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
interleukin-1 receptor-associated kinase 3
interleukin-1 receptor-associated kinase 3
interleukin-1 receptor-associated kinase 3
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
IRAK3 upregulation by lipopolysaccharide (LPS) is largely dependent on TNF-alpha and LPS tolerance in human endotoxemia models is associated with IRAK3 up-regulation.
IRAK3 selectively attenuates Pam3CSK4-induced MAPK14 (p38) activation through an IRAK1 independent and MKP1 dependent pathway.
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.
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.
IRAK3 induction and inhibition of kinase activity of IRAK1 are crucial to peptidoglycan-induced tolerance in macrophages.
IRAK3 regulates Toll-like receptor (TLR) signalling and innate immune homeostasis where IRAK3 is induced upon TLR stimulation and negatively regulates TLR signalling.
IRAK3 is critical to preventing deleterious neutrophil-dependent lung injury during influenza infection of the respiratory tract.
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.
IRAK3 dampens the innate immune response in airway epithelial cells by inhibiting TLR2 signalling in an IL13-dependent manner.
IRAK3 impairs host defence during pneumococcal pneumonia at the primary site of infection. (Demonstrated in mice)
InnateDB Annotation from Orthologs
Summary
[Mus musculus] Irak3 dampens the innate immune response in airway epithelial cells by inhibiting Tlr2 signalling in an Il13-dependent manner. (Demonstrated in human)
[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
Cellular Component
GO:0005634 nucleus
GO:0005737 cytoplasm
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
Toll Like Receptor TLR1:TLR2 Cascade pathway
Toll Like Receptor TLR6:TLR2 Cascade pathway
Cytokine Signaling in Immune system pathway
Innate Immune System pathway
Toll Like Receptor 2 (TLR2) Cascade pathway
Toll-Like Receptors Cascades pathway
Immune System pathway
MyD88:Mal cascade initiated on plasma membrane pathway
Signaling by Interleukins pathway
Interleukin-1 signaling pathway
Toll Like Receptor 4 (TLR4) Cascade pathway
Activated TLR4 signalling pathway
KEGG
Apoptosis pathway
Neurotrophin signaling pathway pathway
INOH
PID BIOCARTA
Signal transduction through il1r [Biocarta view]
PID NCI
IL1-mediated signaling events
Cross-References
SwissProt Q9Y616
TrEMBL
UniProt Splice Variant
Entrez Gene 11213
UniGene Hs.369265 Hs.607432
RefSeq NM_001142523 NM_007199
HUGO HGNC:17020
OMIM 604459
CCDS CCDS44937 CCDS8975
HPRD 05123
IMGT
EMBL AC078889 AC078927 AF113136 AK298645 BC057800 BC069388
GenPept AAD40879 AAH57800 AAH69388 BAG60819
RNA Seq Atlas 11213