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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
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • an extracellular C terminus, also existing as a soluble form
  • AAs 9093 is the predominant furin recognition site
  • stalk region containing putative proprotein convertase recognition motifs at residues 9093 (RPRR) and 102105 (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