InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Gene: TIRAP

Summary

InnateDB Gene

IDBG-75811.6

Last Modified

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

Gene Symbol

TIRAP

Gene Name

toll-interleukin 1 receptor (TIR) domain containing adaptor protein

Synonyms

Species

Homo sapiens

Ensembl Gene

ENSG00000150455

Encoded Proteins

IDBP-245167

toll-interleukin 1 receptor (TIR) domain containing adaptor protein

IDBP-245169

toll-interleukin 1 receptor (TIR) domain containing adaptor protein

IDBP-245171

toll-interleukin 1 receptor (TIR) domain containing adaptor protein

IDBP-602148

toll-interleukin 1 receptor (TIR) domain containing adaptor protein

IDBP-591863

toll-interleukin 1 receptor (TIR) domain containing adaptor protein

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 11526399

TIRAP is a Toll/Interleukin-1 receptor (TIR) domain containing adapter protein that binds to TLR4, serving as a bridge for MYD88 recruitment.

PMID 19717524

TIRAP is dispensable in TLR2 signalling at high ligand concentrations in macrophages and dendritic cells, with MyD88 probably coupling to the TLR2 receptor complex at sufficient levels to allow activation but has an inhibitory role in the signalling of TLR3 to JNK.

PMID 11544529

TIRAP is an adapter in Toll-like receptor 4 (TLR4) signal transduction.

PMID 12447442

TIRAP is differentially involved in signalling by members of the Toll-like receptor (TLR) family and may account for specificity in the downstream signalling of individual TLRs.

PMID 12447441

TIRAP has a crucial role in the MyD88-dependent signalling pathway shared by TLR2 and TLR4.

PMID 20400509

TIRAP is a substrate for IRAK1 and IRAK4 with phosphorylation promoting its ubiquitination and degradation.

PMID 2095775

TIRAP is an activator of TLR2/4 signalling and a negative regulator of TLR3/TRIF signalling. TIRAP is essential in restricting TLR3 signalling thereby protecting the host from unwanted immunopathologies associated with excessive IFN-beta production.

PMID 21705416

TIRAP Ser180Leu polymorphism is significantly associated with Behcet's disease in UK, but not Middle Eastern, patients. It is suggested that the Ser180Leu functional variant of TIRAP will lead to greater cytokine production and tissue damage with persistence of mucosal lesions upon encounter with pathogens.

PMID 24265315

TIR domain-contaning protein from Brucella melitensis, TcpB, disrupts the receptor-adaptor interaction between TLR4 and TIRAP.

InnateDB Annotation from Orthologs

Summary

PMID 21705416

[Mus musculus] Tirap Ser180Leu polymorphism is significantly associated with Behcet's disease in UK, but not Middle Eastern, patients. It is suggested that the Ser180Leu functional variant of Tirap will lead to greater cytokine production and tissue damage with persistence of mucosal lesions upon encounter with pathogens. (Demonstrated in human)

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.

Entrez Gene

Summary

The innate immune system recognizes microbial pathogens through Toll-like receptors (TLRs), which identify pathogen-associated molecular patterns. Different TLRs recognize different pathogen-associated molecular patterns and all TLRs have a Toll-interleukin 1 receptor (TIR) domain, which is responsible for signal transduction. The protein encoded by this gene is a TIR adaptor protein involved in the TLR4 signaling pathway of the immune system. It activates NF-kappa-B, MAPK1, MAPK3 and JNK, which then results in cytokine secretion and the inflammatory response. Alternative splicing of this gene results in several transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

Gene Information

Type

Protein coding

Genomic Location

Chromosome 11:126283065-126298845

Strand

Forward strand

Band

q24.2

Transcripts

ENST00000392680	ENSP00000376447
ENST00000392679	ENSP00000376446
ENST00000392678	ENSP00000376445
ENST00000462401
ENST00000488598	ENSP00000446213
ENST00000467006
ENST00000479770	ENSP00000436967

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 80 experimentally validated interaction(s) in this database.
They are also associated with 7 interaction(s) predicted by orthology.

Experimentally validated
Total	80 [view]
Protein-Protein	74 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	6 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	7 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005080	protein kinase C binding
GO:0005515	protein binding
GO:0005546	phosphatidylinositol-4,5-bisphosphate binding
GO:0030674	protein binding, bridging
GO:0035662	Toll-like receptor 4 binding
GO:0035663	Toll-like receptor 2 binding
GO:0042803	protein homodimerization activity
GO:0046982	protein heterodimerization activity

Biological Process

GO:0002224	toll-like receptor signaling pathway
GO:0002755	MyD88-dependent toll-like receptor signaling pathway
GO:0006954	inflammatory response
GO:0007165	signal transduction
GO:0007166	cell surface receptor signaling pathway
GO:0007249	I-kappaB kinase/NF-kappaB signaling
GO:0030099	myeloid cell differentiation
GO:0030890	positive regulation of B cell proliferation
GO:0032496	response to lipopolysaccharide
GO:0032648	regulation of interferon-beta production
GO:0032735	positive regulation of interleukin-12 production
GO:0032738	positive regulation of interleukin-15 production
GO:0032757	positive regulation of interleukin-8 production
GO:0032760	positive regulation of tumor necrosis factor production
GO:0034134	toll-like receptor 2 signaling pathway
GO:0034137	positive regulation of toll-like receptor 2 signaling pathway
GO:0034141	positive regulation of toll-like receptor 3 signaling pathway
GO:0034142	toll-like receptor 4 signaling pathway
GO:0034145	positive regulation of toll-like receptor 4 signaling pathway
GO:0035665	TIRAP-dependent toll-like receptor 4 signaling pathway
GO:0038123	toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124	toll-like receptor TLR6:TLR2 signaling pathway
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0044130	negative regulation of growth of symbiont in host
GO:0045087	innate immune response (InnateDB)
GO:0045088	regulation of innate immune response
GO:0045410	positive regulation of interleukin-6 biosynthetic process
GO:0046330	positive regulation of JNK cascade
GO:0050830	defense response to Gram-positive bacterium
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0070374	positive regulation of ERK1 and ERK2 cascade
GO:0070935	3'-UTR-mediated mRNA stabilization
GO:0071221	cellular response to bacterial lipopeptide
GO:0071223	cellular response to lipoteichoic acid
GO:0090023	positive regulation of neutrophil chemotaxis
GO:0090073	positive regulation of protein homodimerization activity
GO:2000340	positive regulation of chemokine (C-X-C motif) ligand 1 production
GO:2000343	positive regulation of chemokine (C-X-C motif) ligand 2 production