IRAK3, also called IRAK-M, is an IRAK-family pseudokinase that regulates Toll-like and interleukin-1 receptor signaling. It participates in receptor-associated signaling assemblies and restrains inflammatory activation by stabilizing MyD88-associated IRAK complexes. Its death domain and kinase-like domain mediate protein interactions, and its effects depend on cellular context and stimulus history.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000287 magnesium ion binding | IDA PMID:10383454 IRAK-M is a novel member of the Pelle/interleukin-1 receptor... | UNDECIDED | Summary: magnesium ion binding: The available evidence examined for IRAK3 does not resolve the exact claim of magnesium ion binding. The specific experiment or traced orthology/phylogenetic inference behind PMID:10383454 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper. Reason: The available evidence examined for IRAK3 does not resolve the exact claim of magnesium ion binding. The specific experiment or traced orthology/phylogenetic inference behind PMID:10383454 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper. |
| GO:0000287 magnesium ion binding | IEA GO_REF:0000120 | UNDECIDED | Summary: magnesium ion binding: The available evidence examined for IRAK3 does not resolve the exact claim of magnesium ion binding. The specific experiment or traced orthology/phylogenetic inference behind GO_REF:0000120 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper. Reason: The available evidence examined for IRAK3 does not resolve the exact claim of magnesium ion binding. The specific experiment or traced orthology/phylogenetic inference behind GO_REF:0000120 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper. |
| GO:0001819 positive regulation of cytokine production | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: IRAK-M can promote selected inflammatory outputs in the IL-33/PIN1 context despite restraining canonical TLR responses. The positive signaling annotation should be interpreted as context dependent rather than as a universal activator role. Reason: IRAK-M can promote selected inflammatory outputs in the IL-33/PIN1 context despite restraining canonical TLR responses. The positive signaling annotation should be interpreted as context dependent rather than as a universal activator role. Supporting Evidence: PMID:29686383 Upon IL-33-induced airway inflammation, PIN1 is activated for binding with and isomerization of IRAK-M, resulting in IRAK-M nuclear translocation and induction of selected proinflammatory genes in dendritic cells. |
| GO:0001960 negative regulation of cytokine-mediated signaling pathway | IC PMID:12150927 IRAK-M is a negative regulator of Toll-like receptor signali... | ACCEPT | Summary: negative regulation of cytokine-mediated signaling pathway: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0001960 negative regulation of cytokine-mediated signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: negative regulation of cytokine-mediated signaling pathway: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0002684 positive regulation of immune system process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: IRAK-M can promote selected inflammatory outputs in the IL-33/PIN1 context despite restraining canonical TLR responses. The positive signaling annotation should be interpreted as context dependent rather than as a universal activator role. Reason: IRAK-M can promote selected inflammatory outputs in the IL-33/PIN1 context despite restraining canonical TLR responses. The positive signaling annotation should be interpreted as context dependent rather than as a universal activator role. Supporting Evidence: PMID:29686383 Upon IL-33-induced airway inflammation, PIN1 is activated for binding with and isomerization of IRAK-M, resulting in IRAK-M nuclear translocation and induction of selected proinflammatory genes in dendritic cells. |
| GO:0002755 MyD88-dependent toll-like receptor signaling pathway | TAS PMID:10383454 IRAK-M is a novel member of the Pelle/interleukin-1 receptor... | ACCEPT | Summary: MyD88-dependent toll-like receptor signaling pathway: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0004672 protein kinase activity | IEA GO_REF:0000107 | REMOVE | Summary: protein kinase activity: The human structural analysis establishes an IRAK3 pseudokinase domain lacking the canonical catalytic aspartate; the original discovery paper reported negligible autophosphorylation. Conventional protein kinase activity overstates the supported noncatalytic regulatory mechanism. Reason: The human structural analysis establishes an IRAK3 pseudokinase domain lacking the canonical catalytic aspartate; the original discovery paper reported negligible autophosphorylation. Conventional protein kinase activity overstates the supported noncatalytic regulatory mechanism. Supporting Evidence: PMID:33238146 In contrast to the active kinases IRAK1 and IRAK4, IRAK2 and IRAK3 are pseudokinases lacking catalytic activity and their functions are poorly understood. