InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Gene: IRAK4

Summary

InnateDB Gene

IDBG-28022.6

Last Modified

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

Gene Symbol

IRAK4

Gene Name

interleukin-1 receptor-associated kinase 4

Synonyms

Species

Homo sapiens

Ensembl Gene

ENSG00000198001

Encoded Proteins

IDBP-372638

interleukin-1 receptor-associated kinase 4

IDBP-372642

interleukin-1 receptor-associated kinase 4

IDBP-372646

interleukin-1 receptor-associated kinase 4

IDBP-589477

interleukin-1 receptor-associated kinase 4

IDBP-586834

interleukin-1 receptor-associated kinase 4

IDBP-583293

interleukin-1 receptor-associated kinase 4

IDBP-604058

interleukin-1 receptor-associated kinase 4

IDBP-602545

interleukin-1 receptor-associated kinase 4

IDBP-587414

interleukin-1 receptor-associated kinase 4

IDBP-597759

interleukin-1 receptor-associated kinase 4

IDBP-598339

interleukin-1 receptor-associated kinase 4

IDBP-812334

interleukin-1 receptor-associated kinase 4

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 18794297

IRAK4 is required for interleukin-1 receptor/toll-like receptor-induced MAP3K7 (TAK1)-dependent NF-kappaB activation.

PMID 17997719

IRAK4 and IRAK1 play key roles in a signalling pathway by which bacterial infection or IL-1 trigger the production of inflammatory mediators.

PMID 11923871

IRAK4 is indispensable for the responses of animals and cultured cells to IL-1 and ligands that stimulate various Toll-like receptors (TLRs).

PMID 12682231

IRAK4 plays a critical role in IL-1R and TLR signalling cascades and is an essential component of the IL-18 signalling cascade.

PMID 21220427

IRAK4 activation is impaired during endotoxin tolerization; a process which impairs the production of LPS-induced pro-inflammatory cytokines without inhibition expression of anti-inflammatory or anti-microbial mediators.

InnateDB Annotation from Orthologs

Summary

PMID 20595480

[Mus musculus] IRAK4-mediated innate immune inflammatory responses play critical roles in divergent clinical outcomes in murine malaria models when Irak4 (-/-) mice were used to study two experimental models of malaria.

PMID 24717937

[Mus musculus] Irak4 activation is impaired during endotoxin tolerization; a process which impairs the production of LPS-induced pro-inflammatory cytokines without inhibition expression of anti-inflammatory or anti-microbial mediators.

PMID 23027530

[Mus musculus] Irak4 deficient mice show impaired innate immunity, leading to defective Type 1 T-cell responses, B-cell expansion, and are more susceptible to Toxoplasma gondii infection.

PMID 24717937

[Mus musculus] Mir302b expression is up-regulated upon bacterial infection and is a crucial regulator of NFκB signalling by directly targeting IRAK4

PMID 25548221

[Mus musculus] Irak4 is a molecular target of chlorogenic acid in the treatment of innate immunity-related shock and organ dysfunction following insult of various Toll-like receptor pathogens from bacteria and viruses.

Entrez Gene

Summary

This gene encodes a kinase that activates NF-kappaB in both the Toll-like receptor (TLR) and T-cell receptor (TCR) signaling pathways. The protein is essential for most innate immune responses. Mutations in this gene result in IRAK4 deficiency and recurrent invasive pneumococcal disease. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

Gene Information

Type

Protein coding

Genomic Location

Chromosome 12:43758944-43789543

Strand

Forward strand

Band

q12

Transcripts

ENST00000448290	ENSP00000390651
ENST00000431837	ENSP00000390327
ENST00000440781	ENSP00000408734
ENST00000550616	ENSP00000446571
ENST00000550615	ENSP00000449553
ENST00000547521	ENSP00000449693
ENST00000551736	ENSP00000446490
ENST00000550386	ENSP00000449848
ENST00000547101	ENSP00000449317
ENST00000546780
ENST00000552309	ENSP00000448197
ENST00000550361	ENSP00000449859
ENST00000547928
ENST00000613694	ENSP00000479889

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 54 experimentally validated interaction(s) in this database.
They are also associated with 8 interaction(s) predicted by orthology.

Experimentally validated
Total	54 [view]
Protein-Protein	54 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	8 [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:0005149	interleukin-1 receptor binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups

Biological Process

GO:0001816	cytokine production
GO:0002224	toll-like receptor signaling pathway
GO:0002755	MyD88-dependent toll-like receptor signaling pathway
GO:0006468	protein phosphorylation
GO:0007165	signal transduction
GO:0007254	JNK cascade
GO:0019221	cytokine-mediated signaling pathway
GO:0034134	toll-like receptor 2 signaling pathway
GO:0034142	toll-like receptor 4 signaling pathway
GO:0034146	toll-like receptor 5 signaling pathway
GO:0034162	toll-like receptor 9 signaling pathway
GO:0034166	toll-like receptor 10 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:0045087	innate immune response (InnateDB)
GO:0048661	positive regulation of smooth muscle cell proliferation