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Recombinant Human Stimulator of interferon genes protein (STING1)

  • 货号:
    CSB-CF023754HU
  • 规格:
  • 来源:
    in vitro E.coli expression system
  • 其他:

产品详情

  • 基因名:
  • Uniprot No.:
  • 别名:
    STING1; ERIS; MITA; TMEM173; Stimulator of interferon genes protein; hSTING; Endoplasmic reticulum interferon stimulator; Mediator of IRF3 activation; hMITA; Transmembrane protein 173
  • 种属:
    Homo sapiens (Human)
  • 蛋白长度:
    full length protein
  • 表达区域:
    1-379
  • 氨基酸序列
    MPHSSLHPSIPCPRGHGAQKAALVLLSACLVTLWGLGEPPEHTLRYLVLHLASLQLGLLL NGVCSLAEELRHIHSRYRGSYWRTVRACLGCPLRRGALLLLSIYFYYSLPNAVGPPFTWM LALLGLSQALNILLGLKGLAPAEISAVCEKGNFNVAHGLAWSYYIGYLRLILPELQARIR TYNQHYNNLLRGAVSQRLYILLPLDCGVPDNLSMADPNIRFLDKLPQQTGDHAGIKDRVY SNSIYELLENGQRAGTCVLEYATPLQTLFAMSQYSQAGFSREDRLEQAKLFCRTLEDILA DAPESQNNCRLIAYQEPADDSSFSLSQEVLRHLRQEEKEEVTVGSLKTSAVPSTSTMSQE PELLISGMEKPLPLRTDFS
    Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.
  • 蛋白标签:
    N-terminal 10xHis-tagged
  • 产品提供形式:
    Liquid or Lyophilized powder
    Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
  • 缓冲液:
    Lyophilized from Tris/PBS-based buffer, 6% Trehalose, pH 8.0
  • 储存条件:
    Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
  • 保质期:
    The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
    Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
  • 货期:
    Basically, we can dispatch the products out in 1-3 working days after receiving your orders. Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
    Note: All of our proteins are default shipped with normal blue ice packs, if you request to ship with dry ice, please communicate with us in advance and extra fees will be charged.
  • 注意事项:
    Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
  • Datasheet & COA:
    Please contact us to get it.

