9uym

Structural highlights

Function

RARR2_HUMAN Adipocyte-secreted protein (adipokine) that regulates adipogenesis, metabolism and inflammation through activation of the chemokine-like receptor 1 (CMKLR1). Also acts as a ligand for CMKLR2. Can also bind to C-C chemokine receptor-like 2 (CCRL2), but with a lower affinity than it does to CMKLR1 or CMKLR2 (PubMed:27716822). Positively regulates adipocyte differentiation, modulates the expression of adipocyte genes involved in lipid and glucose metabolism and might play a role in angiogenesis, a process essential for the expansion of white adipose tissue. Also acts as a pro-inflammatory adipokine, causing an increase in secretion of pro-inflammatory and prodiabetic adipokines, which further impair adipose tissue metabolic function and have negative systemic effects including impaired insulin sensitivity, altered glucose and lipid metabolism, and a decrease in vascular function in other tissues. Can have both pro- and anti-inflammatory properties depending on the modality of enzymatic cleavage by different classes of proteases. Acts as a chemotactic factor for leukocyte populations expressing CMKLR1, particularly immature plasmacytoid dendritic cells, but also immature myeloid DCs, macrophages and natural killer cells. Exerts an anti-inflammatory role by preventing TNF/TNFA-induced VCAM1 expression and monocytes adhesion in vascular endothelial cells. The effect is mediated via inhibiting activation of NF-kappa-B and CRK/p38 through stimulation of AKT1/NOS3 signaling and nitric oxide production. Its dual role in inflammation and metabolism might provide a link between chronic inflammation and obesity, as well as obesity-related disorders such as type 2 diabetes and cardiovascular disease. Exhibits an antimicrobial function in the skin.^{[1] [2] [3] [4] [5] [6] [7] [8]}

References

1. ↑ Meder W, Wendland M, Busmann A, Kutzleb C, Spodsberg N, John H, Richter R, Schleuder D, Meyer M, Forssmann WG. Characterization of human circulating TIG2 as a ligand for the orphan receptor ChemR23. FEBS Lett. 2003 Dec 18;555(3):495-9. PMID:14675762 doi:10.1016/s0014-5793(03)01312-7
2. ↑ Goralski KB, McCarthy TC, Hanniman EA, Zabel BA, Butcher EC, Parlee SD, Muruganandan S, Sinal CJ. Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism. J Biol Chem. 2007 Sep 21;282(38):28175-88. PMID:17635925 doi:10.1074/jbc.M700793200
3. ↑ Roh SG, Song SH, Choi KC, Katoh K, Wittamer V, Parmentier M, Sasaki S. Chemerin--a new adipokine that modulates adipogenesis via its own receptor. Biochem Biophys Res Commun. 2007 Nov 3;362(4):1013-8. PMID:17767914 doi:10.1016/j.bbrc.2007.08.104
4. ↑ Takahashi M, Takahashi Y, Takahashi K, Zolotaryov FN, Hong KS, Kitazawa R, Iida K, Okimura Y, Kaji H, Kitazawa S, Kasuga M, Chihara K. Chemerin enhances insulin signaling and potentiates insulin-stimulated glucose uptake in 3T3-L1 adipocytes. FEBS Lett. 2008 Mar 5;582(5):573-8. PMID:18242188 doi:10.1016/j.febslet.2008.01.023
5. ↑ Bozaoglu K, Curran JE, Stocker CJ, Zaibi MS, Segal D, Konstantopoulos N, Morrison S, Carless M, Dyer TD, Cole SA, Goring HH, Moses EK, Walder K, Cawthorne MA, Blangero J, Jowett JB. Chemerin, a novel adipokine in the regulation of angiogenesis. J Clin Endocrinol Metab. 2010 May;95(5):2476-85. PMID:20237162 doi:10.1210/jc.2010-0042
6. ↑ Yamawaki H, Kameshima S, Usui T, Okada M, Hara Y. A novel adipocytokine, chemerin exerts anti-inflammatory roles in human vascular endothelial cells. Biochem Biophys Res Commun. 2012 Jun 22;423(1):152-7. PMID:22634313 doi:10.1016/j.bbrc.2012.05.103
7. ↑ Banas M, Zabieglo K, Kasetty G, Kapinska-Mrowiecka M, Borowczyk J, Drukala J, Murzyn K, Zabel BA, Butcher EC, Schroeder JM, Schmidtchen A, Cichy J. Chemerin is an antimicrobial agent in human epidermis. PLoS One. 2013;8(3):e58709. PMID:23527010 doi:10.1371/journal.pone.0058709
8. ↑ De Henau O, Degroot GN, Imbault V, Robert V, De Poorter C, Mcheik S, Galés C, Parmentier M, Springael JY. Signaling Properties of Chemerin Receptors CMKLR1, GPR1 and CCRL2. PLoS One. 2016 Oct 7;11(10):e0164179. PMID:27716822 doi:10.1371/journal.pone.0164179