CCR2

CCR2
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

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

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C-C chemokine receptor type 2 (CCR2 or CD192 (

.

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

deposition (a core feature of Alzheimer's disease progression).

See also

• CC chemokine receptors
• Cluster of differentiation

References

Further reading

• Sozzani S, Introna M, Bernasconi S, Polentarutti N, Cinque P, Poli G, Sica A, Mantovani A (July 1997). "MCP-1 and CCR2 in HIV infection: regulation of agonist and receptor expression". Journal of Leukocyte Biology. 62 (1): 30–3.
  S2CID 2441407
  .
• Choe H, Martin KA, Farzan M, Sodroski J, Gerard NP, Gerard C (June 1998). "Structural interactions between chemokine receptors, gp120 Env and CD4". Seminars in Immunology. 10 (3): 249–57.
  PMID 9653051
  .
• Cunningham AL, Li S, Juarez J, Lynch G, Alali M, Naif H (September 2000). "The level of HIV infection of macrophages is determined by interaction of viral and host cell genotypes". Journal of Leukocyte Biology. 68 (3): 311–7.
  S2CID 38354228
  .
• Ruibal-Ares BH, Belmonte L, Baré PC, Parodi CM, Massud I, de Bracco MM (January 2004). "HIV-1 infection and chemokine receptor modulation". Current HIV Research. 2 (1): 39–50.
  PMID 15053339
  .
• Yamagami S, Tokuda Y, Ishii K, Tanaka H, Endo N (July 1994). "cDNA cloning and functional expression of a human monocyte chemoattractant protein 1 receptor". Biochemical and Biophysical Research Communications. 202 (2): 1156–62.
  PMID 8048929
  .
• Charo IF, Myers SJ, Herman A, Franci C, Connolly AJ, Coughlin SR (March 1994). "Molecular cloning and functional expression of two monocyte chemoattractant protein 1 receptors reveals alternative splicing of the carboxyl-terminal tails". Proceedings of the National Academy of Sciences of the United States of America. 91 (7): 2752–6.
  PMID 8146186
  .
• Combadiere C, Ahuja SK, Van Damme J, Tiffany HL, Gao JL, Murphy PM (December 1995). "Monocyte chemoattractant protein-3 is a functional ligand for CC chemokine receptors 1 and 2B". The Journal of Biological Chemistry. 270 (50): 29671–5.
  PMID 8530354
  .
• Samson M, Soularue P, Vassart G, Parmentier M (September 1996). "The genes encoding the human CC-chemokine receptors CC-CKR1 to CC-CKR5 (CMKBR1-CMKBR5) are clustered in the p21.3-p24 region of chromosome 3". Genomics. 36 (3): 522–6.
  PMID 8884276
  .
• Wong LM, Myers SJ, Tsou CL, Gosling J, Arai H, Charo IF (January 1997). "Organization and differential expression of the human monocyte chemoattractant protein 1 receptor gene. Evidence for the role of the carboxyl-terminal tail in receptor trafficking". The Journal of Biological Chemistry. 272 (2): 1038–45.
  PMID 8995400
  .
• Polentarutti N, Allavena P, Bianchi G, Giardina G, Basile A, Sozzani S, Mantovani A, Introna M (March 1997). "IL-2-regulated expression of the monocyte chemotactic protein-1 receptor (CCR2) in human NK cells: characterization of a predominant 3.4-kilobase transcript containing CCR2B and CCR2A sequences". Journal of Immunology. 158 (6): 2689–94.
  S2CID 24232430
  .
• Li Q, Lan X, Han X, Wang J (January 2019). "Expression of Tmem119/Sall1 and Ccr2/CD69 in FACS-Sorted Microglia- and Monocyte/Macrophage-Enriched Cell Populations After Intracerebral Hemorrhage". Front Cell Neurosci. 12: 520.
  PMID 30687011
  .
• Gong X, Gong W, Kuhns DB, Ben-Baruch A, Howard OM, Wang JM (May 1997). "Monocyte chemotactic protein-2 (MCP-2) uses CCR1 and CCR2B as its functional receptors". The Journal of Biological Chemistry. 272 (18): 11682–5.
  PMID 9115216
  .
• Daugherty BL, Springer MS (April 1997). "The beta-chemokine receptor genes CCR1 (CMKBR1), CCR2 (CMKBR2), and CCR3 (CMKBR3) cluster within 285 kb on human chromosome 3p21". Genomics. 41 (2): 294–5.
  PMID 9143512
  .
• Berkhout TA, Sarau HM, Moores K, White JR, Elshourbagy N, Appelbaum E, Reape RJ, Brawner M, Makwana J, Foley JJ, Schmidt DB, Imburgia C, McNulty D, Matthews J, O'Donnell K, O'Shannessy D, Scott M, Groot PH, Macphee C (June 1997). "Cloning, in vitro expression, and functional characterization of a novel human CC chemokine of the monocyte chemotactic protein (MCP) family (MCP-4) that binds and signals through the CC chemokine receptor 2B". The Journal of Biological Chemistry. 272 (26): 16404–13.
  PMID 9195948
  .
• Smith MW, Dean M, Carrington M, Winkler C, Huttley GA, Lomb DA, Goedert JJ, O'Brien TR, Jacobson LP, Kaslow R, Buchbinder S, Vittinghoff E, Vlahov D, Hoots K, Hilgartner MW, O'Brien SJ (August 1997). "Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study". Science. 277 (5328): 959–65.
  PMID 9252328
  .
• Monteclaro FS, Charo IF (September 1997). "The amino-terminal domain of CCR2 is both necessary and sufficient for high affinity binding of monocyte chemoattractant protein 1. Receptor activation by a pseudo-tethered ligand". The Journal of Biological Chemistry. 272 (37): 23186–90.
  PMID 9287323
  .
• Aragay AM, Mellado M, Frade JM, Martin AM, Jimenez-Sainz MC, Martinez-A C, Mayor F (March 1998). "Monocyte chemoattractant protein-1-induced CCR2B receptor desensitization mediated by the G protein-coupled receptor kinase 2". Proceedings of the National Academy of Sciences of the United States of America. 95 (6): 2985–90.
  PMID 9501202
  .
• Frade JM, Mellado M, del Real G, Gutierrez-Ramos JC, Lind P, Martinez-A C (December 1997). "Characterization of the CCR2 chemokine receptor: functional CCR2 receptor expression in B cells". Journal of Immunology. 159 (11): 5576–84.
  PMID 9548499
  .
• Mummidi S, Ahuja SS, Gonzalez E, Anderson SA, Santiago EN, Stephan KT, Craig FE, O'Connell P, Tryon V, Clark RA, Dolan MJ, Ahuja SK (July 1998). "Genealogy of the CCR5 locus and chemokine system gene variants associated with altered rates of HIV-1 disease progression". Nature Medicine. 4 (7): 786–93.
  S2CID 30305043
  .

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.