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
interleukin-1 receptor-associated kinase 4
interleukin-1 receptor-associated kinase 4
interleukin-1 receptor-associated kinase 4
interleukin-1 receptor-associated kinase 4
interleukin-1 receptor-associated kinase 4
interleukin-1 receptor-associated kinase 4
interleukin-1 receptor-associated kinase 4
interleukin-1 receptor-associated kinase 4
interleukin-1 receptor-associated kinase 4
interleukin-1 receptor-associated kinase 4
interleukin-1 receptor-associated kinase 4
interleukin-1 receptor-associated kinase 4
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
IRAK4 is required for interleukin-1 receptor/toll-like receptor-induced MAP3K7 (TAK1)-dependent NF-kappaB activation.
IRAK4 and IRAK1 play key roles in a signalling pathway by which bacterial infection or IL-1 trigger the production of inflammatory mediators.
IRAK4 is indispensable for the responses of animals and cultured cells to IL-1 and ligands that stimulate various Toll-like receptors (TLRs).
IRAK4 plays a critical role in IL-1R and TLR signalling cascades and is an essential component of the IL-18 signalling cascade.
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
[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.
[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.
[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.
[Mus musculus] Mir302b expression is up-regulated upon bacterial infection and is a crucial regulator of NFκB signalling by directly targeting IRAK4
[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
Cellular Component
GO:0005615 extracellular space
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0010008 endosome membrane
Orthologs
Species
Mus musculus
Bos taurus
Gene ID
Gene Order
Method
Confidence
Comments
SSD Ortholog
Ortholog supports species divergence
Not yet available
SSD Ortholog
Ortholog supports species divergence
Pathways
NETPATH
IL1 pathway
REACTOME
MyD88 dependent cascade initiated on endosome pathway
Toll Like Receptor 7/8 (TLR7/8) Cascade pathway
Toll Like Receptor TLR1:TLR2 Cascade pathway
Toll Like Receptor 9 (TLR9) Cascade pathway
Toll Like Receptor TLR6:TLR2 Cascade pathway
MyD88 cascade initiated on plasma membrane pathway
Cytokine Signaling in Immune system pathway
Innate Immune System pathway
Toll Like Receptor 2 (TLR2) Cascade pathway
Toll-Like Receptors Cascades pathway
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation pathway
Immune System pathway
MyD88:Mal cascade initiated on plasma membrane pathway
TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling pathway
Signaling by Interleukins pathway
Interleukin-1 signaling pathway
Toll Like Receptor 4 (TLR4) Cascade pathway
Activated TLR4 signalling pathway
Toll Like Receptor 5 (TLR5) Cascade pathway
Toll Like Receptor 10 (TLR10) Cascade pathway
KEGG
Apoptosis pathway
Toll-like receptor signaling pathway pathway
Neurotrophin signaling pathway pathway
Leishmaniasis pathway
Chagas disease (American trypanosomiasis) pathway
Toxoplasmosis pathway
INOH
IL-7 signaling pathway
IL-1 signaling pathway pathway
Toll-like receptor signaling pathway pathway
JAK STAT pathway and regulation pathway
EPO signaling pathway pathway
VEGF signaling pathway pathway
PID BIOCARTA
PID NCI
IL1-mediated signaling events
Endogenous TLR signaling
Cross-References
SwissProt
TrEMBL
UniProt Splice Variant
Entrez Gene
UniGene Hs.138499
RefSeq NM_001114182 NM_001145256 NM_001145257 NM_001145258 NM_016123 XM_005268943 XM_005268944 XM_005268946 XM_005268949
HUGO
OMIM
CCDS CCDS44862 CCDS8744
HPRD 06051
IMGT
EMBL
GenPept
RNA Seq Atlas