Browse RARRES2

Summary
SymbolRARRES2
Nameretinoic acid receptor responder (tazarotene induced) 2
Aliases TIG2; HP10433; chemerin; RAR-responsive protein TIG2; tazarotene-induced gene 2 protein; Retinoic acid recep ......
Chromosomal Location7q36.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Secreted
Domain -
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.

> Gene Ontology
 
Biological Process GO:0001523 retinoid metabolic process
GO:0001701 in utero embryonic development
GO:0002576 platelet degranulation
GO:0002685 regulation of leukocyte migration
GO:0002687 positive regulation of leukocyte migration
GO:0002688 regulation of leukocyte chemotaxis
GO:0002690 positive regulation of leukocyte chemotaxis
GO:0006720 isoprenoid metabolic process
GO:0006721 terpenoid metabolic process
GO:0006887 exocytosis
GO:0008643 carbohydrate transport
GO:0008645 hexose transport
GO:0009894 regulation of catabolic process
GO:0010758 regulation of macrophage chemotaxis
GO:0010759 positive regulation of macrophage chemotaxis
GO:0010827 regulation of glucose transport
GO:0010828 positive regulation of glucose transport
GO:0015749 monosaccharide transport
GO:0015758 glucose transport
GO:0016042 lipid catabolic process
GO:0016101 diterpenoid metabolic process
GO:0019216 regulation of lipid metabolic process
GO:0030335 positive regulation of cell migration
GO:0030595 leukocyte chemotaxis
GO:0032103 positive regulation of response to external stimulus
GO:0032868 response to insulin
GO:0032869 cellular response to insulin stimulus
GO:0040017 positive regulation of locomotion
GO:0043434 response to peptide hormone
GO:0044381 glucose import in response to insulin stimulus
GO:0045055 regulated exocytosis
GO:0045444 fat cell differentiation
GO:0045598 regulation of fat cell differentiation
GO:0045600 positive regulation of fat cell differentiation
GO:0046323 glucose import
GO:0046324 regulation of glucose import
GO:0046326 positive regulation of glucose import
GO:0048246 macrophage chemotaxis
GO:0048565 digestive tract development
GO:0048566 embryonic digestive tract development
GO:0048568 embryonic organ development
GO:0050873 brown fat cell differentiation
GO:0050900 leukocyte migration
GO:0050920 regulation of chemotaxis
GO:0050921 positive regulation of chemotaxis
GO:0050994 regulation of lipid catabolic process
GO:0051272 positive regulation of cellular component movement
GO:0055123 digestive system development
GO:0060326 cell chemotaxis
GO:0071375 cellular response to peptide hormone stimulus
GO:0071417 cellular response to organonitrogen compound
GO:0071621 granulocyte chemotaxis
GO:0071622 regulation of granulocyte chemotaxis
GO:0071674 mononuclear cell migration
GO:0071675 regulation of mononuclear cell migration
GO:0097529 myeloid leukocyte migration
GO:0097530 granulocyte migration
GO:1900076 regulation of cellular response to insulin stimulus
GO:1900078 positive regulation of cellular response to insulin stimulus
GO:1901652 response to peptide
GO:1901653 cellular response to peptide
GO:2000147 positive regulation of cell motility
GO:2001273 regulation of glucose import in response to insulin stimulus
GO:2001275 positive regulation of glucose import in response to insulin stimulus
Molecular Function -
Cellular Component GO:0030141 secretory granule
GO:0031089 platelet dense granule lumen
GO:0031983 vesicle lumen
GO:0034774 secretory granule lumen
GO:0042827 platelet dense granule
GO:0060205 cytoplasmic membrane-bounded vesicle lumen
GO:0099503 secretory vesicle
> KEGG and Reactome Pathway
 
KEGG -
Reactome R-HSA-109582: Hemostasis
R-HSA-76002: Platelet activation, signaling and aggregation
R-HSA-114608: Platelet degranulation
R-HSA-76005: Response to elevated platelet cytosolic Ca2+
Summary
SymbolRARRES2
Nameretinoic acid receptor responder (tazarotene induced) 2
Aliases TIG2; HP10433; chemerin; RAR-responsive protein TIG2; tazarotene-induced gene 2 protein; Retinoic acid recep ......
Chromosomal Location7q36.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between RARRES2 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between RARRES2 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
28166197Hepatocellular CarcinomaPromote immunity (T cell function)Chemerin has a protective role in hepatocellular carcinoma by inhibiting the expression of IL-6 and GM-CSF and MDSC accumulation.
22753924MelanomaPromote immunityIn experiments using the B16 transplantable mouse melanoma, tumor-expressed chemerin inhibited in vivo tumor growth without altering in vitro proliferation. Intratumoral injection of chemerin also inhibited tumor growth, suggesting the potential for therapeutic application.
Summary
SymbolRARRES2
Nameretinoic acid receptor responder (tazarotene induced) 2
Aliases TIG2; HP10433; chemerin; RAR-responsive protein TIG2; tazarotene-induced gene 2 protein; Retinoic acid recep ......
Chromosomal Location7q36.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of RARRES2 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolRARRES2
Nameretinoic acid receptor responder (tazarotene induced) 2
Aliases TIG2; HP10433; chemerin; RAR-responsive protein TIG2; tazarotene-induced gene 2 protein; Retinoic acid recep ......
Chromosomal Location7q36.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of RARRES2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.5310.4
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-1.0710.726
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.1240.953
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.0790.89
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.7670.682
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.7920.741
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.0440.942
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.1470.907
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.1470.928
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 48-0.8130.793
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 28-1.8650.695
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.4180.0493
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of RARRES2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27730001
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27590001
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.804.81
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.5012.51
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91606.2-6.21
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59011.1-11.11
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.206.21
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolRARRES2
Nameretinoic acid receptor responder (tazarotene induced) 2
Aliases TIG2; HP10433; chemerin; RAR-responsive protein TIG2; tazarotene-induced gene 2 protein; Retinoic acid recep ......
Chromosomal Location7q36.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of RARRES2. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolRARRES2
Nameretinoic acid receptor responder (tazarotene induced) 2
Aliases TIG2; HP10433; chemerin; RAR-responsive protein TIG2; tazarotene-induced gene 2 protein; Retinoic acid recep ......
Chromosomal Location7q36.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of RARRES2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by RARRES2.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolRARRES2
Nameretinoic acid receptor responder (tazarotene induced) 2
Aliases TIG2; HP10433; chemerin; RAR-responsive protein TIG2; tazarotene-induced gene 2 protein; Retinoic acid recep ......
Chromosomal Location7q36.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of RARRES2. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolRARRES2
Nameretinoic acid receptor responder (tazarotene induced) 2
Aliases TIG2; HP10433; chemerin; RAR-responsive protein TIG2; tazarotene-induced gene 2 protein; Retinoic acid recep ......
Chromosomal Location7q36.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of RARRES2 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolRARRES2
Nameretinoic acid receptor responder (tazarotene induced) 2
Aliases TIG2; HP10433; chemerin; RAR-responsive protein TIG2; tazarotene-induced gene 2 protein; Retinoic acid recep ......
Chromosomal Location7q36.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between RARRES2 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolRARRES2
Nameretinoic acid receptor responder (tazarotene induced) 2
Aliases TIG2; HP10433; chemerin; RAR-responsive protein TIG2; tazarotene-induced gene 2 protein; Retinoic acid recep ......
Chromosomal Location7q36.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting RARRES2 collected from DrugBank database.
> Drugs from DrugBank database
 

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