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Symbol CCL3 contributors: mct - updated : 28-04-2020
HGNC name chemokine (C-C motif) ligand 3
HGNC id 10627
Location 17q12      Physical location : 34.415.604 - 34.417.506
Synonym name
  • murine macrophage inflammatory protein 1 alpha
  • small inducible cytokine A3 (homologous to mouse Mip-1a)
  • G0/G1 switch regulatory protein 19.1
  • monokine
  • LD78 alpha beta
  • tonsillar lymphocyte LD78 alpha protein
  • PAT 464.1
  • macrophage inflammatory protein 1-alpha
  • Synonym symbol(s) MIP1A, LD78ALPHA, MIP-1-alpha, SCYA3, G0S19-1, SIS-beta
    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
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 813 - 92 - 1992 1296815
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivemale systemprostate   
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/ImmuneT cell
    cell lineage
    cell lines
    at STAGE
  • 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
    interspecies homolog to murine CCL3 (see IMC1@)
    homolog to Drosophila eg:bacr25b3.3
    homolog to C.elegans C06e4.2
    intraspecies paralog to CCL3L1
  • intercrine beta (chemokine CC) family
  • CATEGORY tumor suppressor , signaling cytokine
    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
    signaling signal transduction
  • cell-cell signaling
  • G protein linked receptor protein signaling pathway
  • a component
  • M/P1A/M/P1B heterodimer
    small molecule
  • 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
    induced by LPS (lipopolysaccharides)
    inhibited by EBV (Epstein-Barr virus)
    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
  • 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
  • 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
    diabetetype 1 
    preferential target for therapy of T1DM
    Pharmacological modulation of the CCL3 pathways might, therefore, represent a future therapeutic option to manage Streptococcus pneumoniae meningitis
    inhibition of MIP-1α may thus provide a new therapeutic approach to control tumor progression and bone destruction in patients with multiple myeloma (MM)
  • homozygous knockout mice
  • CCL3-/- mice had loss of mature myeloid populations, while myeloid progenitors and HSPCs were increased, and microenvironmental populations were unchanged