TISIDB

Summary
Symbol	ACKR3
Name	atypical chemokine receptor 3
Aliases	GPR159; CMKOR1; CXCR7; chemokine orphan receptor 1; chemokine (C-X-C motif) receptor 7; CXC-R7; CXCR-7; C-X- ......
Chromosomal Location	2q37.3
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. Cytoplasm, perinuclear region. Early endosome. Recycling endosome Note=Predominantly localizes to endocytic vesicles, and upon stimulation by the ligand is internalized via clathrin-coated pits in a beta-arrestin-dependent manner. Once internalized, the ligand dissociates from the receptor, and is targeted to degradation while the receptor is recycled back to the cell membrane.
Domain	PF00001 7 transmembrane receptor (rhodopsin family)
Function	Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Acts as a receptor for chemokines CXCL11 and CXCL12/SDF1. Chemokine binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization and activation of MAPK signaling pathway. Required for regulation of CXCR4 protein levels in migrating interneurons, thereby adapting their chemokine responsiveness. In glioma cells, transduces signals via MEK/ERK pathway, mediating resistance to apoptosis. Promotes cell growth and survival. Not involved in cell migration, adhesion or proliferation of normal hematopoietic progenitors but activated by CXCL11 in malignant hemapoietic cells, leading to phosphorylation of ERK1/2 (MAPK3/MAPK1) and enhanced cell adhesion and migration. Plays a regulatory role in CXCR4-mediated activation of cell surface integrins by CXCL12. Required for heart valve development. Acts as coreceptor with CXCR4 for a restricted number of HIV isolates.

> Gene Ontology [ TOP ]
Biological Process	GO:0001525 angiogenesis GO:0001570 vasculogenesis GO:0006898 receptor-mediated endocytosis GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage GO:0031623 receptor internalization GO:0043112 receptor metabolic process GO:0043410 positive regulation of MAPK cascade GO:0048514 blood vessel morphogenesis GO:0070098 chemokine-mediated signaling pathway GO:0070371 ERK1 and ERK2 cascade GO:0070372 regulation of ERK1 and ERK2 cascade GO:0070374 positive regulation of ERK1 and ERK2 cascade GO:0097193 intrinsic apoptotic signaling pathway GO:1902229 regulation of intrinsic apoptotic signaling pathway in response to DNA damage GO:1902230 negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage GO:1902532 negative regulation of intracellular signal transduction GO:2001020 regulation of response to DNA damage stimulus GO:2001021 negative regulation of response to DNA damage stimulus GO:2001233 regulation of apoptotic signaling pathway GO:2001234 negative regulation of apoptotic signaling pathway GO:2001242 regulation of intrinsic apoptotic signaling pathway GO:2001243 negative regulation of intrinsic apoptotic signaling pathway
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:0005044 scavenger receptor activity GO:0008528 G-protein coupled peptide receptor activity GO:0015026 coreceptor activity GO:0016494 C-X-C chemokine receptor activity GO:0019955 cytokine binding GO:0019956 chemokine binding GO:0019958 C-X-C chemokine binding GO:0038024 cargo receptor activity
Cellular Component	GO:0005769 early endosome GO:0005905 clathrin-coated pit GO:0055037 recycling endosome GO:0098589 membrane region

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04060 Cytokine-cytokine receptor interaction
Reactome	R-HSA-380108: Chemokine receptors bind chemokines R-HSA-373076: Class A/1 (Rhodopsin-like receptors) R-HSA-418594: G alpha (i) signalling events R-HSA-388396: GPCR downstream signaling R-HSA-500792: GPCR ligand binding R-HSA-375276: Peptide ligand-binding receptors R-HSA-162582: Signal Transduction R-HSA-372790: Signaling by GPCR

Summary
Symbol	ACKR3
Name	atypical chemokine receptor 3
Aliases	GPR159; CMKOR1; CXCR7; chemokine orphan receptor 1; chemokine (C-X-C motif) receptor 7; CXC-R7; CXCR-7; C-X- ......
Chromosomal Location	2q37.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between ACKR3 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	ACKR3
Name	atypical chemokine receptor 3
Aliases	GPR159; CMKOR1; CXCR7; chemokine orphan receptor 1; chemokine (C-X-C motif) receptor 7; CXC-R7; CXCR-7; C-X- ......
Chromosomal Location	2q37.3
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 ACKR3 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	ACKR3
Name	atypical chemokine receptor 3
Aliases	GPR159; CMKOR1; CXCR7; chemokine orphan receptor 1; chemokine (C-X-C motif) receptor 7; CXC-R7; CXCR-7; C-X- ......
Chromosomal Location	2q37.3
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 ACKR3 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	-0.93	0.0385
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.803	0.585
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-1.005	0.246
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.603	0.227
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.598	0.735
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.611	0.777
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.006	0.991
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.012	0.991
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.138	0.917
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.239	0.872
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	1.57	0.449
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.223	0.225

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of ACKR3 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	1.4	-1.4	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	0	1.7	-1.7	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	5.9	-1.1	1
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	7.7	9.1	-1.4	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	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	0	0	0	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	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	ACKR3
Name	atypical chemokine receptor 3
Aliases	GPR159; CMKOR1; CXCR7; chemokine orphan receptor 1; chemokine (C-X-C motif) receptor 7; CXC-R7; CXCR-7; C-X- ......
Chromosomal Location	2q37.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ACKR3. 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	ACKR3
Name	atypical chemokine receptor 3
Aliases	GPR159; CMKOR1; CXCR7; chemokine orphan receptor 1; chemokine (C-X-C motif) receptor 7; CXC-R7; CXCR-7; C-X- ......
Chromosomal Location	2q37.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ACKR3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ACKR3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ACKR3
Name	atypical chemokine receptor 3
Aliases	GPR159; CMKOR1; CXCR7; chemokine orphan receptor 1; chemokine (C-X-C motif) receptor 7; CXC-R7; CXCR-7; C-X- ......
Chromosomal Location	2q37.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ACKR3. 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	ACKR3
Name	atypical chemokine receptor 3
Aliases	GPR159; CMKOR1; CXCR7; chemokine orphan receptor 1; chemokine (C-X-C motif) receptor 7; CXC-R7; CXCR-7; C-X- ......
Chromosomal Location	2q37.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ACKR3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ACKR3
Name	atypical chemokine receptor 3
Aliases	GPR159; CMKOR1; CXCR7; chemokine orphan receptor 1; chemokine (C-X-C motif) receptor 7; CXC-R7; CXCR-7; C-X- ......
Chromosomal Location	2q37.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ACKR3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ACKR3
Name	atypical chemokine receptor 3
Aliases	GPR159; CMKOR1; CXCR7; chemokine orphan receptor 1; chemokine (C-X-C motif) receptor 7; CXC-R7; CXCR-7; C-X- ......
Chromosomal Location	2q37.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ACKR3 collected from DrugBank database.

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

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