Human Gene IRAK3 (ENST00000261233.9) from GENCODE V44
Description: Homo sapiens interleukin 1 receptor associated kinase 3 (IRAK3), transcript variant 1, mRNA. (from RefSeq NM_007199) RefSeq Summary (NM_007199): 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]. Gencode Transcript: ENST00000261233.9 Gencode Gene: ENSG00000090376.11 Transcript (Including UTRs) Position: hg38 chr12:66,189,214-66,254,622 Size: 65,409 Total Exon Count: 12 Strand: + Coding Region Position: hg38 chr12:66,189,300-66,248,171 Size: 58,872 Coding Exon Count: 12
ID:IRAK3_HUMAN DESCRIPTION: RecName: Full=Interleukin-1 receptor-associated kinase 3; Short=IRAK-3; EC=2.7.11.1; AltName: Full=IL-1 receptor-associated kinase M; Short=IRAK-M; FUNCTION: Inhibits dissociation of IRAK1 and IRAK4 from the Toll- like receptor signaling complex by either inhibiting the phosphorylation of IRAK1 and IRAK4 or stabilizing the receptor complex (By similarity). CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Magnesium. INTERACTION: P51617:IRAK1; NbExp=3; IntAct=EBI-447690, EBI-358664; O43187:IRAK2; NbExp=3; IntAct=EBI-447690, EBI-447733; TISSUE SPECIFICITY: Expressed predominantly in peripheral blood lymphocytes. DISEASE: Defects in IRAK3 are associated with susceptibility to asthma-related traits type 5 (ASRT5) [MIM:611064]. Asthma-related traits include clinical symptoms of asthma, such as coughing, wheezing, dyspnea, bronchial hyperresponsiveness as assessed by methacholine challenge test, serum IgE levels, atopy, and atopic dermatitis. SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Pelle subfamily. SIMILARITY: Contains 1 death domain. SIMILARITY: Contains 1 protein kinase domain. CAUTION: Ser-293 is present instead of the conserved Asp which is expected to be an active site residue. Low level autophosphorylation activity has been reported in PubMed:10383454, while other authors describe this as an inactive kinase.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF00531 - Death domain PF00069 - Protein kinase domain
ModBase Predicted Comparative 3D Structure on Q9Y616
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
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:0016310 phosphorylation 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: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
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