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FLASH GENE
Symbol CCL4 contributors: mct - updated : 06-05-2020
HGNC name chemokine (C-C motif) ligand 4
HGNC id 10630
DNA
TYPE functioning gene
SPECIAL FEATURE component of a cluster, head to head, opposite orientation
text
  • separated by 14kb in head to head orientation from CCL3
  • clustered in IMC1@
  • STRUCTURE 1.80 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (TATA box)
    text structure promoter region include a GM-CSF-like decanucleotide sequence (Baixeras 1990)
    MAPPING cloned Y linked N status confirmed
    Map see CCL3L1
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 667 - 92 - 1990 2247088
    EXPRESSION
    Type restricted
    constitutive of
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineadrenal gland   highly
    Nervousbrain   moderately
    Reproductivefemale systemplacenta  highly
     male systemprostate  highly
    Respiratorylung   highly
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    Connectivebone   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES acid Hydrophilic
    STRUCTURE
    motifs/domains
  • a very hydrophobic N terminus, which was predicted to be a signal peptide
  • mono polymer homomer , heteromer , dimer
    HOMOLOGY
    interspecies homolog to murine Mip-1beta (see IMC1@)
    homolog to C.elgans F59B10.5
    homolog to Drosophila eg:bacr25b3.3
    intraspecies paralog to SCYA4L1
    paralog to CCL4L1
    Homologene
    FAMILY
  • intercrine beta family
  • CC subfamily (small inducible cytokine, chemokine beta)
  • CATEGORY adhesion , immunity/defense , signaling cytokine
    SUBCELLULAR LOCALIZATION extracellular
    text secreted
    basic FUNCTION
  • monocyte, chemoattractant, activated T cell and dendritic cell
  • one of the major HIV-suppressive factors produced by CD8+ T cells
  • playing a role in etablishement of cell polarity
  • contributing to intracellular signaling and other chemokine receptor function
  • promote trophoblast migration at the feto-maternal interface
  • with CCL3, may directly or indirectly affect neuronal excitability, and are implicated in the etiology and pathogenesis of temporal lobe epilepsy
  • principal regulator of macrophage migration and signals through CCR5
  • crucial role of CCL4 in the development of dry eye syndrome in CF patients and immunopathogenesis of ocular surface changes in this disease
  • CCL3 and CCL4 are chemokines crucial for immune responses towards infection and inflammation
  • AR-CCL4-STAT3 axis is key regulator during prostate tumor initiation, suggesting important roles of infiltrating macrophages and inflammatory cytokines for the prostate tumorigenesis
  • Tregs produced both CCL3 and CCL4 in response to stimulation, and production of these chemokines was critical for migration of target T cells
  • macrophage-derived foam cells impair endothelial barrier function by inducing endothelial-mesenchymal transition via CCL4
  • can promote tumor development and progression by recruiting regulatory T cells and pro-tumorigenic macrophages, and acting on other resident cells present in the tumor microenvironment, such as fibroblasts and endothelial cells, to facilitate their pro-tumorigenic capacities
  • CELLULAR PROCESS cell life, proliferation/growth
    cell communication
    cell migration & motility
    PHYSIOLOGICAL PROCESS immunity/defense , inflammation
    PATHWAY
    metabolism
    signaling signal transduction
    cell-cell signaling
    a component
  • MIP1A/MIP1B heterodimer
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to CCR8
  • natural ligand for the primary human immunodeficiency virus type 1 (HIV-1) coreceptor CCR5
  • adiponectin stimulates release of CCL2, CCL3, CCL4, CCL5 in primary human monocytes, and induction in cells of overweight probands is partly impaired
  • CCL4 is a novel key mediator, and the peripheral CCL4-CCR5 axis contributes to neuropathic pain
  • secretion of IL1A, IL1B, IL12B, and CCL4 occurs during gelatinase degranulation, a process controlled by STX3
  • TNF drives CCL4 expression in THP-1 monocytic cells/macrophages via the activation of SAPK/JNK and NFKB1 pathways
  • cell & other
    REGULATION
    induced by mitogens
    phytohemagglutinin (in T cells)
    staphylococcus aureus (in B cells)
    lipopolysaccharide (in monocyte)
    Prokineticin 1 (induces CCL4, CXCL1 and IL8 in monocytes but not in macrophages and dendritic cells)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in CD8+ cells and CD4+ cells in sarcoidosis
    Susceptibility
  • to AIDS
  • Variant & Polymorphism SNP influencing HIV Type 1 transmission and AIDS disease progression (Omim: 609423)
    Candidate gene
    Marker
  • variations in the CCL4 gene may help to predict breast cancer progression and metastasis
  • decreased preclinical CCL3 and CCL4 levels might be associated with a subsequently increased risk of nasopharyngeal carcinoma
  • CCL4 rs10491121 may be a factor to predict the tumor size in oral squamous cell carcinoma (OSCC) patients
  • Therapy target
    ANIMAL & CELL MODELS