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FLASH GENE
Symbol CCL5 contributors: mct/npt - updated : 22-02-2013
HGNC name chemokine (C-C motif) ligand 5
HGNC id 10632
Location 17q12      Physical location : 34.198.497 - 34.207.377
Synonym name
  • regulated upon activation,normal T cell expressed and secreted
  • small inducible cytokine A5 (RANTES)
  • T-cell specific protein p288
  • SIS-delta
  • small inducible cytokine subfamily A (Cys-Cys), member 5
  • T-cell specific RANTES protein
  • regulated upon activation, normally T-expressed, and presumably secreted
  • eosinophil-chemotactic cytokine
  • Synonym symbol(s) SISd, SCYA5, RANTES, TCP228, D17S136E, MGC17164, SIS-delta
    DNA
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    text clustered with several other CC cytokines in IMC1@
    STRUCTURE 8.88 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    text structure see IMC1@
    MAPPING cloned Y linked N status provisional
    Map see CCL3L1
    Physical map
    MGC19764 17q21.1 hypothetical protein MGC19764 FLJ34922 17q21.1 hypothetical protein FLJ34922 FLJ10260 17q21.1 hypothetical protein FLJ10260 FLJ31952 17q21.1 hypothetical protein FLJ31952 LOC342615 17q21.1 similar to Adenylosuccinate synthetase 2 (IMP--aspartate ligase 2) (AdSS 2) (AMPSase 2) LOC342616 17q21.1 similar to TAF5L protein LOC342618 17q21.1 similar to FLJ34922 protein PEX12 17q21.1 peroxisomal biogenesis factor 12 AP2B1 17q11.2-q12 adaptor-related protein complex 2, beta 1 subunit VTS58635 GAR17 17q21.1 GAS2-related protein LOC146853 17q21.1 LOC146853 MMP28 17q11-q21.1 matrix metalloproteinase 28 TAF15 17q11.1-q11.2 TAF15 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 68kDa FLJ32830 17q21.1 hypothetical protein FLJ32830 CCL5 17q11.2 chemokine (C-C motif) ligand 5 LOC390786 17 hypothetical gene supported by AL833376 LOC390787 17 similar to KIAA0563 protein RAD52B 17q11.2 RAD52B LOC57151 17q11.2 lysozyme homolog CCL16 17q11.2 chemokine (C-C motif) ligand 16 CCL14 17q11.2 chemokine (C-C motif) ligand 14 CCL14-CCL15 17q21.1 chemokine ligand 14, chemokine ligand 15 transcription unit CCL15 17q11.2 chemokine (C-C motif) ligand 15 CCL23 17q11.2 chemokine (C-C motif) ligand 23 CCL18 17q11.2 chemokine (C-C motif) ligand 18 (pulmonary and activation-regulated) CCL3 17q11.2 chemokine (C-C motif) ligand 3 CCL4 17q11.2 chemokine (C-C motif) ligand 4 LOC388368 17 similar to TBC1 domain family member 3 (Rab GTPase-activating protein PRC17) (Prostate cancer gene 17 protein) (TRE17 alpha protein) LOC388369 17 LOC388369 LOC388370 17 similar to cytokine LOC388371 17 similar to TBC1 domain family member 3 (Rab GTPase-activating protein PRC17) (Prostate cancer gene 17 protein) (TRE17 alpha protein) LOC390788 17 similar to CCL3L1 protein CCL3L1 17q11.2 chemokine (C-C motif) ligand 3-like 1 LOC388372 17 similar to cytokine
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 1237 10 91 - 2000 11030415
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivepharynx   highly
    Lymphoid/Immunelymph node   moderately
    Nervousbrain    
    Reproductivemale systemprostate   
    Respiratorylung    
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoietic    
    Connectiveadipose  highly
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunemacrophage
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two adjacent cysteines
  • two short N terminal beta-strands in each monomer
  • 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
  • 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
  • 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
  • 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
    ANIMAL & CELL MODELS