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:10383454 IRAK-M is a novel member of the Pelle/interleukin-1 receptor... | REMOVE | Summary: protein serine/threonine kinase activity: The human structural analysis establishes an IRAK3 pseudokinase domain lacking the canonical catalytic aspartate; the original discovery paper reported negligible autophosphorylation. Conventional protein kinase activity overstates the supported noncatalytic regulatory mechanism. Reason: The human structural analysis establishes an IRAK3 pseudokinase domain lacking the canonical catalytic aspartate; the original discovery paper reported negligible autophosphorylation. Conventional protein kinase activity overstates the supported noncatalytic regulatory mechanism. Supporting Evidence: PMID:33238146 In contrast to the active kinases IRAK1 and IRAK4, IRAK2 and IRAK3 are pseudokinases lacking catalytic activity and their functions are poorly understood. |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000120 | REMOVE | Summary: protein serine/threonine kinase activity: The human structural analysis establishes an IRAK3 pseudokinase domain lacking the canonical catalytic aspartate; the original discovery paper reported negligible autophosphorylation. Conventional protein kinase activity overstates the supported noncatalytic regulatory mechanism. Reason: The human structural analysis establishes an IRAK3 pseudokinase domain lacking the canonical catalytic aspartate; the original discovery paper reported negligible autophosphorylation. Conventional protein kinase activity overstates the supported noncatalytic regulatory mechanism. Supporting Evidence: PMID:33238146 In contrast to the active kinases IRAK1 and IRAK4, IRAK2 and IRAK3 are pseudokinases lacking catalytic activity and their functions are poorly understood. |
| GO:0005515 protein binding | IPI PMID:29686383 The IL-33-PIN1-IRAK-M axis is critical for type 2 immunity i... | UNDECIDED | Summary: protein binding: The PMID:29686383 interaction annotation does not by itself identify a molecular role for IRAK3. The relevant bait/prey or complex evidence must be examined before choosing a more informative binding/regulatory term; no wrong-gene inference is made from a high-throughput study title. Reason: The PMID:29686383 interaction annotation does not by itself identify a molecular role for IRAK3. The relevant bait/prey or complex evidence must be examined before choosing a more informative binding/regulatory term; no wrong-gene inference is made from a high-throughput study title. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: protein binding: The PMID:32296183 interaction annotation does not by itself identify a molecular role for IRAK3. The relevant bait/prey or complex evidence must be examined before choosing a more informative binding/regulatory term; no wrong-gene inference is made from a high-throughput study title. Reason: The PMID:32296183 interaction annotation does not by itself identify a molecular role for IRAK3. The relevant bait/prey or complex evidence must be examined before choosing a more informative binding/regulatory term; no wrong-gene inference is made from a high-throughput study title. |
| GO:0005524 ATP binding | IDA PMID:10383454 IRAK-M is a novel member of the Pelle/interleukin-1 receptor... | KEEP AS NON CORE | Summary: ATP binding: The pseudokinase can engage nucleotide with low affinity; this is compatible with a kinase-like fold but is not evidence of phosphoryl-transfer catalysis or its principal signaling function. Reason: The pseudokinase can engage nucleotide with low affinity; this is compatible with a kinase-like fold but is not evidence of phosphoryl-transfer catalysis or its principal signaling function. Supporting Evidence: PMID:33238146 IRAK3 Has Low Affinity for ATP but High Affinity for ATP-Competitive Inhibitors |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: ATP binding: The pseudokinase can engage nucleotide with low affinity; this is compatible with a kinase-like fold but is not evidence of phosphoryl-transfer catalysis or its principal signaling function. Reason: The pseudokinase can engage nucleotide with low affinity; this is compatible with a kinase-like fold but is not evidence of phosphoryl-transfer catalysis or its principal signaling function. Supporting Evidence: PMID:33238146 IRAK3 Has Low Affinity for ATP but High Affinity for ATP-Competitive Inhibitors |
