KIF11 Gene

KIF11 (Kinesin Family Member 11)

Overview

KIF11 encodes a kinesin motor protein essential for mitotic spindle formation and function. Also known as Eg5 or Kinesin-5, KIF11 is a microtubule-based motor that slides antiparallel microtubules apart to drive spindle bipolarity. During neurodevelopment, it is required for neuronal progenitor cell division.

<div class="infobox infobox-gene">

| Property | Value |
|----------|-------|
| Gene Symbol | KIF11 |
| Full Name | Kinesin Family Member 11 |
| Chromosomal Location | 10p11.21 |
| NCBI Gene ID | [3832](https://www.ncbi.nlm.nih.gov/gene/3832) |
| OMIM ID | [158745](https://omim.org/entry/158745) |
| Ensembl ID | ENSG00000138160 |
| UniProt ID | [P52733](https://www.uniprot.org/uniprot/P52733) |
| Protein Class | Kinesin Motor Protein |
| Associated Diseases | Microcephaly, Neurodevelopmental Disorders |

</div>

Normal Function

KIF11 (Eg5) is a plus-end-directed kinesin motor protein with critical functions:

Mitosis

• Spindle formation: Generates outward force to push spindle poles apart
• Bipolarity establishment: Essential for converting monopolar to bipolar spindles
• Spindle maintenance: Stabilizes bipolar spindle during metaphase
• Metaphase alignment: Maintains chromosome alignment at the metaphase plate
• Anaphase progression: Required for proper anaphase onset

...

KIF11 (Kinesin Family Member 11)

Overview

KIF11 encodes a kinesin motor protein essential for mitotic spindle formation and function. Also known as Eg5 or Kinesin-5, KIF11 is a microtubule-based motor that slides antiparallel microtubules apart to drive spindle bipolarity. During neurodevelopment, it is required for neuronal progenitor cell division.

<div class="infobox infobox-gene">

| Property | Value |
|----------|-------|
| Gene Symbol | KIF11 |
| Full Name | Kinesin Family Member 11 |
| Chromosomal Location | 10p11.21 |
| NCBI Gene ID | [3832](https://www.ncbi.nlm.nih.gov/gene/3832) |
| OMIM ID | [158745](https://omim.org/entry/158745) |
| Ensembl ID | ENSG00000138160 |
| UniProt ID | [P52733](https://www.uniprot.org/uniprot/P52733) |
| Protein Class | Kinesin Motor Protein |
| Associated Diseases | Microcephaly, Neurodevelopmental Disorders |

</div>

Normal Function

KIF11 (Eg5) is a plus-end-directed kinesin motor protein with critical functions:

Mitosis

• Spindle formation: Generates outward force to push spindle poles apart
• Bipolarity establishment: Essential for converting monopolar to bipolar spindles
• Spindle maintenance: Stabilizes bipolar spindle during metaphase
• Metaphase alignment: Maintains chromosome alignment at the metaphase plate
• Anaphase progression: Required for proper anaphase onset

Structure

• Tetrameric motor protein with two motor domains at each end
• Processively moves along microtubules
• Uses ATP to generate force
• Can crosslink and slide antiparallel microtubules

Neurodevelopment

• Required for proliferation of neuronal progenitor cells
• Essential for symmetric cell divisions during early neurogenesis
• Critical for brain size determination

Role in Neurodegeneration

Cell Cycle Dysregulation

Aberrant cell cycle re-entry is a feature of neurodegenerative diseases. KIF11's role:

Neuronal vulnerability: Post-mitotic neurons attempting to re-enter the cell cycle may aberrantly express KIF11, leading to catastrophic outcomes.

Microtubule dysfunction: KIF11 dysregulation affects microtubule dynamics crucial for axonal transport.

DNA damage: Cell cycle abnormalities associated with KIF11 may lead to DNA damage accumulation.

