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OtherIUPHAR Nomenclature Report
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International Union of Basic and Clinical Pharmacology CIII: Chemerin Receptors CMKLR1 (Chemerin1) and GPR1 (Chemerin2) Nomenclature, Pharmacology, and Function

Amanda J. Kennedy and Anthony P. Davenport
Eliot H. Ohlstein, ASSOCIATE EDITOR
Pharmacological Reviews January 2018, 70 (1) 174-196; DOI: https://doi.org/10.1124/pr.116.013177
Amanda J. Kennedy
Experimental Medicine and Immunotherapeutics, University of Cambridge, Centre for Clinical Investigation, Addenbrooke’s Hospital, Cambridge, United Kingdom
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Anthony P. Davenport
Experimental Medicine and Immunotherapeutics, University of Cambridge, Centre for Clinical Investigation, Addenbrooke’s Hospital, Cambridge, United Kingdom
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Eliot H. Ohlstein
Roles: ASSOCIATE EDITOR
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  • Fig. 1.
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    Fig. 1.

    Agonists and antagonists of the chemerin receptors. (A) The 163-amino-acid sequence of chemerin (Uniprot: Q99969). The signal peptide is underlined; the cysteine residues involved in three disulfide bonds are marked ^, “, and ‘ in pairs. The residues marked with * were found to be important for binding to chemerin receptor 1 by alanine screening. (B) Amino acids corresponding to C9, C13, C15, and C20 synthetic peptides that activate downstream signalling at CMKLR1 and GPR1. Chemspider structures of (C) CMKLR1 agonist RvE1 and (D) CMKLR1 antagonist, α-NETO. NB. The structure of CCX832 is not publicly available.

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    Fig. 2.

    Amino acid sequence of chemerin receptor 1: Cys112 andCys189 (green) are predicted to form a disulfide bond based on sequence similarity, and the G protein–binding motif is shown in blue. Figure made using UniProt (Q99788) and Protter (Omasits et al., 2014).

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    Fig. 3.

    Schematic representation of the structural similarities between chemerin receptors, CMKLR1 and GPR1, and other chemoattractant receptors. Sequences for the receptors were aligned to generate the phylogenetic tree (http://www.phylogeny.fr/). The receptors include chemokine receptors (CCR2, CCR5, CCR7, and CXCR4), leukotriene B receptors (BLT1 and BLT2), and formyl peptide receptors (FRP1, FRP2, and FRP3).

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    Fig. 4.

    Clustal Omega (http://www.uniprot.org/align) sequence alignment of the human, rat, and mouse chemerin receptor 1. Identical amino acids in all species, “*”; conserved amino acid substitution, “:”; and semiconserved amino acid substitution, “.” Blue boxes highlight the transmembrane domains, and the pink line identifies the G protein–binding motif.

  • Fig. 5.
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    Fig. 5.

    Amino acid sequence of chemerin receptor 2: Cys110 and Cys187 (green) are predicted to form a disulfide bond based on sequence similarity, and the G protein–binding motif is shown in blue. Figure made using UniProt (P46091) and Protter (Omasits et al., 2014).

  • Fig. 6.
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    Fig. 6.

    Clustal Omega (http://www.uniprot.org/align) sequence alignment of the human CMKLR1 and GPR1. Identical amino acids in all species, “*”; conserved amino acid substitution, “:”; and semiconserved amino acid substitution, “.” Blue boxes highlight the transmembrane domains.

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    Fig. 7.

    Clustal Omega (http://www.uniprot.org/align) sequence alignment of the human, rat, and mouse chemerin receptor 2. Identical amino acids in all species, “*”; conserved amino acid substitution, “:”; and semiconserved amino acid substitution, “.” Blue boxes highlight the transmembrane domains; the pink line identifies the G protein–binding motif; and the box highlights the differing sequence in humans.

