TISIDB

Summary
Symbol	CCR6
Name	chemokine (C-C motif) receptor 6
Aliases	CKR-L3; GPR-CY4; CMKBR6; GPR29; DRY-6; BN-1; CD196; STRL22; C-C CKR-6; CC-CKR-6; CCR-6; CKRL3; DRY6; GPRCY4; ......
Chromosomal Location	6q27
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	Cell membrane Multi-pass membrane protein Cell surface
Domain	PF00001 7 transmembrane receptor (rhodopsin family)
Function	Receptor for the C-C type chemokine CCL20 (PubMed:9169459). Binds to CCL20 and subsequently transduces a signal by increasing the intracellular calcium ion levels (PubMed:20068036). Although CCL20 is its major ligand it can also act as a receptor for non-chemokine ligands such as beta-defensins (PubMed:25585877). Binds to defensin DEFB1 leading to increase in intracellular calcium ions and cAMP levels. Its binding to DEFB1 is essential for the function of DEFB1 in regulating sperm motility and bactericidal activity (PubMed:25122636). Binds to defensins DEFB4 and DEFB4A/B and mediates their chemotactic effects (PubMed:20068036). The ligand-receptor pair CCL20-CCR6 is responsible for the chemotaxis of dendritic cells (DC), effector/ memory T-cells and B-cells and plays an important role at skin and mucosal surfaces under homeostatic and inflammatory conditions, as well as in pathology, including cancer and various autoimmune diseases. CCR6-mediated signals are essential for immune responses to microbes in the intestinal mucosa and in the modulation of inflammatory responses initiated by tissue insult and trauma (PubMed:21376174). CCR6 is essential for the recruitment of both the proinflammatory IL17 producing helper T-cells (Th17) and the regulatory T-cells (Treg) to sites of inflammation. Required for the normal migration of Th17 cells in Peyers-patches and other related tissue sites of the intestine and plays a role in regulating effector T-cell balance and distribution in inflamed intestine. Plays an important role in the coordination of early thymocyte precursor migration events important for normal subsequent thymocyte precursor development, but is not required for the formation of normal thymic natural regulatory T-cells (nTregs). Required for optimal differentiation of DN2 and DN3 thymocyte precursors. Essential for B-cell localization in the subepithelial dome of Peyers-patches and for efficient B-cell isotype switching to IgA in the Peyers-patches. Essential for appropriate anatomical distribution of memory B-cells in the spleen and for the secondary recall response of memory B-cells (By similarity). Positively regulates sperm motility and chemotaxis via its binding to CCL20 (PubMed:23765988).

