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
transmembrane protein 173
transmembrane protein 173
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
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.
TMEM173 is a critical mediator of virus-triggered type I IFN signalling and a critical mediator of virus-triggered IRF3 activation.
TMEM173 is essential for host defence against DNA pathogens such as HSV-1 and facilitates the adjuvant activity of DNA-based vaccines.
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.
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).
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)
TMEM173 activates STAT6 during viral infection to induce genes responsible for immune cell homing. (Demonstrated in mice)
TMEM173 is cleaved by dengue viral protease to suppress IRF3 activation and subvert antiviral immunity.
Dengue viral NS2B3 protease complex selectively targets TMEM173 (STING) for degradation to inhibit type I IFN production in human dendritic cells.
TMEM173 (STING) is targeted by hepatitis C viral protease to disrupt interferon signalling.
Cyclic-di-GMP-induced levels of IFI16 suppress the expression of TMEM173 (STING).
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.
After viral infection, ELF4 binds to TMEM173 (STING) and induces type I interferon. ELF4 is critical for host antiviral defense.
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.
Familial TMEM173 mutation is associated with inflammatory lupus-like manifestations.
Cytosolic RNA:DNA hybrids are sensed by the MB21D1-TMEM173 (cGAS-STING) pathway of the innate immune system.
Hepatitis B virus (HBV) polymerase inhibits TMEM173-stimulated IRF3 activation and IFNB1 induction.
Upon cytoplasmic DNA stimulation, the endoplasmic reticulum protein AMFR is recruited to and interacts with TMEM173 in an INSIG1-dependent manner.
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.
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.
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
[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.
[Mus musculus] Tmem173 activates Stat6 during viral infection to induce genes responsible for immune cell homing.
[Mus musculus] Dengue viral NS2B3 protease complex cannot degrade murine TMEM173, which confers protection against the viral infection.
[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.
[Mus musculus] Cyclic-di-GMP-induced levels of Ifi202b suppress the expression of Tmem173 (STING).
[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.
[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.
[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.
[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.
[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.
[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
Orthologs
Species
Mus musculus
Bos taurus
Gene ID
Gene Order
Method
Confidence
Comments
SSD Ortholog
Ortholog supports species divergence
Not yet available
SSD Ortholog
Ortholog supports species divergence
Pathways
NETPATH
REACTOME
STING mediated induction of host immune responses pathway
IRF3-mediated induction of type I IFN pathway
ZBP1(DAI) mediated induction of type I IFNs pathway
IRF3 mediated activation of type 1 IFN pathway
Innate Immune System pathway
Regulation of innate immune responses to cytosolic DNA pathway
Immune System pathway
Cytosolic sensors of pathogen-associated DNA pathway
STAT6-mediated induction of chemokines pathway
KEGG
RIG-I-like receptor signaling pathway pathway
Cytosolic DNA-sensing pathway pathway
INOH
PID BIOCARTA
PID NCI
Cross-References
SwissProt
TrEMBL
UniProt Splice Variant
Entrez Gene
UniGene Hs.379754 Hs.610825
RefSeq NM_198282
HUGO
OMIM
CCDS CCDS4215
HPRD 14173
IMGT
EMBL
GenPept
RNA Seq Atlas