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FLASH GENE
Symbol CCL3 contributors: mct - updated : 28-04-2020
HGNC name chemokine (C-C motif) ligand 3
HGNC id 10627
DNA
TYPE functioning gene
SPECIAL FEATURE component of a cluster, head to head, opposite orientation
text separated by 14kb from CCL4 in a head to head orientation clustered in IMC1@
STRUCTURE 1.91 kb     3 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Binding site   transcription factor
text structure
  • a binding site for NF chi B
  • 5' AP1-like recognition elements
  • CK2 and SRE motifs in 5' flanking sequence
  • MAPPING cloned Y linked N status confirmed
    Map see CCL3L1
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 813 - 92 - 1992 1296815
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveliver    
    Nervousbrain    
    Reproductivemale systemprostate   
    Respiratorylung    
    Urinarykidney    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/ImmuneT cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a conserved, positively charged BBXB motif is key for the binding of CC chemokines to glycosaminoglycan (GAG)
  • mono polymer heteromer , dimer
    isoforms Precursor a predicted mature peptide of 69 AA with a molecular mass of 7.9 kDa
    HOMOLOGY
    interspecies homolog to murine CCL3 (see IMC1@)
    homolog to Drosophila eg:bacr25b3.3
    homolog to C.elegans C06e4.2
    intraspecies paralog to CCL3L1
    Homologene
    FAMILY
  • intercrine beta (chemokine CC) family
  • CATEGORY tumor suppressor , signaling cytokine
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,cytosolic
    text secreted
    basic FUNCTION
  • monocyte, chemoattractant, activated T cell and dendritic cell
  • involved in cytoskeletal regulation
  • one of the major HIV-suppressive factors produced by CD8+ T cells
  • playing a role as an important mediator of virus-induced inflammation
  • playing a role in eosinophil recruitment in inflammatory states such as occurs in the asthmatic lung
  • inhibiting stem cell proliferation
  • contributing to intracellular signaling and other chemokine receptor function
  • CCL3/CCR1 axis may have a role in the spread of tumoral cells to the lymph nodes and also in the local host defense against the tumor
  • with CCL4, may directly or indirectly affect neuronal excitability, and are implicated in the etiology and pathogenesis of temporal lobe epilepsy
  • its expression not only reduces viral pathogenicity but also enhances immunogenicity by recruiting dendritic cells and B cells to the site of immunization, the lymph nodes, and the blood
  • CCL3 and CCL4 are chemokines crucial for immune responses towards infection and inflammation
  • for CCL3 activation of migration, no release of intracellular calcium is necessary
  • under conditions of acute inflammation leukocyte-derived CCL3 can induce neutrophil chemotaxis toward the atherosclerotic plaque, thereby accelerating lesion formation
  • CCL2/CCL3 are small chemotactic proteins that have been found in several kinds of tumor tissue samples and function as key regulators of cancer progression
  • chemokine CCL3 is an hippocampal neuromodulator able to regulate synaptic plasticity mechanisms involved in learning and memory functions
  • Tregs produced both CCL3 and CCL4 in response to stimulation, and production of these chemokines was critical for migration of target T cells
  • CCL5 and CCL3 are critical for immune surveillance and inflammation
  • role of CCL3 in the maintenance of homeostatic hematopoiesis that should be evaluated when targeting CCL3 signaling for the treatment of hematologic malignancy
  • CCL3 could up-regulate CD4+T cells to mediate the inflammatory response of rheumatoid arthritis (RA)
  • important chemokine implicated in both immune surveillance and tolerance, that has emerged as a prognostic biomarker in both solid and hematological malignancies
  • CELLULAR PROCESS cell life, proliferation/growth
    cell communication
    cell migration & motility
    PHYSIOLOGICAL PROCESS immunity/defense , inflammation
    text calcium Ca2+ homeostasis
    PATHWAY
    metabolism
    signaling signal transduction
  • cell-cell signaling
  • G protein linked receptor protein signaling pathway
  • a component
  • M/P1A/M/P1B heterodimer
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to receptors CCR1, CCR4
  • natural ligand for the primary human immunodeficiency virus type 1 (HIV-1) coreceptor CCR5
  • interaction between ZFP36 and CCL3 mRNA plays an important role in modulating localized inflammatory processes in tissues that are dissociated from the systemic manifestations of chronic inflammation
  • adiponectin stimulates release of CCL2, CCL3, CCL4, CCL5 in primary human monocytes, and induction in cells of overweight probands is partly impaired
  • CCL3 induced cell migration is dependent on activation of phospholipase C
  • EPO and CCL3 antagonise their functional properties during neuroinflammation
  • JNK signaling is required for the CCL3&
  • 8209;associated regulation of Kupffer cells in the heat stroke response
    cell & other
    REGULATION
    induced by LPS (lipopolysaccharides)
    inhibited by EBV (Epstein-Barr virus)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in myeloma Bone marrow (BM) positively correlated with the percentage of BM-infiltrating macrophages
    tumoral     --over  
    in the plasma of acute myeloid leukemia (AML) patients, and CCL3 inhibited erythroid differentiation of hematopoietic stem cells, common myeloid progenitors and especially megakaryocytic-erythroid progenitors
    constitutional     --over  
    in Chronic Obstructive Pulmonary Disease (COPD) sputum
    constitutional     --over  
    CCL2 and CCL3 are upregulated in the injured peripheral nerve through epigenetic histone modification in infiltrating immune cells such as macrophages
    Susceptibility
  • to multiple sclerosis
  • to HIV/acquired immunodeficiency syndrome (AIDS) (Omim: 609423)
  • Variant & Polymorphism SNP
  • increasing the risk of multiple sclerosis
  • influencing HIV Type 1 transmission and AIDS disease progression
  • Candidate gene
    Marker
  • autoantibody against CCL3 is associated with human type 1 diabetes mellitus (T1DM) and serves as a novel biomarker for its diagnosis
  • specifically predicts future cardiovascular events, and may serve as a predictive biomarker
  • CCL2 and CCL3 are associated with progression of oral squamous cell carcinoma (OSCC) and may be potential biomarkers
  • decreased preclinical CCL3 and CCL4 levels might be associated with a subsequently increased risk of nasopharyngeal carcinoma
  • Therapy target
    SystemTypeDisorderPubmed
    diabetetype 1 
    preferential target for therapy of T1DM
    immunologyinfectious 
    Pharmacological modulation of the CCL3 pathways might, therefore, represent a future therapeutic option to manage Streptococcus pneumoniae meningitis
    cancerhemopathy 
    inhibition of MIP-1α may thus provide a new therapeutic approach to control tumor progression and bone destruction in patients with multiple myeloma (MM)
    ANIMAL & CELL MODELS
  • homozygous knockout mice
  • CCL3-/- mice had loss of mature myeloid populations, while myeloid progenitors and HSPCs were increased, and microenvironmental populations were unchanged