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Browse CCL4

Summary
SymbolCCL4
Namechemokine (C-C motif) ligand 4
Aliases Act-2; AT744.1; SCYA4; small inducible cytokine A4 (homologous to mouse Mip-1b); ACT2; G-26; HC21; MIP1B; MI ......
Chromosomal Location17q12
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 PF00048 Small cytokines (intecrine/chemokine)
Function

Monokine with inflammatory and chemokinetic properties. Binds to CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant MIP-1-beta induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). The processed form MIP-1-beta(3-69) retains the abilities to induce down-modulation of surface expression of the chemokine receptor CCR5 and to inhibit the CCR5-mediated entry of HIV-1 in T-cells. MIP-1-beta(3-69) is also a ligand for CCR1 and CCR2 isoform B.

> Gene Ontology
 
Biological Process GO:0002548 monocyte chemotaxis
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:0006816 calcium ion transport
GO:0007163 establishment or maintenance of cell polarity
GO:0009615 response to virus
GO:0009636 response to toxic substance
GO:0010959 regulation of metal ion transport
GO:0019058 viral life cycle
GO:0019080 viral gene expression
GO:0019083 viral transcription
GO:0019722 calcium-mediated signaling
GO:0019932 second-messenger-mediated signaling
GO:0030335 positive regulation of cell migration
GO:0030593 neutrophil chemotaxis
GO:0030595 leukocyte chemotaxis
GO:0031349 positive regulation of defense response
GO:0032103 positive regulation of response to external stimulus
GO:0032897 negative regulation of viral transcription
GO:0034341 response to interferon-gamma
GO:0034612 response to tumor necrosis factor
GO:0035690 cellular response to drug
GO:0035747 natural killer cell chemotaxis
GO:0035821 modification of morphology or physiology of other organism
GO:0040017 positive regulation of locomotion
GO:0042493 response to drug
GO:0043270 positive regulation of ion transport
GO:0043410 positive regulation of MAPK cascade
GO:0043900 regulation of multi-organism process
GO:0043901 negative regulation of multi-organism process
GO:0043903 regulation of symbiosis, encompassing mutualism through parasitism
GO:0043921 modulation by host of viral transcription
GO:0043922 negative regulation by host of viral transcription
GO:0044033 multi-organism metabolic process
GO:0046782 regulation of viral transcription
GO:0048247 lymphocyte chemotaxis
GO:0048525 negative regulation of viral process
GO:0050727 regulation of inflammatory response
GO:0050729 positive regulation of inflammatory response
GO:0050792 regulation of viral process
GO:0050848 regulation of calcium-mediated signaling
GO:0050850 positive regulation of calcium-mediated signaling
GO:0050900 leukocyte migration
GO:0050920 regulation of chemotaxis
GO:0050921 positive regulation of chemotaxis
GO:0051272 positive regulation of cellular component movement
GO:0051702 interaction with symbiont
GO:0051817 modification of morphology or physiology of other organism involved in symbiotic interaction
GO:0051851 modification by host of symbiont morphology or physiology
GO:0051924 regulation of calcium ion transport
GO:0051928 positive regulation of calcium ion transport
GO:0052312 modulation of transcription in other organism involved in symbiotic interaction
GO:0052472 modulation by host of symbiont transcription
GO:0060326 cell chemotaxis
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:0070555 response to interleukin-1
GO:0070838 divalent metal ion transport
GO:0071346 cellular response to interferon-gamma
GO:0071347 cellular response to interleukin-1
GO:0071356 cellular response to tumor necrosis factor
GO:0071621 granulocyte chemotaxis
GO:0071674 mononuclear cell migration
GO:0072511 divalent inorganic cation transport
GO:0072676 lymphocyte migration
GO:0097529 myeloid leukocyte migration
GO:0097530 granulocyte migration
GO:1901623 regulation of lymphocyte chemotaxis
GO:1903900 regulation of viral life cycle
GO:1903901 negative regulation of viral life cycle
GO:1990266 neutrophil migration
GO:2000147 positive regulation of cell motility
GO:2000401 regulation of lymphocyte migration
GO:2000403 positive regulation of lymphocyte migration
GO:2000501 regulation of natural killer cell chemotaxis
GO:2000503 positive regulation of natural killer cell chemotaxis
Molecular Function GO:0001664 G-protein coupled receptor binding
GO:0005125 cytokine activity
GO:0005126 cytokine receptor binding
GO:0008009 chemokine activity
GO:0031726 CCR1 chemokine receptor binding
GO:0031730 CCR5 chemokine receptor binding
GO:0042379 chemokine receptor binding
GO:0048020 CCR chemokine receptor binding
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa04060 Cytokine-cytokine receptor interaction
hsa04062 Chemokine signaling pathway
hsa04064 NF-kappa B signaling pathway
hsa04620 Toll-like receptor signaling pathway
hsa04623 Cytosolic DNA-sensing pathway
Reactome R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-168256: Immune System
R-HSA-6783783: Interleukin-10 signaling
R-HSA-449147: Signaling by Interleukins
Summary
SymbolCCL4
Namechemokine (C-C motif) ligand 4
