View source for CMKLR1

{{Infobox_gene}}

'''Chemokine like receptor 1'''  also known as '''ChemR23''' (<u>Chem</u>erin <u>R</u>eceptor <u>23</u>) is a [[protein]] that in humans is encoded by the ''CMKLR1'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: CMKLR1 chemokine-like receptor 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1240| accessdate = }}</ref><ref name="pmid8976386">{{cite journal | vauthors = Gantz I, Konda Y, Yang YK, Miller DE, Dierick HA, Yamada T | title = Molecular cloning of a novel receptor (CMKLR1) with homology to the chemotactic factor receptors | journal = Cytogenetics and Cell Genetics | volume = 74 | issue = 4 | pages = 286–90 | year = 1996 | pmid = 8976386 | doi = 10.1159/000134436 }}</ref> Chemokine receptor-like 1 is a [[G protein-coupled receptor]] for the chemoattractant adipokine [[chemerin]]<ref name="pmid14530373">{{cite journal | vauthors = 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 | title = Specific recruitment of antigen-presenting cells by chemerin, a novel processed ligand from human inflammatory fluids | journal = The Journal of Experimental Medicine | volume = 198 | issue = 7 | pages = 977–85 | date = October 2003 | pmid = 14530373 | pmc = 2194212 | doi = 10.1084/jem.20030382 }}</ref> and the [[omega-3 fatty acid]] [[eicosapentaenoic acid]]-derived specialized pro-resolving molecule, [[resolvins|resolvin E1]] (see [[Specialized proresolving mediators#EPA-derived resolvins (i.e. RvE)]]).<ref name="pmid15753205">{{cite journal | vauthors = Arita M, Bianchini F, Aliberti J, Sher A, Chiang N, Hong S, Yang R, Petasis NA, Serhan CN | title = Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1 | journal = The Journal of Experimental Medicine | volume = 201 | issue = 5 | pages = 713–22 | date = March 2005 | pmid = 15753205 | pmc = 2212834 | doi = 10.1084/jem.20042031 }}</ref> The [[murinae|murine]] receptor that shares almost 80% homology with the human receptor, is called Dez.<ref name="pmid9144535">{{cite journal | vauthors = Methner A, Hermey G, Schinke B, Hermans-Borgmeyer I | title = A novel G protein-coupled receptor with homology to neuropeptide and chemoattractant receptors expressed during bone development | journal = Biochemical and Biophysical Research Communications | volume = 233 | issue = 2 | pages = 336–42 | date = April 1997 | pmid = 9144535 | doi = 10.1006/bbrc.1997.6455 }}</ref>

== Tissue distribution ==

CMKLR1 shows wide RNA expression profile but is notably high in [[Dendritic cell#In vivo – primate|plasmacytoid dendritic cells]], [[macrophage]]s, [[cardiac muscle|cardiomyocyte]]s, [[adipocyte]]s and [[endothelium|endothelial]] cells.<ref name="pmid20044979">{{cite journal | vauthors = Kaur J, Adya R, Tan BK, Chen J, Randeva HS | title = Identification of chemerin receptor (ChemR23) in human endothelial cells: chemerin-induced endothelial angiogenesis | journal = Biochemical and Biophysical Research Communications | volume = 391 | issue = 4 | pages = 1762–8 | date = January 2010 | pmid = 20044979 | doi = 10.1016/j.bbrc.2009.12.150 }}</ref>

== Function ==

Activating CMKLR1 by an [[agonist]] mobilizes intracellular [[calcium in biology|calcium]] and causes the activation of several other signaling cascades like the [[MAPK3|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.<ref name="pmid17635925">{{cite journal | vauthors = Goralski KB, McCarthy TC, Hanniman EA, Zabel BA, Butcher EC, Parlee SD, Muruganandan S, Sinal CJ | title = Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism | journal = The Journal of Biological Chemistry | volume = 282 | issue = 38 | pages = 28175–88 | date = September 2007 | pmid = 17635925 | doi = 10.1074/jbc.M700793200 }}</ref> It seems also to have a role in peripheral [[insulin resistance]].<ref name="pmid18242188">{{cite journal | vauthors = Takahashi M, Takahashi Y, Takahashi K, Zolotaryov FN, Hong KS, Kitazawa R, Iida K, Okimura Y, Kaji H, Kitazawa S, Kasuga M, Chihara K | title = Chemerin enhances insulin signaling and potentiates insulin-stimulated glucose uptake in 3T3-L1 adipocytes | journal = FEBS Letters | volume = 582 | issue = 5 | pages = 573–8 | date = March 2008 | pmid = 18242188 | doi = 10.1016/j.febslet.2008.01.023 }}</ref>

Also studies using the mouse [[zymosan]] model and [[chemerin peptides]] showed that these peptides suppressed and helped resolve the [[peritonitis]] in mice.<ref name="pmid18391062">{{cite journal | vauthors = Cash JL, Hart R, Russ A, Dixon JP, Colledge WH, Doran J, Hendrick AG, Carlton MB, Greaves DR | title = Synthetic chemerin-derived peptides suppress inflammation through ChemR23 | journal = The Journal of Experimental Medicine | volume = 205 | issue = 4 | pages = 767–75 | date = April 2008 | pmid = 18391062 | pmc = 2292217 | doi = 10.1084/jem.20071601 }}</ref> The same model showed that this particular molecule enhances macrophage [[efferocytosis]] (phagocyting [[Apoptosis|apoptotic cells]]).<ref name="pmid20363975">{{cite journal | vauthors = Cash JL, Christian AR, Greaves DR | title = Chemerin peptides promote phagocytosis in a ChemR23- and Syk-dependent manner | journal = Journal of Immunology | volume = 184 | issue = 9 | pages = 5315–24 | date = May 2010 | pmid = 20363975 | doi = 10.4049/jimmunol.0903378 | pmc = 4237835 }}</ref>

