General Information of the Ferroptosis Regulator (ID: REG10320)
Regulator Name Retinoic acid receptor responder protein 2 (RARRES2)
Synonyms
TIG2; Chemerin; RAR-responsive protein TIG2; Tazarotene-induced gene 2 protein
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Gene Name RARRES2
Gene ID 5919
Regulator Type Protein coding
Uniprot ID Q99969
Sequence
MRRLLIPLALWLGAVGVGVAELTEAQRRGLQVALEEFHKHPPVQWAFQETSVESAVDTPF
PAGIFVRLEFKLQQTSCRKRDWKKPECKVRPNGRKRKCLACIKLGSEDKVLGRLVHCPIE
TQVLREAEEHQETQCLRVQRAGEDPHSFYFPGQFAFSKALPRS

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Function
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 pro-inflammatory adipokine, causing an increase in secretion of pro-inflammatory 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.

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HGNC ID
HGNC:9868
KEGG ID hsa:5919
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
RARRES2 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
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Browse Disease
Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Hereditary Leiomyomatosis ICD-11: 2C90
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
786-O cells Renal cell carcinoma Homo sapiens CVCL_1051
UOK101 cells Clear cell renal carcinoma Homo sapiens CVCL_B076
A-498 cells Renal cell carcinoma Homo sapiens CVCL_1056
HEK-293T cells Normal Homo sapiens CVCL_0063
HK-2 cells Normal Homo sapiens CVCL_0302
In Vivo Model
Six-week-old female athymic nude mice (Charles River Laboratories) were used for xenograft studies. For subcutaneous tumor growth model, cells were pelleted and resuspended in a PBS/Matrigel Matrix (Corning, Cat# 356234) mix at 1:1 ratio. 2 x 106 cells in a 100 uL solution were injected subcutaneously into each flank.

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Response regulation The adipokine chemerin, which is encoded by the retinoic acid receptor responder 2 (RARRES2) gene, is overexpressed in clear cell renal cell carcinoma (ccRCC) due to both an autocrine, tumor-cell-dependent mechanism, as well as obesity-dependent paracrine production, and plays important roles in regulating lipid metabolism and tumorigenesis.
Hereditary Leiomyomatosis [ICD-11: 2C90]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Retinoic acid receptor responder protein 2 (RARRES2) Protein coding
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
786-O cells Renal cell carcinoma Homo sapiens CVCL_1051
UOK101 cells Clear cell renal carcinoma Homo sapiens CVCL_B076
A-498 cells Renal cell carcinoma Homo sapiens CVCL_1056
HEK-293T cells Normal Homo sapiens CVCL_0063
HK-2 cells Normal Homo sapiens CVCL_0302
In Vivo Model
Six-week-old female athymic nude mice (Charles River Laboratories) were used for xenograft studies. For subcutaneous tumor growth model, cells were pelleted and resuspended in a PBS/Matrigel Matrix (Corning, Cat# 356234) mix at 1:1 ratio. 2 x 106 cells in a 100 uL solution were injected subcutaneously into each flank.

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Response regulation The adipokine chemerin, which is encoded by the retinoic acid receptor responder 2 (RARRES2) gene, is overexpressed in clear cell renal cell carcinoma (ccRCC) due to both an autocrine, tumor-cell-dependent mechanism, as well as obesity-dependent paracrine production, and plays important roles in regulating lipid metabolism and tumorigenesis.
References
Ref 1 Obesity-Dependent Adipokine Chemerin Suppresses Fatty Acid Oxidation to Confer Ferroptosis Resistance. Cancer Discov. 2021 Aug;11(8):2072-2093. doi: 10.1158/2159-8290.CD-20-1453. Epub 2021 Mar 23.