InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Gene: Tmem173

Summary

InnateDB Gene

IDBG-137341.6

Last Modified

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

Gene Symbol

Tmem173

Gene Name

transmembrane protein 173

Synonyms

2610307O08Rik; ERIS; Mita; MPYS; STING

Species

Mus musculus

Ensembl Gene

ENSMUSG00000024349

Encoded Proteins

IDBP-249021

transmembrane protein 173

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 21820332

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

Tmem173 activates Stat6 during viral infection to induce genes responsible for immune cell homing.

PMID 23055924

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

PMID 24119841

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

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

PMID 25517615

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

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

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

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

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

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

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.

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 18:35733678-35740554

Strand

Reverse strand

Band

Transcripts

ENSMUST00000115728

ENSMUSP00000111393

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 13 experimentally validated interaction(s) in this database.
They are also associated with 45 interaction(s) predicted by orthology.

Experimentally validated
Total	13 [view]
Protein-Protein	12 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	45 [view]

Gene Ontology

Molecular Function

Accession	GO Term
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: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 (InnateDB)
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: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:0016021	integral component of membrane
GO:0048471	perinuclear region of cytoplasm