InnateDB Protein
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IDBP-474592.3
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Last Modified
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2014-10-13 [Report errors or provide feedback]
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Gene Symbol
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RARRES2
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Protein Name
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retinoic acid receptor responder (tazarotene induced) 2
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Synonyms
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HP10433; TIG2;
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Species
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Homo sapiens
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Ensembl Protein
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ENSP00000418483
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InnateDB Gene
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IDBG-47881 (RARRES2)
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Protein Structure
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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}.
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Subcellular Localization |
Secreted {ECO:0000305}.
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Disease Associations |
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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}.
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Comments |
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Number of Interactions
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This gene and/or its encoded proteins are associated with 2 experimentally validated interaction(s) in this database.
Experimentally validated |
Total |
2
[view]
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Protein-Protein |
2
[view]
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Protein-DNA |
0
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Protein-RNA |
0
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DNA-DNA |
0
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RNA-RNA |
0
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DNA-RNA |
0
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Molecular Function |
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Biological Process |
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Cellular Component |
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PDB ID |
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InterPro |
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PFAM |
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PRINTS |
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PIRSF |
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SMART |
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TIGRFAMs |
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Modification |
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SwissProt |
Q99969
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PhosphoSite |
PhosphoSite-Q99969
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TrEMBL |
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UniProt Splice Variant |
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Entrez Gene |
5919
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UniGene |
Hs.647064
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RefSeq |
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HUGO |
HGNC:9868
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OMIM |
601973
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CCDS |
CCDS5902
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HPRD |
03577
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IMGT |
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EMBL |
AB015632
AC005586
AK312197
BC000069
CH471173
CR541992
CR542026
U77594
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GenPept |
AAB47975
AAH00069
AAS00384
BAA76499
BAG35130
CAG46789
CAG46823
EAW54120
EAW54121
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