> Gene Ontology [ TOP ]
Biological Process	GO:0001667 ameboidal-type cell migration GO:0002200 somatic diversification of immune receptors GO:0002204 somatic recombination of immunoglobulin genes involved in immune response GO:0002208 somatic diversification of immunoglobulins involved in immune response GO:0002250 adaptive immune response GO:0002263 cell activation involved in immune response GO:0002285 lymphocyte activation involved in immune response GO:0002312 B cell activation involved in immune response GO:0002366 leukocyte activation involved in immune response GO:0002377 immunoglobulin production GO:0002381 immunoglobulin production involved in immunoglobulin mediated immune response GO:0002407 dendritic cell chemotaxis GO:0002440 production of molecular mediator of immune response GO:0002443 leukocyte mediated immunity GO:0002449 lymphocyte mediated immunity GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains GO:0002521 leukocyte differentiation GO:0002523 leukocyte migration involved in inflammatory response GO:0002562 somatic diversification of immune receptors via germline recombination within a single locus 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:0006310 DNA recombination GO:0006874 cellular calcium ion homeostasis GO:0006875 cellular metal ion homeostasis GO:0006959 humoral immune response GO:0006968 cellular defense response GO:0007159 leukocyte cell-cell adhesion GO:0007204 positive regulation of cytosolic calcium ion concentration GO:0007281 germ cell development GO:0007283 spermatogenesis GO:0007286 spermatid development GO:0010631 epithelial cell migration GO:0010632 regulation of epithelial cell migration GO:0010634 positive regulation of epithelial cell migration GO:0016064 immunoglobulin mediated immune response GO:0016444 somatic cell DNA recombination GO:0016445 somatic diversification of immunoglobulins GO:0016447 somatic recombination of immunoglobulin gene segments GO:0019722 calcium-mediated signaling GO:0019724 B cell mediated immunity GO:0019932 second-messenger-mediated signaling GO:0021700 developmental maturation GO:0022412 cellular process involved in reproduction in multicellular organism GO:0030098 lymphocyte differentiation GO:0030217 T cell differentiation GO:0030317 flagellated sperm motility GO:0030335 positive regulation of cell migration GO:0030595 leukocyte chemotaxis GO:0032103 positive regulation of response to external stimulus GO:0033077 T cell differentiation in thymus GO:0036336 dendritic cell migration GO:0040017 positive regulation of locomotion GO:0042110 T cell activation GO:0042113 B cell activation GO:0045190 isotype switching GO:0048232 male gamete generation GO:0048240 sperm capacitation GO:0048290 isotype switching to IgA isotypes GO:0048469 cell maturation GO:0048515 spermatid differentiation GO:0050900 leukocyte migration GO:0050920 regulation of chemotaxis GO:0050921 positive regulation of chemotaxis GO:0051272 positive regulation of cellular component movement GO:0051480 regulation of cytosolic calcium ion concentration GO:0055074 calcium ion homeostasis GO:0060326 cell chemotaxis GO:0060474 positive regulation of flagellated sperm motility involved in capacitation GO:0070098 chemokine-mediated signaling pathway GO:0070486 leukocyte aggregation GO:0070489 T cell aggregation GO:0071593 lymphocyte aggregation GO:0071594 thymocyte aggregation GO:0072503 cellular divalent inorganic cation homeostasis GO:0072507 divalent inorganic cation homeostasis GO:0072676 lymphocyte migration GO:0072678 T cell migration GO:0072679 thymocyte migration GO:0090130 tissue migration GO:0090132 epithelium migration GO:0097722 sperm motility GO:1901317 regulation of flagellated sperm motility GO:1902093 positive regulation of flagellated sperm motility GO:1904155 DN2 thymocyte differentiation GO:1904156 DN3 thymocyte differentiation GO:2000147 positive regulation of cell motility GO:2000401 regulation of lymphocyte migration GO:2000404 regulation of T cell migration GO:2000508 regulation of dendritic cell chemotaxis GO:2000510 positive regulation of dendritic cell chemotaxis
Molecular Function	GO:0001637 G-protein coupled chemoattractant receptor activity GO:0001653 peptide receptor activity GO:0004896 cytokine receptor activity GO:0004950 chemokine receptor activity GO:0008528 G-protein coupled peptide receptor activity GO:0016493 C-C chemokine receptor activity GO:0019955 cytokine binding GO:0019956 chemokine binding GO:0019957 C-C chemokine binding
Cellular Component	GO:0005929 cilium GO:0031514 motile cilium GO:0036126 sperm flagellum GO:0044441 ciliary part GO:0097223 sperm part GO:0097225 sperm midpiece GO:0097228 sperm principal piece GO:0097524 sperm plasma membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04060 Cytokine-cytokine receptor interaction hsa04062 Chemokine signaling pathway
Reactome	R-HSA-6803157: Antimicrobial peptides R-HSA-1461957: Beta defensins R-HSA-380108: Chemokine receptors bind chemokines R-HSA-373076: Class A/1 (Rhodopsin-like receptors) R-HSA-1461973: Defensins R-HSA-418594: G alpha (i) signalling events R-HSA-388396: GPCR downstream signaling R-HSA-500792: GPCR ligand binding R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-375276: Peptide ligand-binding receptors R-HSA-162582: Signal Transduction R-HSA-372790: Signaling by GPCR

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04060 Cytokine-cytokine receptor interaction
hsa04062 Chemokine signaling pathway

Reactome

R-HSA-6803157: Antimicrobial peptides
R-HSA-1461957: Beta defensins
R-HSA-380108: Chemokine receptors bind chemokines
R-HSA-373076: Class A/1 (Rhodopsin-like receptors)
R-HSA-1461973: Defensins
R-HSA-418594: G alpha (i) signalling events
R-HSA-388396: GPCR downstream signaling
R-HSA-500792: GPCR ligand binding
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-375276: Peptide ligand-binding receptors
R-HSA-162582: Signal Transduction
R-HSA-372790: Signaling by GPCR

Summary
Symbol	CCR6
Name	chemokine (C-C motif) receptor 6
Aliases	CKR-L3; GPR-CY4; CMKBR6; GPR29; DRY-6; BN-1; CD196; STRL22; C-C CKR-6; CC-CKR-6; CCR-6; CKRL3; DRY6; GPRCY4; ......
Chromosomal Location	6q27
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CCR6 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 ]
There is no record.

