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FLASH GENE
Symbol CCL26 contributors: mct - updated : 03-06-2020
HGNC name chemokine (C-C motif) ligand 26
HGNC id 10625
Location 7q11.23      Physical location : 75.398.841 - 75.419.064
Synonym name
  • small inducible cytokine subfamily A (Cys-Cys), member 26
  • eotaxin 3
  • macrophage inflammatory protein 4-alpha
  • small inducible cytokine A26
  • thymic stroma chemokine-1
  • Synonym symbol(s) MIP-4alpha, SCYA26, IMAC, TSC-1, MIP-4a, eotaxin-3, MGC126714
    DNA
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    STRUCTURE 22.07 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure a binding site for STAT6
    MAPPING cloned Y linked N status confirmed
    regionally located tightly linked to SCYA24
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 648 - 94 . highly in heart and liver . lowly in skeletal muscle and kidney 2018 29051319
    4 - 475 - 94 . lowly in heart, liver, skeletal muscle and kidney 2018 29051319
    4 - 562 - 94 - 2018 29051319
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine   
     liver   predominantly
    Endocrinepancreas     Homo sapiens
    Reproductivefemale systemovary  lowly
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumcardiac  
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES basic
    STRUCTURE
    motifs/domains
    a 23 amino acid signal peptide
    secondary structure an unstructured N terminus before the first two conserved Cys, an irregularly structured N-loop following the second conserved cys, a single turn of 3(10)-helix, a three stranded antiparallel beta-sheet, an alpha-helix and an unstructured C terminal tail
    mono polymer monomer
    HOMOLOGY
    interspecies homolog to C.elegans y116f11b.1
    homolog to Drosophila eg:bacr25b3.3
    Homologene
    FAMILY intercrine beta family
    CATEGORY immunity/defense , signaling cytokine
    SUBCELLULAR LOCALIZATION extracellular
    basic FUNCTION
  • lymphocyte chemoattractant (chemotractive for eosinophils and basophils)
  • acting as a CCR3 ligand
  • inhibiting CCL2 -mediated responses, thus acting as a natural antagonist for CCR2 and exerting a repulsive effect on monocytes
  • first chemokine that features broadband antagonistic activities, suggesting that it may have a modulatory rather than an inflammatory function
  • CCL26 may be partly responsible for the recruitment of cells expressing CX3CR1 in atopic dermatitis particularly when the expression of CX3CL1 is low
  • CCL26, CCL24, CCL11 have the ability to regulate extravillous trophoblast (EVT) functions critical to their role in vessel remodelling, suggesting a new role for the eotaxin group of chemokines during placentation
  • CCL11, CCL24, and CCL26 are chemokines involved in the recruitment of eosinophils into tissues and that mainly activate CCR3
  • CCL26 may play a unique and important role in the recruitment of eosinophils in persistent asthma
  • CCL11, CCL24, and CCL26 all showed potent bactericidal activity, mediated through membrane disruption, against the airway pathogens Streptococcus pneumoniae, Staphylococcus aureus, Nontypeable Haemophilus influenzae, and Pseudomonas aeruginosa
  • eotaxins can contribute to host defense against common airway pathogens and that their activities are modulated by mast cell proteases
  • CCL26 participates likely in the movement of eosinophils from the tissues to the airway lumen
  • role for CCL26 in the sustained inflammation observed in patients with severe eosinophilic asthma
  • CELLULAR PROCESS cell communication
    PHYSIOLOGICAL PROCESS inflammation
    text anti-pathogen response
    PATHWAY
    metabolism
    signaling signal transduction
    cell to cell signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to receptor CCR3
  • antagonizing CCR1, CCR2, CCR5
  • CCL26 is a functional ligand for CCR3 and abundantly produced by IL4-/IL13-stimulated vascular endothelial cells
  • CCL26 is yet a functional ligand for CX3CR1, the receptor for fractalkine/CX3CL1, which is expressed by CD16(+) NK cells, cytotoxic effector CD8(+) T cells, and CD14(low)CD16(high) monocytes
  • CREB1 gene silencing decreased IL13-induced transcription of eotaxin-3 (CCL26)
  • IL4 and IL13, are critical factors for the induction of CCL26 in the pancreas
  • CISH plays a key role in the eosinophilic inflammation associated with bronchial asthma by regulating IL13-induced CCL26 production
  • cell & other
    REGULATION
    induced by IL13 and IL14 in HUVECand IL4
    T helper type 2 cytokines, interleukin-4 (IL4) and IL13, in time- and dose-dependent manners
    Other regulated by STAT6 (in dermal fibroblasts)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    is associated with fibrotic progression of primary biliary cholangitis
    constitutional       gain of function
    of CCL26 in bullous pemphigoid (BP) is linked to the lesional accumulation of activated eosinophils in the skin
    constitutional     --over  
    serum CCL11, CCL24 and CCL26 are upregulated in primary biliary cholangitis but CCL11 and CCL26 are associated with fibrotic progression
    Susceptibility to asthma and total IgE dosage
    Variant & Polymorphism SNP 77C > T, +716A > G, EOT 3 +1579G > A increasing the risk of asthma
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    allergy  
    CCR3 and CCR5 receptor/ligand signaling pathways may be important targets for development of novel mechanism-based adjunctive therapies designed to abrogate the chronic inflammation associated with airway diseases
    allergyasthm 
    potential target for treating patients with eosinophilic asthma that are refractory to classic therapies
    ANIMAL & CELL MODELS