IBA1 Protein

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IBA1 Protein

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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 |

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

Mermaid diagram (expand to render)

Pathway Diagram

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

Mermaid diagram (expand to render)

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Related Entities

IBA1

▸Metadataorigin_type: v1_polymorphic_backfill

slug	proteins-iba1
kg_node_id	IBA1
entity_type	protein
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-b577fb32911e
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'proteins-iba1'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

100%

Debates

0

Incoming

55

Outgoing

88

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

IBA1 Protein

IBA1 Protein

Overview

Structure

IBA1 Protein

Overview

Structure

Domain Architecture

Calcium Binding

Normal Function

Microglial Marker

Actin Cytoskeleton Regulation

Immunological Functions

Role in Neurodegeneration

Alzheimer's Disease

Parkinson's Disease

Multiple Sclerosis

ALS

Traumatic Brain Injury

Molecular Mechanisms

Actin Cytoskeleton Dynamics

Signaling Pathways

Calcium-Dependent Functions

Therapeutic Targeting

Anti-Inflammatory Approaches

Biomarker Applications

Key Interactions

See Also

External Links

References

Pathway Diagram

Pathway Diagram

💬 Discussion