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Symbol RARRES2 contributors: mct/npt - updated : 12-07-2017
HGNC name retinoic acid receptor responder (tazarotene induced) 2
HGNC id 9868
Location 7q36.1      Physical location : 150.035.407 - 150.038.763
Synonym name
  • chemerin
  • tazarotene induced gene 2
  • RAR-responsive protein TIG2
  • Synonym symbol(s) TIG2, HP10433, CHEM
    TYPE functioning gene
    STRUCTURE 3.29 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 767 17 163 - Sell (2009)
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver     Homo sapiens
    Endocrinepancreas     Homo sapiens
    Reproductivefemale systemplacenta    Homo sapiens
     female systemovary    Homo sapiens
    Visualeyeanterior segment   
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  specific Homo sapiens
    Epithelialbarrier liningretinal pigment epithelium (RPE)  
    Epithelialbarrier/liningepidermisstratum spinosum  Homo sapiens
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell
    not specificadipocyte Homo sapiens
    skin tegumenthair follicle
    cell lineage
    cell lines
    at STAGE
    isoforms Precursor initially secreted as an inactive form, pro-chemerin and processed to an active form via a cleavage of five to nine C-terminal amino acids by serine proteases such as mast cell tryptase and elastase
    interspecies ortholog to murine Rarres2
  • steroid and thyroid hormone receptor superfamily of transcriptional regulators
  • CATEGORY receptor nuclear
    intracellular,nuclear envelope
    text secreted by the mature 3T3-L1 adipocytes
    basic FUNCTION
  • modulate immune system function through its binding to the chemerin receptor
  • adipokine chemerin likely regulating adipocyte function by autocrine/paracrine mechanisms
  • adipose-derived signaling molecule that regulates adipogenesis and adipocyte metabolism
  • modulate immune system function through its binding to the chemerin receptor
  • regulate both adipocyte differentiation and lipid metabolism
  • may be involved in both the initiation and resolution of inflammation (Yoshimura 2008)
  • adipokine that affects adipogenesis and glucose homeostasis in adipocytes and increases with BMI in humans (Sell 2009)
  • induces insulin resistance in skeletal muscle cells at the level of insulin receptor substrate 1, Akt and glycogen synthase kinase 3 phosphorylation, and glucose uptake (Sell 2009)
  • may be involved in the development of the metabolic syndrome (Bozaoglu 2009)
  • role for chemerin as a stimulator of angiogenesis (Bozaoglu 2010)
  • activates key survival and angiogenic signalling cascades like MAPK and Akt pathways (Kaur 2010)
  • inducing functional angiogenesis in human endothelial cells by promoting migration and capillary tube formation, and activation of endothelial gelatinases (MMP-2/-9) (Kaur 2010)
  • adipocytokine which plays a role on inflammation and adipocytes metabolism
  • plays a role not only in the differentiation of adipocytes but also in the inflammatory responses of immune cells such as dendritic cells and macrophages
  • might play a compensate role in the pathogenesis of obesity and/or type II diabetes-related inflammatory vascular diseases
  • plays an inhibitory role on inflammatory state of vascular endothelial cells
  • roles for RARRES2/CMKLR1-mediated in dental epithelial-dental mesenchymal (DE-DM) signaling during tooth morphogenesis
  • oxidative stress mediates RARRES2-induced autophagy in endothelial cells
  • is an antimicrobial agent in human skin
  • in host defense, chemerin plays dual roles as a broad spectrum antimicrobial protein and as a leukocyte attractant for macrophages, dendritic cells, and NK cells
  • is a novel adipokine linked to inflammation
  • role of genetic variation in RARRES2 in the regulation of circulating serum chemerin
  • physiologic role for RARRES2 in skin barrier defense against microbial pathogens
  • may play an important role in regulating mitochondrial remodelling and function in skeletal muscle
  • RARRES2 stimulated vascular smooth muscle cells proliferation and carotid intimal hyperplasia through activation of the mitogen-activated protein kinase signaling pathway, which may lead to vascular inflammation and remodeling, and is relevant to proliferative cardiovascular diseases
  • is a novel tumor suppressor for adrenocortical carcinoma (ACC), which can function through an immune-independent mechanism
    a component RARRES2/CMKLR1 system has been implicated in mediating cellular migration under inflammatory condition (Kaur 2010)
    small molecule
  • ligand for the G protein-coupled receptor CMKLR1 and has a role in adaptive and innate immunity
  • natural ligand of the chemerin receptor (chemerinR), also known as chemokine like receptor 1 (CMKLR1, or GPCR-DEZ)
  • CCRL2 binds RARRES2 and increases local chemerin concentration to efficiently present it to CMKLR1 on nearby cells, providing a link between CCRL2 and CMKLR1
  • RARRES2 plays anti-inflammatory roles by preventing TNF-induced VCAM1 expression and monocytes adhesion in vascular endothelial cells
  • autocrine/paracrine role for RARRES2 in regulating osteoclast differentiation of hematopoietic stem cell (HSC) through modulating intracellular calcium and NFATC1 expression/activation
  • RARRES2 is a protein ligand for the G protein-coupled receptor CMKLR1 and also binds to two atypical heptahelical receptors, CCRL2 and GPR1
  • RARRES2 increased expression of the cytoskeletal protein vimentin, implicating hypothalamic remodelling in this response
  • cell & other
    activated by tazarotene in skin rafts and in the epidermis of psoriatic lesions
    inhibited by psoriatic lesions
    Other upregulated by the synthetic retinoid tazarotene
    strongly induced during the adipocyte differentiation
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in the adipose depots of obese compared with lean animals and was markedly elevated during differentiation of fibroblasts into mature adipocytes (Bozaoglu 2010)
    constitutional     --over  
    in obese subjects
    tumoral     --low  
    in multiple cancer types
    constitutional     --over  
    serum RARRES2 concentrations were significantly higher in atrial fibrillation patients compared with healthy controls
    constitutional     --over  
    circulating chemerin was increased in overweight compared with normal weight polycystic ovary syndrome (PCOS) patients
    constitutional     --over  
    circulating levels of the RARRES2 are elevated in Lipodystrophy (LD), as well as independently and positively associated with HbA1c and CRP
    Variant & Polymorphism
    Candidate gene
  • serum RARRES2 may be used as a novel prognostic marker for adrenocortical carcinoma (ACC)
  • is a novel biomarker of dilated cardiomyopathy
  • may play a role as predictive biomarker for pre-eclampsia and be an important causative factor in the pathogenesis of pre-eclampsia
  • Therapy target