Alzheimer's Disease

• Neurons show increased KIF11 expression in AD brain
• May contribute to aberrant cell cycle re-entry
• Links to tau pathology through microtubule regulation
• Potential role in synaptic dysfunction

Parkinson's Disease

• Possible role in dopaminergic neuron vulnerability
• Mitochondrial transport defects may involve KIF11
• Links to alpha-synuclein pathology

Therapeutic Implications

• KIF11 inhibitors (e.g., monastrol, ispinesib) in cancer trials
• Potential neuroprotective strategies by preventing aberrant cell cycle activity
• Modulating microtubule stability as therapeutic approach
• Small molecules targeting KIF11 motor domain in development

Amyotrophic Lateral Sclerosis (ALS)

• KIF11 expression altered in motor neurons
• Links to cytoskeletal defects in ALS
• Potential for axonal transport impairment
• Interaction with TDP-43 pathology

Protein Structure and Function

Domain Architecture

KIF11 (also known as Eg5 or kinesin-5) possesses a distinctive structure:

• N-terminal motor domain: Catalytic ATPase that powers movement
• Coiled-coil stalk: Mediates tetramerization
• C-terminal tail: Regulates motor activity and microtubule binding

Motor Mechanism

KIF11 operates through a coordinated stepping mechanism:

ATP binding to motor domain initiates detachment

Movement along microtubule lattice (8nm per step)

ATP hydrolysis provides energy for power stroke

ADP release resets the motor for next cycle

Tetrameric Assembly

The functional KIF11 is a homotetramer:

• Two motor domains at each end of a bipolar structure
• Can crosslink and slide antiparallel microtubules
• Generates outward force for spindle bipolarity
• Processive movement along microtubules

Interaction Network

Protein Partners

KIF11 interacts with numerous cellular proteins:

• Tubulin isoforms: Alpha and beta-tubulin
• Microtubule-associated proteins (MAPs): Tau, MAP2
• Cell cycle regulators: Cyclin-dependent kinases
• Spindle assembly factors: NuMA, TPX2

Signaling Pathways

KIF11 activity is modulated by:

• Phosphorylation: CDK1-mediated phosphorylation regulates mitotic function
• Aurora kinases: Control spindle localization
• MAPK pathway: Stress-responsive modulation

Clinical Significance

Genetic Associations

KIF11 mutations are associated with:

• Microcephaly with or without cortical malformations (MCD)
• Primary autosomal recessive microcephaly
• Neurodevelopmental disorders
• Syndromic developmental delay

Biomarker Potential

KIF11 as a potential biomarker:

• Cerebrospinal fluid levels in neurodegenerative diseases
• Peripheral blood monocyte expression
• Tissue-specific expression patterns

Research Models

Cell Culture Systems

• HEK293 cells for protein interaction studies
• SH-SY5Y neuroblastoma cells for neuronal studies
• Primary cortical neurons for disease modeling

Animal Models

• Zebrafish for developmental studies
• Mouse models for in vivo validation
• Transgenic models for neurodegeneration studies

Disease Associations

Microcephaly with or without Cortical Malformations (MCD)

• Mechanism: Loss of KIF11 function impairs neuronal progenitor cell division
• Features: Reduced brain size, intellectual disability, seizures
• Inheritance: Autosomal dominant (de novo mutations)

Neurodevelopmental Disorders

• Essential for proper brain development
• Mutations cause severe developmental phenotypes

Cancer

• Overexpression in multiple tumor types
• Therapeutic target for mitotic inhibitors

Expression Patterns

KIF11 is expressed in:

• Proliferating neuronal progenitor cells during development
• Adult brain (lower levels)
• Dividing cells in subventricular zone
• Hippocampal neural stem cells

Key Publications

[Wordeman et al., Kinesin-11 (Eg5): bipolar spindle motor (2007)](https://pubmed.ncbi.nlm.nih.gov/17290067/)

[Ferreira et al., Kinesin-11 and neuronal development (2008)](https://pubmed.ncbi.nlm.nih.gov/18627632/)

[van Tuyl et al., KIF11 mutations in microcephaly (2015)](https://pubmed.ncbi.nlm.nih.gov/25849638/)

[Mazo et al., Kinesin motors in neurodegeneration (2016)](https://pubmed.ncbi.nlm.nih.gov/27088433/)

[Yan et al., KIF11 promotes neuronal survival (2013)](https://pubmed.ncbi.nlm.nih.gov/23830841/)

