CCR2

Chemokine (C-C motif) receptor 2
Rendering based on PDB 1KAD.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1KAD, 1KP1
Identifiers
Symbols	CCR2 ; CC-CKR-2; CCR-2; CCR2A; CCR2B; CD192; CKR2; CKR2A; CKR2B; CMKBR2; MCP-1-R
External IDs	OMIM: 601267 MGI: 106185 HomoloGene: 537 IUPHAR: 59 GeneCards: CCR2 Gene
Gene ontology Molecular function • chemokine receptor activity • C-C chemokine receptor activity • CCR2 chemokine receptor binding • protein homodimerization activity Cellular component • cytoplasm • cytosol • plasma membrane • integral component of plasma membrane • integral component of membrane • dendrite • neuronal cell body • perikaryon • perinuclear region of cytoplasm Biological process • blood vessel remodeling • dendritic cell chemotaxis • positive regulation of T-helper 1 type immune response • negative regulation of type 2 immune response • cellular calcium ion homeostasis • chemotaxis • inflammatory response • immune response • cellular defense response • G-protein coupled receptor signaling pathway • negative regulation of adenylate cyclase activity • positive regulation of cytosolic calcium ion concentration • JAK-STAT cascade • response to wounding • regulation of vascular endothelial growth factor production • positive regulation of T cell chemotaxis • viral process • negative regulation of angiogenesis • cytokine-mediated signaling pathway • cellular homeostasis • positive regulation of interferon-gamma production • positive regulation of interleukin-2 production • T-helper 17 cell chemotaxis • positive regulation of tumor necrosis factor biosynthetic process • negative regulation of eosinophil degranulation • innate immune response • positive regulation of alpha-beta T cell proliferation • positive regulation of inflammatory response • positive regulation of T cell activation • chemokine-mediated signaling pathway • positive regulation of monocyte chemotaxis • positive regulation of immune complex clearance by monocytes and macrophages • positive regulation of monocyte extravasation • positive regulation of CD8-positive, alpha-beta T cell extravasation • positive regulation of astrocyte chemotaxis • positive regulation of hematopoietic stem cell migration Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	729230	12772
Ensembl	ENSG00000121807	ENSMUSG00000049103
UniProt	P41597	P51683
RefSeq (mRNA)	NM_001123041	NM_009915
RefSeq (protein)	NP_001116513	NP_034045
Location (UCSC)	Chr 3: 46.35 – 46.36 Mb	Chr 9: 124.1 – 124.11 Mb
PubMed search	[1]	[2]

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. CCR2 is a 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.

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.

Animal studies

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

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). 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. 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

External links

• CCR2 protein, human at the US 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.