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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
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