Aliases Act-2; AT744.1; SCYA4; small inducible cytokine A4 (homologous to mouse Mip-1b); ACT2; G-26; HC21; MIP1B; MI ......
Chromosomal Location17q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between CCL4 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 CCL4 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
26729864MelanomaPromote immunityVaccination with combination therapy uniquely restricted Th2-cytokine production by CD4 cells, relative to combination therapy alone, and enhanced IFNγ production by CD8 and CD4 cells. We observed an increase in MIP-1α (macrophage inflammatory protein-1α)/CCL3 [chemokine (C-C motif) ligand 3], MIP-1β/CCL4, RANTES (regulated on activation, normal T-cell expressed and excreted)/CCL5, and GM-CSF production by CD8 and CD4 T cells following treatment.
27407095Cervical carcinomaPromote immunityIntravaginal treatment of IL7-Fc, but not native IL7, induces upregulation of chemokines (CXCL10, CCL3, CCL4, and CCL5), cytokines (IFNγ, TNFα, IL6, and IL1β), and an adhesion molecule (VCAM-1) in the genital tract, leading to the recruitment of several leukocytes, including CD4, CD8, γδ T cells, and dendritic cells.
27879269MelanomaPromote immunity (infiltration)Intratumoral basophils enhanced CD8+ T-cell infiltration via production of chemokines CCL3 and CCL4; antibody-based blocking of these chemokines inhibited CD8+ T-cell infiltration.
21480223Bladder CarcinomaInhibit immunityBoth myeloid cell subsets from cancer patients were highly activated and produced substantial amounts of proinflammatory chemokines/cytokines including CCL2, CCL3, CCL4, G-CSF, IL-8 and IL-6. We demonstrate that these highly activated inflammatory myeloid cells represent a source of multiple chemokines/cytokines and may contribute to inflammation and immune dysfunction in bladder cancer.
Summary
SymbolCCL4
Namechemokine (C-C motif) ligand 4
Aliases Act-2; AT744.1; SCYA4; small inducible cytokine A4 (homologous to mouse Mip-1b); ACT2; G-26; HC21; MIP1B; MI ......
Chromosomal Location17q12
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 CCL4 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
SymbolCCL4
Namechemokine (C-C motif) ligand 4
Aliases Act-2; AT744.1; SCYA4; small inducible cytokine A4 (homologous to mouse Mip-1b); ACT2; G-26; HC21; MIP1B; MI ......
Chromosomal Location17q12
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 CCL4 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.3560.538
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.1280.951
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.7080.646
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.0730.933
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.6520.584
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.6840.665
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.2580.629
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.4430.684
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.0760.948
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 4801
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 2801
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.3710.103
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of CCL4 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)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
SymbolCCL4
Namechemokine (C-C motif) ligand 4
Aliases Act-2; AT744.1; SCYA4; small inducible cytokine A4 (homologous to mouse Mip-1b); ACT2; G-26; HC21; MIP1B; MI ......
Chromosomal Location17q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CCL4. 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
SymbolCCL4
Namechemokine (C-C motif) ligand 4
Aliases Act-2; AT744.1; SCYA4; small inducible cytokine A4 (homologous to mouse Mip-1b); ACT2; G-26; HC21; MIP1B; MI ......
Chromosomal Location17q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CCL4. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CCL4.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolCCL4
Namechemokine (C-C motif) ligand 4
Aliases Act-2; AT744.1; SCYA4; small inducible cytokine A4 (homologous to mouse Mip-1b); ACT2; G-26; HC21; MIP1B; MI ......
Chromosomal Location17q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CCL4. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolCCL4
Namechemokine (C-C motif) ligand 4
Aliases Act-2; AT744.1; SCYA4; small inducible cytokine A4 (homologous to mouse Mip-1b); ACT2; G-26; HC21; MIP1B; MI ......
Chromosomal Location17q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of CCL4 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolCCL4
Namechemokine (C-C motif) ligand 4
Aliases Act-2; AT744.1; SCYA4; small inducible cytokine A4 (homologous to mouse Mip-1b); ACT2; G-26; HC21; MIP1B; MI ......
Chromosomal Location17q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between CCL4 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolCCL4
Namechemokine (C-C motif) ligand 4
Aliases Act-2; AT744.1; SCYA4; small inducible cytokine A4 (homologous to mouse Mip-1b); ACT2; G-26; HC21; MIP1B; MI ......
Chromosomal Location17q12
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting CCL4 collected from DrugBank database.
> Drugs from DrugBank database
 

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