== {{anchor|CCX832}} Receptor antagonist CCX832 ==
CCX832 is an [[oral administration|orally]] active molecule used as a [[tool compound]] in experimental [[pharmacology]]. It [[antagonist (pharmacology)|antagonises]] the effect of CMKLR1.<ref>{{cite journal | vauthors = 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 | title = Adipokine Chemerin Bridges Metabolic Dyslipidemia and Alveolar Bone Loss in Mice | journal = Journal of Bone and Mineral Research | date = December 2016 | pmid = 28029186 | doi = 10.1002/jbmr.3072 | volume=32 | pages=974–984}}</ref><ref>{{cite journal | vauthors = Kennedy AJ, Yang P, Read C, Kuc RE, Yang L, Taylor EJ, Taylor CW, Maguire JJ, Davenport AP | title = Chemerin Elicits Potent Constrictor Actions via Chemokine-Like Receptor 1 (CMKLR1), not G-Protein-Coupled Receptor 1 (GPR1), in Human and Rat Vasculature | journal = Journal of the American Heart Association | volume = 5 | issue = 10 | pages = e004421 | date = October 2016 | pmid = 27742615 | pmc = 5121526 | doi = 10.1161/JAHA.116.004421 }}</ref><ref>{{cite journal | vauthors = Darios ES, Winner BM, Charvat T, Krasinksi A, Punna S, Watts SW | title = The adipokine chemerin amplifies electrical field-stimulated contraction in the isolated rat superior mesenteric artery | journal = American Journal of Physiology. Heart and Circulatory Physiology | volume = 311 | issue = 2 | pages = H498-507 | date = August 2016 | pmid = 27371688 | doi = 10.1152/ajpheart.00998.2015 | pmc=5008655}}</ref> It is listed on the [[Guide to Pharmacology]] database as the only example of a CMKLR1 antagonist. Its chemical structure is undisclosed.<ref>{{cite web | title = Chemerin receptor – IUPHAR/BPS Guide to Pharmacology | url = http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=79 | website = www.guidetopharmacology.org | accessdate = 7 April 2017}}</ref>

The substance was originally developed for use as a pharmaceutical drug against [[inflammatory disease]]s by [[ChemoCentryx]], a pharmaceutical firm based in California, in alliance with [[GlaxoSmithKline]] (GSK).<ref name="urlChemoCentryx - News - Press Releases">{{cite news | url = http://www.chemocentryx.com/news/2010/pr20100408.html | title = ChemoCentryx Identifies Novel Small Molecule ChemR23 Antagonist for the Treatment of Inflammatory Diseases | date = 2010-04-10 | publisher = ChemoCentryx | access-date = 2017-04-14 | archive-url = https://web.archive.org/web/20110519141347/http://www.chemocentryx.com/news/2010/pr20100408.html# | archive-date = 2011-05-19 | dead-url = yes | df =  }}</ref> Development was terminated after a Phase I [[clinical trial]] in 2012.<ref>{{cite news|url=https://www.biocentury.com/bc-extra/clinical-news/2012-02-06/chemocentryx-gsk-discontinue-chemr23-antagonist?kwh=%22ccx832%22|title=ChemoCentryx, GSK discontinue ChemR23 antagonist|publisher=BioCentury|date=7 February 2012}}</ref>

== References ==
{{reflist}}

== External links ==
* {{UCSC gene info|CMKLR1}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Owman C, Lolait SJ, Santén S, Olde B | title = Molecular cloning and tissue distribution of cDNA encoding a novel chemoattractant-like receptor | journal = Biochemical and Biophysical Research Communications | volume = 241 | issue = 2 | pages = 390–4 | date = December 1997 | pmid = 9425281 | doi = 10.1006/bbrc.1997.7822 }}
* {{cite journal | vauthors = Samson M, Edinger AL, Stordeur P, Rucker J, Verhasselt V, Sharron M, Govaerts C, Mollereau C, Vassart G, Doms RW, Parmentier M | title = ChemR23, a putative chemoattractant receptor, is expressed in monocyte-derived dendritic cells and macrophages and is a coreceptor for SIV and some primary HIV-1 strains | journal = European Journal of Immunology | volume = 28 | issue = 5 | pages = 1689–700 | date = May 1998 | pmid = 9603476 | doi = 10.1002/(SICI)1521-4141(199805)28:05<1689::AID-IMMU1689>3.0.CO;2-I }}
* {{cite journal | vauthors = Hillman RT, Green RE, Brenner SE | title = An unappreciated role for RNA surveillance | journal = Genome Biology | volume = 5 | issue = 2 | pages = R8 | year = 2005 | pmid = 14759258 | pmc = 395752 | doi = 10.1186/gb-2004-5-2-r8 }}
* {{cite journal | vauthors = Mårtensson UE, Fenyö EM, Olde B, Owman C | title = Characterization of the human chemerin receptor--ChemR23/CMKLR1--as co-receptor for human and simian immunodeficiency virus infection, and identification of virus-binding receptor domains | journal = Virology | volume = 355 | issue = 1 | pages = 6–17 | date = November 2006 | pmid = 16904155 | doi = 10.1016/j.virol.2006.07.010 }}
{{refend}}

{{NLM content}}
{{Chemokine receptors}}
{{Chemokine receptor modulators}}


[[Category:Chemokine receptors]]

{{transmembranereceptor-stub}}