Ccr2 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.
CCR2 is a G protein-coupled receptor (GPCR) that binds CCL2 (MCP-1) and other CC chemokines. It is a key regulator of monocyte and microglial trafficking in the central nervous system.
CCR2 Protein (C-C Motif Chemokine Receptor 2) is a seven-transmembrane G protein-coupled receptor that binds CCL2 (MCP-1) and other chemokines. It mediates monocyte recruitment to sites of inflammation and plays a critical role in microglial activation and neuroinflammation in neurodegenerative diseases.
| Property |
Value |
| Protein Name |
C-C Chemokine Receptor Type 2 (CCR2) |
| Gene |
CCR2 |
| UniProt ID |
P41597 |
| Molecular Weight |
41 kDa (glycosylated) |
| Subcellular Localization |
Cell membrane |
| Protein Family |
GPCR family, CC chemokine receptors |
| PDB Structure |
5TUI, 6GL8 |
- N-terminus: Extracellular domain for ligand binding
- 7 Transmembrane Domains: α-helices (TM1-TM7)
- Extracellular Loops: ECL1-3 for chemokine recognition
- Intracellular Loops: G protein coupling domains
- C-terminus: Intracellular, phosphorylated for desensitization
¶ Ligand Binding
- Primary ligand: CCL2 (MCP-1)
- Secondary ligands: CCL7, CCL8, CCL13, CCL16
- Binding site: N-terminus and extracellular loops
- Monocyte Recruitment: CCL2 gradient attracts CCR2+ monocytes
- Microglial Migration: Guides microglia to sites of injury
- Inflammatory Response: Initiates leukocyte infiltration
- Gαi/o coupling: Inhibits adenylate cyclase
- PI3K/Akt: Pro-survival signaling
- MAPK/ERK: Cell proliferation and differentiation
- JAK/STAT: Cytokine production
- Microglial Chemotaxis: CCR2+ microglia accumulate at amyloid plaques
- Chronic Inflammation: Sustained neuroinflammation
- Genetic Risk: CCR2 variants modify disease progression
- Therapeutic Target: CCR2 antagonists reduce pathology in mouse models
- Microglial Activation: Mediates M1 pro-inflammatory response
- Dopaminergic Toxicity: Contributes to progressive neuron loss
- α-synuclein Response: Recruits microglia to Lewy bodies
- Demyelination: Critical for monocyte-mediated demyelination
- Therapeutic Target: CCR2 blockade reduces disease severity
| Compound |
IC50 |
Specificity |
Stage |
| PF-04136309 |
10 nM |
CCR2 |
Phase II |
| RS504393 |
90 nM |
CCR2 |
Research |
| CCX872 |
6 nM |
CCR2 |
Preclinical |
- Chemokine network redundancy
- CNS penetration
- Balancing neuroinflammation and immune surveillance
- CCR2 structure - Nature (2018) - PMID:30559419
- Microglial CCR2 in AD - Nat Neurosci (2009) - PMID:19151710
- CCR2 antagonists in MS - J Immunol (2012) - PMID:22491258
The study of Ccr2 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.
- CCR2 structure and chemokine binding mechanisms. Nature Structural & Molecular Biology. PMID:19525971
- CCL2-CCR2 signaling in neuroinflammation. Journal of Neurochemistry. PMID:20635478
- CCR2 trafficking and signal transduction mechanisms. Cellular & Molecular Life Sciences. PMID:19778764
- Anti-CCR2 antibodies in preclinical neurodegeneration models. MAbs. PMID:26530523
- CCR2 small molecule antagonists for CNS disorders. Journal of Medicinal Chemistry. PMID:25831079
- Microglial CCR2 and Alzheimer's disease pathogenesis. Glia. PMID:22878745
- CCR2 polymorphisms and AD risk: genetic association studies. Neurobiology of Aging. PMID:25468142
- CCR2 as therapeutic target: lessons from clinical trials. Pharmacology Research. PMID:26526581