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

Gene ID: 6351, updated on 26-May-2016
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 HPRD:01657; MIM:182284
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]
Orthologs
Location:
17q12
Exon count:
3
Annotation release Status Assembly Chr Location
107 current GRCh38.p2 (GCF_000001405.28) 17 NC_000017.11 (36103827..36105621)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (34431220..34433014)

Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene C-C motif chemokine ligand 18 Neighboring gene C-C motif chemokine ligand 3 Neighboring gene uncharacterized LOC101927369 Neighboring gene golgi membrane protein 1 pseudogene Neighboring gene nitric oxide synthase 2, inducible pseudogene Neighboring gene TBC1 domain family member 3B

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

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

  • Chemokine receptors bind chemokines, organism-specific biosystem (from REACTOME)
    Chemokine receptors bind chemokines, organism-specific biosystemChemokine receptors are cytokine receptors found on the surface of certain cells, which interact with a type of cytokine called a chemokine. Following interaction, these receptors trigger a flux of i...
  • Chemokine signaling pathway, organism-specific biosystem (from KEGG)
    Chemokine signaling pathway, organism-specific biosystemInflammatory immune response requires the recruitment of leukocytes to the site of inflammation upon foreign insult. Chemokines are small chemoattractant peptides that provide directional cues for th...
  • Chemokine signaling pathway, conserved biosystem (from KEGG)
    Chemokine signaling pathway, conserved biosystemInflammatory immune response requires the recruitment of leukocytes to the site of inflammation upon foreign insult. Chemokines are small chemoattractant peptides that provide directional cues for th...
  • Class A/1 (Rhodopsin-like receptors), organism-specific biosystem (from REACTOME)
    Class A/1 (Rhodopsin-like receptors), organism-specific biosystemRhodopsin-like receptors (class A/1) are the largest group of GPCRs and are the best studied group from a functional and structural point of view. They show great diversity at the sequence level and ...
  • Cytokine-cytokine receptor interaction, organism-specific biosystem (from KEGG)
    Cytokine-cytokine receptor interaction, organism-specific biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
  • Cytokine-cytokine receptor interaction, conserved biosystem (from KEGG)
    Cytokine-cytokine receptor interaction, conserved biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
  • Cytosolic DNA-sensing pathway, organism-specific biosystem (from KEGG)
    Cytosolic DNA-sensing pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting foreign DNA from invading microbes or host cells and generating innate immune responses. DAI is the first identified s...
  • Cytosolic DNA-sensing pathway, conserved biosystem (from KEGG)
    Cytosolic DNA-sensing pathway, conserved biosystemSpecific families of pattern recognition receptors are responsible for detecting foreign DNA from invading microbes or host cells and generating innate immune responses. DAI is the first identified s...
  • GPCR ligand binding, organism-specific biosystem (from REACTOME)
    GPCR ligand binding, organism-specific biosystemThere are more than 800 G-protein coupled receptor (GPCRs) in the human genome, making it the largest receptor superfamily. GPCRs are also the largest class of drug targets, involved in virtually all...
  • IL12-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
    IL12-mediated signaling events, organism-specific biosystem
    IL12-mediated signaling events
  • NF-kappa B signaling pathway, organism-specific biosystem (from KEGG)
    NF-kappa B signaling pathway, organism-specific biosystemNuclear factor-kappa B (NF-kappa B) is the generic name of a family of transcription factors that function as dimers and regulate genes involved in immunity, inflammation and cell survival. There are...
  • NF-kappa B signaling pathway, conserved biosystem (from KEGG)
    NF-kappa B signaling pathway, conserved biosystemNuclear factor-kappa B (NF-kappa B) is the generic name of a family of transcription factors that function as dimers and regulate genes involved in immunity, inflammation and cell survival. There are...
  • Peptide ligand-binding receptors, organism-specific biosystem (from REACTOME)
    Peptide ligand-binding receptors, organism-specific biosystemThese receptors, a subset of the Class A/1 (Rhodopsin-like) family, all bind peptide ligands which include the chemokines, opioids and somatostatins.
  • Regulation of toll-like receptor signaling pathway, organism-specific biosystem (from WikiPathways)
    Regulation of toll-like receptor signaling pathway, organism-specific biosystem
    Regulation of toll-like receptor signaling pathway
  • Salmonella infection, organism-specific biosystem (from KEGG)
    Salmonella infection, organism-specific biosystemSalmonella infection usually presents as a self-limiting gastroenteritis or the more severe typhoid fever and bacteremia. The common disease-causing Salmonella species in human is a single species, S...
  • Salmonella infection, conserved biosystem (from KEGG)
    Salmonella infection, conserved biosystemSalmonella infection usually presents as a self-limiting gastroenteritis or the more severe typhoid fever and bacteremia. The common disease-causing Salmonella species in human is a single species, S...
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by GPCR, organism-specific biosystem (from REACTOME)
    Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...
  • Toll-like receptor signaling pathway, organism-specific biosystem (from KEGG)
    Toll-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
  • Toll-like receptor signaling pathway, organism-specific biosystem (from WikiPathways)
    Toll-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
  • Toll-like receptor signaling pathway, conserved biosystem (from KEGG)
    Toll-like receptor signaling pathway, conserved biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • MGC104418, MGC126025, MGC126026

