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FLASH GENE
Symbol CCL21 contributors: mct/npt - updated : 11-02-2017
HGNC name chemokine (C-C motif) ligand 21
HGNC id 10620
Location 9p13.3      Physical location : 34.709.003 - 34.710.147
Synonym name
  • small inducible cytokine subfamily A (Cys-Cys), member 21
  • exodus-2
  • beta chemokine exodus-2
  • efficient Chemoattractant for Lymphocytes
  • secondary lymphoid tissue chemokine
    • Synonym symbol(s) SLC, CKb9, TCA4, SCYA21, ECL, MGC34555, 6Ckine
    DNA
    TYPE functioning gene
    SPECIAL FEATURE component of a cluster
    STRUCTURE 1.15 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 878 14 134 - 1997 9235955
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
     vessels    
    Digestiveintestinesmall intestine  highly
    Endocrinepancreas   lowly
     thyroid   moderately
    Lymphoid/Immunelymph node   highly
    Respiratoryrespiratory tracttrachea  moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    Connectivebone   
    Epithelialsecretoryglandularendocrine 
    Epithelialsecretoryglandularexocrine 
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text heart, spleen
    PROTEIN
    PHYSICAL PROPERTIES globular
    STRUCTURE
    motifs/domains
    HOMOLOGY
    interspecies homolog to murine Scya21b
    Homologene
    FAMILY intercrine beta (chemokine CC) family
    CATEGORY signaling cytokine , receptor membrane
    SUBCELLULAR LOCALIZATION extracellular
    basic FUNCTION
  • lymphocyte chemoattractant, secondary lymphoid tissue chemokine
  • may also play a role in mediating homing of lymphocytes to secondary lymphoid organs
  • play a pivotal role in homing and localization of immune cells to lymphoid tissue and into organ of non-lymphoid origin
  • CCR7 and CCL21 contribute to the migratory capacity of the dendritic cells
  • CCL19/21 induced PI3K-dependent phosphorylation of Akt/protein kinase B, activation of the Rho/Rho-associated coiled-coil forming protein kinases/myosin light chain pathway and MAPKs phosphorylation
  • direct role for CCL21 in lymphatic transmigration that involves the selective use of integrin activation in inflammation
  • up-regulates microglia P2RX4 expression and initiates neuropathic pain development
  • CCL21 together with another CCR7 ligand, CCL19, direct the navigation and compartmentation of T cells within secondary lymphoid tissues
  • CCL21/CCR7 contributes to the time-dependent proliferation of non-small cell lung cancer cells by upregulating cyclin A, cyclin B1, and CDK1 potentially via the ERK pathway
    • CELLULAR PROCESS cell migration & motility
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • part of CCL19, CCL21/CCR7 chemokine system expressed in inflamed muscles of polymyositis and may be involved in the pathomechanism of polymyositis
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • high affinity functional ligand for chemokine receptor 7 (CCR7)
  • CCL21/CCR7 interaction significantly increased the fraction of cells in the G(2)/M phase of the cell cycle
  • CCR7 binds to its cognate ligand, CCL21, to mediate the migration of circulating naive T lymphocytes to the lymph nodes
  • recruits normal immune cells and metastasizing tumor cells to lymph nodes through activation of the G protein-coupled receptor CCR7
  • CCL21 is a GPR174 ligand (involved in sex-dependent control of B-cell positioning and participation in germinal centres)
    • cell & other
    REGULATION
    Other transiently down-regulated within lymphoid tissues during immune responses by a mechanism controlled by the cytokine interferon-gamma
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in hepatitis C, to modulating lymphocyte recruitment and fibrosis
    constitutional     --over  
    specifically in hyperplastic Myasthenia gravis thymuses
    tumoral     --low  
    in colorectal adenocarcinomas
    Susceptibility to inflammatory polyarthritis (IP)
    Variant & Polymorphism other
  • CCL21 risk alleles was associated with premature mortality in IP
    • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneousurinarychronic kidney disease
    CCL21/CCR7 signaling of fibrocytes may provide therapeutic targets for combating renal fibrosis
    miscelleaneouspain 
    target to a preventive therapy in neuropathic pain
    ANIMAL & CELL MODELS
  • mice deficient for CCL21 did not develop any signs of tactile allodynia and failed to up-regulate microglial P2X4 receptor expression