IBA1 Protein

IBA1 Protein

title: IBA1 Protein
description: Ionized calcium-binding adapter molecule 1, microglial activation marker, actin cytoskeleton regulation
<div class="infobox infobox-protein">
<table>
<tr><th colspan="2">IBA1 Protein</th></tr>
<tr><td><strong>Symbol</strong></td><td>IBA1 / AIF1</td></tr>
<tr><td><strong>Full Name</strong></td><td>Ionized Calcium-Binding Adapter Molecule 1</td></tr>
<tr><td><strong>Gene</strong></td><td>[AIF1](/genes/aif1) (Allograft Inflammatory Factor 1)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[P55008](https://www.uniprot.org/uniprotkb/P55008)</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>17.0 kDa</td></tr>
<tr><td><strong>Length</strong></td><td>147 amino acids</td></tr>
<tr><td><strong>Subcellular Location</strong></td><td>Cytoplasm, associated with actin filaments</td></tr>
<tr><td><strong>PDB Structures</strong></td><td>[2D58](https://www.rcsb.org/structure/2D58)</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [Multiple Sclerosis](/diseases/multiple-sclerosis)</td></tr>
</table>
</div>

Overview

--- is a protein encoded by the [AIF1](/genes/aif1) gene that ### Microglial Marker. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.

Structure

IBA1 is a 17 kDa calcium-binding protein that belongs to the EF-hand protein family:

...

IBA1 Protein

title: IBA1 Protein
description: Ionized calcium-binding adapter molecule 1, microglial activation marker, actin cytoskeleton regulation
<div class="infobox infobox-protein">
<table>
<tr><th colspan="2">IBA1 Protein</th></tr>
<tr><td><strong>Symbol</strong></td><td>IBA1 / AIF1</td></tr>
<tr><td><strong>Full Name</strong></td><td>Ionized Calcium-Binding Adapter Molecule 1</td></tr>
<tr><td><strong>Gene</strong></td><td>[AIF1](/genes/aif1) (Allograft Inflammatory Factor 1)</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[P55008](https://www.uniprot.org/uniprotkb/P55008)</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>17.0 kDa</td></tr>
<tr><td><strong>Length</strong></td><td>147 amino acids</td></tr>
<tr><td><strong>Subcellular Location</strong></td><td>Cytoplasm, associated with actin filaments</td></tr>
<tr><td><strong>PDB Structures</strong></td><td>[2D58](https://www.rcsb.org/structure/2D58)</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [Multiple Sclerosis](/diseases/multiple-sclerosis)</td></tr>
</table>
</div>

Overview

--- is a protein encoded by the [AIF1](/genes/aif1) gene that ### Microglial Marker. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.

Structure

IBA1 is a 17 kDa calcium-binding protein that belongs to the EF-hand protein family:

Domain Architecture

• Two EF-hand motifs (residues 40-71 and 87-118): Calcium-binding domains
• N-terminal region (residues 1-39): Contains basic residues for actin interaction
• C-terminal region (residues 119-147): Involved in protein-protein interactions

Calcium Binding

• Binds two calcium ions with micromolar affinity
• Calcium binding induces conformational changes exposing hydrophobic surfaces
• Calcium-bound form shows enhanced actin-bundling activity

Normal Function

Microglial Marker

IBA1 is one of the most reliable markers for [microglia](/cell-types/microglia-neuroinflammation) in the CNS:

Specific Expression: Expressed almost exclusively in microglia and macrophages

Constitutive Expression: Present in both resting and activated microglia

Upregulation: Significantly increased upon microglial activation

Actin Cytoskeleton Regulation

• Actin bundling: Crosslinks actin filaments into bundles
• Membrane ruffling: Required for formation of membrane ruffles and lamellipodia
• Motility: Essential for microglial migration and chemotaxis
• Phagocytosis: Participates in phagocytic cup formation

Immunological Functions

• Antigen presentation: Associated with MHC class II expression
• Inflammatory signaling: Modulates cytokine production
• Pathogen recognition: Participates in innate immune responses

Role in Neurodegeneration

Alzheimer's Disease

IBA1 is a critical marker and mediator of microglial activation in AD:

Plaque-associated microglia: IBA1-positive microglia cluster around amyloid plaques

Disease stage correlation: IBA1 expression increases with disease progression

Neuroinflammation: Elevated IBA1 correlates with pro-inflammatory cytokine release

Phagocytic activity: IBA1+ microglia show altered [Aβ](/proteins/amyloid-beta) phagocytosis capacity

Parkinson's Disease

• [Alpha-synuclein](/proteins/alpha-synuclein) response: IBA1 expression increases in response to α-synuclein aggregates
• Dopaminergic neurodegeneration: IBA1+ microglia activated around dying [neurons](/entities/neurons)
• Inflammatory amplification: Contributes to neuroinflammatory cascade in PD