| GO:0005634 nucleus | EXP PMID:29686383 The IL-33-PIN1-IRAK-M axis is critical for type 2 immunity i... | KEEP AS NON CORE | Summary: IL-33/PIN1-dependent nuclear translocation of IRAK-M is directly supported. It is a stimulus-specific signaling mode, not a contradiction of the cytoplasmic TLR-feedback role. Reason: IL-33/PIN1-dependent nuclear translocation of IRAK-M is directly supported. It is a stimulus-specific signaling mode, not a contradiction of the cytoplasmic TLR-feedback role. Supporting Evidence: PMID:29686383 Upon IL-33-induced airway inflammation, PIN1 is activated for binding with and isomerization of IRAK-M, resulting in IRAK-M nuclear translocation and induction of selected proinflammatory genes in dendritic cells. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IL-33/PIN1-dependent nuclear translocation of IRAK-M is directly supported. It is a stimulus-specific signaling mode, not a contradiction of the cytoplasmic TLR-feedback role. Reason: IL-33/PIN1-dependent nuclear translocation of IRAK-M is directly supported. It is a stimulus-specific signaling mode, not a contradiction of the cytoplasmic TLR-feedback role. Supporting Evidence: PMID:29686383 Upon IL-33-induced airway inflammation, PIN1 is activated for binding with and isomerization of IRAK-M, resulting in IRAK-M nuclear translocation and induction of selected proinflammatory genes in dendritic cells. |
| GO:0005634 nucleus | IDA PMID:17379480 Differential regulation and role of interleukin-1 receptor a... | KEEP AS NON CORE | Summary: IL-33/PIN1-dependent nuclear translocation of IRAK-M is directly supported. It is a stimulus-specific signaling mode, not a contradiction of the cytoplasmic TLR-feedback role. Reason: IL-33/PIN1-dependent nuclear translocation of IRAK-M is directly supported. It is a stimulus-specific signaling mode, not a contradiction of the cytoplasmic TLR-feedback role. Supporting Evidence: PMID:29686383 Upon IL-33-induced airway inflammation, PIN1 is activated for binding with and isomerization of IRAK-M, resulting in IRAK-M nuclear translocation and induction of selected proinflammatory genes in dendritic cells. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: IL-33/PIN1-dependent nuclear translocation of IRAK-M is directly supported. It is a stimulus-specific signaling mode, not a contradiction of the cytoplasmic TLR-feedback role. Reason: IL-33/PIN1-dependent nuclear translocation of IRAK-M is directly supported. It is a stimulus-specific signaling mode, not a contradiction of the cytoplasmic TLR-feedback role. Supporting Evidence: PMID:29686383 Upon IL-33-induced airway inflammation, PIN1 is activated for binding with and isomerization of IRAK-M, resulting in IRAK-M nuclear translocation and induction of selected proinflammatory genes in dendritic cells. |
| GO:0005737 cytoplasm | EXP PMID:29686383 The IL-33-PIN1-IRAK-M axis is critical for type 2 immunity i... | ACCEPT | Summary: IRAK-M is distributed within the cell and becomes exclusively cytoplasmic after Pam3CSK4 stimulation. Cytoplasmic residence is supported directly and is consistent with its receptor-proximal regulatory role. Reason: IRAK-M is distributed within the cell and becomes exclusively cytoplasmic after Pam3CSK4 stimulation. Cytoplasmic residence is supported directly and is consistent with its receptor-proximal regulatory role. Supporting Evidence: PMID:17379480 IRAK-M is ubiquitously present in the cell, and becomes exclusively cytoplasmic upon bacterial lipoprotein Pam(3)CSK(4) challenge. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: IRAK-M is distributed within the cell and becomes exclusively cytoplasmic after Pam3CSK4 stimulation. Cytoplasmic residence is supported directly and is consistent with its receptor-proximal regulatory role. Reason: IRAK-M is distributed within the cell and becomes exclusively cytoplasmic after Pam3CSK4 stimulation. Cytoplasmic residence is supported directly and is consistent with its receptor-proximal regulatory role. Supporting Evidence: PMID:17379480 IRAK-M is ubiquitously present in the cell, and becomes exclusively cytoplasmic upon bacterial lipoprotein Pam(3)CSK(4) challenge. |
| GO:0005737 cytoplasm | IDA PMID:17379480 Differential regulation and role of interleukin-1 receptor a... | ACCEPT | Summary: IRAK-M is distributed within the cell and becomes exclusively cytoplasmic after Pam3CSK4 stimulation. Cytoplasmic residence is supported directly and is consistent with its receptor-proximal regulatory role. Reason: IRAK-M is distributed within the cell and becomes exclusively cytoplasmic after Pam3CSK4 stimulation. Cytoplasmic residence is supported directly and is consistent with its receptor-proximal regulatory role. Supporting Evidence: PMID:17379480 IRAK-M is ubiquitously present in the cell, and becomes exclusively cytoplasmic upon bacterial lipoprotein Pam(3)CSK(4) challenge. