CMKLR1

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CMKLR1
Identifiers
Aliases CMKLR1, CHEMERINR, ChemR23, DEZ, RVER1, chemerin chemokine-like receptor 1
External IDs MGI: 109603 HomoloGene: 129967 GeneCards: CMKLR1
RNA expression pattern
PBB GE CMKLR1 207652 s at fs.png

PBB GE CMKLR1 210659 at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_004072
NM_001142343
NM_001142344
NM_001142345

NM_008153

RefSeq (protein)

NP_001135815
NP_001135816
NP_001135817
NP_004063

NP_032179.1
NP_032179

Location (UCSC) Chr 12: 108.29 – 108.34 Mb Chr 5: 113.61 – 113.65 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Chemokine like receptor 1 also known as ChemR23 (Chemerin Receptor 23) is a protein that in humans is encoded by the CMKLR1 gene.[3][4] Chemokine receptor-like 1 is a G protein-coupled receptor for the chemoattractant adipokine chemerin[5] and the omega-3 fatty acid eicosapentaenoic acid-derived specialized pro-resolving molecule, resolvin E1 (see Specialized proresolving mediators#EPA-derived resolvins (i.e. RvE)).[6] The murine receptor that shares almost 80% homology with the human receptor, is called Dez.[7]

Tissue distribution[edit]

CMKLR1 shows wide RNA expression profile but is notably high in plasmacytoid dendritic cells, macrophages, cardiomyocytes, adipocytes and endothelial cells.[8]

Function[edit]

Activating CMKLR1 by an agonist mobilizes intracellular calcium and causes the activation of several other signaling cascades like the ERK1 and NF-κB. Initial studies of CMKLR1 suggested that it might have a role in the inflammatory pathways. Its cognate ligand, chemerin was found in joint aspirate from rheumatoid arthritis and absent in aspirate from degenerative arthritis. CMKLR1 expression by plasmacytoid dendritic cells and macrophages also helped foster this idea. In vitro chemotaxis assays showed it to be utilized in attracting these cells. As an adipokine receptor it has a role in adipogenesis and adipocyte maturation.[9] It seems also to have a role in peripheral insulin resistance.[10]

Also studies using the mouse zymosan model and chemerin peptides showed that these peptides suppressed and helped resolve the peritonitis in mice.[11] The same model showed that this particular molecule enhances macrophage efferocytosis (phagocyting apoptotic cells).[12]

Receptor antagonist CCX832[edit]

CCX832 is an orally active molecule used as a tool compound in experimental pharmacology. It antagonises the effect of CMKLR1.[13][14][15] It is listed on the Guide to Pharmacology database as the only example of a CMKLR1 antagonist. Its chemical structure is undisclosed.[16]

The substance was originally developed for use as a pharmaceutical drug against inflammatory diseases by ChemoCentryx, a pharmaceutical firm based in California, in alliance with GlaxoSmithKline (GSK).[17] Development was terminated after a Phase I clinical trial in 2012.[18]

