CCL4 C-C motif chemokine ligand 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CCL4provided by HGNC
Official Full Name: C-C motif chemokine ligand 4provided by HGNC
Primary source: HGNC:HGNC:10630
See related: Ensembl:ENSG00000275302 MIM:182284; AllianceGenome:HGNC:10630
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ACT2; G-26; HC21; LAG1; LAG-1; MIP1B; SCYA2; SCYA4; MIP1B1; AT744.1; MIP-1-beta
Summary: The protein encoded by this gene is a mitogen-inducible monokine and is one of the major HIV-suppressive factors produced by CD8+ T-cells. The encoded protein is secreted and has chemokinetic and inflammatory functions. [provided by RefSeq, Dec 2012]
Expression: Broad expression in bone marrow (RPKM 61.4), liver (RPKM 36.1) and 18 other tissues See more
Orthologs: all
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Genomic context

Location:: 17q12

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (36103827..36105614)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (37051742..37053529)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (34431220..34433007)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

m7G-related genes-NCBP2 and EIF4E3 determine immune contexture in head and neck squamous cell carcinoma by regulating CCL4/CCL5 expression.
Title: m7G-related genes-NCBP2 and EIF4E3 determine immune contexture in head and neck squamous cell carcinoma by regulating CCL4/CCL5 expression.
Expression and potential role of CCL4 in CD8+T cells in NSCLC.
Title: Expression and potential role of CCL4 in CD8+T cells in NSCLC.
STAT3 Promotes Cell Proliferation by Potentiating the CCL4 Transcriptional Activity in Diffuse Large B-Cell Lymphoma.
Title: STAT3 Promotes Cell Proliferation by Potentiating the CCL4 Transcriptional Activity in Diffuse Large B-Cell Lymphoma.
Beryllium-specific CD4+ T cells induced by chemokine neoantigens perpetuate inflammation.
Title: Beryllium-specific CD4+ T cells induced by chemokine neoantigens perpetuate inflammation.
Association of gene and protein expression and genetic polymorphism of CC chemokine ligand 4 in colorectal cancer.
Title: Association of gene and protein expression and genetic polymorphism of CC chemokine ligand 4 in colorectal cancer.
Intratumoral gammadelta T-Cell Infiltrates, Chemokine (C-C Motif) Ligand 4/Chemokine (C-C Motif) Ligand 5 Protein Expression and Survival in Patients With Hepatocellular Carcinoma.
Title: Intratumoral γδ T-Cell Infiltrates, Chemokine (C-C Motif) Ligand 4/Chemokine (C-C Motif) Ligand 5 Protein Expression and Survival in Patients With Hepatocellular Carcinoma.
Hypertension delays viral clearance and exacerbates airway hyperinflammation in patients with COVID-19.
Title: Hypertension delays viral clearance and exacerbates airway hyperinflammation in patients with COVID-19.
A Four-Chemokine Signature Is Associated with a T-cell-Inflamed Phenotype in Primary and Metastatic Pancreatic Cancer.
Title: A Four-Chemokine Signature Is Associated with a T-cell-Inflamed Phenotype in Primary and Metastatic Pancreatic Cancer.
Cholesterol is essential for macrophage inflammatory protein 1 beta binding and signaling and conformational integrity of CC chemokine receptor 5. (Is MIP-1 beta the entry SCYA4 or LD78? If so, please add the term to SCYA4 or LD78.)
Title: Cholesterol is essential for macrophage inflammatory protein 1 beta binding and conformational integrity of CC chemokine receptor 5.
Protein Concentrations of Thrombospondin-1, MIP-1beta, and S100A8 Suggest the Reflection of a Pregnancy Clock in Mid-Trimester Amniotic Fluid.
Title: Protein Concentrations of Thrombospondin-1, MIP-1β, and S100A8 Suggest the Reflection of a Pregnancy Clock in Mid-Trimester Amniotic Fluid.

