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FLASH GENE
Symbol INCENP contributors: mct/npt - updated : 13-09-2023
HGNC name inner centromere protein antigens 135/155kDa
HGNC id 6058
PROTEIN
PHYSICAL PROPERTIES basic
STRUCTURE
motifs/domains
  • centromere targeting and transfer to the spindle region
  • multiple nuclear localization signals
  • chromosome binding region and spindle midzone targeting
  • central region with single alpha-Helix (SAH) domain that binds directly to microtubules and is important for chromosome passenger complex (CPC) localization and function in mitosis
  • C-terminal IN box region of INCENP is responsible for binding and activating Aurora B kinase
  • mono polymer dimer
    HOMOLOGY
    interspecies ortholog to murine Incenp
    Homologene
    FAMILY
  • INCENP family
  • CATEGORY structural protein , antigen
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,nucleoplasm,nuclear bodies
    intracellular,nucleus,chromatin/chromosome,centromere
    intracellular,nucleus,chromatin/chromosome,kinetochore
    intracellular,nucleus,nucleolus
    text
  • localized to metaphase chromosomes and to the mitotic spindle and equatorial cortex at anaphase and also in the cleavage furrow
  • cytoplasmic face of the plasma membrane
  • as mitosis progresses, with Survivin, Aurora B, CDCA8 dynamically colocalize to mitotic structures
  • accumulate in the interphase nucleolus in an RNA polymerase I-dependent manner (Wong 2007)
  • unlike wild-type INCENP, truncated INCENP localizes to pre-anaphase spindle microtubules
  • basic FUNCTION
  • required for chromosome segregation and the onset of cytokinesis during mitosis
  • moves from the central spindle to the furrow of a dividing cell by a KIF12-dependent pathway (once INCENP reaches the equatorial cortex, it associates with the actin cytoskeleton where it then concentrates toward the end of cytokinesis) (Chen 2007)
  • playing a role in the regulation of sister chromatid separation in mitosis (loss of INCENP is accompanied by loss of cohesion)
  • essential for central spindle and midbody localization of chromosomal passenger complex
  • dual recognition of chromatin and microtubules by INCENP is important for mitotic progression
  • plays a catalytic role in AURKB autophosphorylation (Yang 2009)
  • modulates AURKB kinase activity and chromosomal passenger complex (CPC) localization, which is essential for timely mitotic progression
  • CELLULAR PROCESS cell cycle, division, mitosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • component of a complex with BIRC5 that links centromere to microtubules
  • interacts with CDCA8, AURKB and BIRC5 to form the chromosomal passenger complex (CPC), which is involved in the regulation of microtubule-kinetochore attachments and cytokinesis
  • complexes of AURKB and its binding partner INCENP autophosphorylate in trans to achieve full AURKB activation
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to CBX3, tubulin beta chain
  • binding partner Aurora-B/AIMdetected at the inactive centromere)-1 kinase (both can be)
  • binds and activates Aurora-C
  • associating with CDCA8
  • interacting with BIRC5 on the localization of Aurora B and CDCA8, respectively (different complexes of chromosomal passenger proteins may exist not only during mitosis, but also before NEB (nuclear envelope breakdown )
  • interacting with CENPV
  • the putative coiled-coil domain within INCENP drives midzone localization of AURKB via a direct, electrostatic interaction with microtubules
  • AURKA associates with inner centromere protein (INCENP) during mitosis and INCENP is competent to drive accumulation of the kinase to the centromere region of mitotic chromosomes
  • AURKB/AURKC) are activated by binding to the C-terminal domain of INCENP
  • AURKB, together with IN-box, the C-terminal part of INCENP, forms an enzymatic complex that ensures faithful cell division
  • when the physiological AURKB-INCENP recruitment mechanisms are present, an engineered AURKB-INCENP recruitment to the outer kinetochore, but not to the inner kinetochore, during metaphase (after biorientation establishment) disrupts biorientation, which is dependent on the AURKBB kinase activity
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    significantly higher nuclear expression in high grade B-cell lymphomas versus low grade ones (Barbanis 2009)
    tumoral     --over  
    in neuroblastoma, significantly associated with poor prognosis in primary tumors of neuroblastoma patients with high-risk disease
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerbrainglioma/neuroblstoma
    targeting INCENP presents a novel strategy to disrupt the activity of chromosomal passenger complex and inhibit neuroblastoma progression
    ANIMAL & CELL MODELS