Tables

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    TABLE 1

    Detailed reviews

    Focus of the reviewReference
    Chemerin activationZabel et al., 2006; Ernst and Sinal, 2010; Mattern et al., 2014
    Chemerin receptorsYoshimura and Oppenheim, 2011
    Function of chemerinMattern et al., 2014; Ferland and Watts, 2015; Mariani and Roncucci, 2015; Fatima et al., 2014; Zabel et al., 2014; Bondue et al., 2011b
    General overviewErnst and Sinal, 2010; Fatima et al., 2014; Mattern et al., 2014
    InflammationZabel et al., 2014; Mariani and Roncucci, 2015
    ObesityRoman et al., 2012
    Cardiovascular diseaseFerland and Watts, 2015
    CancerMariani and Roncucci, 2015
    • View popup
    TABLE 2

    Nomenclature of chemerin and its receptors

    ChemerinSpeciesGeneProtein
    Receptor 1HumanCMKLR1Chemerin receptor 1
    Nonhumancmklr1Chemerin receptor 1
    Receptor 2HumanGPR1Chemerin receptor 2
    Nonhumangpr1Chemerin receptor 2
    PeptideHumanRARRES2Chemerin
    Nonhumanrarres2Chemerin
    • View popup
    TABLE 3

    Classification of chemerin receptor 1

    Receptor Structure, Pharmacology, and DistributionReceptor Amino Acid Sequences, Pharmacological Parameters, Tissue DistributionReferences
    Previous NamesCMKLR1, ChemR23, ChemerinR, GPCR27, DEZ, RVER1, TIG2 receptor
    Structural information7TM
    Humans373 aa (UniProt Q99788) chr. 12q24.1 (Entrez 1240)
    Rats371 aa (UniProt O35786) chr. 12q16 (Entrez 60669)
    Mice371 aa (UniProt P97468) chr. 5F (Entrez 14747)
    Functional assaysCHO cells transfected with CMKLR1Wittamer et al., 2003; Barnea et al., 2008
    Chemotaxis migration assaysWittamer et al., 2003; Vermi et al., 2005; Zabel et al., 2005b; Albanesi et al., 2009
    In vitro pharmacology using isolated human vesselsKennedy et al., 2016
    In vitro pharmacology using isolated rat aortaWatts et al., 2013
    Endogenous agonistsHuman chemerin(21–157) (pEC50 = 9.37 ± 0.05)Wittamer et al., 2003
    RvE1 (pEC50 = 9.37 ± 0.05)Arita et al., 2005
    AgonistsC9 [chemerin(149–157)]Wittamer et al., 2009
    C13 [chemerin(145–157)]Wittamer et al., 2003
    C15 [chemerin(141–155)]Cash et al., 2008
    C19 [chemerin(139–157)]Wittamer et al., 2004
    C20 [chemerin(138–157)]Li et al., 2014a
    Selective antagonistCCX832 (pIC50 = 8.34 ± 0.04)Watts et al., 2013; Kennedy et al., 2016
    Radioligands[125I]-C9 (KD = 4.9 nM)Barnea et al., 2008; Kennedy et al., 2016
    Human [125I]-chemerin(21–157) (KD = 0.88 nM)De Henau et al., 2016
    Human [125I]Tyr-[Phe149]-chemerin146–157 (KD = 22 nM)Wittamer et al., 2003
    [3H]RvE1 (KD = 11.3 ± 5.4)Arita et al., 2005, 2007
    Mouse [125I]-chemerin(21–148) (EC50 = 1.6 nM)Zabel et al., 2008; Bondue et al., 2012
    Transduction mechanismsCoupled to Gi/o proteinsWittamer et al., 2003; Cash et al., 2008; Kennedy et al., 2016
    Receptor distribution
    HumansRT-PCR showed highest expression of CMKLR1 mRNA in the skin, adipose tissue, spleen, lymph nodes, and lungWittamer et al., 2003; Roh et al., 2007
    Immunostaining and FACS analysis confirmed high expression on dendritic cells, monocytes, and macrophagesWittamer et al., 2003; Vermi et al., 2005; Zabel et al., 2005b; Herová et al., 2015
    CMKLR1 protein expression was found on smooth muscle cells of human vessels by immunohistochemistryKostopoulos et al., 2014
    MiceRT-PCR showed highest CMKLR1 expression in white adipose tissue and the lungGoralski et al., 2007
    CMKLR1 immunoreactivity was identified in adipocytesGoralski et al., 2007
    RatsRT-PCR–detected CMKLR1 mRNA were in the reproductive system (testis and ovary)Wang et al., 2012; Li et al., 2014b
    Western blot analysis and immunohistochemistry identified CMKLR1 expression in vascular endothelial cells, cardiomyocytes and the smooth muscle, and endothelium of aorta and mesenteric vesselsWatts et al., 2013; Zhao et al., 2013; Zhang et al., 2014
    Tissue functionChemotaxis of leukocytes; adipogenesis; antimicrobial agent; vasoconstrictor of saphenous vein and resistance arteriesWittamer et al., 2003; Goralski et al., 2007; Cash et al., 2010; Banas et.al., 2013; Kennedy et al., 2016
    • aa, Amino acid; chr., chromosome; FACS, fluorescence-activated cell sorter; RT-PCR, reverse-transcription polymerase chain reaction.