产品评价

靶点详情

  • 功能:
    Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm. Acts by binding cyclic dinucleotides: recognizes and binds cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic GMP-AMP (cGAMP), a messenger produced by CGAS in response to DNA virus in the cytosol. Upon binding of c-di-GMP or cGAMP, STING1 oligomerizes, translocates from the endoplasmic reticulum and is phosphorylated by TBK1 on the pLxIS motif, leading to recruitment and subsequent activation of the transcription factor IRF3 to induce expression of type I interferon and exert a potent anti-viral state. In addition to promote the production of type I interferons, plays a direct role in autophagy. Following cGAMP-binding, STING1 buds from the endoplasmic reticulum into COPII vesicles, which then form the endoplasmic reticulum-Golgi intermediate compartment (ERGIC). The ERGIC serves as the membrane source for WIPI2 recruitment and LC3 lipidation, leading to formation of autophagosomes that target cytosolic DNA or DNA viruses for degradation by the lysosome. The autophagy- and interferon-inducing activities can be uncoupled and autophagy induction is independent of TBK1 phosphorylation. Autophagy is also triggered upon infection by bacteria: following c-di-GMP-binding, which is produced by live Gram-positive bacteria, promotes reticulophagy. Exhibits 2',3' phosphodiester linkage-specific ligand recognition: can bind both 2'-3' linked cGAMP (2'-3'-cGAMP) and 3'-3' linked cGAMP but is preferentially activated by 2'-3' linked cGAMP. The preference for 2'-3'-cGAMP, compared to other linkage isomers is probably due to the ligand itself, whichs adopts an organized free-ligand conformation that resembles the STING1-bound conformation and pays low energy costs in changing into the active conformation. May be involved in translocon function, the translocon possibly being able to influence the induction of type I interferons. May be involved in transduction of apoptotic signals via its association with the major histocompatibility complex class II (MHC-II).; (Microbial infection) Antiviral activity is antagonized by oncoproteins, such as papillomavirus (HPV) protein E7 and adenovirus early E1A protein. Such oncoproteins prevent the ability to sense cytosolic DNA.
  • 基因功能参考文献:
    1. We present physiological evidence that UBXN3B positively regulates stimulator-of-interferon genes (STING) signaling. Mechanistic studies demonstrate that UBXN3B interacts with both STING and its E3 ligase TRIM56, and facilitates STING ubiquitination, dimerization, trafficking, and consequent recruitment and phosphorylation of TBK1. PMID: 29899553
    2. STAG2 deficiency induces interferon responses via cGAS-STING pathway and restricts virus infection. PMID: 29662124
    3. STING-IRF3 pathway promotes hepatocyte injury and dysfunction by inducing inflammation and apoptosis and by disturbing glucose and lipid metabolism. PMID: 29106945
    4. Data show that both cyclic GMP-AMP synthase (cGAS) and interferon-gamma inducible protein 16 (IFI16) are required for the activation of membrane protein STING (STING) and an innate immune response to exogenous DNA and DNA viruses. PMID: 28194029
    5. PUMA promotes the cytosolic release of mitochondrial DNA and activation of the DNA sensors DAI/Zbp1 and STING, leading to enhanced RIP3 and MLKL phosphorylation in a positive feedback loop. PMID: 29581256
    6. identified nitro-fatty acids as endogenously formed inhibitors of STING signaling and propose for these lipids to be considered in the treatment of STING-dependent inflammatory diseases. PMID: 30061387
    7. Cells of human individuals carrying HAQ TMEM173, which encodes a common hypomorphic variant of STING, were largely or partly defective in inducing type I IFNs and proinflammatory cytokines upon infection. PMID: 29263110
    8. Our studies indicate that the (extracellular vesicles) EVs released by HSV-1-infected cells carry innate immune components such as STING and other host and viral factors; they can activate innate immune responses in recipient cells and inhibit HSV-1 replication. The implication of these data is that the EVs released by HSV-1-infected cells could control HSV-1 dissemination promoting its persistence in the host. PMID: 29976662
    9. data demonstrate that numerous RNA viruses evade cGAS/STING-dependent signaling and affirm the importance of this pathway in shaping the host range of ZIKV. PMID: 29915078
    10. Immune activation of STING requires palmitoylation at the Golgi. PMID: 27324217
    11. In the Title. PMID: 27554814
    12. This study demonstrated that HSV-1 tegument protein VP22 counteracts the cGAS/STING-mediated DNA-sensing antiviral innate immunity signaling pathway by inhibiting the enzymatic activity of cGAS. PMID: 29793952
    13. an electrophoretic mobility shift assay showed that signal transducers and activators of transcription 1 (STAT1) attach to the GAS motif on the human STING promoter region. This indicates that IFN-gamma/Janus kinases/STAT1 signaling is essential for the STING upregulation in human keratinocytes. PMID: 29143896
    14. The cGAS-STING cascade contributes to antibacterial defense against L. pneumophila in mice and men, and provides important insight into how the common HAQ TMEM173/STING variant affects antimicrobial immune responses and susceptibility to infection. PMID: 29298342
    15. pharmacological activation of STING in macrophages and hepatocytes induces host innate responses that can efficiently control hepatitis B virus replication. Hence, despite not playing a significant role in host innate immune response to HBV infection of hepatocytes, STING is potentially a valuable target for immunotherapy of chronic hepatitis B. PMID: 28717041
    16. summarize recent findings that have pointed towards the STING pathway as an innate immune sensing mechanism driving type I interferon production in the tumor context PMID: 28639100
    17. this review summarizes important features of the STING activation pathway and recent highlights about the role of STING in bacterial infections by Chlamydia, Listeria, Francisella, Brucella, Shigella, Salmonella, Streptococcus, and Neisseria genera, with a special focus on mycobacteria. PMID: 28625530
    18. STING serves to detect - and promote immune defense against - DNA viruses and intracellular bacteria, as described in its initial discovery. The role of STING has since been expanded to include tumor surveillance and immune responses to cancer; indeed, defective STING responses are associated with certain cancers. PMID: 28724326
    19. C11 depends on signaling through STING to produce antiviral type I interferon, which further supports its potential as a therapeutic drug or research tool. PMID: 29263267