Summary
Symbol	CCR6
Name	chemokine (C-C motif) receptor 6
Aliases	CKR-L3; GPR-CY4; CMKBR6; GPR29; DRY-6; BN-1; CD196; STRL22; C-C CKR-6; CC-CKR-6; CCR-6; CKRL3; DRY6; GPRCY4; ......
Chromosomal Location	6q27
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

[ TOP ]

Statistical results of CCR6 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	CCR6
Name	chemokine (C-C motif) receptor 6
Aliases	CKR-L3; GPR-CY4; CMKBR6; GPR29; DRY-6; BN-1; CD196; STRL22; C-C CKR-6; CC-CKR-6; CCR-6; CKRL3; DRY6; GPRCY4; ......
Chromosomal Location	6q27
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

[ TOP ]

Points in the above scatter plot represent the expression difference of CCR6 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	0.41	0.375
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.811	0.282
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.112	0.863
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.52	0.379
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.462	0.66
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.59	0.636
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.924	0.0988
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.031	0.224
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.864	0.331
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.659	0.362
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	0.009	0.992
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.413	0.0724

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of CCR6 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	14.3	0	14.3	0.196
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	20	0	20	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	3.7	4.1	-0.4	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	3.7	5.1	-1.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	5.9	-5.9	0.447
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	9.1	-9.1	0.458
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	7.9	0	7.9	0.26
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	13.6	0	13.6	0.279
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	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	CCR6
Name	chemokine (C-C motif) receptor 6
Aliases	CKR-L3; GPR-CY4; CMKBR6; GPR29; DRY-6; BN-1; CD196; STRL22; C-C CKR-6; CC-CKR-6; CCR-6; CKRL3; DRY6; GPRCY4; ......
Chromosomal Location	6q27
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CCR6. 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	CCR6
Name	chemokine (C-C motif) receptor 6
Aliases	CKR-L3; GPR-CY4; CMKBR6; GPR29; DRY-6; BN-1; CD196; STRL22; C-C CKR-6; CC-CKR-6; CCR-6; CKRL3; DRY6; GPRCY4; ......
Chromosomal Location	6q27
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CCR6. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CCR6. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CCR6
Name	chemokine (C-C motif) receptor 6
Aliases	CKR-L3; GPR-CY4; CMKBR6; GPR29; DRY-6; BN-1; CD196; STRL22; C-C CKR-6; CC-CKR-6; CCR-6; CKRL3; DRY6; GPRCY4; ......
Chromosomal Location	6q27
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CCR6. 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	CCR6
Name	chemokine (C-C motif) receptor 6
Aliases	CKR-L3; GPR-CY4; CMKBR6; GPR29; DRY-6; BN-1; CD196; STRL22; C-C CKR-6; CC-CKR-6; CCR-6; CKRL3; DRY6; GPRCY4; ......
Chromosomal Location	6q27
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CCR6 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CCR6
Name	chemokine (C-C motif) receptor 6
Aliases	CKR-L3; GPR-CY4; CMKBR6; GPR29; DRY-6; BN-1; CD196; STRL22; C-C CKR-6; CC-CKR-6; CCR-6; CKRL3; DRY6; GPRCY4; ......
Chromosomal Location	6q27
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CCR6 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CCR6
Name	chemokine (C-C motif) receptor 6
Aliases	CKR-L3; GPR-CY4; CMKBR6; GPR29; DRY-6; BN-1; CD196; STRL22; C-C CKR-6; CC-CKR-6; CCR-6; CKRL3; DRY6; GPRCY4; ......
Chromosomal Location	6q27
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CCR6 collected from DrugBank database.

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

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