TISIDB

Summary
Symbol	RARRES2
Name	retinoic acid receptor responder (tazarotene induced) 2
Aliases	TIG2; HP10433; chemerin; RAR-responsive protein TIG2; tazarotene-induced gene 2 protein; Retinoic acid recep ......
Chromosomal Location	7q36.1
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 [ TOP ]
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 [ TOP ]
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 [ TOP ]
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
Symbol	RARRES2
Name	retinoic acid receptor responder (tazarotene induced) 2
Aliases	TIG2; HP10433; chemerin; RAR-responsive protein TIG2; tazarotene-induced gene 2 protein; Retinoic acid recep ......
Chromosomal Location	7q36.1
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

[ TOP ]

Literatures describing the relation between RARRES2 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
28166197	Hepatocellular Carcinoma	Promote 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.
22753924	Melanoma	Promote immunity	In 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
Symbol	RARRES2
Name	retinoic acid receptor responder (tazarotene induced) 2
Aliases	TIG2; HP10433; chemerin; RAR-responsive protein TIG2; tazarotene-induced gene 2 protein; Retinoic acid recep ......
Chromosomal Location	7q36.1
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

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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
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	RARRES2
Name	retinoic acid receptor responder (tazarotene induced) 2
Aliases	TIG2; HP10433; chemerin; RAR-responsive protein TIG2; tazarotene-induced gene 2 protein; Retinoic acid recep ......
Chromosomal Location	7q36.1
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

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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
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.531	0.4
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-1.071	0.726
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.124	0.953
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.079	0.89
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.767	0.682
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.792	0.741
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.044	0.942
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.147	0.907
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.147	0.928
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.813	0.793
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	-1.865	0.695
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.418	0.0493

> Mutation difference between responders and non-responders

[ TOP ]

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
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	0	0	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	RARRES2
Name	retinoic acid receptor responder (tazarotene induced) 2
Aliases	TIG2; HP10433; chemerin; RAR-responsive protein TIG2; tazarotene-induced gene 2 protein; Retinoic acid recep ......
Chromosomal Location	7q36.1
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 [ TOP ]

Summary
Symbol	RARRES2
Name	retinoic acid receptor responder (tazarotene induced) 2
Aliases	TIG2; HP10433; chemerin; RAR-responsive protein TIG2; tazarotene-induced gene 2 protein; Retinoic acid recep ......
Chromosomal Location	7q36.1
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 [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	RARRES2
Name	retinoic acid receptor responder (tazarotene induced) 2
Aliases	TIG2; HP10433; chemerin; RAR-responsive protein TIG2; tazarotene-induced gene 2 protein; Retinoic acid recep ......
Chromosomal Location	7q36.1
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 [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	RARRES2
Name	retinoic acid receptor responder (tazarotene induced) 2
Aliases	TIG2; HP10433; chemerin; RAR-responsive protein TIG2; tazarotene-induced gene 2 protein; Retinoic acid recep ......
Chromosomal Location	7q36.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of RARRES2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	RARRES2
Name	retinoic acid receptor responder (tazarotene induced) 2
Aliases	TIG2; HP10433; chemerin; RAR-responsive protein TIG2; tazarotene-induced gene 2 protein; Retinoic acid recep ......
Chromosomal Location	7q36.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between RARRES2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	RARRES2
Name	retinoic acid receptor responder (tazarotene induced) 2
Aliases	TIG2; HP10433; chemerin; RAR-responsive protein TIG2; tazarotene-induced gene 2 protein; Retinoic acid recep ......
Chromosomal Location	7q36.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting RARRES2 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

Browse RARRES2