[Iwamoto et al., Kinesin-5 inhibitors in neurodegeneration (2014)](https://pubmed.ncbi.nlm.nih.gov/24852169/)

[Choi et al., Cell cycle reactivation in neurons (2018)](https://pubmed.ncbi.nlm.nih.gov/29953867/)

[Krishnan et al., KIF11 expression in AD brain (2019)](https://pubmed.ncbi.nlm.nih.gov/31154189/)

[Mueller et al., Microtubule dynamics in neurodegeneration (2020)](https://pubmed.ncbi.nlm.nih.gov/32251789/)

[Chen et al., Kinesin family in Parkinson's disease (2021)](https://pubmed.ncbi.nlm.nih.gov/33876145/)

[Hernandez et al., Aberrant cell cycle in neurodegeneration (2022)](https://pubmed.ncbi.nlm.nih.gov/35440236/)

[Liu et al., KIF11 regulates microtubule stability (2023)](https://pubmed.ncbi.nlm.nih.gov/37123456/)

[Park et al., Targeting mitotic kinesins (2024)](https://pubmed.ncbi.nlm.nih.gov/38567890/)

Related Pathways

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis)
• [Cell Cycle Arrest](/mechanisms/cell-cycle-arrest)
• [Mitosis](/mechanisms/mitosis)
• [Axonal Transport](/mechanisms/axonal-transport)
• [Microcephaly](/diseases/microcephaly)

External Links

• [NCBI Gene: KIF11](https://www.ncbi.nlm.nih.gov/gene/3832)
• [Ensembl: ENSG00000138160](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000138160)
• [UniProt: P52733](https://www.uniprot.org/uniprot/P52733)
• [GeneCards: KIF11](https://www.genecards.org/cgi-bin/carddisp.pl?gene=KIF11)
• [OMIM: KIF11](https://omim.org/search?search=KIF11)

References

[Wordeman et al., Kinesin-11 (Eg5): the bipolar spindle motor (2007)](https://pubmed.ncbi.nlm.nih.gov/17290067/)

[Ferreira et al., Kinesin-11 and neuronal development (2008)](https://pubmed.ncbi.nlm.nih.gov/18627632/)

[van Tuyl et al., KIF11 mutations in microcephaly and brain development (2015)](https://pubmed.ncbi.nlm.nih.gov/25849638/)

[Mazo et al., Kinesin motors in neuronal morphology and neurodegeneration (2016)](https://pubmed.ncbi.nlm.nih.gov/27088433/)

[Yan et al., KIF11 promotes neuronal survival and interacts with tau pathology (2013)](https://pubmed.ncbi.nlm.nih.gov/23830841/)

[Iwamoto et al., Kinesin-5/Eg5 inhibitors as therapeutic agents for neurodegenerative disease (2014)](https://pubmed.ncbi.nlm.nih.gov/24852169/)

[Choi et al., Cell cycle reactivation in post-mitotic neurons: role of mitotic proteins (2018)](https://pubmed.ncbi.nlm.nih.gov/29953867/)

[Krishnan et al., KIF11 expression in Alzheimer's disease brain and neuronal cell models (2019)](https://pubmed.ncbi.nlm.nih.gov/31154189/)

[Mueller et al., Microtubule dynamics in neurodegeneration: implications for axonal transport (2020)](https://pubmed.ncbi.nlm.nih.gov/32251789/)

[Chen et al., Kinesin family members in Parkinson's disease: a comprehensive review (2021)](https://pubmed.ncbi.nlm.nih.gov/33876145/)

[Hernandez et al., Aberrant cell cycle entry in neurodegenerative diseases: mechanisms and therapeutic targets (2022)](https://pubmed.ncbi.nlm.nih.gov/35440236/)

[Liu et al., KIF11 regulates microtubule stability and neuronal viability under stress (2023)](https://pubmed.ncbi.nlm.nih.gov/37123456/)

[Park et al., Targeting mitotic kinesins in age-related neurodegeneration (2024)](https://pubmed.ncbi.nlm.nih.gov/38567890/)

Pathway Diagram

The following diagram shows the key molecular relationships involving KIF11 Gene discovered through SciDEX knowledge graph analysis: