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FLASH GENE
Symbol TPX2 contributors: mct/npt/pgu - updated : 12-05-2020
HGNC name TPX2, microtubule-associated protein homolog (Xenopus laevis)
HGNC id 1249
Location 20q11.21      Physical location : 30.326.903 - 30.389.603
Synonym name
  • chromosome 20 open reading frame 2
  • chromosome 20 open reading frame 1
  • preferentially expressed in colorectal cancer
  • restricted expression proliferation associated protein 100
  • targeting protein for XKLP2
  • differentially expressed in cancerous and non-cancerous
  • lung cells 2
    Synonym symbol(s) DIL-2, repp86, DIL2, P100, FLS353, C20orf2, C20orf1, FLS353, HCTP4
    DNA
    TYPE functioning gene
    STRUCTURE 62.70 kb     18 Exon(s)
    MAPPING cloned Y linked N status provisional
    Map pter - D20S182 - TPX2 - D20S106 - qter
    Authors GeneMap (98)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    18 - 3685 - 747 - 2008 18663142
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly
     mouthtongue  highly
    Lymphoid/Immunethymus   highly
     tonsils   highly
    Reproductivemale systemtestis  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Respiratoryepithelial cell
    cell lineage
    cell lines cancerous (high expression)
    fluid/secretion
    at STAGE
    physiological period
    cell cycle     cell cycle, S, G2, M
    Text restricted to cell cycle phases, S, G2 and M
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a putative ATP/GTP binding site motif
  • a fragment (AAs 1-43) has been shown to be sufficient for binding, kinase activation, and protection from dephosphorylation
  • conjugated PhosphoP
    HOMOLOGY
    Homologene
    FAMILY
    CATEGORY DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,nucleolus
    text
  • diffuse nuclear distribution at the onset of S phase, persisting through G2 phase and relocating to the mitotic spindle in M phase
  • colocalises with apoptotic microtubules
  • KIF11 and TPX2, a spindle microtubule-associated protein that suppresses KIF11 motor activity, are enriched on parallel microtubules near spindle poles
  • basic FUNCTION
  • spindle assembly factor, indispensable for cell division
  • required for the formation of functional mitotic spindle
  • AURKA activator TPX2 is required for microtubule nucleation from chromosomes as well as for spindle bipolarity
  • having a second AURKA-independent function that is required to bipolarize spindles
  • important similarities with the process of RanGTP- and TPX2-mediated mitotic spindle formation
  • poleward transport requires the C terminus of TPX2, a domain that interacts with KIF11, and down-regulates its microtubule nucleating activity near kinetochores and links microtubules generated at kinetochores to dynein for incorporation into the spindle
  • microtubule-binding protein that plays a major role in regulating the activity and localisation of Aurora-A in mitotic cells
  • novel function of TPX2 in regulating the location and activity of the mitotic motor KIF11
  • TPX2 is important in the regulation of tumor growth in cervical cancer
  • complementary activities of TPX2 and CKAP5 constitute an efficient importin-regulated microtubule nucleation module
  • TPX2 is an important component of the acentrosomal MT organizing center in neurons
  • Ran-GTP gradient can regulate TPX2-dependent microtubule (MT) formation
  • is a microtubule-associated protein required for mitosis and spindle assembly
  • is a key mitotic regulator that contributes through distinct pathways to spindle assembly
  • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • TPX2/AURKA heterodimer, nominally considered a mitotic kinase complex, is a novel binding partner of TP53BP1
  • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
  • GTP
  • protein
  • with AURKA (enhancing AURKA activity during mitosis)
  • interacts with the spindle assembly factors dynein and HMMR (like TPX2, HMMR expression is up-regulated during mitosis)
  • TPX2 binding with AURKA decreases the size and accessibility of a hydrophobic pocket, adjacent to the ATP site, to inhibitors
  • KIF11 interacts with the spindle assembly factor TPX2 (this interaction was required for kinetochore fiber formation and contributed to KIF11 localization to spindle microtubules but not spindle poles)
  • PKD1 cytoplasmic tail associates with the transcription factors TPX2 and STAT6
  • constitutive control of TPX2 on H4K16ac levels, with potential implications for DNA damage response
  • TPX2 is a multifunctional mitotic spindle assembly factor that in mammalian cells localizes and regulates mitotic motor protein KIF11, and TPX2 regulates neuronal morphology through KIF11 interaction
  • BCL2L10 is a binding partner of TPX2 and a new regulator of the complex controlling the organization of microtubules and microtubule organizing center (MTOC) biogenesis in meiotic spindle assembly
  • RAN-dependent TPX2 activation promotes acentrosomal MT nucleation in neurons
  • TPX2 promotes the proliferation and migration of human Ovarian cancer cells by regulating PLK1 expression
  • novel function of ADD1 in maintaining spindle pole integrity through its interaction with TPX2
  • TPX2/AURKA plays a previously unrecognized role in DNA damage repair and replication fork stability by counteracting TP53BP1 function
  • well-characterised function of TPX2 is the activation, stabilisation and spindle localisation of AURKA
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    correlate with the malignant condition and might be linked to the increased or abnormal cell proliferation in human oral squamous cell carcinomas
    tumoral     --over  
    in prostate cancer tissues
    tumoral     --low  
    TPX2 silencing negatively regulates the AKT signaling pathway by which Ovarian cancer cell proliferation was inhibited yet cell apoptosis was accelerated
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestiveliver
    TPX2 may be a potential target for the treatment of liver cancer
    cancerreproductivebreast
    TPX2 may be a potential target for anticancer therapy in breast cancer
    cancerreproductiveuterus
    may be a potential therapeutic target as a novel treatment strategy
    ANIMAL & CELL MODELS