InnateDB: Systems Biology of the Innate Immune Response

Bos taurus Gene: TMEM173

Summary

InnateDB Gene

IDBG-646026.3

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

TMEM173

Gene Name

Transmembrane protein 173

Synonyms

STING

Species

Bos taurus

Ensembl Gene

ENSBTAG00000002296

Encoded Proteins

IDBP-698791

Transmembrane protein 173

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation from Orthologs

Summary

PMID 18724357

[Homo sapiens] TMEM173 (STING) is an endoplasmic reticulum (ER) receptor that facilitates interferon (IFN) induction by binding to DDX58 (RIG-I) and to subunits of TRAP complex that facilitates translocation of proteins into the ER following translation.

PMID 18818105

[Homo sapiens] TMEM173 is a critical mediator of virus-triggered type I IFN signalling and a critical mediator of virus-triggered IRF3 activation.

PMID 19776740

[Homo sapiens] TMEM173 is essential for host defence against DNA pathogens such as HSV-1 and facilitates the adjuvant activity of DNA-based vaccines.

PMID 19285439

[Homo sapiens] TMEM173 is an adaptor protein that links virus-sensing receptors to IRF3 activation. RNF5 negatively regulates this virus-triggered signaling by targeting TMEM173 for ubiquitination and degradation at the mitochondria.

PMID 19926846

[Homo sapiens] TMEM173 is required for double stranded DNA-triggered innate immune responses where, upon sensing dsDNA, TMEM173 moves from the endoplasmic reticulum (ER) to the Golgi apparatus and finally reaches the cytoplasmic punctate structures to assemble with TANK-binding kinase 1 (TBK1).

PMID 21820332

[Homo sapiens] TMEM173 is involved in the innate immune recognition of Plasmodium falciparum AT-rich DNA and in the subsequent induction of type I IFNs. (Demonstrated in mouse)

PMID 22000020

[Homo sapiens] TMEM173 activates STAT6 during viral infection to induce genes responsible for immune cell homing. (Demonstrated in mice)

PMID 22761576

[Homo sapiens] TMEM173 is cleaved by dengue viral protease to suppress IRF3 activation and subvert antiviral immunity.

PMID 23055924

[Homo sapiens] Dengue viral NS2B3 protease complex selectively targets TMEM173 (STING) for degradation to inhibit type I IFN production in human dendritic cells.

PMID 23542348

[Homo sapiens] TMEM173 (STING) is targeted by hepatitis C viral protease to disrupt interferon signalling.

PMID 24131791

[Homo sapiens] Cyclic-di-GMP-induced levels of IFI16 suppress the expression of TMEM173 (STING).

PMID 24449861

[Homo sapiens] In herpes simplex virus 1 (HSV-1) infected cells, the stability and function of IFI16 and TMEM173 are dependent on cell derivation and the functional integrity of HSV-1 proteins ICP0 and US3 protein kinase.

PMID 24185615

[Homo sapiens] After viral infection, ELF4 binds to TMEM173 (STING) and induces type I interferon. ELF4 is critical for host antiviral defense.

PMID 24449861

[Homo sapiens] The end result of the interplay between TMEM173 (STING), IFI16, and herpes simplex virus 1 (HSV-1) is determined by the genotype of the infected cells and the functional integrity of HSV-1 proteins infected cell protein 0 (ICP0) and US3 protein kinase.

PMID 25401470

[Homo sapiens] Familial TMEM173 mutation is associated with inflammatory lupus-like manifestations.

PMID 25425575

[Homo sapiens] Cytosolic RNA:DNA hybrids are sensed by the MB21D1-TMEM173 (cGAS-STING) pathway of the innate immune system.

PMID 25505063

[Homo sapiens] Hepatitis B virus (HBV) polymerase inhibits TMEM173-stimulated IRF3 activation and IFNB1 induction.

PMID 25526307

[Homo sapiens] Upon cytoplasmic DNA stimulation, the endoplasmic reticulum protein AMFR is recruited to and interacts with TMEM173 in an INSIG1-dependent manner.

PMID 25792739

[Homo sapiens] Stimulation of TMEM173-dependent IRF3 activation by ultraviolet radiation is due to apoptotic signalling-dependent disruption of ULK1, a pro-autophagic protein that negatively regulates TMEM173.

PMID 26646986

[Homo sapiens] 4-(2-chloro-6-fluorobenzyl)-N-(furan-2-ylmethyl)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxamide (G10) requires STING to trigger IRF3/IFN-associated transcription in human fibroblasts and subsequently blocking replication of Chikungunya virus, Venezuelan Encephalitis virus, and Sindbis virus.

