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Browse CCR5

Summary
SymbolCCR5
Namechemokine (C-C motif) receptor 5 (gene/pseudogene)
Aliases CKR-5; CC-CKR-5; CKR5; CD195; IDDM22; CMKBR5; chemokine (C-C motif) receptor 5; CCCKR5; CCR-5; C-C motif che ......
Chromosomal Location3p21
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 Cell membrane Multi-pass membrane protein
Domain PF00001 7 transmembrane receptor (rhodopsin family)
Function

Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May play a role in the control of granulocytic lineage proliferation or differentiation. ; FUNCTION: (Microbial infection) Acts as a coreceptor (CD4 being the primary receptor) of human immunodeficiency virus-1/HIV-1.

> Gene Ontology
 
Biological Process GO:0002237 response to molecule of bacterial origin
GO:0002407 dendritic cell chemotaxis
GO:0006816 calcium ion transport
GO:0006874 cellular calcium ion homeostasis
GO:0006875 cellular metal ion homeostasis
GO:0006968 cellular defense response
GO:0007204 positive regulation of cytosolic calcium ion concentration
GO:0014808 release of sequestered calcium ion into cytosol by sarcoplasmic reticulum
GO:0019058 viral life cycle
GO:0019064 fusion of virus membrane with host plasma membrane
GO:0019722 calcium-mediated signaling
GO:0019932 second-messenger-mediated signaling
GO:0030260 entry into host cell
GO:0030595 leukocyte chemotaxis
GO:0032496 response to lipopolysaccharide
GO:0032844 regulation of homeostatic process
GO:0032845 negative regulation of homeostatic process
GO:0036314 response to sterol
GO:0036336 dendritic cell migration
GO:0039663 membrane fusion involved in viral entry into host cell
GO:0044409 entry into host
GO:0044800 multi-organism membrane fusion
GO:0044803 multi-organism membrane organization
GO:0046718 viral entry into host cell
GO:0050900 leukocyte migration
GO:0051208 sequestering of calcium ion
GO:0051209 release of sequestered calcium ion into cytosol
GO:0051235 maintenance of location
GO:0051238 sequestering of metal ion
GO:0051282 regulation of sequestering of calcium ion
GO:0051283 negative regulation of sequestering of calcium ion
GO:0051480 regulation of cytosolic calcium ion concentration
GO:0051701 interaction with host
GO:0051806 entry into cell of other organism involved in symbiotic interaction
GO:0051828 entry into other organism involved in symbiotic interaction
GO:0055074 calcium ion homeostasis
GO:0060326 cell chemotaxis
GO:0060401 cytosolic calcium ion transport
GO:0060402 calcium ion transport into cytosol
GO:0061025 membrane fusion
GO:0070098 chemokine-mediated signaling pathway
GO:0070296 sarcoplasmic reticulum calcium ion transport
GO:0070509 calcium ion import
GO:0070588 calcium ion transmembrane transport
GO:0070723 response to cholesterol
GO:0070838 divalent metal ion transport
GO:0071216 cellular response to biotic stimulus
GO:0071219 cellular response to molecule of bacterial origin
GO:0071222 cellular response to lipopolysaccharide
GO:0071396 cellular response to lipid
GO:0072503 cellular divalent inorganic cation homeostasis
GO:0072507 divalent inorganic cation homeostasis
GO:0072511 divalent inorganic cation transport
GO:0097305 response to alcohol
GO:0097553 calcium ion transmembrane import into cytosol
GO:1902656 calcium ion import into cytosol
GO:1903514 calcium ion transport from endoplasmic reticulum to cytosol
GO:2000021 regulation of ion homeostasis
Molecular Function GO:0001618 virus receptor activity
GO:0001637 G-protein coupled chemoattractant receptor activity
GO:0001653 peptide receptor activity
GO:0003779 actin binding