Submit: New GeneRIF Correction See all GeneRIFs (128)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Asp	asp	ASP-YL9 peptide (89YLYNSLLQL97) induces release of IL-2, IFN-gamma, TNF-alpha, or MIP-1beta in antigen-specific CD8+ T-cells	PubMed
Envelope surface glycoprotein gp120	env	HIV-1 gp120 induces the release of cytokines MIP-1 alpha, MIP-1 beta, IL-6, IL10, and TNF-alpha in immature dentritic cells	PubMed
	env	The CCR5 chemokine receptor is required for the entry of macrophage-tropic HIV-1 into target cells; the HIV-1 gp120-CD4 complex binds CCR5, which inhibits the binding of the natural CCR5 ligands macrophage inflammatory protein (MIP)-1alpha and MIP-1beta	PubMed
	env	Neuroprotective chemokine CCL4 reduces HIV-1 gp120-mediated p38 MAPK activation	PubMed
	env	Exposure of macrophages to purified CCR5- or CXCR4-tropic HIV-1 envelope glycoprotein gp120 induces secretion of high levels of macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, RANTES, and tumor necrosis factor alpha	PubMed
	env	NK cells exposed to CXCR4-tropic HIV-1 gp120 produce lower levels of CC chemokines RANTES, MIP-1alpha, and MIP-1beta compared with that produced from untreated NK cells	PubMed
	env	HIV-1 gp120 induced cell death is inhibited by a CCR5-mediated neuroprotective pathway that involves protein kinase Akt/PKB as an essential component and can be triggered by the CCR5 agonists MIP-1beta and RANTES	PubMed
	env	The chemokine receptor CCR5 is posttranslationally modified by sulfation of its N-terminal tyrosines; sulfated tyrosines contribute to the binding of CCR5 to MIP-1 alpha, MIP-1 beta, and HIV-1 gp120/CD4 complexes and to the ability of HIV-1 to enter cells	PubMed
	env	N-formyl-methionyl-leucylphenyl-alanine binding to formyl peptide receptor (FPR) results in significant attenuation of cell responses to CCR5 ligands and in inhibition of HIV-1 gp120-mediated fusion and infection of cells expressing CD4, CCR5, and FPR	PubMed
Envelope surface glycoprotein gp160, precursor	env	A significant level of MIP1B is upregulated when PBMCs are stimulated with HIV-1 gp140	PubMed
Envelope transmembrane glycoprotein gp41	env	A synthetic peptide corresponding to the immunosuppressive domain (amino acids 574-592) of HIV-1 gp41 inhibits activation of PBMCs and upregulates the expression of MIP-1beta in peptide-treated PBMCs	PubMed
	env	RANTES, MIP-1beta, and anti-CD4 antibodies inhibit CCR5-dependent cell-cell fusion mediated by HIV-1 gp120 and gp41 from macrophage-tropic isolates	PubMed
Nef	nef	HIV-1 Nef induces the production of two CC-chemokines, macrophage inflammatory proteins 1alpha and 1beta, in HIV-1-infected macrophages	PubMed
	nef	HIV-1 Nef-stimulated CD8+ T cells upregulate mRNAs expression for IFN-gamma, MIP-1alpha, MIP-1alphaP, MIP-1beta, TNFRSF9, XCL1, and GM-CSF compared to unstimulated cells	PubMed
	nef	The proportion of HIV-1 Nef-specific CD8+ T cells endowed with TNF-alpha+, IFN-gamma+, CD107A+, and MIP-1beta+ is significantly higher in patients with the lowest virus set point than those with the highest virus set point	PubMed
	nef	Secretion of MIP-1beta from Nef-specific CD8+ T cells is associated with nonprogressive HIV-1 infection	PubMed
	nef	A novel domain (K(92)EK) within Nef is required for Nef-dependent MIP-1beta production by infected macrophages	PubMed
	nef	HIV-1 Nef-pulsed iDCs downregulate MIP-1beta and RANTES expression in NK cells	PubMed
	nef	HIV-1 Nef expression by immature human and macaque dendritic cells (DCs) upregulates IL-6, IL-12, TNF-alpha, CXCL8, CCL3, and CCL4 release, but without upregulating co-stimulatory and other molecules characteristic of mature DCs	PubMed
Pr55(Gag)	gag	MVA-gag induces a significant release of cytokines such as IL-2R, IL-6, IL-8, TNF-alpha, IFN-gamma, MCP-1, MIP-1alpha, MIP-1beta, and RANTES by the infected monocyte-derived dendritic cells in comparison with uninfected cells	PubMed
	gag	The proportion of HIV-1 Gag-specific CD8+ T cells endowed with TNF-alpha+, IFN-gamma+, CD107A+, and MIP-1beta+ is significantly higher in patients with the lowest virus set point than those with the highest virus set point	PubMed
Tat	tat	HIV-1 Tat upregulates MIP-1beta expression in microglia, monocyte-derived dendritic cells, and activated APC, an effect that may play a role in HIV encephalitis and immunosuppression of uninfected T cells	PubMed
	tat	Wild-type Tat but not Cys-22 and oxidized Tat induces CD1A-expressing monocyte-derived dendritic cells (MDDC) maturation and increases the production of cytokines TNF-alpha, IL-12, MIP-1alpha, and MIP-1beta	PubMed
Vpr	vpr	HIV-1 Vpr downregulates the expression of beta chemokines in primary lymphocytes and macrophages, including MIP-1 alpha, MIP-1 beta, and RANTES	PubMed
capsid	gag	PLA-p24-loaded human monocyte-derived dendritic cells enhance the secretion of MIP-1beta, IL-6, IL-8, and TNF-alpha in comparison with PLA-loaded cells alone	PubMed
	gag	HIV-1 CA-stimulated CD8+ T cells upregulate mRNAs expression for IFN-gamma, MIP-1alpha, MIP-1alphaP, MIP-1beta, TNFRSF9, XCL1, and GM-CSF compared to unstimulated cells	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:489733

