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FLASH GENE
Symbol CCL5 contributors: mct/npt - updated : 22-02-2016
HGNC name chemokine (C-C motif) ligand 5
HGNC id 10632
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • two adjacent cysteines
  • two short N terminal beta-strands in each monomer
  • a conserved, positively charged BBXB motif is key for the binding of CC chemokines to glycosaminoglycan (GAG)
  • a C terminal alpha helix packing against a three-standed antiparallel beta-sheet
    • mono polymer homomer , dimer
    HOMOLOGY
    interspecies homolog to murine CCL5
    homolog to Drosophila eg:bacr25b3.3
    homolog to C.elegans Y32g9a.l
    Homologene
    FAMILY
  • intercrine beta (chemokine CC) family
    • CATEGORY adhesion , immunity/defense , signaling cytokine
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm
    text secreted
    basic FUNCTION
  • monocyte, eosinophil, basophil, specific, activated T cell and dendritic cell
  • functioning as a chemoattractant for blood monocytes, memory T helper cells and eosinophils
  • causing the release of histamine from basophils and activating eosinophils
  • plays a crucial role for tumor invasion in the interplay of tissue resident stem cells from the fat tissue and breast cancer cells
  • could participate in the inflammation of obese WAT (white adipose tissue) by recruiting blood monocytes and exerting antiapoptotic properties on WAT macrophages
  • one of the major HIV-suppressive factors produced by CD8+ cells
  • is a proinflammatory chemokine that regulates the trafficking of Th1 T cells, macrophages, dendritic cells, and natural killer cells, mediated by activation of the receptors CCR1, CCR3, and/or CCR5
  • activates GLI2 via PI3K/AKT signaling)
  • play an important role in the formation of granuloma during infection with Mycobacterium tuberculosis
  • important role in sustaining CD8 T cell responses during a systemic chronic viral infection
  • proinflammatory chemokine known to activate leukocytes through its receptor, CCR5
  • role for CCL5-mediated glucose uptake and ATP accumulation to meet the energy demands of chemotaxis in activated T cells
  • CCL5 and CCL3 are critical for immune surveillance and inflammation
  • CCL5 is a chemotactic cytokine, and its expression and secretion are regulated in T cells
    • CELLULAR PROCESS cell communication
    cell migration & motility
    PHYSIOLOGICAL PROCESS immunity/defense , inflammation
    text immuno-regulatory and inflammatory calcium Ca2+ homeostasis
    PATHWAY
    metabolism
    signaling signal transduction
    cell-cell signaling
    a component
  • dimerisation occurs between the N termianl region of each monomer
  • CCL5-GLI2-IL6 axis in the stromal microenvironment regulating Ig secretion by malignant cells
  • monomeric form of CCL5 is sufficient to cause cell migration, but its propensity for aggregation is essential for migration, T cell activation and apoptosis, and HIV entry into cell
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to CCR1, CCR3, CCR4
  • activating a defined profile of at least 42 genes in monocytes
  • interacting with CCL5 (to protect against virus-inducible apoptosis and to influence host defense against common paramyxoviral infections)
  • CCL5 may contribute to modulation of I-13 production and F2R expression in mast cells, through which participates in the mast cell related inflammation
  • CCL5-GLI2-IL6 interaction in B cell malignancies regulates immunoglobulin secretion
  • adiponectin stimulates release of CCL2, CCL3, CCL4, CCL5 in primary human monocytes, and induction in cells of overweight probands is partly impaired
  • stimulated IL6 secretion in WM (Waldenstrom macroglobulinemia) stromal cells resulting in increased IgM secretion by WM malignant cells via the JAK/STAT signaling pathway
  • IL15 can signal via IL15RA, JNK, and NFKB1 to drive CCL5 production by myeloid cells
  • CCL5 simultaneously activates AMPK and MTOR signaling cascades to regulate glucose uptake and chemotaxis in activated T cells
  • KLF13 controls the late (3-5 days after activation) expression of CCL5 in T lymphocytes and that KLF13 itself is translationally regulated through the 5prime -untranslated region of its mRNA
  • FLI1 drives transcription from the CCL5 promoter in a dose-dependent manner
  • ETS1, another Ets family member, and FLI1 drive transcription from the CCL5 promoter, although FLI1 transactivation was significantly stronger
    • cell & other
    REGULATION
    induced by mitogens
    TNF alpha
    repressed by IL17 (inhibiting of TNF alpha induction)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    of CCL5 and median chemokine receptor 7 (CCR7) mRNA expression in localized scleroderma lesions as compared to healthy controls
    constitutional     --over  
    in both serum and synovial fluid of rheumatoid arthritis
    tumoral     --over  
    in Waldenstrom macroglobulinemia, and CCL5 levels positively correlated with features of disease aggressiveness such as elevated IgM levels and bone marrow involvement
    Susceptibility
  • to emphysema in COPD
  • to pulmonary tuberculosis (PTB)
  • to Kawasaki disease (KD)
  • to oral cancer
    • Variant & Polymorphism SNP
  • increasing the risk of emphysema in COPD
  • SNPs in CCL5-28 and -403 genes could increase the risk to have oral cancer
  • haplotype A-C-C and the diplotype G/A-T/C may be associated with resistance to PTB
  • CCL5 -403A variant may be associated with coronary involvement in KD
    • Candidate gene
    Marker
  • may serve as a useful marker of rheumatoid arthritis activity
  • CCR5 and CCL5 are potential markers for metastatic Pancreatic cancer (PC) cancer
    • Therapy target
    SystemTypeDisorderPubmed
    digestiveliver 
    successful therapeutic approach to reduce experimental liver fibrosis by antagonizing CCL5 receptors
    cancerhemopathy 
    a potential target for the treatment of Waldenstrom macroglobulinemia
    cancerdigestivestomach
    therapeutic strategies to inhibit the CCL5/CCR5 axis in different ways in the treatment of Gastric cancer
    cancerdigestivepancreas
    blocking CCR5/CCL5 axis might prove beneficial to prevent metastasis and provide a more therapeutic strategy to control PC progression
    ANIMAL & CELL MODELS