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  • Product Name
    Phospho-TMEM173/STING (Ser366) Antibody
  • Catalog No.
    AF7416
  • RRID
    AB_2843856
  • Source
    Rabbit
  • Application
    WB,IHC,IF/ICC,ELISA(peptide)
  • Reactivity
    Human, Mouse, Rat
  • Prediction
    Pig, Bovine, Horse, Sheep, Rabbit
  • UniProt
  • Mol.Wt
    35-40kD;
    42kDa(Calculated).
  • Concentration
    1mg/ml
  • Browse similar products>>

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Product Information

Alternative Names:Expand▼

endoplasmic reticulum IFN stimulator; Endoplasmic reticulum interferon stimulator; ERIS; FLJ38577; hMITA; hSTING; Mediator of IRF3 activation; MITA; Mitochondrial mediator of IRF3 activation; MPYS; N terminal methionine proline tyrosine serine plasma membrane tetraspanner; NET23; Stimulator of interferon genes; Stimulator of interferon genes protein; STING; TM173_HUMAN; Tmem173; Transmembrane protein 173;

Applications:

WB 1:500-1:2000, IHC 1:50-1:200, IF/ICC 1:100-1:500, ELISA(peptide) 1:20000-1:40000
*The optimal dilutions should be determined by the end user.

Reactivity:

Human, Mouse, Rat

Predicted Reactivity:

Pig, Bovine, Horse, Sheep, Rabbit

Source:

Rabbit

Clonality:

Polyclonal

Purification:

The antibody is from purified rabbit serum by affinity purification via sequential chromatography on phospho-peptide and non-phospho-peptide affinity columns.

Specificity:

Phospho-TMEM173/STING (Ser366) Antibody detects endogenous levels of TMEM173/STING only when phosphorylated at Ser366.

RRID:

AB_2843856
Please cite this product as: Affinity Biosciences Cat# AF7416, RRID:AB_2843856.

Format:

Liquid

Concentration:

1mg/ml

Storage Condition and Buffer:

Rabbit IgG in phosphate buffered saline , pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol.Store at -20 °C.Stable for 12 months from date of receipt.

Immunogen Information in 3D

Immunogen:

A synthesized peptide derived from human TMEM173/STING around the phosphorylation site of Ser366.

Uniprot:



>>Visit The Human Protein Atlas

Gene ID:

Gene Name:

TMEM173

Molecular Weight:

Observed Mol.Wt.: 35-40kD.
Predicted Mol.Wt.: 42kDa(Calculated)..

Subcellular Location:

Endoplasmic reticulum membrane. Mitochondrion outer membrane. Cell membrane. Cytoplasm > perinuclear region. In response to double-stranded DNA stimulation, relocalizes to perinuclear region, where the kinase TBK1 is recruited.

Tissue Specificity:

Q86WV6 STING_HUMAN:
Ubiquitously expressed. Expressed in skin endothelial cells, alveolar type 2 pneumocytes, bronchial epithelium and alveolar macrophages.

Sequence:
MPHSSLHPSIPCPRGHGAQKAALVLLSACLVTLWGLGEPPEHTLRYLVLHLASLQLGLLLNGVCSLAEELRHIHSRYRGSYWRTVRACLGCPLRRGALLLLSIYFYYSLPNAVGPPFTWMLALLGLSQALNILLGLKGLAPAEISAVCEKGNFNVAHGLAWSYYIGYLRLILPELQARIRTYNQHYNNLLRGAVSQRLYILLPLDCGVPDNLSMADPNIRFLDKLPQQTGDHAGIKDRVYSNSIYELLENGQRAGTCVLEYATPLQTLFAMSQYSQAGFSREDRLEQAKLFCRTLEDILADAPESQNNCRLIAYQEPADDSSFSLSQEVLRHLRQEEKEEVTVGSLKTSAVPSTSTMSQEPELLISGMEKPLPLRTDFS

Research Background

Function:

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 (By similarity). 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) (By similarity).

(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.

