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FLASH GENE
Symbol TNFAIP8L2 contributors: mct - updated : 02-01-2017
HGNC name tumor necrosis factor, alpha-induced protein 8-like 2
HGNC id 26277
Location 1q21.3      Physical location : 151.129.104 - 151.132.225
Synonym name
  • inflammation factor protein 20
  • TNFAIP8-like protein 2
  • Synonym symbol(s) RP11-68I18.4, FLJ23467, TIPE2
    DNA
    TYPE functioning gene
    STRUCTURE 3.12 kb     2 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 1248 20.4 184 - PMID: 18455981
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier liningretinal pigment epithelium (RPE)   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmature hematopoietic Homo sapiens
    Lymphoid/Immunemacrophage Homo sapiens
    cell lineage high levels were detected in monocyte/macrophage derived cell lines
    cell lines high levels in ovarian adenocarcinoma cells
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal lysine or arginine AAs, Lys-15, Lys-16, and Arg-24, are important for TNFAIP8L2RAC1 interaction because replacing them with glutamine or alanine markedly reduced the RAC1 binding
  • a large, hydrophobic central cavity that is poised for cofactor binding
  • HOMOLOGY
    Homologene
    FAMILY
  • TNFAIP8 family
  • TNFAIP8L2 subfamily
  • TNF-alpha-induced protein 8 (TNFAIP8, TIPE) family
  • CATEGORY immunity/defense
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    basic FUNCTION
  • death effector domains protein that negatively regulates both T cell receptor and Toll-like receptor signaling
  • has an essential role in immune homeostasis
  • having tissue-specific functions in both lymphoid and non-lymphoid compartments and its deficiency enhanced cellular but not humoral immunity
  • TNFAIP8L1, TNFAIP8L2, TNFAIP8L3, share high degrees of sequence homology and involve in proliferation, inflammation, and cell death
  • essential negative regulator of both innate and adaptive immunity and its depletion would cause serve inflammatory disease
  • is an inhibitor of both inflammation and cancer
  • is involved in the pathogenesis of stroke, suggesting that it plays an essential role in a signal transduction pathway that links the inflammatory immune response to specific conditions after cerebral ischemia
  • serves as a negative regulator of innate immunity by linking TLRs to RAC1
  • controls innate immunity by targeting the Rac GTPases
  • inhibits immunity to bacteria
  • is a potential inhibitor of atherosclerosis
  • can negatively regulate inflammation through inhibiting immune receptor signaling, and plays a crucial atheroprotective role likely by regulating macrophage responses to oxidized low-density lipoprotein (ox-LDL)
  • plays an important role in shifting L-arginase metabolism from production of nitric oxide (NO) to urea, during host inflammatory response
  • is an inhibitor of gastric cancer cell growth, and likely might promote a CDKN1B-associated signaling cascade that leads to restored control of the cell cycle and cell division
  • might serve as a tumor suppressor in NSCLC progression
  • inhibited the phosphorylation of AKT1, while promoting the phosphorylation of MAPK14, but had no effect on NFKBIA and ERK pathway
  • negative regulator of innate and adaptive immunity which participates in inflammatory homeostasis
  • anti-inflammatory TNFAIP8L2 inhibits angiogenic VEGFA in retinal pigment epithelium
  • plays a key role in non-small cell lung cancer (NSCLC) metastasis
  • death effector domain protein that is a negative regulator of the innate and adaptive immune response
  • acts as a novel negative regulator of inflammatory and immune responses through MAP3K7 signaling
  • involved in the invasion and metastasis of human tumors
  • its overexpression may suppress proliferation, migration, and invasion in prostate cancer cells by inhibiting the PI3K/AKT1 signaling pathway
  • suppressed breast cancer tumorigenesis, growth and metastasis possibly via regulation of the AKT1 and MAPK14 signaling pathways
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • TNFAIP8L1, TNFAIP8L2 showed a very weak interaction with GNAI3
  • binds to the C terminus of RAC1 suggesting that it may regulate membrane translocation of RAC1
  • negatively regulates inflammation through inhibiting Toll-like receptor signaling
  • can regulate TLR4 inflammatory effect and inhibit further amplification of cascade reaction via CASP8
  • interacts with MAP3K7, a crucial regulatory molecule of inflammatory and immune signals, and consequently acts as a powerful negative regulator of MAP3K7
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    associated with systemic autoimmunity (Zhang 2010)
    constitutional     --low  
    is closely associated with SLE (systemic lupus erythematosus) suggesting an important role for TIPE2 gene in the pathogenesis of SLE (Zhang 2009)
    tumoral     --low  
    in breast cancer tissues compared to the level in adjacent normal tissues
    tumoral     --low  
    in human prostate cancer tissues and cell lines
    tumoral     --low  
    in human glioma cell lines
    constitutional     --low  
    in patients with infectious or autoimmune disorders
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • potential biomarker for gastric cancer progression, stimulates an IRF4-associated signaling cascade that promotes CDKN1B expression and controls cell growth
  • might be a novel marker for lung cancer diagnosis and therapy
  • Therapy target
    SystemTypeDisorderPubmed
    cancer  
    potential drug target for inflammatory and neoplastic diseases
    cancerreproductivebreast
    may be a potential therapeutic target for breast cancer therapy
    cancerreproductiveprostate
    might serve as a potential therapeutic target for human prostate cancer
    cancerlung 
    forced TNFAIP8L2 expression might be a novel strategy for the treatment of non-small cell lung cancer (NSCLC)
    cardiovascularatheroma 
    inhibitor of atherosclerosis and a potential drug target for treating the disease
    ANIMAL & CELL MODELS
  • TIPE2 deficiency in mice causes fetal inflammatory diseases (Zhang 2010)
  • Tipe2-/- mice are resistant to L. monocytogenes and S. aureus infection