CCR2

CCR2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1KAD, 1KP1
Identifiers
Aliases	CCR2, CC-CKR-2, CCR-2, CCR2A, CCR2B, CD192, CKR2, CKR2A, CKR2B, CMKBR2, MCP-1-R, C-C motif chemokine receptor 2
External IDs	OMIM: 601267 MGI: 106185 HomoloGene: 537 GeneCards: CCR2
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3p21.31 Start 46,353,864 bp[1] End 46,360,940 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9 F4|9 75.05 cM Start 123,901,987 bp[2] End 123,913,594 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte blood bone marrow cells appendix spleen lymph node spongy bone parietal pleura rectum gallbladder Top expressed in blood ankle intercostal muscle body of femur bone marrow ankle joint subcutaneous adipose tissue spleen submandibular gland sciatic nerve More reference expression data BioGPS n/a
Gene ontology Molecular function CCR2 chemokine receptor binding G protein-coupled receptor activity protein homodimerization activity signal transducer activity chemokine receptor activity C-C chemokine receptor activity protein binding cytokine binding chemokine (C-C motif) ligand 2 binding chemokine (C-C motif) ligand 12 binding chemokine (C-C motif) ligand 7 binding chemokine binding C-C chemokine binding Cellular component integral component of membrane perikaryon membrane plasma membrane integral component of plasma membrane neuronal cell body dendrite perinuclear region of cytoplasm cytoplasm cytosol external side of plasma membrane Biological process negative regulation of adenylate cyclase activity receptor signaling pathway via JAK-STAT chemokine-mediated signaling pathway cellular calcium ion homeostasis positive regulation of monocyte chemotaxis dendritic cell chemotaxis chemotaxis blood vessel remodeling response to wounding immune response inflammatory response viral process positive regulation of astrocyte chemotaxis signal transduction positive regulation of cytosolic calcium ion concentration G protein-coupled receptor signaling pathway monocyte chemotaxis positive regulation of T-helper 1 type immune response negative regulation of type 2 immune response humoral immune response cellular defense response regulation of vascular endothelial growth factor production positive regulation of T cell chemotaxis negative regulation of angiogenesis sensory perception of pain cellular homeostasis regulation of cell migration positive regulation of interferon-gamma production positive regulation of interleukin-2 production T-helper 17 cell chemotaxis negative regulation of eosinophil degranulation positive regulation of alpha-beta T cell proliferation homeostasis of number of cells within a tissue positive regulation of inflammatory response positive regulation of T cell activation leukocyte adhesion to vascular endothelial cell positive regulation of immune complex clearance by monocytes and macrophages neutrophil clearance positive regulation of leukocyte tethering or rolling positive regulation of monocyte extravasation positive regulation of CD8-positive, alpha-beta T cell extravasation positive regulation of hematopoietic stem cell migration cytokine-mediated signaling pathway hemopoiesis calcium-mediated signaling cell chemotaxis positive regulation of cold-induced thermogenesis regulation of T cell cytokine production monocyte extravasation regulation of T cell differentiation regulation of inflammatory response positive regulation of synaptic transmission, glutamatergic inflammatory response to wounding macrophage migration positive regulation of thymocyte migration positive regulation of NMDA glutamate receptor activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 729230 12772 Ensembl ENSG00000121807 ENSMUSG00000049103 UniProt P41597 P51683 RefSeq (mRNA) NM_001123041 NM_001123396 NM_009915 RefSeq (protein) NP_001116513 NP_001116868 NP_001116868.1 NP_034045 Location (UCSC) Chr 3: 46.35 – 46.36 Mb Chr 9: 123.9 – 123.91 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

C-C chemokine receptor type 2 (CCR2 or CD192 (cluster of differentiation 192) is a protein that in humans is encoded by the CCR2 gene.^[5] CCR2 is a CC chemokine receptor.

Gene

This CCR2 gene is located in the chemokine receptor gene cluster region. Two alternatively spliced transcript variants are expressed by the gene.^[5]

Function

This gene encodes two isoforms of a receptor for monocyte chemoattractant protein-1 (CCL2), a chemokine which specifically mediates monocyte chemotaxis. Monocyte chemoattractant protein-1 is involved in monocyte infiltration in inflammatory diseases such as rheumatoid arthritis as well as in the inflammatory response against tumors. The receptors encoded by this gene mediate agonist-dependent calcium mobilization and inhibition of adenylyl cyclase.^[5]

Animal studies

Alzheimer

CCR2 deficient mice have been shown to develop an accelerated Alzheimer's-like pathology in comparison to wild type mice.^[6][7] This is not the first time that immune function and inflammation have been linked to age-related cognitive decline (i.e. dementia).^[8]

Obesity

Within the fat (adipose) tissue of CCR2 deficient mice, there is an increased number of eosinophils, greater alternative macrophage activation, and a propensity towards type 2 cytokine expression. Furthermore, this effect was exaggerated when the mice became obese from a high fat diet.^[9]

Myocardial Infarct

CCR2 surface expression on blood monocytes changes in a time-of-day–dependent manner (being higher at the beginning of the active phase) and affects monocytes recruitment in tissues including the heart. As a consequence when an acute ischemic event happens during the active phase, monocytes are more susceptible to invade the heart.^[10] An excessive monocytes infiltration generates higher inflammation and increases the risk of heart failure.

Clinical significance

In an observational study of gene expression in blood leukocytes in humans, Harries et al. found evidence of a relationship between expression of CCR2 and cognitive function (assessed using the mini-mental state examination, MMSE).^[11] Higher CCR2 expression was associated with worse performance on the MMSE assessment of cognitive function. The same study found that CCR2 expression was also associated with cognitive decline over 9-years in a sub-analysis on inflammatory related transcripts only. Harries et al. suggest that CCR2 signaling may have a direct role in human cognition, partly because expression of CCR2 was associated with the ApoE haplotype (previously associated with Alzheimer's disease), but also because CCL2 is expressed at high concentrations in macrophages found in atherosclerotic plaques and in brain microglia.^[6] The difference in observations between mice (CCR2 depletion causes cognitive decline) and humans (higher CCR2 associated with lower cognitive function) could be due to increased demand for macrophage activation during cognitive decline, associated with increased β-amyloid deposition (a core feature of Alzheimer's disease progression).

See also

• CC chemokine receptors
• Cluster of differentiation

References

Further reading

External links

• Human CCR2 genome location and CCR2 gene details page in the UCSC Genome Browser.
• "Chemokine Receptors: CCR2". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2008-06-07. Retrieved 2008-11-25.
• CCR2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• description at Information Hyperlinked Over Proteins

This article incorporates text from the United States National Library of Medicine, which is in the public domain.