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: IRAK-M is distributed within the cell and becomes exclusively cytoplasmic after Pam3CSK4 stimulation. Cytoplasmic residence is supported directly and is consistent with its receptor-proximal regulatory role. Reason: IRAK-M is distributed within the cell and becomes exclusively cytoplasmic after Pam3CSK4 stimulation. Cytoplasmic residence is supported directly and is consistent with its receptor-proximal regulatory role. Supporting Evidence: PMID:17379480 IRAK-M is ubiquitously present in the cell, and becomes exclusively cytoplasmic upon bacterial lipoprotein Pam(3)CSK(4) challenge. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | UNDECIDED | Summary: plasma membrane: The available evidence examined for IRAK3 does not resolve the exact claim of plasma membrane. The specific experiment or traced orthology/phylogenetic inference behind GO_REF:0000033 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper. Reason: The available evidence examined for IRAK3 does not resolve the exact claim of plasma membrane. The specific experiment or traced orthology/phylogenetic inference behind GO_REF:0000033 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper. |
| GO:0006468 protein phosphorylation | IDA PMID:10383454 IRAK-M is a novel member of the Pelle/interleukin-1 receptor... | UNDECIDED | Summary: protein phosphorylation: The available evidence examined for IRAK3 does not resolve the exact claim of protein phosphorylation. The specific experiment or traced orthology/phylogenetic inference behind PMID:10383454 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper. Reason: The available evidence examined for IRAK3 does not resolve the exact claim of protein phosphorylation. The specific experiment or traced orthology/phylogenetic inference behind PMID:10383454 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper. |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | ACCEPT | Summary: signal transduction: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0008063 Toll signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Toll signaling pathway: This broad Toll-family signaling annotation is compatible with IRAK3-dependent innate signaling, while the specific TLR/IL-1 regulatory mechanism is more informative. Reason: This broad Toll-family signaling annotation is compatible with IRAK3-dependent innate signaling, while the specific TLR/IL-1 regulatory mechanism is more informative. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0009615 response to virus | IC PMID:12150927 IRAK-M is a negative regulator of Toll-like receptor signali... | UNDECIDED | Summary: response to virus: The available evidence examined for IRAK3 does not resolve the exact claim of response to virus. The specific experiment or traced orthology/phylogenetic inference behind PMID:12150927 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper. Reason: The available evidence examined for IRAK3 does not resolve the exact claim of response to virus. The specific experiment or traced orthology/phylogenetic inference behind PMID:12150927 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper. |
| GO:0009615 response to virus | IEA GO_REF:0000117 | UNDECIDED | Summary: response to virus: The available evidence examined for IRAK3 does not resolve the exact claim of response to virus. The specific experiment or traced orthology/phylogenetic inference behind GO_REF:0000117 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper. Reason: The available evidence examined for IRAK3 does not resolve the exact claim of response to virus. The specific experiment or traced orthology/phylogenetic inference behind GO_REF:0000117 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper. |
| GO:0010933 positive regulation of macrophage tolerance induction | IEA GO_REF:0000107 | ACCEPT | Summary: positive regulation of macrophage tolerance induction: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0010933 positive regulation of macrophage tolerance induction | ISS PMID:12150927 IRAK-M is a negative regulator of Toll-like receptor signali... | ACCEPT | Summary: positive regulation of macrophage tolerance induction: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0010936 negative regulation of macrophage cytokine production | IEA GO_REF:0000107 | ACCEPT | Summary: negative regulation of macrophage cytokine production: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0010936 negative regulation of macrophage cytokine production | ISS PMID:12150927 IRAK-M is a negative regulator of Toll-like receptor signali... | ACCEPT | Summary: negative regulation of macrophage cytokine production: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0019221 cytokine-mediated signaling pathway | IEA GO_REF:0000107 | UNDECIDED | Summary: cytokine-mediated signaling pathway: The available evidence examined for IRAK3 does not resolve the exact claim of cytokine-mediated signaling pathway. The specific experiment or traced orthology/phylogenetic inference behind GO_REF:0000107 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper. Reason: The available evidence examined for IRAK3 does not resolve the exact claim of cytokine-mediated signaling pathway. The specific experiment or traced orthology/phylogenetic inference behind GO_REF:0000107 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper. |
