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FLASH GENE
Symbol KIF11 contributors: mlc/npt/pgu - updated : 04-05-2020
HGNC name kinesin family member 11
HGNC id 6388
Corresponding disease
EVR8 familial, exudative vitreoretinopathy 8
MLCD2 microcephaly, lymphedema, chorioretinopathy syndrome 2
Location 10q23.33      Physical location : 94.352.824 - 94.415.150
Synonym name
  • thyroid receptor interacting protein 5
  • kinesin-like 1
  • kinesin-like spindle protein HKSP
  • Kinesin-5
  • Synonym symbol(s) EG5, KHR1, TRIP5, KNSL1, HKSP, MCLMR
    DNA
    TYPE functioning gene
    STRUCTURE 62.33 kb     22 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    22 - 5101 119 1056 - 2011 21522128
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node   highly
    Nervousbrainlimbic systemhippocampus   Homo sapiens
    Reproductivefemale systemuteruscervix highly
     male systemtestis  highly
    Visualeyeanterior segment    Homo sapiens
     eyeretina    Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Connectivebone   
    Epithelialbarrier liningretinal pigment epithelium (RPE)   Homo sapiens
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    Visualcone photoreceptor Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    cell cycle     cell cycle, M
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a highly conserved N-terminal catalytic motor domain that can hydrolyze ATP to move processively toward the plus ends of microtubules
  • a kinesin-motor domain, with TNXB-binding region
  • an ATP and a microtubule binding sites
  • a central coiled-coil domain
  • a C-terminal tail that contains a bimC box, a conserved sequence of positively charged amino acid residues, implicated in contact with microtubules
  • mono polymer homomer , tetramer
    HOMOLOGY
    interspecies homolog to Xenopus eg5
    homolog to rattus Kif11
    Homologene
    FAMILY
  • kinesin-like protein family, kinesin-5 family
  • CATEGORY motor/contractile
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus,chromatin/chromosome,kinetochore
    text
  • TNXB and KIF11 proteins were co-localized in the cytoplasm in interphase and mitosis, but TNXB did not localize on mitotic spindle microtubules, on which KIF11 prominently localized in mitosis
  • localizes to spindle microtubules during mitosis
  • KIF11 and TPX2, a spindle microtubule-associated protein that suppresses KIF11 motor activity, are enriched on parallel microtubules near spindle poles
  • KIF11, 21B, 13B with distinct effects on synaptic transmission are expressed in the same hippocampal neuron
  • basic FUNCTION
  • mitotic spindle assembly
  • microtubule motor activity
  • involved in chromosome positioning, centrosome separation, establishing a bipolar spindle during mitosis
  • plus-end-directed motor involved in separation of centrosomes, and in bipolar spindle formation and maintenance during mitosis
  • having essential and nonredundant functions that are necessary for cell viability and early embryonic development
  • critical for spindle assembly during mitosis and has recently been implicated in tumorigenesis
  • functions as a homotetramer, with two motor domains at each end of a central stalk, and contributes to spindle assembly by cross-linking and pushing apart adjacent interpolar microtubules
  • permits microtubules to selectively invade one side of the growth cone by opposing their entry into the other side
  • critical for proper spindle assembly and represents an attractive anticancer target
  • similar to KIF11, KIF15 can drive centrosome separation during bipolar spindle assembly
  • RARRES1, AGBL2, KIF11, another EEY-bearing protein (EB1), and the microtubule tyrosination cycle are important in tumorigenesis
  • actin-dependent KIF11-opposing forces slow down separation in G2 phase
  • role of KIF11, PLK1 and the NIMA-family kinases in the control of centrosome separation and normal mitotic progression
  • KIF11, KIF15, and dynein work together to build a bipolar spindle and reveal an important role for antagonistic motors in chromosome segregation
  • pauses at microtubule plus ends and enhances polymerization by stabilizing longitudinal tubulin-tubulin interactions, and these activities underlie the ability KIF11 to slide and stabilize microtubule bundles in cells
  • essential role of PTEN in mitosis through regulation of the mitotic kinesin motor EG5 for proper spindle architecture and chromosome congression (pMID: 27492783)
