InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Gene: TICAM1

Summary

InnateDB Gene

IDBG-19505.6

Last Modified

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

Gene Symbol

TICAM1

Gene Name

toll-like receptor adaptor molecule 1

Synonyms

Species

Homo sapiens

Ensembl Gene

ENSG00000127666

Encoded Proteins

IDBP-19507

toll-like receptor adaptor molecule 1

IDBP-810585

toll-like receptor adaptor molecule 1

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 19412184

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

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

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

PMID 14982987

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

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

PMID 14517278

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

PMID 14519765

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

PMID 21454965

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

PMID 21494017

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

PMID 21602824

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

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

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

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

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 22072781

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

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. (Demonstrated in mice)

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. (Demonstrated in mouse)

PMID 23723066

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

PMID 24255114

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

InnateDB Annotation from Orthologs

Summary

PMID 21454965

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

PMID 21494017

[Mus musculus] Ticam1 deficiency results in the impairment of LPS-stimulated TNF-alpha protein translation.

PMID 21602824

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

PMID 21697485

[Mus musculus] 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

[Mus musculus] 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

[Mus musculus] 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

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

PMID 22124111

[Mus musculus] 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

[Mus musculus] 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

[Mus musculus] 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

[Mus musculus] Myd88 and Ticam1 pathways differently regulate Tlr4-induced immune responses in B cells.

PMID 25505250

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

PMID 25548220

[Mus musculus] 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

[Mus musculus] 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

[Mus musculus] 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

[Mus musculus] 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

[Mus musculus] 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.

Entrez Gene

Summary

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 19:4815932-4831704

Strand

Reverse strand

Band

p13.3

Transcripts

ENST00000248244	ENSP00000248244
ENST00000621756	ENSP00000479467

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 63 experimentally validated interaction(s) in this database.
They are also associated with 25 interaction(s) predicted by orthology.

Experimentally validated
Total	63 [view]
Protein-Protein	63 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	25 [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:0002224	toll-like receptor signaling pathway
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:0007249	I-kappaB kinase/NF-kappaB signaling
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:0034138	toll-like receptor 3 signaling pathway
GO:0034142	toll-like receptor 4 signaling pathway
GO:0035666	TRIF-dependent toll-like receptor signaling pathway
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