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coiled coil myosin-like BCL2-interacting protein
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The approved gene symbol for chemerin is RARRES2 [retinoic acid receptor responder 2].
Chemerin is a chemoattractant protein (see also: chemotaxis) structurally and evolutionary related to the cathelicidin precursors (antibacterial peptides), cystatin C and related peptides (cysteine protease inhibitors), and kininogens. The protein promotes calcium mobilization and chemotaxis of immature dendritic cells and macrophages but is not chemotactic for mature dendritic cells (Wittmamer et al, 2003). The nonapeptide 149-YFPGQFAFS-157 (chemerin-9), corresponding to the C-terminus of processed chemerin, has been shown to retain most of the activity of the full-size protein and to activate the chemerin receptor with low nanomolar potency (Wittamer et al, 2004).
The protein is secreted as a precursor of low biological activity, which requires proteolytic cleavage of its COOH-terminal domain to be converted into a potent and highly specific agonist of ChemR23. Prochemerin, which is poorly active on ChemR23 can be converted rapidly into a full ChemR23 agonist by proteolytic removal of a carboxy-terminal peptide. This maturation step is mediated by the neutrophil serine proteases elastase and cathepsin G (Wittamer et al, 2005). Guillabert et al (2008) have reported that neutrophil PR3 [Proteinase-3] and mast cell chymase generate specific inactive chemerin variants. PR3 cleavage yields a chemerin form that lacks the last eight carboxyterminal amino acids. Mast cell chymase abolishes chemerin activity by the removal of additional amino acids from its C-terminus.
Goralski and Sinai (2009) have demonstrated a role for chemerin signaling through its receptor, CMKLR1, as a positive regulator of adipocyte differentiation and metabolic function.
The chemerin receptor, designated ChemerinR, has been identified as ChemR23 (approved gene symbol: CMKLR1 [chemokine-like receptor 1]), a G-protein-coupled receptor related to related to the C3a, C5a and fMLP receptors and more distantly to other receptors for chemokines (Samson et al, 1998). The receptor has been described independently also as Dez. The receptor acts as a coreceptor for SIV and some primary HIV-1 strains. It is expressed in monocyte-derived dendritic cells and macrophages, CD4(+) T-lymphocytes (Samson et al, 1998), human trophoblasts (Mognetti et al, 2000), and human fetal and simian adult astrocytes (Croitoru-Lamoury et al, 2003). The receptor also has another ligand, tazarotene-induced gene-2 (TIG2) (Meder et al, 2003), which is the unprocessed form of the chemerin precursor.
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ENTRY LAST MODIFIED: April 2004
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