PMID 26199418

[Homo sapiens] Viral interferon regulatory factor 1 (vIRF1), targets TMEM173 by preventing it from interacting with TBK1, thereby inhibiting TMEM173's phosphorylation and concomitant activation, resulting in an inhibition of the DNA sensing pathway.

PMID 21820332

[Mus musculus] Tmem173 is involved in the innate immune recognition of Plasmodium falciparum AT-rich DNA and in the subsequent induction of type I IFNs.

PMID 22000020

[Mus musculus] Tmem173 activates Stat6 during viral infection to induce genes responsible for immune cell homing.

PMID 23055924

[Mus musculus] Dengue viral NS2B3 protease complex cannot degrade murine TMEM173, which confers protection against the viral infection.

PMID 24119841

[Mus musculus] Cyclic dinucleotides initiate the production of Tmem173(STING)-dependent proinflammatory genes and a negative-feedback to prevent sustained production that may otherwise lead to inflammation.

PMID 24131791

[Mus musculus] Cyclic-di-GMP-induced levels of Ifi202b suppress the expression of Tmem173 (STING).

PMID 25517615

[Mus musculus] The innate immune system plays a role in immunogenic tumour recognition. Tumor-cell-derived DNA triggers Ifnb1 production and dendritic cell activation via Tmem173 and Irf3 cytosolic DNA sensing pathways.

PMID 25692705

[Mus musculus] Unrepaired DNA lesions induce type I interferons via the Tmem173 pathway, resulting in enhanced anti-viral and anti-bacterial responses in Atm (-/-) mice.

PMID 25646421

[Mus musculus] Tmem173-deficient macrophages fail to express negative regulators of immune activation and are hyperresponsive to TLR ligands, producing abnormally high levels of proinflammatory cytokines.

PMID 25642965

[Mus musculus] Aberrant mitochondrial DNA (mtDNA) packaging promotes escape of mtDNA into the cytosol, where it engages the DNA sensor Mb21d1 and promotes Tmem173-Irf3-dependent signalling to elevate IFN-stimulated gene expression, potentiate type I IFN responses and confer broad viral resistance.

PMID 26590319

[Mus musculus] DNA vaccine-induced, Irf7-dependent signalling, as part of the Tmem173 (Sting) pathway, is critical for generation of both innate cytokine signalling and antigen-specific B and T cell responses.

PMID 26944200

[Mus musculus] The cationic polymer and vaccine adjuvant chitosan can engage the Tmem173/Mb21d1 (STING/cGAS) pathway to trigger innate and adaptive immune responses.

Entrez Gene

Summary

This gene does not have any Entrez summary - the following is the summary from its human ortholog ENSG00000184584:

Gene Information

Type

Protein coding

Genomic Location

Chromosome 7:52361793-52368150

Strand

Reverse strand

Band

Transcripts

ENSBTAT00000002962

ENSBTAP00000002962

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 0 experimentally validated interaction(s) in this database.
They are also associated with 44 interaction(s) predicted by orthology.

Predicted by orthology
Total	44 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000166	nucleotide binding
GO:0005515	protein binding
GO:0008134	transcription factor binding
GO:0019901	protein kinase binding
GO:0031625	ubiquitin protein ligase binding
GO:0035438	cyclic-di-GMP binding
GO:0042802	identical protein binding
GO:0042803	protein homodimerization activity
GO:0061507	cyclic-GMP-AMP binding

Biological Process

GO:0002218	activation of innate immune response
GO:0002230	positive regulation of defense response to virus by host
GO:0002376	immune system process
GO:0006915	apoptotic process
GO:0032092	positive regulation of protein binding
GO:0032481	positive regulation of type I interferon production
GO:0032608	interferon-beta production
GO:0033160	positive regulation of protein import into nucleus, translocation
GO:0035458	cellular response to interferon-beta
GO:0042993	positive regulation of transcription factor import into nucleus
GO:0045087	innate immune response
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0051607	defense response to virus
GO:0071360	cellular response to exogenous dsRNA

Cellular Component

GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005741	mitochondrial outer membrane
GO:0005777	peroxisome
GO:0005783	endoplasmic reticulum
GO:0005789	endoplasmic reticulum membrane
GO:0005794	Golgi apparatus
GO:0005886	plasma membrane
GO:0016020	membrane
GO:0016021	integral component of membrane
GO:0048471	perinuclear region of cytoplasm