GO:0004435 phosphatidylinositol phospholipase C activity
GO:0004620 phospholipase activity
GO:0004629 phospholipase C activity
GO:0004896 cytokine receptor activity
GO:0004950 chemokine receptor activity
GO:0008081 phosphoric diester hydrolase activity
GO:0008528 G-protein coupled peptide receptor activity
GO:0015026 coreceptor activity
GO:0016298 lipase activity
GO:0016493 C-C chemokine receptor activity
GO:0019955 cytokine binding
GO:0019956 chemokine binding
GO:0019957 C-C chemokine binding
GO:0042578 phosphoric ester hydrolase activity
GO:0071791 chemokine (C-C motif) ligand 5 binding
Cellular Component GO:0009897 external side of plasma membrane
GO:0098552 side of membrane
> KEGG and Reactome Pathway
 
KEGG hsa04060 Cytokine-cytokine receptor interaction
hsa04062 Chemokine signaling pathway
hsa04144 Endocytosis
Reactome R-HSA-173107: Binding and entry of HIV virion
R-HSA-380108: Chemokine receptors bind chemokines
R-HSA-373076: Class A/1 (Rhodopsin-like receptors)
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-1643685: Disease
R-HSA-162594: Early Phase of HIV Life Cycle
R-HSA-418594: G alpha (i) signalling events
R-HSA-388396: GPCR downstream signaling
R-HSA-500792: GPCR ligand binding
R-HSA-162906: HIV Infection
R-HSA-162587: HIV Life Cycle
R-HSA-168256: Immune System
R-HSA-5663205: Infectious disease
R-HSA-6783783: Interleukin-10 signaling
R-HSA-375276: Peptide ligand-binding receptors
R-HSA-162582: Signal Transduction
R-HSA-372790: Signaling by GPCR
R-HSA-449147: Signaling by Interleukins
Summary
SymbolCCR5
Namechemokine (C-C motif) receptor 5 (gene/pseudogene)
Aliases CKR-5; CC-CKR-5; CKR5; CD195; IDDM22; CMKBR5; chemokine (C-C motif) receptor 5; CCCKR5; CCR-5; C-C motif che ......
Chromosomal Location3p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between CCR5 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 CCR5 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
27070705Colorectal CarcinomaInhibit immunity (T cell function)While two distinct subsets of myeloid cells induce an influx of T cells into the invasive margin via CXCL9/CXCL10, CCL5 is produced by these T cells and stimulates pro-tumoral effects via CCR5.
23152559MelanomaInhibit immunityExpression of CCR5 was preferentially detected on regulatory T cells (Tregs). Accordingly, tumor-infiltrating MO-MDSCs directly attracted high numbers of Tregs via CCR5 in vitro. Intratumoral injection of CCL4 or CCL5 increased tumor-infiltrating Tregs, and deficiency of CCR5 led to their profound decrease. Moreover, in CCR5-deficient mice, RMA-S and B16 tumor growth was delayed emphasizing the importance of CCR5 in the control of antitumor immune responses.
19688743MelanomaPromote immunity (T cell function)Gadd45b, a signaling molecule highly up-regulated during Th1 type responses, is studied for its role in limiting tumor growth. Mouse B16 melanoma cells implanted into Gadd45b(-/-) mice grew faster than those in WT or Gadd45b(+/-) littermate controls. The defect of Gadd45b(-/-) mice in tumor immunosurveillance was attributed to the reduced expression of IFN-gamma, granzyme B, and CCR5 in Gadd45b(-/-) CD8(+) T cells at the tumor site.
28868628Ovarian CarcinomaInhibit immunity (T cell function)Ovarian cancer stem cells promote tumour immune privilege and invasion via CCL5 and regulatory T cells. The expression of its receptor, C-C motif chemokine receptor 5 (CCR5), was also increased on the surface of Tregs in ovarian cancer patients. This receptor-ligand expression profile indicated that ovarian CSCs recruit Tregs via CCL5-CCR5 interactions.
