RARRES2是一種與腫瘤發(fā)生有關的蛋白質(zhì)，其確切的作用機制仍需要進一步研究。最近的研究表明，RARRES2可能參與調(diào)節(jié)腫瘤的生長和擴散，并影響腫瘤細胞對化療的敏感性。

Adipocyte-secreted protein (adipokine) that regulates adipogenesis, metabolism and inflammation through activation of the chemokine-like receptor 1 (CMKLR1). Acts also as a ligand for CMKLR2. Can also bind to C-C chemokine receptor-like 2 (CCRL2), but with a lower affinity than it does to CMKLR1 or CMKLR2. 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.

1. chemerin and leptin are elevated and omentin-1 and visfatin levels are decreased in Gestational diabetes mellitus women complicated by obesity. PMID: 29337272
2. The elevated levels of circulating TIG2 (chemerin) were associated with gestational diabetes mellitus.[meta-analysis] PMID: 30041634
3. This study show the serum PARRES2 levels had significant positive correlation with seizure severity Chalfont score and the duration of epilepsy. PMID: 29860632
4. findings of this study suggest that chemerin in synovial fluid may play role as a predisposing factor and may represent a novel potential prognostic biochemical marker in the pathogenesis of temporomandibular joint disorders PMID: 29331039
5. G allele of chemerin rs17173608 compared to T allele decreased the risk of end-stage renal disease in a sample of Iranian population. PMID: 29644922
6. Data suggest that down-regulation of serum levels of chemerin (an inflammatory cytokine biomarker) can occur in weight-loss therapy as short in duration as 4-week aerobic exercise plus dieting in obese female adolescents; this effect was not observed by dieting alone. This study was conducted in weight-loss summer camp in China. PMID: 29306931
7. results demonstrate a strong inverse association between serum chemerin levels and renal function. PMID: 28833355
8. The aims of this study were to evaluate and correlate circulating chemerin, apelin, vaspin, and omentin-1 levels in obese type 2 diabetic Egyptian patients with coronary artery stenosis (CAS), and to assess their usefulness as noninvasive diagnostic biomarkers. PMID: 28957639
9. Data suggest that, in overweight and obese subjects, weight reduction induces changes in chemerin serum levels in parallel with adiponectin plasma levels; chemerin is down-regulated and adiponectin is up-regulated in both insulin-resistant and insulin-sensitive subjects after weight reduction; however, only changes in chemerin in insulin-sensitive subjects were found to be statistically significant. PMID: 28323510
10. No associations were observed between SNPs in RARRES2 and obesity. PMID: 28947843
11. Serum chemerin level during the first trimester of pregnancy has the potential to predict risk of gestational diabetes mellitus. PMID: 28454507
12. The SD to LD transition was mimicked by 2 weeks of ICV infusion of human chemerin into rats. It also increased expression of the cytoskeletal protein vimentin, implicating hypothalamic remodeling in this response.Acute ICV bolus injection of chemerin on a 12 h:12 h photoperiod inhibited food intake and decreased body weight with associated changes in hypothalamic neuropeptides involved in growth and feeding after 24 hr. PMID: 27225311
13. We studied the association between retinoic acid receptor responder 2 rs17173608 and rs4721 gene polymorphisms and gestational diabetes mellitus. We found that RARRES2 rs4721 polymorphism increased the risk of gestational diabetes mellitus. RARRES2 rs17173608 polymorphism is not associated with gestational diabetes mellitus. PMID: 29360607
14. High chemerin expression is associated with metabolic complications. PMID: 28551507
15. results show that chemerin not only increases osteoclasts activity in vitro, but also that increased level of chemerin in dyslipidemic mice plays a critical role in bone homeostasis. PMID: 28029186
16. Suggest chemerin is a major factor in the secretome of senescent fibroblasts, promoting cutaneous squamous carcinoma cell migration, and possibly progression, relaying its signals through CCRL2 and GPR1 receptors with subsequent MAPK activation. PMID: 27907906
17. Data suggest that chemerin acts at CMKLR1, but not GPR1, to increase blood pressure. Chemerin is expressed in vascular endothelium, smooth muscle, and adventitia. PMID: 27742615
18. Data suggest that primary cells from papillary renal cell carcinoma secrete the chemokines IL8, CXCL16, and chemerin; these chemokines attract primary human monocytes and induce shift/transdifferentiation in monocytes toward M2 macrophage/foam cell phenotype. (IL8 = interleukin-8; CXCL16 = C-X-C motif chemokine ligand 16) PMID: 28759013
19. Chemerin-CMKLR1 activates Akt/mTOR and ERK pathways and facilitates preadipocyte proliferation, adipogenesis, and angiogenesis. Gax weakens the effect of chemerin on preadipocyte biofunctions. PMID: 28326537
20. study reveals the tumor-inhibitory effect of chemerin by suppressing inflammatory tumor microenvironment with therapeutic implications for inflammation-associated cancer-like Hepatocellular carcinoma. PMID: 28166197