| GO:0019221 cytokine-mediated signaling pathway | ISS GO_REF:0000024 | UNDECIDED | Summary: cytokine-mediated signaling pathway: The available evidence examined for IRAK3 does not resolve the exact claim of cytokine-mediated signaling pathway. The specific experiment or traced orthology/phylogenetic inference behind GO_REF:0000024 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper. Reason: The available evidence examined for IRAK3 does not resolve the exact claim of cytokine-mediated signaling pathway. The specific experiment or traced orthology/phylogenetic inference behind GO_REF:0000024 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper. |
| GO:0019901 protein kinase binding | IPI PMID:33238146 Dimeric Structure of the Pseudokinase IRAK3 Suggests an Allo... | ACCEPT | Summary: protein kinase binding: The human IRAK3 structural study establishes homodimerization and an interaction surface involved in IRAK4 regulation. Protein association rather than catalysis supplies the molecular mechanism. Reason: The human IRAK3 structural study establishes homodimerization and an interaction surface involved in IRAK4 regulation. Protein association rather than catalysis supplies the molecular mechanism. Supporting Evidence: PMID:33238146 IRAK3 dimerizes in a unique way through a head-to-head arrangement not observed in any other kinases. Multiple conserved cysteine residues imply a potential redox control of IRAK3 conformation and dimerization. By analyzing asthma-associated mutations, we identify an evolutionarily conserved surface on IRAK3 that could form an interaction interface with IRAK4, suggesting a model for the negative regulation of IRAK4 by IRAK3. PMID:17379480 IRAK-M is ubiquitously present in the cell, and becomes exclusively cytoplasmic upon bacterial lipoprotein Pam(3)CSK(4) challenge. |
| GO:0031663 lipopolysaccharide-mediated signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: lipopolysaccharide-mediated signaling pathway: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0031663 lipopolysaccharide-mediated signaling pathway | IMP PMID:18156187 Early and preferential induction of IL-1 receptor-associated... | ACCEPT | Summary: lipopolysaccharide-mediated signaling pathway: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0032494 response to peptidoglycan | IEA GO_REF:0000107 | ACCEPT | Summary: response to peptidoglycan: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0032494 response to peptidoglycan | ISS PMID:12150927 IRAK-M is a negative regulator of Toll-like receptor signali... | ACCEPT | Summary: response to peptidoglycan: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0032496 response to lipopolysaccharide | IEA GO_REF:0000120 | ACCEPT | Summary: response to lipopolysaccharide: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0032496 response to lipopolysaccharide | ISS PMID:12150927 IRAK-M is a negative regulator of Toll-like receptor signali... | ACCEPT | Summary: response to lipopolysaccharide: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0032695 negative regulation of interleukin-12 production | IEA GO_REF:0000120 | ACCEPT | Summary: negative regulation of interleukin-12 production: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0032695 negative regulation of interleukin-12 production | IMP PMID:18156187 Early and preferential induction of IL-1 receptor-associated... | ACCEPT | Summary: negative regulation of interleukin-12 production: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0032695 negative regulation of interleukin-12 production | ISS PMID:12150927 IRAK-M is a negative regulator of Toll-like receptor signali... | ACCEPT | Summary: negative regulation of interleukin-12 production: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0032715 negative regulation of interleukin-6 production | IEA GO_REF:0000120 | ACCEPT | Summary: negative regulation of interleukin-6 production: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0032715 negative regulation of interleukin-6 production | IMP PMID:18156187 Early and preferential induction of IL-1 receptor-associated... | ACCEPT | Summary: negative regulation of interleukin-6 production: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0032715 