CCR2

CCR2
Available structures
PDBOrtholog search: PDBe RCSB
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 MGI: 106185 HomoloGene: 537 GeneCards: CCR2
Orthologs
Species Human Mouse
Entrez

729230

12772

Ensembl

ENSG00000121807

ENSMUSG00000049103

UniProt

P41597

P51683

RefSeq (mRNA)

NM_001123041
NM_001123396

NM_009915

RefSeq (protein)

NP_001116513.2
NP_001116868.1
NP_001116868.1

NP_034045.1

Location (UCSC) Chr 3: 46.35 – 46.36 Mb Chr 9: 124.1 – 124.11 Mb
PubMed search [1] [2]
Wikidata
View/Edit HumanView/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.[3] 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.[3]

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.[3]

Animal studies

CCR2 deficient mice have been shown to develop an accelerated Alzheimer's-like pathology in comparison to wild type mice.[4][5] This is not the first time that immune function and inflammation have been linked to age-related cognitive decline (i.e. dementia).[6]

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.[7]

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).[8] 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.[4] 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

References

  1. ↑ "Human PubMed Reference:".
  2. ↑ "Mouse PubMed Reference:".
  3. 1 2 3 "Entrez Gene: CCR2 chemokine (C-C motif) receptor 2".
  4. 1 2 El Khoury J, Toft M, Hickman SE, Means TK, Terada K, Geula C, Luster AD (April 2007). "Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease". Nat. Med. 13 (4): 432–8. doi:10.1038/nm1555. PMID 17351623.
  5. ↑ Philipson O, Lord A, Gumucio A, O'Callaghan P, Lannfelt L, Nilsson LN (March 2010). "Animal models of amyloid-beta-related pathologies in Alzheimer's disease". FEBS J. 277 (6): 1389–409. doi:10.1111/j.1742-4658.2010.07564.x. PMID 20136653.
  6. ↑ Gorelick PB (October 2010). "Role of inflammation in cognitive impairment: results of observational epidemiological studies and clinical trials". Ann. N. Y. Acad. Sci. 1207: 155–62. doi:10.1111/j.1749-6632.2010.05726.x. PMID 20955439.
  7. ↑ Bolus, WR; Gutierrez, DA; Kennedy, AJ; Anderson-Baucum, EK; Hasty, AH (October 2015). "CCR2 deficiency leads to increased eosinophils, alternative macrophage activation, and type 2 cytokine expression in adipose tissue.". Journal of leukocyte biology. 98 (4): 467–77. doi:10.1189/jlb.3HI0115-018R. PMC 4763864Freely accessible. PMID 25934927.
  8. ↑ Harries LW, Bradley-Smith RM, Llewellyn DJ, Pilling LC, Fellows A, Henley W, Hernandez D, Guralnik JM, Bandinelli S, Singleton A, Ferrucci L, Melzer D (May 2012). "Leukocyte CCR2 Expression Is Associated with Mini-Mental State Examination Score in Older Adults". Rejuvenation Res. 15 (4): 395–404. doi:10.1089/rej.2011.1302. PMID 22607625.

Further reading

  • Sozzani S, Introna M, Bernasconi S, et al. (1997). "MCP-1 and CCR2 in HIV infection: regulation of agonist and receptor expression". J. Leukoc. Biol. 62 (1): 30–3. PMID 9225989. 
  • Choe H, Martin KA, Farzan M, et al. (1998). "Structural interactions between chemokine receptors, gp120 Env and CD4". Semin. Immunol. 10 (3): 249–57. doi:10.1006/smim.1998.0127. PMID 9653051. 
  • Cunningham AL, Li S, Juarez J, et al. (2000). "The level of HIV infection of macrophages is determined by interaction of viral and host cell genotypes". J. Leukoc. Biol. 68 (3): 311–7. PMID 10985245. 
  • Ruibal-Ares BH, Belmonte L, Baré PC, et al. (2004). "HIV-1 infection and chemokine receptor modulation". Curr. HIV Res. 2 (1): 39–50. doi:10.2174/1570162043484997. PMID 15053339. 
  • Yamagami S, Tokuda Y, Ishii K, et al. (1994). "cDNA cloning and functional expression of a human monocyte chemoattractant protein 1 receptor". Biochem. Biophys. Res. Commun. 202 (2): 1156–62. doi:10.1006/bbrc.1994.2049. PMID 8048929. 
  • Charo IF, Myers SJ, Herman A, et al. (1994). "Molecular cloning and functional expression of two monocyte chemoattractant protein 1 receptors reveals alternative splicing of the carboxyl-terminal tails". Proc. Natl. Acad. Sci. U.S.A. 91 (7): 2752–6. doi:10.1073/pnas.91.7.2752. PMC 43448Freely accessible. PMID 8146186. 
  • Combadiere C, Ahuja SK, Van Damme J, et al. (1996). "Monocyte chemoattractant protein-3 is a functional ligand for CC chemokine receptors 1 and 2B". J. Biol. Chem. 270 (50): 29671–5. doi:10.1074/jbc.270.50.29671. PMID 8530354. 
  • Samson M, Soularue P, Vassart G, Parmentier M (1997). "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. doi:10.1006/geno.1996.0498. PMID 8884276. 
  • Wong LM, Myers SJ, Tsou CL, et al. (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". J. Biol. Chem. 272 (2): 1038–45. doi:10.1074/jbc.272.2.1038. PMID 8995400. 
  • Polentarutti N, Allavena P, Bianchi G, et al. (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". J. Immunol. 158 (6): 2689–94. PMID 9058802. 
  • Gong X, Gong W, Kuhns DB, et al. (1997). "Monocyte chemotactic protein-2 (MCP-2) uses CCR1 and CCR2B as its functional receptors". J. Biol. Chem. 272 (18): 11682–5. doi:10.1074/jbc.272.18.11682. PMID 9115216. 
  • Daugherty BL, Springer MS (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. doi:10.1006/geno.1997.4626. PMID 9143512. 
  • Berkhout TA, Sarau HM, Moores K, et al. (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". J. Biol. Chem. 272 (26): 16404–13. doi:10.1074/jbc.272.26.16404. PMID 9195948. 
  • Smith MW, Dean M, Carrington M, et al. (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. doi:10.1126/science.277.5328.959. PMID 9252328. 
  • Monteclaro FS, Charo IF (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". J. Biol. Chem. 272 (37): 23186–90. doi:10.1074/jbc.272.37.23186. PMID 9287323. 
  • Aragay AM, Mellado M, Frade JM, et al. (1998). "Monocyte chemoattractant protein-1-induced CCR2B receptor desensitization mediated by the G protein-coupled receptor kinase 2". Proc. Natl. Acad. Sci. U.S.A. 95 (6): 2985–90. doi:10.1073/pnas.95.6.2985. PMC 19681Freely accessible. PMID 9501202. 
  • Frade JM, Mellado M, del Real G, et al. (1998). "Characterization of the CCR2 chemokine receptor: functional CCR2 receptor expression in B cells". J. Immunol. 159 (11): 5576–84. PMID 9548499. 
  • Mummidi S, Ahuja SS, Gonzalez E, et al. (1999). "Genealogy of the CCR5 locus and chemokine system gene variants associated with altered rates of HIV-1 disease progression". Nat. Med. 4 (7): 786–93. doi:10.1038/nm0798-786. PMID 9662369. 

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