindle microtubules, comprised of NDC80/NUF2 and SPC24/SPC25 dimers, directly connects kinetochores to spindle microtubules
  • NUF2-NDC80 complex, members of centromere protein complex
  • NDC80 complex is a key site of regulated kinetochore/microtubule attachment (a process required for cell division)
  • NDC80, MIS12, and CASC5 complexes form the core of the KMN network
  • constituent of the NDC80 complex, which mediates kinetochore (KT)-microtubule (MT) attachments at mitosis and is upregulated in various cancer types
  • KMN network (for CASC5, MIS12 and NDC80 complexes) is a hub for signalling at the outer kinetochore
  • likely SPAG5-SKAP complex acts together with the NDC80 complex to stabilize correctly formed kinetochore-microtubule interactions
  • INTERACTION
    DNA
    RNA
    small molecule other,
  • microtubules (
  • protein
  • MSS1, p45, Nek2, and Smc1/Smc2 (
  • SPC25 and SPC24 (
  • ZW10 interacting protein, Zwint-1 and Zeste White 10, ZW10 (
  • HAUS8
  • MLF1IP
  • interrelationship between MLF1IP and NDC80 in the stabilization of kinetochore-microtubule attachment, and this interaction is under Aurora-B modulation
  • AURKB phosphorylation antagonizes the interaction between the SKA complex and the KMN network (named according to the acronym for KNL1, MIS12, and NDC80), thereby controlling SKA recruitment to kinetochore (KT) and stabilization of KT-MT attachments
  • CENPT is a direct centromere receptor of the microtubule-binding NDC80 complex
  • integrated kinetochore-microtubule interface formed by the SKA1 and NDC80 complexes that associates with depolymerizing microtubules, potentially by interacting with curved microtubule protofilaments
  • NDC80 interacts with TTK and specifies its kinetochore localization via its calponin homology (CH) domain and N-terminal 80 amino acids
  • competition between TTK and microtubules for NDC80C binding thus constitutes a direct mechanism for the detection of unattached kinetochores
  • MIS12 binds NDC80 complex far from the microtubule-binding domain and confers increased microtubule interaction of the complex
  • binding of the MIS12 and NDC80 outer kinetochore subcomplexes to CENPC and CENPT
  • cell & other
    REGULATION
    activated by CREB1, ATF4 (overexpression of either CREB1 or ATF4 enhanced the activation of its promoter and overexpression of both of them had an additive effect on the activation of the NDC80 transcription)
    Phosphorylated by NEK2 and, phosphorylation modulates chromosome alignment and signaling of the spindle assembly checkpoint
    AURKB, that weakens its interaction with microtubules but promotes NDC80 binding to TTK
    Other cell-cycle regulated serine phosphorylation by NEK2,essential for faithful chromosome segregation
    regulated by CENPK and CASC5 (CASC5 and CENPK, coordinately direct NDC80 complex localization)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification --low  
    in esophageal squamous cell carcinoma
    tumoral     --over  
    in lung cancer
    tumoral     --over  
    in colorectal and gastric cancers
    tumoral     --over  
    high levels may occur at the early stage of gastric tumorigenesis
    tumoral     --over  
    not only in osteosarcoma, but also in other sarcomas including liposarcoma, myxofibrosarcoma, and leiomyosarcoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • is a clinically actionable biomarker for prognostic prediction and therapy decisions in osteosarcoma
  • Therapy target
    SystemTypeDisorderPubmed
    cancerlung 
    suppression of NUF2 or NDC80 activity and/or inhibition of the NUF2-NDC80 complex formation could be a promising therapeutic target for treatment of lung cancers
    ANIMAL & CELL MODELS