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FLASH GENE
Symbol STING1 contributors: mct/pgu - updated : 01-12-2021
HGNC name stimulator of interferon response cGAMP interactor 1
HGNC id 27962
Location 5q31.2      Physical location : -
Synonym name
  • N-terminal methionine-proline-tyrosine-serine plasma membrane tetraspanner
  • mitochondrial mediator of IRF3 activation
  • stimulator of interferon genes
  • transmembrane protein 173
  • endoplasmic reticulum IFN stimulator
  • Synonym symbol(s) FLJ38577, MITA, MPYS, STING, ERIS, NET23, TMEM173
    EC.number 3.6.4.13
    DNA
    TYPE functioning gene
    STRUCTURE 6.74 kb     8 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    8 - 1714 - 379 - 2007 17584744
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunespleen   highly
    Reproductivefemale systemovary  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • five putative transmembrane regions
  • extended C-terminal cytoplasmic tail (approximately 140 amino acids) with multiple embedded signaling motifs, that forms a V-shaped dimer and binds a cyclic diguanylate monophosphate (c-di-GMP) at the dimer interface by both direct and solvent-mediated hydrogen bonds
  • conjugated ubiquitinated
    HOMOLOGY
    Homologene
    FAMILY
    CATEGORY adaptor , signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria,outer
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text
  • endoplasmic reticulum (ER) resident transmembrane protein
  • both TMEM173 and RNF5 were located at the mitochondria and endoplasmic reticulum (ER) and viral infection caused their redistribution to the ER and mitochondria, respectively
  • basic FUNCTION
  • tetraspanner that is associated with MHC-II and mediates its transduction of death signals
  • may facilitate the detection of intracellular viral RNA species as well as B-form DNA
  • is essential for host defense against DNA pathogens such as HSV-1 and facilitates the adjuvant activity of DNA-based vaccines
  • functions as an essential signalling adaptor, linking the cytosolic detection of DNA to the TBK1-IRF3 signalling axis
  • control a new sensing pathway that is essential for detecting aberrant cytosolic DNA species and for triggering the production of host defense genes such as type I interferon (IFN)
  • seems to function as a direct sensor of cyclic dinucleotides, in addition to its established role as a signalling adaptor in the IFN response to cytosolic DNA
  • seems to function as a direct sensor of cyclic dinucleotides, in addition to its established role as a signalling adaptor in the IFN response to cytosolic DNA
  • DDX41 may function in dendritic cells as a DNA sensor to activate TMEM173-dependent innate immune responses
  • functions as a scaffold protein to specify and promote the phosphorylation of IRF3 by TBK1
  • play essential roles for cytosolic dsDNA-mediated production of type I IFN and inflammatory cytokines through activating th TBK1-IIRF3 axis
  • essential signaling adaptor that mediates cytokine production in response to microbial invasion by directly sensing bacterial secondary messengers such as the cyclic dinucleotide bis-(3prime-5prime)-cyclic dimeric GMP (c-di-GMP)
  • functions as both an adaptor protein signaling cytoplasmic double-stranded DNA and a direct immunosensor of cyclic diguanylate monophosphate (c-di-GMP)
  • critical adaptor protein that links virus-sensing receptors to IRF3 activation upon infection by both RNA and DNA pathogens
  • essential for the protection of the host against DNA pathogens
  • TMEM173 recognition of dsDNA triggers a transient nonconventional autophagy-related process required for IRF3/7 and NFKB activation
  • in the presence of cytosolic DNA, rapidly traffics with TBK1 via VPS34-related autophagosomes to associate with endosomal compartments containing NFKB and IRF3
  • essential for host immune responses triggered by microbial DNAs
  • CGAS restoration or TMEM173 stimulation by small molecules during infancy might improve the age-dependent susceptibility to DNA virus infection
