Homo sapiens Gene: IRAK1
Summary
InnateDB Gene IDBG-90782.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol IRAK1
Gene Name interleukin-1 receptor-associated kinase 1
Synonyms IRAK; pelle;
Species Homo sapiens
Ensembl Gene ENSG00000184216
Encoded Proteins
interleukin-1 receptor-associated kinase 1
interleukin-1 receptor-associated kinase 1
interleukin-1 receptor-associated kinase 1
interleukin-1 receptor-associated kinase 1
interleukin-1 receptor-associated kinase 1
interleukin-1 receptor-associated kinase 1
interleukin-1 receptor-associated kinase 1
interleukin-1 receptor-associated kinase 1
interleukin-1 receptor-associated kinase 1
interleukin-1 receptor-associated kinase 1
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
IRAK1 plays an essential role in Toll-like receptor/interleukin-1 receptor (TLR/IL-1R) -associated NF-kappaB activation through its involvement in IKK activation, which then leads to subsequent IkappaB degradation and NF-kappaB nuclear translocation and both cytosolic and nuclear actions of IRAK1 participate in the activation of NF-kappaB-dependent transcriptional events.
IRAK1 and IRAK4 play key roles in a signalling pathway by which bacterial infection or interleukin-1 (IL1) trigger the production of inflammatory mediators. Pellino isoforms are the E3 ubiquitin ligases that mediate the IL1-stimulated formation of K63-pUb-IRAK1 in cells, which contribute to the activation of IKBKB and NF-kappaB, as well as other signalling pathways dependent on IRAK1 and IRAK4.
IRAK1 is a component of a novel signal transduction pathway through which TNF receptor activates NF-kappaB-dependent gene expression.
IRAK1 plays an essential proximal role in coordinating multiple IL1 signalling pathways for optimal induction of cellular responses.
IRAK1 functionally associates with PKC-epsilon and VASP in the regulation of macrophage migration.
IRAK1 and MYD88 autosomal recessive deficiencies impair Toll-like receptor (TLR)- and interleukin-1 receptor-mediated immunity and predispose patients to recurrent life-threatening bacterial diseases, such as invasive pneumococcal disease in particular, in infancy and early childhood, with weak signs of inflammation.
IRAK1 is polyubiquitinated and disassembled 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.
IRAK1 mediates the proteasome-dependent degradation of TRAF6 and acts as a negative regulator of TLR-signalling. (Demonstrated in mice)
IRAK1 accumulation triggers ischemia-induced inflammation in the small intestine.
MIR146A is a potent negative regulator of the innate immune response in keratinocytes through downregulation of the IRAK1/TRAF6/NFκB pathway.
Endotoxin tolerance re-programs TLR4 signalling via suppression of PELI1, a positive regulator of MyD88- and TIR domain-containing adapter inducing IFN-β (TRIF)-dependent signalling that promotes K63-linked polyubiquitination of IRAK1, TBK1, and TAK1.
InnateDB Annotation from Orthologs
Summary
[Mus musculus] Irak1 is polyubiquitinated and disassembled 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] Irak1 mediates the proteasome-dependent degradation of Traf6 and acts as a negative regulator of TLR-signalling.
[Mus musculus] IRAK1 accumulation triggers ischemia-induced inflammation in the small intestine.
[Mus musculus] Mir146 attenuates sepsis-induced cardiac dysfunction by preventing NFκB activation, inflammatory cell infiltration, and inflammatory cytokine production via targeting of Irak1 and Traf6 in both cardiomyocytes and inflammatory monocytic cells
Entrez Gene
Summary This gene encodes the interleukin-1 receptor-associated kinase 1, one of two putative serine/threonine kinases that become associated with the interleukin-1 receptor (IL1R) upon stimulation. This gene is partially responsible for IL1-induced upregulation of the transcription factor NF-kappa B. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Gene Information
Type Protein coding
Genomic Location Chromosome X:154010500-154019980
Strand Reverse strand
Band q28
Transcripts
ENST00000369980 ENSP00000358997
ENST00000369974 ENSP00000358991
ENST00000369973 ENSP00000358990
ENST00000393687 ENSP00000377291
ENST00000429936 ENSP00000392662
ENST00000444230 ENSP00000399974
ENST00000455690 ENSP00000411809
ENST00000444254 ENSP00000410953
ENST00000437278 ENSP00000406249
ENST00000443220 ENSP00000403730
ENST00000477274
ENST00000467236
ENST00000463031
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 196 experimentally validated interaction(s) in this database.