Post-translational Modifications:

Phosphorylation by TBK1 leads to activation and production of IFN-beta. Following cyclic nucleotide (c-di-GMP or cGAMP)-binding, activation and translocation from the endoplasmic reticulum, STING1 is phosphorylated by TBK1 at Ser-366 in the pLxIS motif. The phosphorylated pLxIS motif constitutes an IRF3-binding motif, leading to recruitment of the transcription factor IRF3 to induce type-I interferons and other cytokines. Phosphorylated on tyrosine residues upon MHC-II aggregation (By similarity).

Ubiquitinated. Ubiquitinated via 'Lys-63'-linked ubiquitin chains in response to double-stranded DNA treatment, leading to relocalization to autophagosomes and subsequent degradation; this process is dependent on SQSTM1 (By similarity). 'Lys-63'-linked ubiquitination mediated by TRIM56 at Lys-150 promotes homodimerization and recruitment of the antiviral kinase TBK1 and subsequent production of IFN-beta. 'Lys-48'-linked polyubiquitination at Lys-150 occurring after viral infection is mediated by RNF5 and leads to proteasomal degradation. 'Lys-11'-linked polyubiquitination at Lys-150 by RNF26 leads to stabilize STING1: it protects STING1 from RNF5-mediated 'Lys-48'-linked polyubiquitination.

Subcellular Location:

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.
Note: In response to double-stranded DNA stimulation, translocates from the endoplasmic reticulum through the endoplasmic reticulum-Golgi intermediate compartment and Golgi to post-Golgi vesicles, where the kinase TBK1 is recruited (PubMed:19433799, PubMed:30842659, PubMed:30842653, PubMed:29694889). Upon cGAMP-binding, translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) in a process that is dependent on COPII vesicles; STING1-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis (PubMed:30842662).

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte

Tissue Specificity:

Ubiquitously expressed. Expressed in skin endothelial cells, alveolar type 2 pneumocytes, bronchial epithelium and alveolar macrophages.

Subunit Structure:

Homodimer; forms a homodimer in absence of cyclic nucleotide (c-di-GMP or cGAMP); 'Lys-63'-linked ubiquitination at Lys-150 is required for homodimerization. Homotetramer; in presence of cyclic nucleotide (c-di-GMP or cGAMP), forms tetramers and higher-order oligomers through side-by-side packing (Probable). Interacts (when phosphorylated) with IRF3; following activation and phosphorylation on the pLxIS motif by TBK1, recruits IRF3. Interacts with DDX58/RIG-I, MAVS and SSR2. Interacts with RNF5 and TRIM56. Interacts with TBK1; when homodimer, leading to subsequent production of IFN-beta. Interacts with IFIT1 and IFIT2. Interacts with TRIM29; this interaction induces STING1 ubiquitination and subsequent degradation. Associates with the MHC-II complex (By similarity). Interacts with SEC24C; promoting translocation to the COPII vesicles. Interacts (when ubiquitinated) with SQSTM1; leading to relocalization to autophagosomes (By similarity). Interacts with SURF4. Interacts with HNRNPA2B1.

(Microbial infection) Interacts with human papillomavirus (HPV) protein E7.

(Microbial infection) Interacts with adenovirus early E1A protein.

(Microbial infection) Interacts with herpes simplex virus 1 protein ICP34.5; this interaction inhibits the intracellular DNA sensing pathway.

Similarity:

In absence of cGAMP, the transmembrane and cytoplasmic regions interact to form an integrated, domain-swapped dimeric assembly (By similarity). In absence of cyclic nucleotide (c-di-GMP or cGAMP), the protein is autoinhibited by an intramolecular interaction between the cyclic dinucleotide-binding domain (CBD) and the C-terminal tail (CTT) (PubMed:22579474, PubMed:22705373, PubMed:22728658, PubMed:22728660, PubMed:22728659). Following cGAMP-binding, the cyclic dinucleotide-binding domain (CBD) is closed, leading to a 180 degrees rotation of the CBD domain relative to the transmembrane domain. This rotation is coupled to a conformational change in a loop on the side of the CBD dimer, which leads to the formation of the STING1 tetramer and higher-order oligomers through side-by-side packing (By similarity). The N-terminal part of the CBD region was initially though to contain a fifth transmembrane region (TM5) but is part of the folded, soluble CBD (PubMed:22579474, PubMed:22705373, PubMed:22728658, PubMed:22728660, PubMed:22728659).