  • is essential to mitosis and cell cycle progression
  • role for KIF11 not only in ocular development but also in maintaining retinal morphology and function
  • acts as a potential oncogene that regulates the development and progression of breast cancer
  • one of the first steps in mitotic spindle assembly is the dissolution of the centrosome linker followed by centrosome separation driven by KIF11
  • endogenous KIF11 enhances the self-renewal of breast cancer cells by activating the Wnt/CTNNB1 signaling pathway
  • promotes bipolar spindle formation and chromosome movement, and during interphase, KIF11 mediates diverse trafficking processes in the cytoplasm
  • CELLULAR PROCESS cell cycle, division, mitosis
    cell organization/biogenesis
    PHYSIOLOGICAL PROCESS
    text formation and maintenance of mitotic spindle
    PATHWAY
    metabolism
    signaling
    a component
  • homotetrameric, slow-processive, plus-end-directed spindle motor protein
  • INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
  • protein
  • interacting with the thyroid hormone receptor in the presence of T3
  • NPM1 directly interacts with KIF11, in the cytosol (NPM1 acts as an upstream regulator of KIF11 in promoting microtubule polymerization)
  • poleward transport requires the C terminus of TPX2, a domain that interacts with KIF11
  • interaction with LMNB1 (LMNB1 only very weakly antagonizes KIF11 in mediating poleward microtubule-flux
  • interaction with PLK1 (PLK1 is required for both CEP250 displacement and for KIF11 localization on the centrosome)
  • 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)
  • during mitosis KIF11 appears to interact with NUMA1 in the vicinity of the spindle poles, whereas the interaction does not occur in interphase cells, where KIF11 is distributed throughout the cytoplasm but NUMA1 exclusively localizes to the nucleus
  • specific interaction of KIF11 with IGF2BP1 regulates the transport of ACTB mRNA and cell motility
  • 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
  • FBXO30 specifically interacts with the bipolar spindle kinesin KIF11, and FBXO30-KIF11 interaction is a critical checkpoint in mammopoiesis with a critical role for ubiquitinylation-regulated KIF11 oscillation in the cell cycle
  • PTEN regulates spindle pole movement through DLG1-mediated recruitment of KIF11 to centrosomes
  • functional interplay between PTEN and KIF11 in controlling mitotic spindle structure and chromosome behaviour during mitosis
  • NEK7 regulates dendrite morphogenesis in neurons via KIF11-dependent microtubule stabilization
  • expression of PCLO constrained KIF11 function in synaptic transmission
  • KIFC3 is eventually inactivated by NEK2 to enable KIF11-driven bipolar spindle assembly
  • TRIM8 interacts with KIFC1, and KIF11, two master regulators of mitotic spindle assembly and cytoskeleton reorganization
  • cell & other
  • microtubule associated
  • REGULATION
    inhibited by by Parkin (PARK2), an E3 ubiquitin ligase well known for its role in the development of Parkinson disease
    Other CDC2, regulating KNSL1 localization
    phosphorylated only on serine during S phase, and on serine and threonine during mitosis
    phosphoregulatory mechanism tunes KIF11 enzymatic activity for optimal spindle morphology
    ASSOCIATED DISORDERS
    corresponding disease(s) MLCD2 , EVR8
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in breast cancer correlated with worse outcomes
    Susceptibility to type 2 diabetes
    Variant & Polymorphism other polymorphism increasing the risk of type 2 diabetes
    Candidate gene
    Marker
  • potential prognostic biomarker in breast cancer
  • KIF11 expression might be indicative of prostate cancer (Pca) aggressiveness and could be useful as a prognostic marker for patients with PCa
  • Therapy target
    SystemTypeDisorderPubmed
    cancerbrainglioma/neuroblstoma
    KIF11 inhibitors, when able to permeate the blood-brain-barrier, could represent an interesting class of anticancer drugs with low neurotoxic effects in the treatment of brain tumors
    ANIMAL & CELL MODELS
  • in mice, Kif11 function in early postnatal CNS ECs is most significant in the two CNS regions-the retina and cerebellum-that exhibit the most rapid rate of postnatal growth, which may sensitize endothelial cells (ECs) to impaired mitotic spindle function