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

Gene ID: 6351, updated on 27-Nov-2024

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
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Genomic context

See CCL4 in Genome Data Viewer
Location:
17q12
Exon count:
3
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (36103827..36105614)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (37051742..37053529)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (34431220..34433007)

Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene C-C motif chemokine ligand 18 Neighboring gene CCL3 antisense RNA 1 Neighboring gene C-C motif chemokine ligand 3 Neighboring gene MPRA-validated peak2824 silencer Neighboring gene RNA, 7SL, cytoplasmic 301, pseudogene Neighboring gene uncharacterized LOC101927369 Neighboring gene golgi membrane protein 1 pseudogene

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

HIV-1 interactions

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

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Clone Names

  • MGC104418, MGC126025, MGC126026

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 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

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.

Genomic

  1. NG_033066.2 RefSeqGene

    Range
    5002..6789
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_002984.4NP_002975.1  C-C motif chemokine 4 precursor

    See identical proteins and their annotated locations for NP_002975.1

    Status: REVIEWED

    Source sequence(s)
    AY766446
    Consensus CDS
    CCDS11308.1
    UniProtKB/Swiss-Prot
    P13236, P22617, Q13704, Q3SXL8, Q6FGI8
    UniProtKB/TrEMBL
    B7ZW36
    Related
    ENSP00000482259.1, ENST00000615863.2
    Conserved Domains (1) summary
    pfam00048
    Location:3286
    IL8; Small cytokines (intecrine/chemokine), interleukin-8 like

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000017.11 Reference GRCh38.p14 Primary Assembly

    Range
    36103827..36105614
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p14 ALT_REF_LOCI_1

Genomic

  1. NT_187614.1 Reference GRCh38.p14 ALT_REF_LOCI_1

    Range
    338748..340535
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p14 ALT_REF_LOCI_2

Genomic

  1. NT_187661.1 Reference GRCh38.p14 ALT_REF_LOCI_2

    Range
    57924..59711
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060941.1 Alternate T2T-CHM13v2.0

    Range
    37051742..37053529
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)