InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Gene: Ticam1

Summary

InnateDB Gene

IDBG-191912.6

Last Modified

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

Gene Symbol

Ticam1

Gene Name

toll-like receptor adaptor molecule 1

Synonyms

AW046014; AW547018; TICAM-1; TRIF

Species

Mus musculus

Ensembl Gene

ENSMUSG00000047123

Encoded Proteins

IDBP-191914

toll-like receptor adaptor molecule 1

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 21454965

The Ticam1 signalling pathway in murine dendritic cells is crucial for dsRNA-mediated natural killer cell activation.

PMID 21494017

Ticam1 deficiency results in the impairment of LPS-stimulated TNF-alpha protein translation.

PMID 21602824

Ticam1 is crucial for Nlrp3 inflammasome activation in response specific to viable, but not heat-killed, E. coli infections.

PMID 21697485

Ticam1 is proteolytically cleaved by Enterovirus 71 to inhibit the induction of innate immunity by Tlr3-signalling. Ticam1 cleavage results in the inhibition of NFkB and IFNB promoter activation. (Demonstrated in human)

PMID 21703541

Ticam1 forms a dsRNA sensor complex with components Ddx1, Ddx21 and Dhx36 to trigger the type I interferon and cytokine response to poly I:C, influenza A virus, and reovirus.

PMID 21760953

Ticam1 is a potent negative regulator of TLR agonist-triggered immune responses, specifically suppressing Il12 in dendritic cells and Ifng in natural killer cells.

PMID 22072781

Ticam1-Tlr3-mediated signalling pathway plays an essential role in the anti-viral response against poliovirus infection.

PMID 22124111

Ticam1 plays a role in host resistance to Gram-negative enteropathogens. Ticam1-mediated protective immunity is orchestrated by macrophage-induced IFN-beta and natural killer cell production of IFN-gamma.

PMID 22123964

Ticam1 forms a complex with Ripk3 upon Toll-like receptors (TLR) 3 and 4 activation resulting in Ripk3-dependent but TNF-independent necrosis in macrophages.

PMID 25389373

High-potency Tlr4 agonists can act as clinically useful vaccine adjuvants by selectively activating Ticam1-dependent immunostimulatory signalling events and only weakly activating potentially harmful Myd88-dependent inflammatory responses.

PMID 25448706

Myd88 and Ticam1 pathways differently regulate Tlr4-induced immune responses in B cells.

PMID 25505250

Adaptor proteins Ticam1 and Ticam2 have a novel function in Tlr2-mediated signal transduction.

PMID 25548220

Ticam1 but not Myd88 signalling is critical for the Trl4 protective adjuvant effect in neonates; where Ticam1(-/-) but not Myd88(-/-) neonates are highly susceptible to Escherichia coli peritonitis and bacteremia.

PMID 25736436

Wdfy1 is a crucial adaptor protein in the Tlr3/4 signalling pathway. Wdfy1 interacts with Tlr3 and Tlr4 and mediates the recruitment of Ticam1 to these receptors.

PMID 25808990

Intracellular Sef/IL-17R (SEFIR) domain of Il17rd targets TIR adaptor proteins Myd88, Tirap, Ticam1, Ticam2 and Traf6 to inhibit TLR downstream signalling.

PMID 26651944

Yersinia pseudotuberculosis type III secretion system effector, YopJ, suppresses Trif(Ticam1)-dependent responses during infection of primary phagocytic cells, including dendritic cells and macrophages.

PMID 26351279

Ticam1-dependent type I interferon signalling in T cells is essential to Th1 lineage differentiation and reactivation of memory T cells. Ticam1 activated memory T cells facilitate local neutrophil influx and enhance bacterial elimination.

InnateDB Annotation from Orthologs

Summary

PMID 19412184

[Homo sapiens] TICAM1 adaptor protein is displaced from TICAM2 by a splice variant of TICAM2, TAG, resulting in the negative regulation of the MyD88-independent TLR4 pathway.

PMID 20019748

[Homo sapiens] TICAM1 (TRIF)-dependent activation of CASP8 is involved in pro-apoptotic signalling through TLR3 and this under the control of inhibitor of apoptosis proteins in melanoma cells.

PMID 12471095

[Homo sapiens] TICAM1 preferentially activates the IFN-beta promoter in the Toll-like receptor signalling, particularly in the MyD88-independent pathway.

PMID 14982987

[Homo sapiens] TICAM1 (TRIF) recruits TRAF6-TAK1-TAB2 to TLR3 through its TRAF6-binding site, which is required for NF-kappaB but not IRF3 activation. TLR3/TICAM1-mediated NF-kappaB and IRF3 activation is induced by double-stranded RNA.

PMID 12539043

[Homo sapiens] TICAM-1 is an adaptor molecule that participates in TLR3-mediated interferon-beta induction.

PMID 14517278

[Homo sapiens] TICAM1 and TICAM2 both function in LPS-TLR4 signalling to regulate the MyD88-independent pathway during the innate immune response to LPS.