They are also associated with 33 interaction(s) predicted by orthology.
Experimentally validated
Total 196 [view]
Protein-Protein 190 [view]
Protein-DNA 3 [view]
Protein-RNA 0
DNA-DNA 1 [view]
RNA-RNA 2 [view]
DNA-RNA 0
Predicted by orthology
Total 33 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004704 NF-kappaB-inducing kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0004842 ubiquitin-protein transferase activity
GO:0005149 interleukin-1 receptor binding
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016772 transferase activity, transferring phosphorus-containing groups
GO:0031072 heat shock protein binding
GO:0042803 protein homodimerization activity
GO:0046982 protein heterodimerization activity
Biological Process
GO:0000187 activation of MAPK activity
GO:0001959 regulation of cytokine-mediated signaling pathway
GO:0002224 toll-like receptor signaling pathway
GO:0002755 MyD88-dependent toll-like receptor signaling pathway
GO:0002756 MyD88-independent toll-like receptor signaling pathway
GO:0006468 protein phosphorylation
GO:0007165 signal transduction
GO:0007178 transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0007250 activation of NF-kappaB-inducing kinase activity
GO:0007254 JNK cascade
GO:0007568 aging
GO:0008152 metabolic process
GO:0016567 protein ubiquitination
GO:0019221 cytokine-mediated signaling pathway
GO:0031663 lipopolysaccharide-mediated signaling pathway
GO:0032088 negative regulation of NF-kappaB transcription factor activity
GO:0032494 response to peptidoglycan
GO:0032496 response to lipopolysaccharide
GO:0034134 toll-like receptor 2 signaling pathway
GO:0034138 toll-like receptor 3 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:0034605 cellular response to heat
GO:0035666 TRIF-dependent toll-like receptor signaling pathway
GO:0035872 nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
GO:0038123 toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124 toll-like receptor TLR6:TLR2 signaling pathway
GO:0043066 negative regulation of apoptotic process
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0045087 innate immune response (InnateDB)
GO:0045893 positive regulation of transcription, DNA-templated
GO:0046777 protein autophosphorylation
GO:0048011 neurotrophin TRK receptor signaling pathway
GO:0048661 positive regulation of smooth muscle cell proliferation
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051259 protein oligomerization
GO:0051403 stress-activated MAPK cascade
GO:0070423 nucleotide-binding oligomerization domain containing signaling pathway
GO:0070498 interleukin-1-mediated signaling pathway
GO:0070555 response to interleukin-1
GO:0071222 cellular response to lipopolysaccharide
GO:0071456 cellular response to hypoxia
Cellular Component
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005811 lipid particle
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0010008 endosome membrane
GO:0016020 membrane
GO:0045323 interleukin-1 receptor complex
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
Signalling by NGF pathway
Toll Like Receptor 7/8 (TLR7/8) Cascade pathway
p75NTR recruits signalling complexes 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
NF-kB is activated and signals survival pathway
IRAK1 recruits IKK complex pathway
Toll Like Receptor 3 (TLR3) Cascade pathway
Toll Like Receptor 2 (TLR2) Cascade pathway
Toll-Like Receptors Cascades pathway
p75 NTR receptor-mediated signalling pathway
p75NTR signals via NF-kB pathway
Signal Transduction pathway
IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation pathway
MAP kinase activation in TLR cascade pathway
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways pathway
NOD1/2 Signaling Pathway pathway
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation pathway
Immune System pathway
MyD88-independent cascade pathway
MyD88:Mal cascade initiated on plasma membrane pathway
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 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
activated TAK1 mediates p38 MAPK activation pathway
TRIF-mediated TLR3/TLR4 signaling pathway
Toll Like Receptor 5 (TLR5) Cascade pathway
TAK1 activates NFkB by phosphorylation and activation of IKKs complex 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
Toll-like receptor pathway [Biocarta view]
Nf-kb signaling pathway [Biocarta view]
Inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages [Biocarta view]
Signal transduction through il1r [Biocarta view]
PID NCI
IL1-mediated signaling events
p75(NTR)-mediated signaling
Endogenous TLR signaling
Cross-References
SwissProt
TrEMBL
UniProt Splice Variant
Entrez Gene
UniGene Hs.522819
RefSeq NM_001025242 NM_001025243 NM_001569 XM_005274668
HUGO
OMIM
CCDS CCDS14740 CCDS35443 CCDS35444
HPRD 02235
IMGT
EMBL
GenPept
RNA Seq Atlas