22282655Colorectal CarcinomaPromote immunity (infiltration); Inhibit immunity (T cell function)We found that higher levels of CCL5 expression in human and murine colon tumor cells correlated with higher levels of apoptosis of CD8+ T cells and infiltration of T-regulatory cells (T(reg)). We also found tumor growth to be diminished in mice lacking CCR5, a CCL5 receptor, where a similar decrease in both T(reg) cell infiltration and CD8(+) T-cell apoptosis was noted. TGF-β signaling blockade diminished apoptosis of CD8(+) T cells, implicating TGF-β as an effector of CCL5 action. In support of this concept, CCL5 failed to enhance the production of TGF-β by CCR5-deficient T(reg) or to enhance their cytotoxic effects against CD8(+) T cells.
28416485Triple-Negative Breast CarcinomaInhibit immunityWe demonstrate here that an autocrine CCL5-CCR5 axis is a major regulator of immunosuppressive myeloid cells (IMC) of both monocytic and granulocytic lineages. An analysis of human triple-negative breast cancer specimens demonstrated an inverse correlation between "immune CCR5" levels and the maturation status of tumor-infiltrating neutrophils as well as 5-year-survival rates. Targeting the host CCL5 in bone marrow via nanoparticle-delivered expression silencing, in combination with the CCR5 inhibitor Maraviroc, resulted in strong reductions of IMC and robust antitumor immunities.
19155524Pancreatic CarcinomaInhibit immunity (infiltration)When CCR5/CCL5 signaling is disrupted, either by reducing CCL5 production by tumor cells or by systemic administration of a CCR5 inhibitor (N,N-dimethyl-N-{{4-{[2-(4-methylphenyl)-6,7-dihydro-5H-benzocyclohepten-8-yl]carbonyl}amino}}benzyl]-N,N-dimethyl-N- {{{4-{{{[2-(4-methylphenyl)-6,7-dihydro-5H-benzocycloheptan-8-yl]carbonyl}amino}}benzyl}}}tetrahydro-2H-pyran-4-aminiumchloride; TAK-779), Treg migration to tumors is reduced and tumors are smaller than in control mice. Thus, this study demonstrates the importance of Tregs in immune evasion by tumors, how blockade of Treg migration might inhibit tumor growth, and, specifically in pancreatic adenocarcinoma, the role of CCR5 in the homing of tumor-associated Tregs.
29617574Non-Small Cell Lung CarcinomaInhibit immunityThe frequency of C-C chemokine receptor 5 (CCR5) expression on circulating M-MDSCs was significantly higher in the patients than in the HDs.
29104081Colon CacinomaPromote immunityAdditionally, TWS119 can induce the expression of CD62L or CCR5 to generate a population of CD62L+γδT or CCR5+γδT cells in a dose-dependent manner.
18645037HepatomaPromote immunity (infiltration)Tumor-infiltrating DCs expressed chemokine receptors CCR1 and CCR5, and T cells and macrophages expressed CCL3, a ligand for CCR1 and CCR5. Thus, we provide definitive evidence indicating that CCR1 and CCR5 and their ligand CCL3 play a crucial role in the regulation of intratumoral DC accumulation and the subsequent establishment of tumor immunity following induction of tumor apoptosis by suicide genes.
28904130Skin Squamous Cell CarcinomaInhibit immunityAnalysis of tumor lesions in wild-type (WT) and CCR5KO mice revealed that lack of CCR5 lead to significant reduction in frequency of Tregs and increased of CD4 T cells into the tumors. In this study, we also demonstrated that Treg migration to the tumor microenvironment is mediated by CCR5, and these cells are promoting tumor growth via inhibition of antitumor cells such as cytotoxic CD8+T cells.
21715565FibrosarcomaPromote immunityCCR5 activation in CD4(+) cells resulted in CD40L upregulation, leading to full maturation of antigen-presenting cells and enhanced CD8(+) T-cell crosspriming and tumor infiltration. CCR5 reduced chemical-induced fibrosarcoma incidence and growth, but did not affect the onset or progression of spontaneous breast cancers in tolerogenic Tg(MMTV-neu) mice. Our results indicate that CCR5 boosts T-cell responses to tumors by modulating helper-dependent CD8(+) T-cell activation.