PMID 14519765

[Homo sapiens] TICAM1 and TICAM2 form an adaptor complex that plays a crucial role in LPS-TLR4-mediated activation of IFN-beta.

PMID 21454965

[Homo sapiens] The TICAM1 signalling pathway in murine dendritic cells is crucial for dsRNA-mediated natural killer cell activation. (Demonstrated in murine model)

PMID 21494017

[Homo sapiens] TICAM1 deficiency results in the impairment of LPS-stimulated TNF-alpha protein translation. (Demonstrated in murine model)

PMID 21602824

[Homo sapiens] TICAM1 is crucial for NLRP3 inflammasome activation in response specific to viable, but not heat-killed, E. coli infections. (Demonstrated in murine model)

PMID 21697485

[Homo sapiens] TICAM1 is proteolytically cleaved by Enterovirus 71 3C to inhibit the induction of innate immunity by TLR3-signalling. TICAM1 cleavage results in the inhibition of NFkB and IFN-beta promoter activation.

PMID 21703541

[Homo sapiens] TICAM1 forms a dsRNA sensor complex with components DDX1, DDX21 and DHX36 to trigger the type I interferon and cytokine response to poly I:C, influenza A virus, and reovirus. (Demonstrated in murine model)

PMID 21760953

[Homo sapiens] TICAM1 is a potent negative regulator of TLR agonist-triggered immune responses, specifically suppressing IL12 in dendritic cells and IFNG in natural killer cells. (Demonstrated in mouse)

PMID 21760953

PMID 22072781

[Homo sapiens] TICAM1-TLR3-mediated signalling pathway plays an essential role in the anti-viral response against poliovirus infection. (Demonstrated in mouse)

PMID 22124111

[Homo sapiens] TICAM1 plays a role in host resistance to Gram-negative enteropathogens. TICAM1-mediated protective immunity is orchestrated by macrophage-induced IFN-beta and natural killer cell production of IFN-gamma. (Demonstrated in mice)

PMID 22123964

[Homo sapiens] TICAM1 forms a complex with RIPK3 upon Toll-like receptors (TLR) 3 and 4 activation resulting in RIPK3-dependent but TNF-independent necrosis in macrophages. (Demonstrated in mouse)

PMID 23723066

[Homo sapiens] TICAM1 (TRIF) enhances expression of Kaposi�??s sarcoma-associated herpesviral protein RTA.

PMID 24255114

[Homo sapiens] The homotypic interaction of TICAM2 Toll/interleukin-1 receptor (TIR) domain is essential to form a scaffold for recruiting the TICAM1 TIR domain.

Entrez Gene

Summary

This gene does not have any Entrez summary - the following is the summary from its human ortholog ENSG00000127666:
This gene encodes an adaptor protein containing a Toll/interleukin-1 receptor (TIR) homology domain, which is an intracellular signaling domain that mediates protein-protein interactions between the Toll-like receptors (TLRs) and signal-transduction components. This protein is involved in native immunity against invading pathogens. It specifically interacts with toll-like receptor 3, but not with other TLRs, and this association mediates dsRNA induction of interferon-beta through activation of nuclear factor kappa-B, during an antiviral immune response. [provided by RefSeq, Jan 2012]

Gene Information

Type

Protein coding

Genomic Location

Chromosome 17:56269319-56276786

Strand

Reverse strand

Band

Transcripts

ENSMUST00000058136

ENSMUSP00000055104

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 33 experimentally validated interaction(s) in this database.
They are also associated with 34 interaction(s) predicted by orthology.

Experimentally validated
Total	33 [view]
Protein-Protein	33 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	34 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004871	signal transducer activity
GO:0005515	protein binding
GO:0019901	protein kinase binding

Biological Process

GO:0002281	macrophage activation involved in immune response
GO:0002756	MyD88-independent toll-like receptor signaling pathway
GO:0006954	inflammatory response
GO:0007165	signal transduction
GO:0030890	positive regulation of B cell proliferation
GO:0031398	positive regulation of protein ubiquitination
GO:0031663	lipopolysaccharide-mediated signaling pathway
GO:0032092	positive regulation of protein binding
GO:0032481	positive regulation of type I interferon production
GO:0032496	response to lipopolysaccharide
GO:0032755	positive regulation of interleukin-6 production
GO:0032760	positive regulation of tumor necrosis factor production
GO:0032816	positive regulation of natural killer cell activation
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043330	response to exogenous dsRNA
GO:0043496	regulation of protein homodimerization activity
GO:0045080	positive regulation of chemokine biosynthetic process
GO:0045087	innate immune response (InnateDB)
GO:0045359	positive regulation of interferon-beta biosynthetic process
GO:0045429	positive regulation of nitric oxide biosynthetic process
GO:0050871	positive regulation of B cell activation
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0051607	defense response to virus
GO:0097190	apoptotic signaling pathway