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FLASH GENE
Symbol TNFSF12 contributors: mct/npt/pgu - updated : 05-11-2015
HGNC name tumor necrosis factor (ligand) superfamily, member 12
HGNC id 11927
Location 17p13.1      Physical location : 7.452.374 - 7.461.206
Synonym name
  • TNF-like weak inducer of apoptosis
  • tumor necrosis factor-like weak inducer of apoptosis
  • apoprotein 2 ligand
  • APO3/DR3 ligand
  • TNF-related WEAK inducer of apoptosis
    • Synonym symbol(s) TWEAK, APO3L, DR3LG, MGC20669, MGC129581
    DNA
    TYPE functioning gene
    SPECIAL FEATURE head to head
    STRUCTURE 8.83 kb     7 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 1407 27.2 249 - 2010 20385556
  • membrane-anchored form
  • can bind TNFRSF12A on neighboring cells and activate the NF-KB signaling pathway
    • - - 1642 14.4 134 - 2010 20385556
  • also called TWEAK
  • smaller secreted form that is probably generated by TWEAK proteolytic processing
    		•
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivefemale systemovary  highly
     male systemprostate  highly
    Urinarykidney   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an extracellular C terminus, also existing as a soluble form
  • AAs 90–93 is the predominant furin recognition site
  • stalk region containing putative proprotein convertase recognition motifs at residues 90–93 (RPRR) and 102–105 (RARR), with cleavage predicted to occur at each motif after the terminal arginine residue
    • conjugated GlycoP
    HOMOLOGY
    interspecies ortholog to rattus Tnfsf12
    ortholog to murine Tnfsf12
    Homologene
    FAMILY
  • tumor necrosis factor (ligand) superfamily
    • CATEGORY signaling cytokine
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm
    text type II transmembrane glycoprotein
    basic FUNCTION
  • weakly inducer of apoptosis, inducing IL8
  • might play a critical role in hepatocellular carcinoma proliferation using both autocrine and paracrine mechanisms, and modulate tumor-related angiogenesis
  • inhibiting stimulation of the transcriptional activator STAT-1
  • inducing p65 nuclear factor (NF)-kappaB association with histone deacetylase 1, repressing cytokine production
  • suppressing production of IFN-gamma and IL-12 than curtailing the innate response and its transition to adaptive TH1 immunity
  • may be involved in pathogenesis of hemophagocytic lymphohistiocytosis and is useful as a clinical marker
  • implicated as a mediator of chronic inflammatory processes via prolonged activation of the NF-kappaB pathway in several tissues, including the kidney
  • may regulate cell proliferation, cell death, cell differentiation, angiogenesis and inflammation
  • multifunctional cytokine known to regulate cellular functions in contexts of injury and disease through its receptor TNFRSF12A
  • TWEAK/TWEAKR may be important in regulating myocardial structural remodeling and function and may play a role in the pathogenesis of dilated cardiomyopathy
  • can act in a juxtacrine manner to initiate cellular responses, and this property may be important for its function during physiological wound repair and disease pathogenesis
  • roles for TNFSF12, BIRC3, and noncanonical NFKB signaling in the regulation of myoblast fusion and highlight a role for cytokine signaling during adult skeletal myogenesis
    • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS immunity/defense
    PATHWAY
    metabolism
    signaling
    TNFRSF12A/TNFSF12 pathway is a novel regulator of skeletal muscle precursor cells and illustrate an important mechanism by which inflammatory cytokines influence tissue regeneration and repair
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to one of at least two distinct receptors that induce differential activation of downstream signaling pathways
  • TWEAK/TWEAKR interaction may have proinflammatory effects in retinal pigment epithelial cells
  • TNSFS12/TNFSFR12A implicated in the pathogenesis of several diseases, including acute ischemic stroke and rheumatoid arthritis
  • TNFSF12 and TNF, downregulate Klotho expression through an NFKB-dependent mechanism
  • TNFSF12 inhibits TRAF2-mediated CD40 signaling by destabilization of CD40 signaling complexes
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in hepatocellular carcinoma
    constitutional     --over  
    differentially upregulated in patients with idiopathic dilated cardiomyopathy compared with other forms of heart disease and normal control subjects
    Susceptibility
    Variant & Polymorphism
    Candidate gene
  • candidate clinical biomarker for lupus nephritis
    • Marker
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneousurinary 
    might be a target for therapeutic intervention in renal and vascular injury
    cancerreproductiveovary
    targeted therapy against TWEAK-TWEAKR signaling system as an adjuvant to surgery may improve clinical management of invasive ovarian cancer cells and advance the outcome of this devastating cancer
    ANIMAL & CELL MODELS