RARRES2

This gene encodes a secreted chemotactic protein that initiates chemotaxis via the ChemR23 G protein-coupled seven-transmembrane domain ligand. Expression of this gene is upregulated by the synthetic retinoid tazarotene and occurs in a wide variety of tissues. The active protein has several roles, including that as an adipokine, and is truncated on both termini from the proprotein. [provided by RefSeq]

retinoic acid receptor responder (tazarotene induced) 2

Adipocyte-secreted protein (adipokine) that regulates adipogenesis, metabolism and inflammation through activation of the chemokine-like receptor 1 (CMKLR1). Acts also 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.

Biological Process antifungal humoral responseManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process antifungal innate immune responseManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process cell differentiationIEA:UniProtKB-KW
Biological Process chemotaxisIEA:UniProtKB-KW
Biological Process defense response to Gram-negative bacteriumManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process defense response to Gram-positive bacteriumManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process embryonic digestive tract developmentManual Assertion Based On ExperimentIMP:DFLAT
Biological Process inflammatory responseIEA:UniProtKB-KW
Biological Process innate immune responseManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process insulin receptor signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of chemotaxisISS:UniProtKB
Biological Process positive regulation of fat cell differentiationISS:UniProtKB
Biological Process positive regulation of macrophage chemotaxisManual Assertion Based On ExperimentIMP:DFLAT
Biological Process positive regulation of protein phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of lipid catabolic processISS:UniProtKB
Biological Process retinoid metabolic processManual Assertion Based On ExperimentIDA:UniProtKB

Secreted

Secreted in an inactive precursor form, prochemerin, which is proteolytically processed by a variety of extracellular proteases to generate forms with differing levels of bioactivity. For example, the removal of six amino acids results in chemerin-157, which exhibits the highest activity, while removal of seven amino acids results in chemerin-156 which has slightly less activity. Some proteases are able to cleave at more than one site and chemerin forms may be sequentially processed by different enzymes to modulate activity levels. The coordinated expression and activity of chemerin-modifying enzymes is essential for regulating its bioactivation, inactivation and, consequently, biological function. Cathepsin G cleaves seven C-terminal amino acids from prochemerin (chemerin-156), elastase is able to cleave six (chemerin-157), eight (chemerin-155) or eleven (chemerin-152), plasmin cleaves five amino acids (chemerin-158), and tryptase cleaves five (chemerin-158) or eight (chemerin-155). Multiple cleavages might be required to fully activate chemerin, with an initial tryptase cleavage resulting in chemerin with low activity (chemerin-158), and a second cleavage by carboxypeptidase N or B producing highly active chemerin (chemerin-157).