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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
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