21. Further analysis of chemerin functions in vivo might constitute a crucial step toward optimizing Mesenchymal stromal cells-based therapy for inflammatory diseases. PMID: 27939374
22. Stimulation of mesenchymal stromal cells (MSCs) by chemerin increases phosphorylation of p42/44, p38 and JNK-II kinases and inhibitors of these kinases and PKC reverse chemerin-stimulated MSC migration. PMID: 25127029
23. Elevated chemerin levels in colons from ulcerative colitis patients correlate with disease severity PMID: 24727542
24. cathepsin S and chemerin only correlated positively with insulin resistance and inflammation PMID: 24390241
25. Cathepsin L- and K-cleaved chemerin trigger robust migration of human blood-derived plasmacytoid dendritic cells ex vivo PMID: 21715684
26. Plasma chemerin levels are correlated with obesity, blood pressure, and high-density lipoprotein cholesterol, suggesting that it may play a role in the pathogenesis of metabolic syndrome. PMID: 24338392
27. High serum RARRES2 expression is associated with Adrenocortical Carcinoma. PMID: 27336360
28. Hypoxia-induced chemerin expression is mediated by TNF-alpha and at least in part by the ERK pathway PMID: 27792771
29. Low chemerin and high resistin levels were associated with carotid disease severity, suggesting that these adipokines may act as potential markers for plaque instability and stroke risk. PMID: 27312219
30. Serum chemerin concentrations are associated with the presence of atrial fibrillation and atrial remodeling. PMID: 27496791
31. Chemerin mRNA is reduced in the liver of nonalcoholic steatohepatitis patients. PMID: 27797398
32. Results show that chemerin stimulates the migration, invasion and proliferation of oesophageal cancer cells by a pathway sensitive to the ChemR23 antagonist CCX832. PMID: 27092781
33. In type 2 diabetes mellitus, both chemerin and omentin enhance the body sensitivity to insulin, which results in increased glucose uptake PMID: 27516571
34. High chemerin expression is associated with Overweight/obese. PMID: 27941174
35. Circulating levels of the adipokine chemerin are elevated in lipodystrophy, as well as independently and positively associated with HbA1c and CRP. PMID: 26572532
36. There was no difference in serum chemerin, vaspin and omentin-1 between polycystic ovary syndrome patients and healthy controls. PMID: 27225862
37. Study demonstrated that circulating chemerin plasma levels are high in patients with chronic obstructive pulmonary disease. PMID: 24865134
38. We conclude that LDL apheresis decreases the circulating level of chemerin by binding the protein to the column and thus improves lipoprotein subfraction pattern. PMID: 27756331
39. The production of the two adipokines, chemerin and RBP-4, is strongly associated with obesity in patients with NAFLD. PMID: 27740519
40. this study suggested that a role of STRA6 polymorphism could also be of value in predicting the risk of type 2 diabetes mellitus(T2DM) while RARRES2 polymorphism could not predict the risk of T2DM. PMID: 27446956
41. Studied levels of salivary visfatin, chemerin, and progranulin and in gingivitis, periodontitis, as well as healthy patients. Salivary progranulin levels were similar in all groups; chemerin was detected at higher levels in the periodontitis group compared to the gingivitis and the healthy groups; visfatin levels were higher in patients with gingivitis and periodontitis compared to those of healthy subjects. PMID: 25164155
42. Data show inverse Relationship of the CMKLR1 Relative Expression and Chemerin Serum Levels in Obesity with Dysmetabolic Phenotype and Insulin Resistance PMID: 27239101
43. Oral lipid loading is linked to reduced circulating pro-inflammatory chemokines CCL2, IP-10, and chemerin and to increased RANTES levels, suggesting that dietary lipids affect immune function. PMID: 26950614
44. Metabolic syndrome in Egyptian females is associated with the minor allele of chemerin rs17173608 polymorphism. PMID: 26472663
45. Serum chemerin was significantly higher in the obese PCOS group compared with non-obese PCOS and the obese and non-obese control groups. PMID: 26291816
46. The synovial fluid and synovial membrane levels of chemerin are increased in knee osteoarthritis patients PMID: 26722546
47. Together, these findings suggest that CCL2, RARRES2 and EFNB2 are host cell factors involved in respiratory syncytial virus replication. PMID: 26277777
48. serum chemerin may have a role in acute ischemic stroke and carotid artery plaque instability in Chinese populations PMID: 26471865
49. Suggest reduction of chemerin could contribute to the antiobesity/antidiabetic properties described for alpha-lipoic acid. PMID: 26721419
50. chemerin is a novel biomarker of dilated cardiomyopathy PMID: 26057200

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Secreted.

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

HGNC: 9868

OMIM: 601973

KEGG: hsa:5919

STRING: 9606.ENSP00000223271

UniGene: Hs.647064