RH17517 (e-PCR)
- UniSTS:45079

STS-X53683 (e-PCR)
- UniSTS:25644

STS-M69203 (e-PCR)
- UniSTS:25645

PMC108024P1 (e-PCR)
- UniSTS:270130

ovineDNA_CCL4 (e-PCR)
- UniSTS:514616

PMC152049P1 (e-PCR)
- UniSTS:271198

RH11493 (e-PCR)
- UniSTS:51430

G28333 (e-PCR)
- UniSTS:42991

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables CCR chemokine receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables CCR1 chemokine receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables CCR5 chemokine receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables chemokine activity	IBA Inferred from Biological aspect of Ancestor more info
enables cytokine activity	TAS Traceable Author Statement more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in antimicrobial humoral immune response mediated by antimicrobial peptide	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell adhesion	TAS Traceable Author Statement more info	PubMed
involved_in cell-cell signaling	TAS Traceable Author Statement more info	PubMed
involved_in chemokine-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in eosinophil chemotaxis	IBA Inferred from Biological aspect of Ancestor more info
involved_in establishment or maintenance of cell polarity	TAS Traceable Author Statement more info	PubMed
involved_in immune response	TAS Traceable Author Statement more info	PubMed
involved_in inflammatory response	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation by host of viral transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of GTPase activity	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of calcium ion transport	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of calcium-mediated signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell migration	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of natural killer cell chemotaxis	IDA Inferred from Direct Assay more info	PubMed
involved_in response to toxic substance	IDA Inferred from Direct Assay more info	PubMed
involved_in response to virus	TAS Traceable Author Statement more info	PubMed
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: C-C motif chemokine 4

Names: G-26 T-lymphocyte-secreted protein; MIP-1-beta(1-69); PAT 744; SIS-gamma; T-cell activation protein 2; chemokine (C-C motif) ligand 4; lymphocyte activation gene 1 protein; macrophage inflammatory protein 1-beta; secreted protein G-26; small inducible cytokine A4 (homologous to mouse Mip-1b)

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.