InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Gene: TMEM173

Summary

InnateDB Gene

IDBG-47893.6

Last Modified

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

Gene Symbol

TMEM173

Gene Name

transmembrane protein 173

Synonyms

Species

Homo sapiens

Ensembl Gene

ENSG00000184584

Encoded Proteins

IDBP-47895

transmembrane protein 173

IDBP-480716

transmembrane protein 173

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 18724357

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

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

PMID 19776740

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

PMID 19285439

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

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

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

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

PMID 22761576

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

PMID 23055924

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

PMID 23542348

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

PMID 24131791

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

PMID 24449861

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

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

PMID 24449861

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

Familial TMEM173 mutation is associated with inflammatory lupus-like manifestations.

PMID 25425575

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

PMID 25505063

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

PMID 25526307

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

PMID 25792739

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

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

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.

InnateDB Annotation from Orthologs

Summary

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

Currently no Entrez Summary Available. You might want to check the Summary Sections of the Orthologs.

Gene Information

Type

Protein coding

Genomic Location

Chromosome 5:139475534-139482935

Strand

Reverse strand

Band

q31.2

Transcripts

ENST00000330794	ENSP00000331288
ENST00000507297
ENST00000509573
ENST00000512606
ENST00000503287
ENST00000511886
ENST00000502825
ENST00000510817	ENSP00000427455
ENST00000514119
ENST00000515507
ENST00000511850
ENST00000503838
ENST00000502362
ENST00000514348
ENST00000514542

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 69 experimentally validated interaction(s) in this database.
They are also associated with 4 interaction(s) predicted by orthology.

Experimentally validated
Total	69 [view]
Protein-Protein	69 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	4 [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:0032479	regulation of type I interferon production
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:0030659	cytoplasmic vesicle membrane
GO:0048471	perinuclear region of cytoplasm