InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: RARRES2

Summary

InnateDB Protein

IDBP-483186.3

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

RARRES2

Protein Name

retinoic acid receptor responder (tazarotene induced) 2

Synonyms

HP10433; TIG2;

Species

Homo sapiens

Ensembl Protein

ENSP00000418009

InnateDB Gene

IDBG-47881 (RARRES2)

Protein Structure

UniProt Annotation

Function

Adipocyte-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. 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. {ECO:0000269PubMed:14675762, ECO:0000269PubMed:17635925, ECO:0000269PubMed:17767914, ECO:0000269PubMed:18242188, ECO:0000269PubMed:20237162, ECO:0000269PubMed:22634313, ECO:0000269PubMed:23527010}.

Subcellular Localization

Secreted {ECO:0000305}.

Disease Associations

Tissue Specificity

Expressed at the highest levels in placenta, liver, and white adipose tissue (WAT), and to a lesser extent in many other tissues such as lung, brown adipose tissue, heart, ovary, kidney, skeletal muscle and pancreas. Within WAT, expression is enriched in adipocytes as compared to the stromal vascular fraction. Expression and secretion increases dramatically with adipogenesis. Highly expressed in skin (basal and suprabasal layers of the epidermis, hair follicles and endothelial cells). Expression is elevated in numerous metabolic and inflammatory diseases including psoriasis, obesity, type 2 diabetes, metabolic syndrome and cardiovascular disease. {ECO:0000269PubMed:17635925, ECO:0000269PubMed:17767914, ECO:0000269PubMed:23527010}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 2 experimentally validated interaction(s) in this database.

Experimentally validated
Total	2 [view]
Protein-Protein	2 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005102	receptor binding
GO:0005515	protein binding

Biological Process

GO:0001523	retinoid metabolic process
GO:0001701	in utero embryonic development
GO:0001934	positive regulation of protein phosphorylation
GO:0006935	chemotaxis
GO:0006954	inflammatory response
GO:0010759	positive regulation of macrophage chemotaxis
GO:0045087	innate immune response (InnateDB)
GO:0045600	positive regulation of fat cell differentiation
GO:0048566	embryonic digestive tract development
GO:0050873	brown fat cell differentiation
GO:0050921	positive regulation of chemotaxis
GO:0050994	regulation of lipid catabolic process
GO:2001275	positive regulation of glucose import in response to insulin stimulus