    20. This study demonstrates that the HCMV tegument protein pp65 inhibits IFN-beta production by binding and inactivating cGAS early during infection. In addition, this inhibitory activity specifically targets cGAS, since it can be bypassed via the addition of exogenous cGAMP, even in the presence of pp65. Notably, STING proteasome-mediated degradation was observed in both the presence and absence of pp65. PMID: 29263269
    21. The DNA binding domain of Ku70 was essential for formation of the Ku70-STING complex. Knocking down STING in primary human macrophages inhibited their ability to produce IFN-lambda1 in response to transfection with DNA or infection with the DNA virus HSV-2 (herpes simplex virus-2); STING mediates the Ku70-mediated IFN-lambda1 innate immune response to exogenous DNA or DNA virus infection. PMID: 28720717
    22. Data show that human cytomegalovirus (HCMV; human betaherpesvirus 5) glycoprotein US9 inhibits the IFN-beta response by targeting the mitochondrial antiviral-signaling protein (MAVS) and stimulator of interferon genes (STING)-mediated signaling pathways. PMID: 29317664
    23. In the current study, we studied the role of MITA (Mediator of IRF3 Activation), a regulator of innate immunity, in the regulation of autophagy and its implication in cell death of breast cancer cells. Here, we report that MITA inhibits the fusion of autophagosome with lysosome as evident from different autophagy flux assays PMID: 28366813
    24. these studies demonstrate that transcription factors CREB and c-Myc maintain the transcriptional activity of STING PMID: 27835584
    25. TheTREX1 and STING, which are opposing regulators of the cytosolic DNA-sensing pathway. PMID: 28475463
    26. STING-regulated pathways underlie the pathogenesis of many diseases including infectious diseases and cancers. It has also become evident from these studies that STING is a promising therapeutic target for the treatment of cancer. PMID: 26980676
    27. using a murine HNSCC model that does not express STING, we demonstrate that STING ligands are an effective therapy regardless of expression of STING by the cancer cells PMID: 29135982
    28. Human T-lymphotropic virus 1 Tax protein impairs K63-linked ubiquitination of STING and disrupted the interactions between STING and TBK1 to evade host innate immunity. PMID: 28119118
    29. STING activated an antiviral/type I interferon response with live but not killed S. aureus. PMID: 28704551
    30. study identifies the AIM2 inflammasome and cGAS/IFI16-STING-type I IFN pathway as a novel mechanism for host innate immunity to the ALVAC vaccine vector. PMID: 28947539
    31. NEMO was critically involved in the cGAS-STING pathway. PMID: 28939760
    32. Studied association of genetic variants of the MAVS, MITA and MFN2 genes with leprosy in Han Chinese from Southwest China; found no association between the variants and susceptibility to leprosy. PMID: 27553710
    33. both IL-6 and RIG-I are downstream molecules of STING along the DNA sensor pathway. PMID: 28806404
    34. our data provide an important insight into STING-mediated induction of type I and III IFNs and subsequent antiviral signaling pathways that regulate VZV replication in human dermal cells. PMID: 28647346
    35. STING, a critical innate sensor, also functions intrinsically in cells of the adaptive immune system to inhibit proliferation. PMID: 28484079
    36. We discuss three newly described monogenic autoinflammatory diseases [deficiency of adenosine deaminase 2 (DADA2), a subtype of macrophage activation syndrome (MAS), and stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI)], discuss the possibilities of somatic mosaicism and digenic inheritance, and give an update on new concepts in pathways involved in familial Mediterranean fever PMID: 27362340
    37. Human Cytomegalovirus tegument protein UL82 negatively regulates STING-mediated signaling. PMID: 28132838
    38. Structural analysis indicates that the 3 disease-associated mutations at positions 206, 281, and 284 of the STING protein define a novel cluster of amino acids with functional importance in the regulation of type I interferon signaling PMID: 28087229
    39. a critical role of p38-mediated USP21 phosphorylation in regulating STING-mediated antiviral functions and identifies p38-USP21 axis as an important pathway that DNA virus adopts to avoid innate immunity responses. PMID: 28254948
    40. We conclude that the R71H-G230A-R293Q (HAQ) of TMEM173 is a null TMEM173 allele. PMID: 27927967
    41. The s found that the herpes simplex virus 1 UL46 protein interacts with and colocalizes with STING. PMID: 28592536
    42. Essential roles of the cGAS-cGAMP-STING pathway. [review] PMID: 27706894
    43. These results suggest that pDCs sense cytosolic DNA and cyclic dinucleotides via the cGAS-STING pathway and that targeting this pathway could be of therapeutic interest. PMID: 27125983
    44. Human herpesvirus 1 ICP27 interacted with TBK1 and STING in a manner that was dependent on TBK1 activity and the RGG motif in ICP27 and inhibited type I IFN induction through the cGAS-STING-TBK1 pathway in human macrophages. PMID: 27234299
    45. Multivariate analysis supported TMEM173 as an independent prognostic factor. PMID: 27814372
    46. The mitochondrial damage-cGAS-STING-IRF3 pathway is critically involved in metabolic stress-induced endothelial inflammation. PMID: 28302626
    47. These data uncover a promycobacterial role for STING-dependent OASL production during Mycobacterium leprae infection that directs the host immune response toward a niche that permits survival of the pathogen. PMID: 27190175
    48. A heterozygous gain-of-function mutation in STING can cause familial chilblain lupus. PMID: 27566796
    49. cGAs recognizes bacterial/viral DNA, and is a strong activator of STING that can further activate IRF3 and subsequent type I interferon production. (Review) PMID: 27696330
    50. In the present study, the s found that herpes simplex virus 1 tegument protein UL41 was involved in counteracting the cGAS/STING-mediated DNA-sensing pathway. PMID: 28077645

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  • 相关疾病:
    STING-associated vasculopathy, infantile-onset (SAVI)
  • 亚细胞定位:
    Endoplasmic reticulum membrane; Multi-pass membrane protein. Cytoplasm, perinuclear region. Endoplasmic reticulum-Golgi intermediate compartment membrane; Multi-pass membrane protein. Cytoplasmic vesicle, autophagosome membrane; Multi-pass membrane protein. Mitochondrion outer membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein.
  • 蛋白家族:
    TMEM173 family
  • 组织特异性:
    Ubiquitously expressed. Expressed in skin endothelial cells, alveolar type 2 pneumocytes, bronchial epithelium and alveolar macrophages.
  • 数据库链接:

    HGNC: 27962

    OMIM: 612374

    KEGG: hsa:340061

    STRING: 9606.ENSP00000331288

    UniGene: Hs.379754