InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Gene: IRAK3

Summary

InnateDB Gene

IDBG-45584.6

Last Modified

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

Gene Symbol

IRAK3

Gene Name

interleukin-1 receptor-associated kinase 3

Synonyms

ASRT5; IRAKM

Species

Homo sapiens

Ensembl Gene

ENSG00000090376

Encoded Proteins

IDBP-45586

interleukin-1 receptor-associated kinase 3

IDBP-379540

interleukin-1 receptor-associated kinase 3

IDBP-584233

interleukin-1 receptor-associated kinase 3

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 17982103

IRAK3 upregulation by lipopolysaccharide (LPS) is largely dependent on TNF-alpha and LPS tolerance in human endotoxemia models is associated with IRAK3 up-regulation.

PMID 17379480

IRAK3 selectively attenuates Pam3CSK4-induced MAPK14 (p38) activation through an IRAK1 independent and MKP1 dependent pathway.

PMID 12620219

IRAK3 is part of the interleukin-1 receptor-associated kinase (IRAK) family of proteins that mediate activation of nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein kinase (MAPK) pathways.

PMID 19809574

IRAK3 is one of the negative regulators that contribute to the attenuation of NF-kappaB activation and it negatively regulates the alternative NF-kappaB pathway in a ligand-specific manner.

PMID 14660668

IRAK3 induction and inhibition of kinase activity of IRAK1 are crucial to peptidoglycan-induced tolerance in macrophages.

PMID 12150927

IRAK3 regulates Toll-like receptor (TLR) signalling and innate immune homeostasis where IRAK3 is induced upon TLR stimulation and negatively regulates TLR signalling.

PMID 20042589

IRAK3 is critical to preventing deleterious neutrophil-dependent lung injury during influenza infection of the respiratory tract.

PMID 21098228

IRAK3 is strongly expressed in resting alveolar macrophages and blunts TNF expression to protect the host from the injurious effect of bacterial-induced inflammation. The inhibitory function of IRAK3 is abolished when it is cleaved by CASP6, which allows the induction of the NFKB pathway and the expression of TNF.

PMID 22154382

IRAK3 dampens the innate immune response in airway epithelial cells by inhibiting TLR2 signalling in an IL13-dependent manner.

PMID 22492852

IRAK3 impairs host defence during pneumococcal pneumonia at the primary site of infection. (Demonstrated in mice)

InnateDB Annotation from Orthologs

Summary

PMID 22154382

[Mus musculus] Irak3 dampens the innate immune response in airway epithelial cells by inhibiting Tlr2 signalling in an Il13-dependent manner. (Demonstrated in human)

PMID 22492852

[Mus musculus] Irak3 impairs host defence during pneumococcal pneumonia at the primary site of infection.

Entrez Gene

Summary

This gene encodes a member of the interleukin-1 receptor-associated kinase protein family. Members of this family are essential components of the Toll/IL-R immune signal transduction pathways. This protein is primarily expressed in monocytes and macrophages and functions as a negative regulator of Toll-like receptor signaling. Mutations in this gene are associated with a susceptibility to asthma. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

Gene Information

Type

Protein coding

Genomic Location

Chromosome 12:66188879-66254622

Strand

Forward strand

Band

q14.3

Transcripts

ENST00000261233	ENSP00000261233
ENST00000457197	ENSP00000409852
ENST00000545837	ENSP00000441321

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 3 interaction(s) predicted by orthology.

Experimentally validated
Total	33 [view]
Protein-Protein	32 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000287	magnesium ion binding
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0042803	protein homodimerization activity
GO:0046982	protein heterodimerization activity

Biological Process

GO:0001960	negative regulation of cytokine-mediated signaling pathway
GO:0002755	MyD88-dependent toll-like receptor signaling pathway
GO:0006468	protein phosphorylation
GO:0007165	signal transduction
GO:0009615	response to virus
GO:0010933	positive regulation of macrophage tolerance induction
GO:0010936	negative regulation of macrophage cytokine production
GO:0019221	cytokine-mediated signaling pathway
GO:0032088	negative regulation of NF-kappaB transcription factor activity
GO:0032494	response to peptidoglycan
GO:0032496	response to lipopolysaccharide
GO:0032695	negative regulation of interleukin-12 production
GO:0032715	negative regulation of interleukin-6 production
GO:0032720	negative regulation of tumor necrosis factor production
GO:0034122	negative regulation of toll-like receptor signaling pathway
GO:0042177	negative regulation of protein catabolic process
GO:0043242	negative regulation of protein complex disassembly
GO:0043244	regulation of protein complex disassembly
GO:0043330	response to exogenous dsRNA
GO:0043407	negative regulation of MAP kinase activity
GO:0045087	innate immune response (InnateDB)
GO:0045824	negative regulation of innate immune response
GO:0046777	protein autophosphorylation
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0070498	interleukin-1-mediated signaling pathway
GO:0070555	response to interleukin-1