CCL4 Protein
Introduction <table class="infobox infobox-protein"> <tr> <th class="infobox-header" colspan="2">CCL4 Protein</th> </tr> <tr> <td class="label">Protein Name</td> <td>Chemokine C-C Motif Ligand 4</td> </tr> <tr> <td class="label">UniProt ID</td> <td>Q14139</td> </tr> <tr> <td class="label">Gene Symbol</td> <td>CCL4</td> </tr> <tr> <td class="label">Protein Length</td> <td>92 amino acids (precursor), 69 aa (mature)</td> </tr> <tr> <td class="label">Molecular Weight</td> <td>~10 kDa</td> </tr> <tr> <td class="label">Secreted</td> <td>Yes</td> </tr> <tr> <td class="label">Also Known As</td> <td>MIP-1β, ACT-2, LAG-1</td> </tr> <tr> <td class="label">Receptor</td> <td>Affinity</td> </tr> <tr> <td class="label">CCR5</td> <td>High</td> </tr> <tr> <td class="label">CCR8</td> <td>Moderate</td> </tr> <tr> <td class="label">Approach</td> <td>Description</td> </tr> <tr> <td class="label">CCR5 antagonists</td> <td>Maraviroc (approved for HIV)</td> </tr> <tr> <td class="label">CCL4 neutralizing antibodies</td> <td>Block CCL4 activity</td> </tr> <tr> <td class="label">Broad-spectrum modulators</td> <td>Inhibit multiple chemokines</td> </tr> <tr> <td class="label">Associated Diseases</td> <td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/autoimmune" style="color:#ef9a9a">Autoimmune</a>, <a href="/wiki/fibrosis" style="color:#ef9a9a">Fibrosis</a>, <a href="/wiki/huntingt
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CCL4 Protein
Introduction <table class="infobox infobox-protein"> <tr> <th class="infobox-header" colspan="2">CCL4 Protein</th> </tr> <tr> <td class="label">Protein Name</td> <td>Chemokine C-C Motif Ligand 4</td> </tr> <tr> <td class="label">UniProt ID</td> <td>Q14139</td> </tr> <tr> <td class="label">Gene Symbol</td> <td>CCL4</td> </tr> <tr> <td class="label">Protein Length</td> <td>92 amino acids (precursor), 69 aa (mature)</td> </tr> <tr> <td class="label">Molecular Weight</td> <td>~10 kDa</td> </tr> <tr> <td class="label">Secreted</td> <td>Yes</td> </tr> <tr> <td class="label">Also Known As</td> <td>MIP-1β, ACT-2, LAG-1</td> </tr> <tr> <td class="label">Receptor</td> <td>Affinity</td> </tr> <tr> <td class="label">CCR5</td> <td>High</td> </tr> <tr> <td class="label">CCR8</td> <td>Moderate</td> </tr> <tr> <td class="label">Approach</td> <td>Description</td> </tr> <tr> <td class="label">CCR5 antagonists</td> <td>Maraviroc (approved for HIV)</td> </tr> <tr> <td class="label">CCL4 neutralizing antibodies</td> <td>Block CCL4 activity</td> </tr> <tr> <td class="label">Broad-spectrum modulators</td> <td>Inhibit multiple chemokines</td> </tr> <tr> <td class="label">Associated Diseases</td> <td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/autoimmune" style="color:#ef9a9a">Autoimmune</a>, <a href="/wiki/fibrosis" style="color:#ef9a9a">Fibrosis</a>, <a href="/wiki/huntington" style="color:#ef9a9a">Huntington</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a></td> </tr> <tr> <td class="label">KG Connections</td> <td><a href="/atlas" style="color:#4fc3f7">93 edges</a></td> </tr> </table>
Ccl4 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 CCL4 (Chemokine C-C Motif Ligand 4), also known as MIP-1β (Macrophage Inflammatory Protein-1 beta), is a CC chemokine that mediates inflammation and immune cell recruitment. It plays important roles in neuroinflammation associated with neurodegenerative diseases. [@reale2019]
Structure
Signal peptide : 1-23 aa
Mature protein : 24-92 aa
Cys-Cys motif : Positions 33-34 (CC chemokine signature)
Heparin-binding domain : C-terminal region
Molecular Function CCL4 primarily binds to CCR5 and CCR8 receptors to recruit immune cells.
Receptor Interactions:
Role in Neurodegeneration
Alzheimer's Disease
CCL4 protein elevated in AD brain ([hippocampus](/brain-regions/hippocampus), cortex)
Increased in CSF of AD patients
Promotes microglial activation and chemotaxis
Contributes to chronic neuroinflammation
May have role in amyloid plaque association
Parkinson's Disease
CCL4 increased in PD substantia nigra
Attracts [microglia](/cell-types/microglia-neuroinflammation) to dopaminergic [neurons](/entities/neurons)
Contributes to progressive neuroinflammation
CSF levels correlate with disease progression
ALS
CCL4 elevated in ALS spinal cord and CSF
Promotes inflammatory response in motor neuron environment
Attracts activated microglia and macrophages
CCL4 blockade may be therapeutic
HIV-Associated Neurocognitive Disorders
CCL4 elevated due to HIV infection in brain
CCR5 is HIV co-receptor - relevance to HAND
Contributes to chronic neuroinflammation
Therapeutic Targeting
Biomarker Potential
CCL4 levels in CSF: biomarker for neuroinflammation
Blood CCL4: potential peripheral marker for disease progression
Interactions
CCR5 : Primary receptor on macrophages, microglia, T cells
CCR8 : Secondary receptor on Th2 and Treg cells
Proteoglycans : Heparin-binding for gradient formation
Other chemokines : Can form heterodimers (CCL3-CCL4)
Animal Models
Ccl4 knockout mice: Reduced inflammation
Overexpression models: Neuroinflammation phenotype
See Also
[CCL4 Gene](/proteins/ccl4-protein)
[Neuroinflammation Pathway](/mechanisms/neuroinflammation-pathway)
[CCL3 Protein](/proteins/ccl3-protein)
[CCR5 Protein](/proteins/ccr5-protein)
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease)
Background The study of Ccl4 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.
External Links
[PubMed](https://pubmed.ncbi.nlm.nih.gov/) - Biomedical literature
[Alzheimer's Disease Neuroimaging Initiative](https://adni.loni.usc.edu/) - Research data
[Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data
References
Galimberti D, et al, (2020) (2020)
Reale M, et al, (2019) (2019)
Kou W, et al, (2018) (2018)
Draberova L, et al, (2021) (2021)
Ubogu EE, et al, (2020) (2020)
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