Article Figures & Data
Figures
- 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.
- 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).
- 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).
- 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.
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.
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.
- 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
Focus of the review Reference Chemerin activation Zabel et al., 2006; Ernst and Sinal, 2010; Mattern et al., 2014 Chemerin receptors Yoshimura and Oppenheim, 2011 Function of chemerin Mattern et al., 2014; Ferland and Watts, 2015; Mariani and Roncucci, 2015; Fatima et al., 2014; Zabel et al., 2014; Bondue et al., 2011b General overview Ernst and Sinal, 2010; Fatima et al., 2014; Mattern et al., 2014 Inflammation Zabel et al., 2014; Mariani and Roncucci, 2015 Obesity Roman et al., 2012 Cardiovascular disease Ferland and Watts, 2015 Cancer Mariani and Roncucci, 2015 Chemerin Species Gene Protein Receptor 1 Human CMKLR1 Chemerin receptor 1 Nonhuman cmklr1 Chemerin receptor 1 Receptor 2 Human GPR1 Chemerin receptor 2 Nonhuman gpr1 Chemerin receptor 2 Peptide Human RARRES2 Chemerin Nonhuman rarres2 Chemerin Receptor Structure, Pharmacology, and Distribution Receptor Amino Acid Sequences, Pharmacological Parameters, Tissue Distribution References Previous Names CMKLR1, ChemR23, ChemerinR, GPCR27, DEZ, RVER1, TIG2 receptor Structural information 7TM Humans 373 aa (UniProt Q99788) chr. 12q24.1 (Entrez 1240) Rats 371 aa (UniProt O35786) chr. 12q16 (Entrez 60669) Mice 371 aa (UniProt P97468) chr. 5F (Entrez 14747) Functional assays CHO cells transfected with CMKLR1 Wittamer et al., 2003; Barnea et al., 2008 Chemotaxis migration assays Wittamer et al., 2003; Vermi et al., 2005; Zabel et al., 2005b; Albanesi et al., 2009 In vitro pharmacology using isolated human vessels Kennedy et al., 2016 In vitro pharmacology using isolated rat aorta Watts et al., 2013 Endogenous agonists Human chemerin(21–157) (pEC50 = 9.37 ± 0.05) Wittamer et al., 2003 RvE1 (pEC50 = 9.37 ± 0.05) Arita et al., 2005 Agonists C9 [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 antagonist CCX832 (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 mechanisms Coupled to Gi/o proteins Wittamer et al., 2003; Cash et al., 2008; Kennedy et al., 2016 Receptor distribution Humans RT-PCR showed highest expression of CMKLR1 mRNA in the skin, adipose tissue, spleen, lymph nodes, and lung Wittamer et al., 2003; Roh et al., 2007 Immunostaining and FACS analysis confirmed high expression on dendritic cells, monocytes, and macrophages Wittamer 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 immunohistochemistry Kostopoulos et al., 2014 Mice RT-PCR showed highest CMKLR1 expression in white adipose tissue and the lung Goralski et al., 2007 CMKLR1 immunoreactivity was identified in adipocytes Goralski et al., 2007 Rats RT-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 vessels Watts et al., 2013; Zhao et al., 2013; Zhang et al., 2014 Tissue function Chemotaxis of leukocytes; adipogenesis; antimicrobial agent; vasoconstrictor of saphenous vein and resistance arteries Wittamer 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.
Receptor Structure, Pharmacology, and Distribution Receptor Amino Acid Sequences, Pharmacological Parameters, Tissue Distribution References Previous names GPR1 Structural information 7TM Humans 355 aa (UniProt P46091) chr. 2q33.3 (Entrez 2825) Rats 353 aa (UniProt P46090) chr. 9q31 (Entrez 25457) Mice 353 aa (UniProt Q8K087) chr. 1C2 (Entrez 241070) Functional assays CHO cells transfected with GPR1 Barnea et al., 2008; Kennedy et al., 2016 Endogenous agonists Human chemerin(21–157) (pEC50∼9) Barnea et al., 2008; Southern et al., 2013; Kennedy et al., 2016 Agonists C9 [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 antagonist None 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 mechanisms Coupled to Gi/o proteins: predicted Rourke et al., 2015 Receptor distribution Humans Northern blot analysis identified the GPR1 gene in the hippocampus Marchese et al., 1994b RT-PCR showed highest expression of GPR1 mRNA in the adrenal cortex, cardiomyocytes, and superior cervical ganglion Wu et al., 2009 Immunohistochemistry confirmed GPR1 expression in smooth muscle cells of the vasculature Karagiannis et al., 2013; Kennedy et al., 2016 Mice RT-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 ovaries Regard et al., 2008; Takahashi et al., 2011; Rourke et al., 2014; Yang et al., 2016 Rats RT-PCR detected GPR1 mRNA in the male reproductive system, with high levels in the testis Li et al., 2014b Tissue function HIV/SIV coreceptor; lipid metabolism Edinger 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.
In this issue
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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
- Figures & Data
- Info & Metrics
- eLetters