    • View popup
    TABLE 4

    Classification of chemerin receptor 2

    Receptor Structure, Pharmacology, and DistributionReceptor Amino Acid Sequences, Pharmacological Parameters, Tissue DistributionReferences
    Previous namesGPR1
    Structural information7TM
    Humans355 aa (UniProt P46091) chr. 2q33.3 (Entrez 2825)
    Rats353 aa (UniProt P46090) chr. 9q31 (Entrez 25457)
    Mice353 aa (UniProt Q8K087) chr. 1C2 (Entrez 241070)
    Functional assaysCHO cells transfected with GPR1Barnea et al., 2008; Kennedy et al., 2016
    Endogenous agonistsHuman chemerin(21–157) (pEC50∼9)Barnea et al., 2008; Southern et al., 2013; Kennedy et al., 2016
    AgonistsC9 [chemerin(149–157)] (pEC50 = 8.65 ± 0.14)Kennedy et al., 2016
    C13 [chemerin(145–157)] (pEC50 = 9.05 ± 0.09)Kennedy et al., 2016
    C20 [chemerin(138–157)]Li et al., 2014a
    Selective antagonistNone
    Radioligands[125I]-C9 (KD = 5.3 nM) (pIC50 = 9.3)Barnea et al., 2008; Kennedy et al., 2016
    Human [125I]-chemerin(21–157) (KD = 0.21 nM)De Henau et al., 2016
    Transduction mechanismsCoupled to Gi/o proteins: predictedRourke et al., 2015
    Receptor distribution
    HumansNorthern blot analysis identified the GPR1 gene in the hippocampusMarchese et al., 1994b
    RT-PCR showed highest expression of GPR1 mRNA in the adrenal cortex, cardiomyocytes, and superior cervical ganglionWu et al., 2009
    Immunohistochemistry confirmed GPR1 expression in smooth muscle cells of the vasculatureKaragiannis et al., 2013; Kennedy et al., 2016
    MiceRT-PCR identifed highest GPR1 mRNA expression in white adipose tissue (predominately the stromal vascular fraction), with high levels also detected in skin, brown adipose tissue, skeletal muscle, the brain (particularly the hypothalamus), bladder, esophagus, and ovariesRegard et al., 2008; Takahashi et al., 2011; Rourke et al., 2014; Yang et al., 2016
    RatsRT-PCR detected GPR1 mRNA in the male reproductive system, with high levels in the testisLi et al., 2014b
    Tissue functionHIV/SIV coreceptor; lipid metabolismEdinger et al., 1997; Shimizu et al., 2009; Rourke et al., 2014
    • aa, Amino acid; chr., chromosome; RT-PCR, reverse-transcription polymerase chain reaction; SIV, simian immunodeficiency virus.

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Pharmacological Reviews: 70 (1)
Pharmacological Reviews
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1 Jan 2018
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OtherIUPHAR Nomenclature Report

Chemerin Receptor (Chemerin1 and Chemerin2) Nomenclature

Amanda J. Kennedy and Anthony P. Davenport
Pharmacological Reviews January 1, 2018, 70 (1) 174-196; DOI: https://doi.org/10.1124/pr.116.013177

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Chemerin Receptor (Chemerin1 and Chemerin2) Nomenclature

Amanda J. Kennedy and Anthony P. Davenport
Pharmacological Reviews January 1, 2018, 70 (1) 174-196; DOI: https://doi.org/10.1124/pr.116.013177
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  • Article
    • Abstract
    • I. Introduction
    • II. Chemokine-Like Receptor 1 Designated as Chemerin Receptor 1
    • III. G Protein–Coupled Receptor 1 Designated as Chemerin Receptor 2
    • IV. Distribution
    • V. Radiolabeled Ligands
    • VI. Agonists
    • VII. Antagonists
    • VIII. Receptor Signaling
    • IX. Physiologic Roles
    • X. Pathophysiological Roles
    • XI. Genetically Modified Animals
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
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