CCR2 Gene (C-C Motif Chemokine Receptor 2): Function, Expression, and Disease Associations
Comprehensive biomedical overview of the CCR2 gene, including genomic context, protein function, tissue expression, and clinical significance.
Gene Information Card
| Symbol | CCR2 |
|---|---|
| Full Name | C-C motif chemokine receptor 2 |
| Gene Type | protein coding |
| Chromosomal Location | 3p21.31 |
| NCBI Gene ID | 729230 ncbi.nlm.nih.gov/gene/729230 |
| Ensembl ID | ENSG00000121807 |
| UniProt ID | P41597 |
| OMIM ID | 601267 |
| HGNC ID | 1603 |
| Aliases | CD192, CKR2, CCR2A, CCR2B, CMKBR2, CC-CKR-2, MCP-1 receptor |
Description
The CCR2 gene encodes the C-C motif chemokine receptor 2, a G protein-coupled receptor (GPCR) that is primarily expressed on the surface of monocytes, macrophages, and other immune cells. It is the principal receptor for monocyte chemoattractant protein-1 (MCP-1/CCL2) and several other chemokines, including CCL7, CCL8, CCL13, and CCL16. CCR2 plays a critical role in the recruitment of monocytes to sites of inflammation, tissue injury, and infection. It is involved in various physiological processes, including immune surveillance, inflammation, and wound healing. Dysregulation of CCR2 signaling is implicated in a range of diseases, including atherosclerosis, multiple sclerosis, insulin resistance, and cancer. The gene produces two isoforms, CCR2A and CCR2B, through alternative splicing, which differ in their C-terminal tails and have distinct signaling properties.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Atherosclerosis | CCR2 mediates monocyte infiltration into the arterial wall, promoting plaque formation and progression. CCR2 deficiency in mouse models reduces atherosclerotic lesion size. | Mouse models (e.g., CCR2 knockout in ApoE-/- mice) show reduced atherosclerosis. Human studies show increased CCR2 expression in atherosclerotic plaques. |
| Multiple Sclerosis (MS) | CCR2 is involved in the recruitment of inflammatory monocytes into the central nervous system, contributing to demyelination and neuroinflammation. | Elevated CCR2 expression on peripheral blood monocytes in MS patients. CCR2 antagonists have shown efficacy in experimental autoimmune encephalomyelitis (EAE) models. |
| Insulin Resistance / Type 2 Diabetes | CCR2-mediated macrophage infiltration into adipose tissue and liver contributes to chronic low-grade inflammation, a key driver of insulin resistance. | Increased CCR2 expression in adipose tissue of obese individuals. CCR2 antagonist treatment improves insulin sensitivity in mouse models of diet-induced obesity. |
| Rheumatoid Arthritis (RA) | CCR2 promotes the recruitment of monocytes/macrophages to the inflamed synovium, contributing to joint destruction. | Elevated levels of CCL2 (the ligand for CCR2) in synovial fluid of RA patients. CCR2-positive cells are found in the inflamed synovium. |
| Cancer (various) | CCR2 expression on tumor-associated macrophages (TAMs) and tumor cells can promote tumor growth, angiogenesis, and metastasis by recruiting immunosuppressive cells. | CCR2 expression correlates with poor prognosis in several cancers (e.g., breast, pancreatic, gastric). CCR2 blockade reduces tumor growth and metastasis in preclinical models. |
| HIV Infection | CCR2 acts as a co-receptor for some strains of HIV-1 (R5-tropic viruses), facilitating viral entry into CD4+ T cells and macrophages. | A common CCR2 variant (CCR2-V64I) is associated with delayed progression to AIDS, possibly due to altered receptor function. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Blood | High (nTPM ~ 50-100) | High expression in monocytes and other immune cells. |
| Spleen | Medium (nTPM ~ 10-20) | Expression in splenic macrophages and dendritic cells. |
| Bone Marrow | Medium (nTPM ~ 10-20) | Expression in myeloid progenitor cells and monocytes. |
| Lung | Low (nTPM ~ 5-10) | Expression in alveolar macrophages. |
| Liver | Low (nTPM ~ 1-5) | Expression in Kupffer cells (liver macrophages). |
