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FLASH GENE
Symbol LGALS9 contributors: mct - updated : 02-02-2017
HGNC name lectin, galactoside-binding, soluble, 9
HGNC id 6570
Location 17q11.2      Physical location : 25.958.173 - 25.976.585
Synonym name
  • oesinophil-activating factor
  • galectin 9
  • ecalectin
  • urate transporter/channel protein
  • tumor Ag HOM-HD-21
  • Synonym symbol(s) ECALECTIN, LEG9, UAT, HOM-HD-21, HUATA, MGC117375, MGC125973, MGC125974, LGALS9A
    DNA
    TYPE functioning gene
    STRUCTURE 18.41 kb     11 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
    10 - 1739 36 323 - 2009 19335620
  • isoform short
  • acting as an eosinophil chemoattractant
  • increasing E-selectin in LoVo colon carcinoma cells (Zhang 2009)
  • 11 - 1835 40 355 lymphoid tissues, spleen, peripheral blood lymphocytes 2009 19335620
  • isoform long
  • decreases E-selectin levels in LoVo colon carcinoma cells (Zhang 2009)
  • 9 splicing - - - - 2014 24333696
  • found to induce a small inhibitory effect on angiogenesis
  • endothelial cells regulate the expression and splicing of LGALS9 during angiogenesis
  • EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen   highly
    Nervousbrain   moderately
    Respiratorylung   moderately
    Urinarykidney   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte
    Lymphoid/ImmuneT cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N and C terminal carbohydrate-binding domains connected by a link peptide
  • four membrane spanning domains
  • two galectin domains
  • conjugated Other
    mono polymer monomer
    HOMOLOGY
    intraspecies homolog to sequences found in the SMS repeat gene clusters SMS-REPM,SMS-REPP (see symbols)
    Homologene
    FAMILY
  • beta galactoside binding protein family (galophin family)
  • CATEGORY regulatory , secretory
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,lysosome
    intracellular,nucleus
    text
  • LGALS9 is enriched in lysosomes
  • basic FUNCTION
  • cell adhesion
  • inflammation apoptosis and metastasis
  • T cell derived regulator of eosinophil recruitment in tissues during inflammatory reactions
  • eosinophil chemoattractant
  • induces osteoblast differentiation through the CD44/Smad signaling in the absence of BMPs (Tanikawa 2010)
  • increases alkaline phosphatase activities in osteoblasts and induces the phosphorylation of Smad1/5/8 and translocation of Smad4 tot he nucleus in the absence of BMPs (Tanikawa 2010)
  • also inducing binding of smad4 to the Id1 promoter and increases its activity (Tanikawa 2010)
  • involved in modulating cell-cell and cell-matrix interactions
  • might participate in the interaction between the hormone and receptor cells with their surrounding cells and might thus play a role in the pathogenesis of this disease and/or its associated immunodeficiency
  • may play a role in thymocyte-eptihelial interactions relevant to the biology of the thymus
  • inhibits cell proliferation
  • inducing Th1 death
  • ligand for HAVCR2/TIM3
  • inducing proliferation of osteoblasts through clustering lipid rafts on membrane and subsequent phosphorylation of the c-Src/ERK signaling pathway (Tanikawa 2008)
  • autocrine regulator of mast cell function to suppress excessive degranulation (niki 2009)
  • may have an immunoregulatory function during the ongoing cytotoxic response during a rejection episode (Naka 2009)
  • LPS-responsive factor that transactivates inflammatory cytokines gene in monocytes through direct interaction with CEBPB (Matsuura 2009)
  • regulates T helper cell function independently of HAVCR2
  • suppresses Th17 cell development in an IL2-dependent but HAVCR2-independent manner
  • LGALS9/HAVCR2 interactions inducing resistance of activated CD4(+) T cells to HIV-1 infection which suggest that LGALS9 may play a role in HIV-1 pathogenesis
  • LGALS9 engagement impairs the function of NK cells, including cytotoxicity and cytokine production
  • contributes to the inducible immunomodulatory functions of mesenchymal stromal cells (MSCs)
  • has likely dual properties as both a regulator and an activator of mast cells
  • exogenous LGALS9, in addition to being an effector molecule for Treg cells, acts synergistically with TGFB1 to enforce nduced regulatory T cells (iTreg) differentiation and maintenance
  • activation of CNS LGALS9 likely modulates neuroinflammatory processes in which TNF and IL6 contribute to either pathology or reparation
  • tandem repeat type of galectin, was originally identified as a chemotactic factor for eosinophils, and is also involved in the regulatory process of inflammation
  • possible involvement of the HAVCR2/LGALS9 system in the modulation of inflammatory bone destruction
  • LGALS9 is enriched in lysosomes and predominantly binds to lysosome-associated membrane protein 2 (LAMP2) in a Asn(N)-glycan dependent manner
  • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component S-type lectin
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to CD44 and inducing the formation of a CD44/BMP receptor complex (Tanikawa 2010)
  • LGALS9 is a ligand for HAVCR2, a type I glycoprotein induced on T cells during chronic inflammation
  • HAVCR2 serves as a functional receptor in structural cells of the airways and via the ligand LGALS9 can modulate the inflammatory response
  • cell & other
  • high affinity for the Forssman pentasaccharide
  • REGULATION
    induced by by TNF in astrocytes via the JNK/JUN pathway and astrocyte-derived LGALS9 may function as an immunoregulatory protein in response to ongoing neuroinflammation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   insertion    
    in colorectal cancer
    constitutional     --low  
    in end-stage dilated cardiomyopathy (Colak 2009)
    tumoral     --over  
    overexpressed in Hodgkin's disease tissue
    tumoral     --low  
    is a predictor of worse prognosis in pancreatic cancer patients
    Susceptibility
    Variant & Polymorphism
    Candidate gene
  • LGALS9-induced apoptosis of hyperproliferative rheumatoid arthritis (RA) fibroblast-like synoviocytes may play a role in the suppression of RA (Seki 2007)
  • decreased LGALS9 expression is inversely associated with malignant potential or differentiation of cervical intraepithelial neoplasia and cervical squamous cell carcinoma as a differentiation biomarker (Liang 2008)
  • Marker
    Therapy target
  • may have a beneficial utility fir the treatment of allergic disorders including asthma (Niki 2009)
  • blocking LGALS9-HAVCR2 interaction in vivo might alleviate the Th1-suppressive effect of NPC exosomes and sustain antitumoral T-cell responses and thereby improve clinical efficacy of immunotherapeutic approaches against nasopharyngeal carcinoma (Klibi 2009)
  • ANIMAL & CELL MODELS