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FLASH GENE

Symbol

RARRES2

contributors: mct/npt - updated : 12-07-2017

HGNC name	retinoic acid receptor responder (tazarotene induced) 2
HGNC id	9868

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive liver         Homo sapiens Endocrine pancreas         Homo sapiens Reproductive female system placenta       Homo sapiens   female system ovary       Homo sapiens Visual eye anterior segment         eye uvea choroid

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     specific Homo sapiens Epithelial barrier lining retinal pigment epithelium (RPE)     Epithelial barrier/lining epidermis stratum spinosum   Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Cardiovascular endothelial cell not specific adipocyte Homo sapiens skin tegument hair follicle

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

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

HOMOLOGY

interspecies

ortholog to murine Rarres2

Homologene

FAMILY

steroid and thyroid hormone receptor superfamily of transcriptional regulators

CATEGORY

receptor nuclear

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	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

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

RARRES2/CMKLR1 system has been implicated in mediating cellular migration under inflammatory condition (Kaur 2010)

INTERACTION

DNA

RNA

small molecule

protein	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

REGULATION

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

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	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

ANIMAL & CELL MODELS