ASPM Protein

<!-- Protein Page -->
<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#e8f4ea;">ASPM (Abnormal Spindle-like Microcephaly-associated)</th></tr>
<tr><td><b>Gene</b></td><td><a href="/genes/ASPM">ASPM</a></td></tr> [@horvath2023]
<tr><td><b>UniProt</b></td><td><a href="https://www.uniprot.org/uniprot/Q9P2E3" target="_blank">Q9P2E3</a></td></tr> [@pulvers2024]
<tr><td><b>PDB Structures</b></td><td>4MTX, 4MTY</td></tr> [@letelier2023]
<tr><td><b>Molecular Weight</b></td><td>347 kDa</td></tr> [@fujimori2024]
<tr><td><b>Localization</b></td><td>Centrosome, spindle poles</td></tr>
<tr><td><b>Protein Family</b></td><td>ASPM family</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">5 edges</a></td>
</tr>
</table>
</div>

ASPM (Abnormal Spindle-like Microcephaly-associated)

Introduction

Aspm Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

This page provides comprehensive information about this protein. See the content below for detailed information.

ASPM is the most frequently mutated gene in primary microcephaly. It encodes a centrosomal protein that regulates mitotic spindle function and is essential for normal neurogenesis during brain development.

Structure

...

<!-- Protein Page -->
<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#e8f4ea;">ASPM (Abnormal Spindle-like Microcephaly-associated)</th></tr>
<tr><td><b>Gene</b></td><td><a href="/genes/ASPM">ASPM</a></td></tr> [@horvath2023]
<tr><td><b>UniProt</b></td><td><a href="https://www.uniprot.org/uniprot/Q9P2E3" target="_blank">Q9P2E3</a></td></tr> [@pulvers2024]
<tr><td><b>PDB Structures</b></td><td>4MTX, 4MTY</td></tr> [@letelier2023]
<tr><td><b>Molecular Weight</b></td><td>347 kDa</td></tr> [@fujimori2024]
<tr><td><b>Localization</b></td><td>Centrosome, spindle poles</td></tr>
<tr><td><b>Protein Family</b></td><td>ASPM family</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">5 edges</a></td>
</tr>
</table>
</div>

ASPM (Abnormal Spindle-like Microcephaly-associated)

Introduction

Aspm Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

This page provides comprehensive information about this protein. See the content below for detailed information.

ASPM is the most frequently mutated gene in primary microcephaly. It encodes a centrosomal protein that regulates mitotic spindle function and is essential for normal neurogenesis during brain development.

Structure

ASPM is one of the largest proteins in the human genome:

• N-terminal calponin homology domains (x2) - microtubule binding
• Multiple CH domains - repeated throughout protein
• C-terminal ASPM domain - conserved microcephaly domain
• Spindle pole targeting domain - centrosomal localization
• Phosphorylation sites - cell cycle regulation

The protein contains 81 predicted calponin homology domains, making it structurally unique.

Normal Function

During neurogenesis, ASPM plays critical roles:

• Spindle orientation - maintains symmetric cell divisions
• Centrosome function - proper mitotic apparatus
• Neural progenitor proliferation - expands the progenitor pool
• Cleavage plane specification - determines division symmetry
• Cytokinesis - completes cell division

Role in Disease

Primary Microcephaly (MCPH5)

ASPM mutations cause the most common form of autosomal recessive primary microcephaly:

• Frequency - ~30-50% of MCPH cases
• Head circumference - >3-4 SD below mean
• Brain size - reduced cerebral [cortex](/brain-regions/cortex)
• Cognitive outcome - usually mild intellectual disability
• Brain structure - simplified gyral pattern

Pathogenic Mechanisms

Spindle orientation defects - shifts from symmetric to asymmetric divisions

Reduced progenitor pool - fewer neural stem cells

Accelerated neurogenesis - premature differentiation

Reduced neuron number - smaller brain

Normal neuronal function - preserved cognitive capacity per neuron

Cancer

• ASPM overexpression in gliomas
• Potential cancer stem cell marker
• Role in cell proliferation

Key Publications

Bond J, et al. (2003). "ASPM is a major determinant of cerebral cortical size." Nat Genet. 35(4):298-301. [DOI:10.1038/ng1259](https://doi.org/10.1038/ng1259)

Fish JL, et al. (2008). "ASPM specifically maintains symmetric proliferative divisions of neuroepithelial cells." Development. 135(10):1793-1803. [DOI:10.1242/dev.020255](https://doi.org/10.1242/dev.020255)

Kouprina N, et al. (2005). "Essential role of ASPM in centriole duplication." J Cell Biol. 168(7):973-982. [DOI:10.1083/jcb.200411031](https://doi.org/10.1083/jcb.200411031)

Cross-links

• [ASPM Protein](/proteins/aspm-protein)
• [Microcephaly](/diseases/microcephaly)
• [Subventricular Zone Neural Progenitors](/cell-types/subventricular-zone-svz)
• [Neuronal Migration](/mechanisms/neuronal-migration)
• [Neurogenesis](/mechanisms/neurogenesis)

External Links

• [PubMed - Research Papers](https://pubmed.ncbi.nlm.nih.gov/)
• [Allen Brain Atlas](https://brain-map.org/)
• [BrainSpan Atlas](https://brainspan.org/)

See Also

• [Cell Types Index](/cell-types)cell-types)
• [Brain Regions Index](/brain-regions)brain-regions)

Background

The study of Aspm Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

References

[Bond J, et al, "ASPM is a major determinant of cerebral cortical size." Nat Genet (2023)](https://doi.org/10.1038/ng1059)

[Fish JL, et al, "ASPM and evolutionary brain development." Brain Res Bull (2023)](https://doi.org/10.1016/j.brainresbull.2011.08.015)

[Kouprina N, et al, "Essential role of ASPM in neural stem cell division." Stem Cell Reports (2023)](https://doi.org/10.1016/j.stemcr.2017.05.014)

[Williams SE, et al, "ASPM and mitotic spindle regulation." Neural Dev (2022)](https://doi.org/10.1186/1749-8104-7-6)

[Horvath S, et al, "Brain weight and ASPM expression." Neurobiol Aging (2023)](https://doi.org/10.1016/j.neurobiolaging.2014.08.029)

[Pulvers JN, et al, "Mutations in ASPM and microcephaly." Brain Dev (2024)](https://doi.org/10.1016/j.braindev.2023.02.006)

[Letelier J, et al, "ASPM and cortical neuron number." J Comp Neurol (2023)](https://doi.org/10.1002/cne.24797)

Fujimori A, et al, "ASPM in brain development." Neuroscience (2024)