CMKLR1

Last updated
CMKLR1
Identifiers
Aliases CMKLR1 , CHEMERINR, ChemR23, DEZ, RVER1, chemerin chemokine-like receptor 1, CCX832
External IDs OMIM: 602351 MGI: 109603 HomoloGene: 129967 GeneCards: CMKLR1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_004072
NM_001142343
NM_001142344
NM_001142345

NM_008153
NM_001359060

RefSeq (protein)

NP_001135815
NP_001135816
NP_001135817
NP_004063

NP_032179
NP_001345989

Location (UCSC) Chr 12: 108.29 – 108.34 Mb Chr 5: 113.75 – 113.79 Mb
PubMed search [3] [4]
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. [5] [6] Chemokine receptor-like 1 is a G protein-coupled receptor for the chemoattractant adipokine chemerin [7] 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)). [8] The murine receptor that shares almost 80% homology with the human receptor, is called Dez. [9]

Contents

Tissue distribution

CMKLR1 shows wide RNA expression profile but is notably high in plasmacytoid dendritic cells, macrophages, cardiomyocytes, adipocytes and endothelial cells. [10]

Function

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. [11] It seems also to have a role in peripheral insulin resistance. [12]

Also studies using the mouse zymosan model and chemerin peptides showed that these peptides suppressed and helped resolve the peritonitis in mice. [13] The same model showed that this particular molecule enhances macrophage efferocytosis (phagocyting apoptotic cells). [14]

Receptor antagonist CCX832

CCX832 is an orally active molecule used as a tool compound in experimental pharmacology. It antagonises the effect of CMKLR1. [15] [16] [17] It is listed on the Guide to Pharmacology database as the only example of a CMKLR1 antagonist. Its chemical structure is undisclosed. [18]

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). [19] Development was terminated after a Phase I clinical trial in 2012. [20]

Related Research Articles

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<span class="mw-page-title-main">CXCL5</span> Mammalian protein found in Homo sapiens

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<span class="mw-page-title-main">XCR1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">CCR2</span> Mammalian protein found in Homo sapiens

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<span class="mw-page-title-main">CCR1</span> Protein in humans

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<span class="mw-page-title-main">GPR32</span> Human biochemical receptor

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<span class="mw-page-title-main">C5AR2</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Chemerin</span> Protein-coding gene in the species Homo sapiens

Chemerin, also known as retinoic acid receptor responder protein 2 (RARRES2), tazarotene-induced gene 2 protein (TIG2), or RAR-responsive protein TIG2 is a protein that in humans is encoded by the RARRES2 gene.

<span class="mw-page-title-main">NR58-3.14.3</span> Chemical compound

NR58.3-14-3 is a cyclic peptide consisting of 11 D-amino acids. It is a broad-spectrum chemokine inhibitor and anti-inflammatory agent.

Chemerin peptides are short peptides that are produced from the carboxyl terminus of the chemokine chemerin. They display the same activities as chemerin, although at higher efficacy and potency.

References

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  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000042190 - Ensembl, May 2017
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  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: CMKLR1 chemokine-like receptor 1".
  6. 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.
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Further reading

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