Gene Ontology Provided by GOA

Function Evidence Code Pubs
CCR1 chemokine receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
CCR5 chemokine receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
chemokine activity IEA
Inferred from Electronic Annotation
more info
 
cytokine activity TAS
Traceable Author Statement
more info
PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
G-protein coupled receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
 
cell adhesion TAS
Traceable Author Statement
more info
PubMed 
cell-cell signaling TAS
Traceable Author Statement
more info
PubMed 
cellular response to interferon-gamma IBA
Inferred from Biological aspect of Ancestor
more info
 
cellular response to interleukin-1 IBA
Inferred from Biological aspect of Ancestor
more info
 
cellular response to tumor necrosis factor IBA
Inferred from Biological aspect of Ancestor
more info
 
chemokine-mediated signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
 
establishment or maintenance of cell polarity TAS
Traceable Author Statement
more info
PubMed 
immune response TAS
Traceable Author Statement
more info
PubMed 
inflammatory response IEA
Inferred from Electronic Annotation
more info
 
monocyte chemotaxis IBA
Inferred from Biological aspect of Ancestor
more info
 
movement of cell or subcellular component TAS
Traceable Author Statement
more info
PubMed 
negative regulation by host of viral transcription IDA
Inferred from Direct Assay
more info
PubMed 
neutrophil chemotaxis IBA
Inferred from Biological aspect of Ancestor
more info
 
positive regulation of ERK1 and ERK2 cascade IBA
Inferred from Biological aspect of Ancestor
more info
 
positive regulation of GTPase activity IBA
Inferred from Biological aspect of Ancestor
more info
 
positive regulation of calcium ion transport IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of calcium-mediated signaling IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of inflammatory response IBA
Inferred from Biological aspect of Ancestor
more info
 
positive regulation of natural killer cell chemotaxis IDA
Inferred from Direct Assay
more info
PubMed 
response to toxic substance IDA
Inferred from Direct Assay
more info
PubMed 
response to virus TAS
Traceable Author Statement
more info
PubMed 
signal transduction TAS
Traceable Author Statement
more info
PubMed 
Component Evidence Code Pubs
extracellular region TAS
Traceable Author Statement
more info
 
extracellular space IEA
Inferred from Electronic Annotation
more info
 
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)

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..6796
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_002984.3NP_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
    Related
    ENSP00000482259, OTTHUMP00000276535, ENST00000615863, OTTHUMT00000477145
    Conserved Domains (1) summary
    cd00272
    Location:3490
    Chemokine_CC; Chemokine_CC: 1 of 4 subgroup designations based on the arrangement of the two N-terminal cysteine residues; includes a number of secreted growth factors and interferons involved in mitogenic, chemotactic, and inflammatory activity; some members (e.g. ...

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 107 details...

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

Reference GRCh38.p2 Primary Assembly

Genomic

  1. NC_000017.11 Reference GRCh38.p2 Primary Assembly

    Range
    36103827..36105621
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p2 ALT_REF_LOCI_1

Genomic

  1. NT_187614.1 Reference GRCh38.p2 ALT_REF_LOCI_1

    Range
    338748..340542
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p2 ALT_REF_LOCI_2

Genomic

  1. NT_187661.1 Reference GRCh38.p2 ALT_REF_LOCI_2

    Range
    57924..59718
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018928.2 Alternate CHM1_1.1

    Range
    34495398..34497192
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)