| IBA1 Protein |
|---|
| Symbol | IBA1 / AIF1 |
| Full Name | Ionized Calcium-Binding Adapter Molecule 1 |
| Gene | [AIF1](/genes/aif1) (Allograft Inflammatory Factor 1) |
| UniProt ID | [P55008](https://www.uniprot.org/uniprotkb/P55008) |
| Molecular Weight | 17.0 kDa |
| Length | 147 amino acids |
| Subcellular Location | Cytoplasm, associated with actin filaments |
| PDB Structures | [2D58](https://www.rcsb.org/structure/2D58) |
| Associated Diseases | [Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [Multiple Sclerosis](/diseases/multiple-sclerosis) |
--- is a protein encoded by the AIF1 gene that ### Microglial Marker. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
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
- Binds two calcium ions with micromolar affinity
- Calcium binding induces conformational changes exposing hydrophobic surfaces
- Calcium-bound form shows enhanced actin-bundling activity
IBA1 is one of the most reliable markers for microglia 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 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
- Antigen presentation: Associated with MHC class II expression
- Inflammatory signaling: Modulates cytokine production
- Pathogen recognition: Participates in innate immune responses
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 phagocytosis capacity
- Alpha-synuclein response: IBA1 expression increases in response to α-synuclein aggregates
- Dopaminergic neurodegeneration: IBA1+ microglia activated around dying neurons
- Inflammatory amplification: Contributes to neuroinflammatory cascade in PD
- Lesion activity: IBA1 marks active MS lesions
- Demyelination: IBA1+ microglia participate in myelin stripping
- Disease monitoring: CSF IBA1 levels correlate with disease activity
- Motor neuron degeneration: IBA1+ microglia activated around degenerating motor neurons
- TDP-43 pathology: Microglial activation correlates with TDP-43 pathology
- SOD1 models: Robust IBA1 upregulation in SOD1 mutant models
- Acute activation: Rapid IBA1 upregulation following TBI
- Chronic neuroinflammation: Sustained IBA1 elevation in chronic traumatic encephalopathy
- Phagocytic response: IBA1+ microglia clear cellular debris
| 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 |
- Rac1/PAK pathway: IBA1 interacts with Rac GTPase signaling
- MAPK activation: Contributes to ERK/JNK signaling cascades
- NF-κB modulation: Influences inflammatory transcription
- Calcium binding enhances actin-bundling activity
- Calcium levels modulate IBA1 subcellular localization
- Calcium transients during microglial activation affect IBA1 function
- IBA1 inhibitors: Small molecules that reduce IBA1 expression/activity
- Microglial modulators: Compounds that shift IBA1+ microglia to anti-inflammatory states
- 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
| Interacting Protein |
Function |
Disease Relevance |
| Actin |
Cytoskeletal bundling |
Migration, phagocytosis |
| Rac1 |
GTPase signaling |
Process extension |
| LRP1 |
Receptor signaling |
AD pathology |
| P2RY12 |
Homeostatic signaling |
Microglial surveillance |