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ "Entrez Gene: CMKLR1 chemokine-like receptor 1". 
  4. ^ Gantz I, Konda Y, Yang YK, Miller DE, Dierick HA, Yamada T (1996). "Molecular cloning of a novel receptor (CMKLR1) with homology to the chemotactic factor receptors". Cytogenetics and Cell Genetics. 74 (4): 286–90. doi:10.1159/000134436. PMID 8976386. 
  5. ^ Wittamer V, Franssen JD, Vulcano M, Mirjolet JF, Le Poul E, Migeotte I, Brézillon S, Tyldesley R, Blanpain C, Detheux M, Mantovani A, Sozzani S, Vassart G, Parmentier M, Communi D (October 2003). "Specific recruitment of antigen-presenting cells by chemerin, a novel processed ligand from human inflammatory fluids". The Journal of Experimental Medicine. 198 (7): 977–85. doi:10.1084/jem.20030382. PMC 2194212Freely accessible. PMID 14530373. 
  6. ^ Arita M, Bianchini F, Aliberti J, Sher A, Chiang N, Hong S, Yang R, Petasis NA, Serhan CN (March 2005). "Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1". The Journal of Experimental Medicine. 201 (5): 713–22. doi:10.1084/jem.20042031. PMC 2212834Freely accessible. PMID 15753205. 
  7. ^ Methner A, Hermey G, Schinke B, Hermans-Borgmeyer I (April 1997). "A novel G protein-coupled receptor with homology to neuropeptide and chemoattractant receptors expressed during bone development". Biochemical and Biophysical Research Communications. 233 (2): 336–42. doi:10.1006/bbrc.1997.6455. PMID 9144535. 
  8. ^ Kaur J, Adya R, Tan BK, Chen J, Randeva HS (January 2010). "Identification of chemerin receptor (ChemR23) in human endothelial cells: chemerin-induced endothelial angiogenesis". Biochemical and Biophysical Research Communications. 391 (4): 1762–8. doi:10.1016/j.bbrc.2009.12.150. PMID 20044979. 
  9. ^ Goralski KB, McCarthy TC, Hanniman EA, Zabel BA, Butcher EC, Parlee SD, Muruganandan S, Sinal CJ (September 2007). "Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism". The Journal of Biological Chemistry. 282 (38): 28175–88. doi:10.1074/jbc.M700793200. PMID 17635925. 
  10. ^ Takahashi M, Takahashi Y, Takahashi K, Zolotaryov FN, Hong KS, Kitazawa R, Iida K, Okimura Y, Kaji H, Kitazawa S, Kasuga M, Chihara K (March 2008). "Chemerin enhances insulin signaling and potentiates insulin-stimulated glucose uptake in 3T3-L1 adipocytes". FEBS Letters. 582 (5): 573–8. doi:10.1016/j.febslet.2008.01.023. PMID 18242188. 
  11. ^ Cash JL, Hart R, Russ A, Dixon JP, Colledge WH, Doran J, Hendrick AG, Carlton MB, Greaves DR (April 2008). "Synthetic chemerin-derived peptides suppress inflammation through ChemR23". The Journal of Experimental Medicine. 205 (4): 767–75. doi:10.1084/jem.20071601. PMC 2292217Freely accessible. PMID 18391062. 
  12. ^ Cash JL, Christian AR, Greaves DR (May 2010). "Chemerin peptides promote phagocytosis in a ChemR23- and Syk-dependent manner". Journal of Immunology. 184 (9): 5315–24. doi:10.4049/jimmunol.0903378. PMID 20363975. 
  13. ^ Ramos-Junior ES, Leite GA, Carmo-Silva CC, Taira TM, Neves KB, Colón DF, da Silva LA, Salvador SL, Tostes RC, Cunha FQ, Fukada SY (December 2016). "Adipokine Chemerin Bridges Metabolic Dyslipidemia and Alveolar Bone Loss in Mice". Journal of Bone and Mineral Research. doi:10.1002/jbmr.3072. PMID 28029186. 
  14. ^ Kennedy AJ, Yang P, Read C, Kuc RE, Yang L, Taylor EJ, Taylor CW, Maguire JJ, Davenport AP (October 2016). "Chemerin Elicits Potent Constrictor Actions via Chemokine-Like Receptor 1 (CMKLR1), not G-Protein-Coupled Receptor 1 (GPR1), in Human and Rat Vasculature". Journal of the American Heart Association. 5 (10): e004421. doi:10.1161/JAHA.116.004421. PMC 5121526Freely accessible. PMID 27742615. 
  15. ^ Darios ES, Winner BM, Charvat T, Krasinksi A, Punna S, Watts SW (August 2016). "The adipokine chemerin amplifies electrical field-stimulated contraction in the isolated rat superior mesenteric artery". American Journal of Physiology. Heart and Circulatory Physiology. 311 (2): H498–507. doi:10.1152/ajpheart.00998.2015. PMID 27371688. 
  16. ^ "Chemerin receptor – IUPHAR/BPS Guide to Pharmacology". www.guidetopharmacology.org. Retrieved 7 April 2017. 
  17. ^ "ChemoCentryx Identifies Novel Small Molecule ChemR23 Antagonist for the Treatment of Inflammatory Diseases". ChemoCentryx. 2010-04-10. 
  18. ^ "ChemoCentryx, GSK discontinue ChemR23 antagonist". BioCentury. 7 February 2012. 

External links[edit]

Further reading[edit]

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