21792901renal cell carcinoma; melanoma; colon carcinomaPromote immunity (T cell function)The CD8 tumor-infiltrating T lymphocytes in 6-gingerol-treated mice strongly expressed IFN-γ, a marker of activation of cytotoxic T lymphocytes (CTL) CD107a and chemokine receptors that are expressed on T(H) 1 cells, such as CXCR3 and CCR5.
Summary
SymbolCCR5
Namechemokine (C-C motif) receptor 5 (gene/pseudogene)
Aliases CKR-5; CC-CKR-5; CKR5; CD195; IDDM22; CMKBR5; chemokine (C-C motif) receptor 5; CCCKR5; CCR-5; C-C motif che ......
Chromosomal Location3p21
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 CCR5 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
SymbolCCR5
Namechemokine (C-C motif) receptor 5 (gene/pseudogene)
Aliases CKR-5; CC-CKR-5; CKR5; CD195; IDDM22; CMKBR5; chemokine (C-C motif) receptor 5; CCCKR5; CCR-5; C-C motif che ......
Chromosomal Location3p21
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 CCR5 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.1620.72
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.0660.956
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.2250.791
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.9910.0791
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.0970.929
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 472.1210.104
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.680.195
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15111.1110.361
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.1910.888
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 481.8090.185
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.5360.471
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.130.541
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of CCR5 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) 27733.71.42.30.469
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.71.720.532
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
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
SymbolCCR5
Namechemokine (C-C motif) receptor 5 (gene/pseudogene)
Aliases CKR-5; CC-CKR-5; CKR5; CD195; IDDM22; CMKBR5; chemokine (C-C motif) receptor 5; CCCKR5; CCR-5; C-C motif che ......
Chromosomal Location3p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CCR5. 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
SymbolCCR5
Namechemokine (C-C motif) receptor 5 (gene/pseudogene)
Aliases CKR-5; CC-CKR-5; CKR5; CD195; IDDM22; CMKBR5; chemokine (C-C motif) receptor 5; CCCKR5; CCR-5; C-C motif che ......
Chromosomal Location3p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CCR5. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CCR5.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolCCR5
Namechemokine (C-C motif) receptor 5 (gene/pseudogene)
Aliases CKR-5; CC-CKR-5; CKR5; CD195; IDDM22; CMKBR5; chemokine (C-C motif) receptor 5; CCCKR5; CCR-5; C-C motif che ......
Chromosomal Location3p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CCR5. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolCCR5
Namechemokine (C-C motif) receptor 5 (gene/pseudogene)
Aliases CKR-5; CC-CKR-5; CKR5; CD195; IDDM22; CMKBR5; chemokine (C-C motif) receptor 5; CCCKR5; CCR-5; C-C motif che ......
Chromosomal Location3p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of CCR5 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolCCR5
Namechemokine (C-C motif) receptor 5 (gene/pseudogene)
Aliases CKR-5; CC-CKR-5; CKR5; CD195; IDDM22; CMKBR5; chemokine (C-C motif) receptor 5; CCCKR5; CCR-5; C-C motif che ......
Chromosomal Location3p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between CCR5 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolCCR5
Namechemokine (C-C motif) receptor 5 (gene/pseudogene)
Aliases CKR-5; CC-CKR-5; CKR5; CD195; IDDM22; CMKBR5; chemokine (C-C motif) receptor 5; CCCKR5; CCR-5; C-C motif che ......
Chromosomal Location3p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting CCR5 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting CCR5.
ID Name Drug Type Targets #Targets
DB04835MaravirocSmall MoleculeCCR51
DB05501AMD-070Small MoleculeCCR5, CXCR42
DB06652VicrivirocSmall MoleculeCCR51
DB12698IbalizumabBiotechCCR5, CD4, CXCR43
DB12960INCB-9471Small MoleculeCCR51