| Brain | Low (nTPM ~ 1-5) | Expression in microglia. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocytic leukemia) | High | Monocytic cell line with high CCR2 expression. |
| U937 (histiocytic lymphoma) | High | Monocytic cell line with high CCR2 expression. |
| HL-60 (promyelocytic leukemia) | Medium | Can be induced to express CCR2 upon differentiation. |
| Jurkat (T cell leukemia) | Low | Low CCR2 expression. |
| HeLa (cervical cancer) | Low | Low CCR2 expression. |
| A549 (lung carcinoma) | Low | Low CCR2 expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| V64I (rs1799864) | SNP (missense) | ~10-20% in various populations | Isoleucine to valine substitution in transmembrane domain 2. Associated with delayed progression to AIDS. May alter receptor signaling or trafficking. |
| A38T (rs1799865) | SNP (missense) | Rare | Alanine to threonine substitution. Functional significance is unclear. |
| R335C | SNP (missense) | Rare | Arginine to cysteine substitution in the C-terminal tail. May affect receptor internalization or signaling. |
| G174A | SNP (missense) | Rare | Glycine to alanine substitution. Functional significance is unclear. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in CCR2 are rare. The V64I variant has been suggested to have reduced function in some assays, potentially contributing to its protective effect in HIV infection. Complete loss of CCR2 function in humans is not well-documented, but knockout mouse models show impaired monocyte migration and reduced inflammation.
Gain of Function (GOF)
No clear gain-of-function mutations have been identified for CCR2. Some variants may alter receptor expression or signaling, but none have been definitively shown to increase receptor activity.
Dominant Negative (DN)
No dominant-negative mutations have been described for CCR2. Since CCR2 functions as a monomer or possibly a dimer, a dominant-negative effect would require a mutant subunit to interfere with the wild-type receptor's function, which has not been reported.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • C-C chemokine receptor activity |
| • C-C chemokine binding | • signal transducer activity |
| • plasma membrane | • integral component of plasma membrane |
| • cell surface | • chemokine-mediated signaling pathway |
| • cell chemotaxis | • inflammatory response |
| • immune response | • positive regulation of cytosolic calcium ion concentration |
| • receptor internalization |
Pathways
• Chemokine signaling pathway (KEGG: hsa04062)
• Cytokine-cytokine receptor interaction (KEGG: hsa04060)
• HIF-1 signaling pathway (KEGG: hsa04066)
• Toll-like receptor signaling pathway (KEGG: hsa04620)
• PI3K-Akt signaling pathway (KEGG: hsa04151)
• MAPK signaling pathway (KEGG: hsa04010)
Protein Summary
CCR2 is a 7-transmembrane G protein-coupled receptor (GPCR) of 374 amino acids (isoform B). It is a class A (rhodopsin-like) GPCR. Upon binding its primary ligand CCL2 (MCP-1), CCR2 undergoes a conformational change that activates heterotrimeric G proteins, primarily of the Gi/o family. This leads to inhibition of adenylyl cyclase, activation of phospholipase C (PLC), and subsequent increases in intracellular calcium and activation of downstream signaling pathways such as PI3K/Akt and MAPK/ERK. These signaling cascades promote cell migration, actin polymerization, and integrin activation, which are essential for monocyte chemotaxis. CCR2 also undergoes ligand-dependent internalization via clathrin-coated pits, which is important for receptor desensitization and signaling regulation. The receptor is a key mediator of monocyte egress from the bone marrow and their recruitment to inflamed tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CCR2 Knockout HEK293 Cell Line | EDJ-KQ442 | Human | 729230 | Details Get a Quote |
| CCR2 Knockout HeLa Cell Line | EDJ-KQ60735 | Human | 729230 | Details Get a Quote |
| CCR2 Knockout A-549 Cell Line | EDJ-KQ69205 | Human | 729230 | Details Get a Quote |
| CCR2 Knockout HCT 116 Cell Line | EDJ-KQ77562 | Human | 729230 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