Multiple Sclerosis

• Lesion activity: IBA1 marks active MS lesions
• Demyelination: IBA1+ microglia participate in myelin stripping
• Disease monitoring: CSF IBA1 levels correlate with disease activity

ALS

• Motor neuron degeneration: IBA1+ microglia activated around degenerating motor neurons
• [TDP-43](/mechanisms/tdp-43-proteinopathy) pathology: Microglial activation correlates with TDP-43 pathology
• SOD1 models: Robust IBA1 upregulation in SOD1 mutant models

Traumatic Brain Injury

• Acute activation: Rapid IBA1 upregulation following TBI
• Chronic neuroinflammation: Sustained IBA1 elevation in chronic traumatic encephalopathy
• Phagocytic response: IBA1+ microglia clear cellular debris

Molecular Mechanisms

Actin Cytoskeleton Dynamics

| Process | IBA1 Function | Consequence |
|---------|---------------|-------------|
| Filament bundling | Crosslinks F-actin | Membrane protrusion |
| Rac signaling | Interacts with Rac | Lamellipodia formation |
| Calcium sensing | EF-hand binding | Activity modulation |

Signaling Pathways

• Rac1/PAK pathway: IBA1 interacts with Rac GTPase signaling
• MAPK activation: Contributes to ERK/JNK signaling cascades
• [NF-κB](/entities/nf-kb) modulation: Influences inflammatory transcription

Calcium-Dependent Functions

• Calcium binding enhances actin-bundling activity
• Calcium levels modulate IBA1 subcellular localization
• Calcium transients during microglial activation affect IBA1 function

Therapeutic Targeting

Anti-Inflammatory Approaches

• IBA1 inhibitors: Small molecules that reduce IBA1 expression/activity
• Microglial modulators: Compounds that shift IBA1+ microglia to anti-inflammatory states

Biomarker Applications

• PET imaging: Developing IBA1-targeted PET tracers for microglial imaging
• CSF/serum levels: IBA1 as biomarker for neuroinflammation
• Post-mortem analysis: IBA1 immunohistochemistry standard for microglial assessment

Key Interactions

| Interacting Protein | Function | Disease Relevance |
|-------------------|----------|-------------------|
| Actin | Cytoskeletal bundling | Migration, phagocytosis |
| Rac1 | GTPase signaling | Process extension |
| [LRP1](/proteins/lrp1) | Receptor signaling | AD pathology |
| P2RY12 | Homeostatic signaling | Microglial surveillance |

See Also

• [AIF1 Gene](/genes/aif1)
• [Microglia](/cell-types/microglia)
• [Neuroinflammation](/mechanisms/neuroinflammation)
• [TREM2](/proteins/trem2)
• [P2RY12](/proteins/p2ry12)

External Links

• [UniProt: P55008](https://www.uniprot.org/uniprotkb/P55008)
• [NCBI Gene: 199](https://www.ncbi.nlm.nih.gov/gene/199)
• [Allen Brain Atlas: AIF1](https://celltypes.brain-map.org/rnaseq/human_v1)

References

[Ohsawa et al., IBA1 is an actin-crosslinking protein in microglia (2004) (2004)](https://doi.org/10.1111/j.1365-2990.2004.00626.x)

[Ito et al., IBA1 expression in neurodegenerative diseases (2018) (2018)](https://doi.org/10.1016/j.neuint.2018.03.007)

[Sasaki et al., Microglial IBA1 and disease (2020) (2020)](https://doi.org/10.3390/cells9102199)

[Streit et al., Dystrophic microglia in AD show altered IBA1 (2009) (2009)](https://doi.org/10.1016/j.neurobiolaging.2008.06.018)

[Hopperton et al., Microglial markers in AD (2018) (2018)](https://doi.org/10.1016/j.pneurobio.2018.01.003)

[Kettenmann et al., Microglia in health and disease (2013) (2013)](https://doi.org/10.1038/nrn.2013.11)

[Masuda et al., Microglial diversity in health and disease (2020) (2020)](https://doi.org/10.1038/s41586-020-2479-8)

[Paolicelli et al., Synaptic pruning by microglia (2011) (2011)](https://doi.org/10.1126/science.1202529)

[Zhang et al., IBA1 as biomarker in neurological disorders (2021) (2021)](https://doi.org/10.3389/fncel.2021.752727)

[Unknown, Saijo and Glass, Microglial cell origin and roles (2011) (2011)](https://doi.org/10.1038/nri.2011.11)

Pathway Diagram

Pathway Diagram

The following diagram shows the key molecular relationships involving IBA1 Protein discovered through SciDEX knowledge graph analysis: