LMPD Database

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LMP003246

UniProt Annotations

Entry Information
Gene Nameretinoic acid receptor responder (tazarotene induced) 2
Protein EntryRARR2_MOUSE
UniProt IDQ9DD06
SpeciesMouse
Comments
Comment typeDescription
FunctionAdipocyte-secreted protein (adipokine) that regulates adipogenesis, metabolism and inflammation through activation of the chemokine-like receptor 1 (CMKLR1). Its other ligands include G protein-coupled receptor 1 (GPR1) and chemokine receptor-like 2 (CCRL2). 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 proinflammatory adipokine, causing an increase in secretion of proinflammatory 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. Exhibits an antimicrobial function in the skin. {ECO:0000269|PubMed:17635925, ECO:0000269|PubMed:18242188}.
InductionStrongly induced during adipocyte differentiation. {ECO:0000269|PubMed:18242188}.
PtmSecreted 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-156, which exhibits the highest activity, while removal of seven amino acids results in chemerin-155 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-155), elastase is able to cleave six (chemerin-156), eight (chemerin-154) or eleven (chemerin-151), plasmin cleaves five amino acids (chemerin-157), and tryptase cleaves five (chemerin-157) or eight (chemerin-154). Multiple cleavages might be required to fully activate chemerin, with an initial tryptase cleavage resulting in chemerin with low activity (chemerin-157), and a second cleavage by carboxypeptidase N or B producing highly active chemerin (chemerin-156) (By similarity). {ECO:0000250}.
Subcellular LocationSecreted {ECO:0000269|PubMed:17635925, ECO:0000269|PubMed:18242188}.
Tissue SpecificityExpressed in the differentiated adipocytes (at protein level). Abundantly expressed in the liver, adipose tissue including visceral, epididymal, and brown adipose tissue. {ECO:0000269|PubMed:17635925, ECO:0000269|PubMed:17767914, ECO:0000269|PubMed:18242188}.