  • endoplasmic reticulum-resident membrane protein that mediates cytosolic pathogen DNA-induced innate immunity and inflammatory responses in host defenses
  • is an adaptor protein that is critical for effective innate antiviral and antitumor immunity
  • is a vital element of the innate immune system against DNA viruses
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • may link RARRES3 and DNA-mediated intracellular innate signaling to the translocon
  • activated TMEM173, accompanied by TBK1, then undergoes dramatic autophagy-related trafficking involving ATG9 and associates with endosomes containing the transcription factors interferon regulatory factor 3 (IRF3) and NFKB
  • is an adaptor that links virus-sensing receptors to IRF3 activation
  • RNF5 negatively regulates virus-triggered signaling by targeting TMEM173 for ubiquitination and degradation at the mitochondria
  • IFIT1, virus-induced protein is associated with TMEM173
  • TRIM56 is an interferon-inducible E3 ubiquitin ligase that modulates TMEM173 to confer double-stranded DNA-mediated innate immune responses
  • DDX41 is an additional DNA sensor that depends on TMEM173 to sense pathogenic DNA
  • innate immune sensor of cyclic dinucleotides
  • TRIM32 interacted with TMEM173A, and was located at the mitochondria and endoplasmic reticulum
  • MRE11A physically interacted with dsDNA in the cytoplasm and was required for activation of TMEM173 and IRF3
  • phosphorylation of TMEM173 on S366 strongly prevents the transcriptional activity of IRF3
  • CGAS-induced activation of TMEM173 also involves the activation of the NFKB1 and IRF3 pathways
  • TBK1 is a downstream kinase controlling dsDNA-mediated IRF3 and NFKB1 signaling dependent on TMEM173
  • AMFR and INSIG1, an E3 ubiquitin ligase complex, then catalyzed the K27-linked polyubiquitination of TMEM173
  • MAVS and TMEM173 transduce signals from the cytosolic nucleic acid sensors DDX58 and CGAS, respectively
  • unique innate immune activation cascade in which TBK1-IKBKB formed a positive feedback loop to assure robust cytokine production during CGAS-TMEM173 activation
  • loss of the CGAS-TMEM173 pathway may be required to evade Extrachromosomal telomere repeat (ECTR)-induced anti-proliferation effects and permit alternative lengthening of telomeres (ALT) development in cancer
  • STING1 activates ADAM17 and this activation produces soluble proinflammatory SEMA4D independently of the TBK1/IRF3-mediated transcriptional pathway
  • IFNA1-mediated deregulation of mitochondrial metabolism and impairment of autophagic degradation, leading to cytosolic accumulation of mtDNA that is sensed via stimulator of interferon genes (STING1) to promote induction of autoinflammatory Dendritic,cells
  • YIPF5 is a positive regulator of STING1 trafficking
  • TBK1 acts redundantly with IKBKE to drive NFKB1 upon STING1 activation
  • OTUD5 interacts with STING1, cleaves its K48-linked polyubiquitin chains, and promotes its stability
  • PLD3 and PLD4 regulate both endosomal TLR and cytoplasmic/STING1 nucleic acid sensing pathways
  • activation of STING1 inhibits cancer cell migration and invasion by suppressing PLAU
  • mechanistically, SELENOK interacts with STING1 in the ER and promotes STING1 oligomerization, which in turn promotes its translocation from the ER to the Golgi
  • SELENOK deficiency suppresses STING1-dependent innate responses and facilitates viral replication
  • cell & other
    REGULATION
    induced by during virus infection and facilitated innate immune responses against herpes simplex virus-1 (HSV-1)
    Phosphorylated by serine/threonine UNC-51-like kinase (ULK1/ULK2)
    Other tyrosine phosphorylated upon MHC-II aggregation and associates with inositol lipid and tyrosine phosphatases
    TRIM32 ubiquitinated TMEM173 and dramatically enhanced TMEM173-mediated induction of IFNB
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Sting-deficient mice have lost their ability to produce type I IFN in response to dsDNA