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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
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