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FLASH GENE
Symbol TNFSF15 contributors: mct/pgu - updated : 04-12-2012
HGNC name tumor necrosis factor (ligand) superfamily, member 15
HGNC id 11931
Location 9q33.1      Physical location : 117.551.612 - 117.568.408
Synonym name
  • vascular endothelial growth inhibitor
  • TNF superfamily ligand TL1A
  • TNF ligand-related molecule 1
  • vascular endothelial growth inhibitor-192A
  • Synonym symbol(s) TL1, TL1A, VEGI, VEGI192A, MGC129934, MGC129935
    DNA
    TYPE functioning gene
    STRUCTURE 21.49 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    CDC26 9q32 cell division cycle 26 PRPF4 9q31-q33 PRP4 pre-mRNA processing factor 4 homolog (yeast) MGC4734 9q33.1 hypothetical protein MGC4734 WDR31 9q33.1 WD repeat domain 31 BSPRY 9q33.1 B-box and SPRY domain containing MGC12904 9q33.1 hypothetical protein MGC12904 ALAD 9q33.3 aminolevulinate, delta-, dehydratase POLE3 9q33 polymerase (DNA directed), epsilon 3 (p17 subunit) C9orf43 9q33.1 chromosome 9 open reading frame 43 RGS3 9q31-q33 regulator of G-protein signalling 3 FLJ31713 9q33.1 hypothetical protein FLJ31713 LOC392385 9 similar to programmed cell death 2 isoform 1; zinc finger protein Rp-8; programmed cell death 2/Rp8 homolog KIAA1952 9q33.1 KIAA1952 protein AMBP 9q32-q33 alpha-1-microglobulin/bikunin precursor KIF12 9q33.1 kinesin family member 12 COL27A1 9q33.1 collagen, type XXVII, alpha 1 ORM1 9q32 orosomucoid 1 ORM2 9q32 orosomucoid 2 AKNA 9q32 AT-hook transcription factor AKNA CIP98 9q33.1 CASK-interacting protein CIP98 ATP6V1G1 9q33.1 ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G isoform 1 DKFZp547P234 9q33.1 DKFZp547P234 protein LOC389786 9 LOC389786 TNFSF15 9q32 tumor necrosis factor (ligand) superfamily, member 15 LOC392386 9 similar to serine/threonine-protein kinase PRP4K; serine/threonine-protein kinase PRP4 homolog TNFSF8 9q33 tumor necrosis factor (ligand) superfamily, member 8 TNC 9q33.3 tenascin C (hexabrachion) DEC1 9q32 tenascin C (hexabrachion) C9orf27 9q31.3 chromosome 9 open reading frame 27 PAPPA 9q33.1 pregnancy-associated plasma protein A
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 6705 27.9 251 - 2005 16061878
  • VEGI-251
  • 2 - 6412 - 192 - 2005 16061878
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine   
     intestinelarge intestinecolon  
     liver    
    Endocrinepancreas    
    Lymphoid/Immunespleen    
    Reproductivefemale systemplacenta   
     male systemprostate   
    Respiratorylung    
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularsmoothvessel  
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmonocyte
    Cardiovascularendothelial cell
    Lymphoid/Immunemacrophage Homo sapiens
    cell lineage hematopoietic and endothelial cells
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an extracellular C terminus
  • a single transmembrane domain
  • a short cytoplasmic tail
  • conjugated GlycoP
    mono polymer homomer , trimer
    HOMOLOGY
    interspecies homolog to rattus Tnfsf15 (70.9pc)
    Homologene
    FAMILY
  • tumor necrosis factor (ligand) superfamily
  • CATEGORY signaling cytokine
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    text type 2 membrane protein or secreted
    basic FUNCTION
  • modulator of vascular homeostasis
  • may play an important role in a Th1-mediated disease such as Crohn disease
  • angiogenesis inhibitor of the TNF family and functioning in part by directly inhibiting endothelial cell proliferation
  • acts as an autocrine factor to induce apoptosis in endothelial cells
  • can activate NF-KappaB and MAP kinases
  • may serve as an inflammatory marker in rhumatoid arthritis
  • may contribute to renal inflamattion and injury through TNFRSF25-mediated activation of NF-KappaB and caspase 3
  • involved in Th1 response to pathogens
  • involved in atherosclerosis via the induction of proinflammatory cytokines/chemokines and decreasing plaque stability by inducing extracellular matrix degrading enzymes
  • is potentially involved in the regulation of endothelial cell senescence, via a novel fragment produced by differential ectodomain shedding
  • costimulates T cells through its receptor DR3 (TNFRSF25) and is required for autoimmune pathology driven by diverse T-cell subsets
  • costimulates T cells to produce a wide variety of cytokines and can promote expansion of activated and regulatory T cells
  • endogenous inhibitor of neovascularization, that is a critical component of the negative control mechanism that operates in normal ovary but is missing in ovarian cancer
  • TNFSF15 and TNFRSF25 may play an important role in the pathophysiological process of the aged bladder
  • CELLULAR PROCESS cell cycle
    cell life, proliferation/growth
    cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS immunity/defense
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • ligand for TNFRSF25 and TNFRSF26
  • novel link between TNFSF15 and IL13 responses that results in small intestinal inflammation, and also establish that TNFSF15-TNFRSF25 interactions are necessary and sufficient for T cell-dependent inflammatory bowel disease
  • TRADD is essential for TNFSF15/TNFRSF25 signaling
  • cell & other
    REGULATION
    induced by
  • TNF and IL-1 alpha
  • ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in colon adenocarcinoma
          --over  
    up-regulated in rhumatoid arthritis
    tumoral     --low  
    by cancer cells and tumor infiltrating macrophages and lymphocytes is a pre-requisite for tumor neovascularization
    Susceptibility
  • to Crohn disease
  • to primary biliary cirrhosis
  • to irritable bowel syndrome (IBS)
  • Variant & Polymorphism SNP
  • increasing the risk of Crohn disease
  • rs4979462 is significantly associated to biliary cirrhosis
  • rs4263839 G in the TNFSF15 gene was significantly associated with an increased risk of IBS
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunologyautoimmune 
    may be a viable target for therapies designed to inhibit the T-cell-dependent component of diverse autoimmune diseases
    cancer  
    highly valuable toward angiogenesis-based cancer therapy
    bloodcoagulation 
    proatherogenic role for both TNFSF15 and TNFRSF25 that implicates this pathway as a target for the therapeutic intervention of atherosclerosis
    ANIMAL & CELL MODELS