The pLxIS motif constitutes an IRF3-binding motif: following phosphorylation by TBK1, the phosphorylated pLxIS motif of STING1 recruits IRF3 (PubMed:25636800). IRF3 is then phosphorylated and activated by TBK1 to induce type-I interferons and other cytokines (PubMed:25636800).

Belongs to the STING family.

Research Fields

Research Fields:

· Organismal Systems > Immune system > NOD-like receptor signaling pathway.(View pathway)
· Organismal Systems > Immune system > RIG-I-like receptor signaling pathway.(View pathway)
· Organismal Systems > Immune system > Cytosolic DNA-sensing pathway.(View pathway)

Reference Citations:

1). Zhao X;Zhou Z; et al. Expression and Regulation of the GABAA Receptor/STEP61 Signaling Pathway in Cerebral Cortical Neurons Treated with Emulsified Isoflurane In Vitro. ACS Chem Neurosci 2020 Dec 16;11(24):4329-4335. (PubMed: 33232128) [IF=4.486]

2). Song Y;Zhang Z;Yu Z;Xia G;Wang Y;Wang L;Peng C;Jiang B;Liu S; et al. Wip1 Aggravates the Cerulein-Induced Cell Autophagy and Inflammatory Injury by Targeting STING/TBK1/IRF3 in Acute Pancreatitis. Inflammation 2021 Jan 8. (PubMed: 33417178) [IF=3.212]

3). Sen T et al. Aberrant ER-stress induced neuronal-IFNβ elicits white matter injury due to microglial activation and T-cell infiltration after TBI. J Neurosci 2019 Nov 6 (PubMed: 31694961)

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Catalog Number :

AF7416-BP
(Blocking peptide available as AF7416-BP)

Price/Size :

$350/1mg.
Tips: For modified antibodies, we provide modified peptides(0.5mg) and non-modified peptides(0.5mg).

Function :

Blocking peptides are peptides that bind specifically to the target antibody and block antibody binding. These peptide usually contains the epitope recognized by the antibody. Antibodies bound to the blocking peptide no longer bind to the epitope on the target protein. This mechanism is useful when non-specific binding is an issue, for example, in Western blotting (immunoblot) and immunohistochemistry (IHC). By comparing the staining from the blocked antibody versus the antibody alone, one can see which staining is specific; Specific binding will be absent from the western blot or immunostaining performed with the neutralized antibody.

Format and storage :

Synthetic peptide was lyophilized with 100% acetonitrile and is supplied as a powder. Reconstitute with 0.1 ml DI water for a final concentration of 10 mg/ml.The purity is >90%,tested by HPLC and MS.Storage Maintain refrigerated at 2-8°C for up to 6 months. For long term storage store at -20°C.

Precautions :

This product is for research use only. Not for use in diagnostic or therapeutic procedures.

Sheep
100%
Pig
90%
Bovine
90%
Horse
80%
Rabbit
80%
Dog
67%
Xenopus
0%
Zebrafish
0%
Chicken
0%
High similarity Medium similarity Low similarity No similarity
Q86WV6 as Substrate
Site PTM Type Enzyme
T84 Phosphorylation
K150 Ubiquitination
K289 Ubiquitination
K338 Ubiquitination
S345 Phosphorylation
S358 Phosphorylation Q9UHD2 (TBK1)
S366 Phosphorylation O75385 (ULK1)
K370 Ubiquitination
IMPORTANT: For western blots, incubate membrane with diluted antibody in 5% w/v milk , 1X TBS, 0.1% Tween®20 at 4°C with gentle shaking, overnight.

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