negative regulation of interleukin-6 production | ISS PMID:12150927 IRAK-M is a negative regulator of Toll-like receptor signali... | ACCEPT | Summary: negative regulation of interleukin-6 production: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0032720 negative regulation of tumor necrosis factor production | IEA GO_REF:0000120 | ACCEPT | Summary: negative regulation of tumor necrosis factor production: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0032720 negative regulation of tumor necrosis factor production | IMP PMID:15728517 Tumor cells deactivate human monocytes by up-regulating IL-1... | ACCEPT | Summary: negative regulation of tumor necrosis factor production: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0034122 negative regulation of toll-like receptor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: negative regulation of toll-like receptor signaling pathway: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0034122 negative regulation of toll-like receptor signaling pathway | ISS PMID:12150927 IRAK-M is a negative regulator of Toll-like receptor signali... | ACCEPT | Summary: negative regulation of toll-like receptor signaling pathway: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0035556 intracellular signal transduction | IBA GO_REF:0000033 | ACCEPT | Summary: intracellular signal transduction: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0042177 negative regulation of protein catabolic process | IEA GO_REF:0000120 | ACCEPT | Summary: IRAK-M stabilizes MKP-1 and selectively attenuates p38 activation after bacterial lipopeptide challenge. This is a supported noncatalytic route for restraining MAPK signaling. Reason: IRAK-M stabilizes MKP-1 and selectively attenuates p38 activation after bacterial lipopeptide challenge. This is a supported noncatalytic route for restraining MAPK signaling. Supporting Evidence: PMID:17379480 Our findings indicate that IRAK-M selectively attenuates p38 activation and inhibits innate immunity through stabilizing MKP-1. |
| GO:0042177 negative regulation of protein catabolic process | IMP PMID:17379480 Differential regulation and role of interleukin-1 receptor a... | ACCEPT | Summary: IRAK-M stabilizes MKP-1 and selectively attenuates p38 activation after bacterial lipopeptide challenge. This is a supported noncatalytic route for restraining MAPK signaling. Reason: IRAK-M stabilizes MKP-1 and selectively attenuates p38 activation after bacterial lipopeptide challenge. This is a supported noncatalytic route for restraining MAPK signaling. Supporting Evidence: PMID:17379480 Our findings indicate that IRAK-M selectively attenuates p38 activation and inhibits innate immunity through stabilizing MKP-1. |
| GO:0042803 protein homodimerization activity | IDA PMID:33238146 Dimeric Structure of the Pseudokinase IRAK3 Suggests an Allo... | ACCEPT | Summary: protein homodimerization activity: The human IRAK3 structural study establishes homodimerization and an interaction surface involved in IRAK4 regulation. Protein association rather than catalysis supplies the molecular mechanism. Reason: The human IRAK3 structural study establishes homodimerization and an interaction surface involved in IRAK4 regulation. Protein association rather than catalysis supplies the molecular mechanism. Supporting Evidence: PMID:33238146 IRAK3 dimerizes in a unique way through a head-to-head arrangement not observed in any other kinases. Multiple conserved cysteine residues imply a potential redox control of IRAK3 conformation and dimerization. By analyzing asthma-associated mutations, we identify an evolutionarily conserved surface on IRAK3 that could form an interaction interface with IRAK4, suggesting a model for the negative regulation of IRAK4 by IRAK3. PMID:17379480 IRAK-M is ubiquitously present in the cell, and becomes exclusively cytoplasmic upon bacterial lipoprotein Pam(3)CSK(4) challenge. |
| GO:0042803 protein homodimerization activity | IPI PMID:10383454 IRAK-M is a novel member of the Pelle/interleukin-1 receptor... | ACCEPT | Summary: protein homodimerization activity: The human IRAK3 structural study establishes homodimerization and an interaction surface involved in IRAK4 regulation. Protein association rather than catalysis supplies the molecular mechanism. Reason: The human IRAK3 structural study establishes homodimerization and an interaction surface involved in IRAK4 regulation. Protein association rather than catalysis supplies the molecular mechanism. Supporting Evidence: PMID:33238146 IRAK3 dimerizes in a unique way through a head-to-head arrangement not observed in any other kinases. Multiple conserved cysteine residues imply a potential redox control of IRAK3 conformation and dimerization. By analyzing asthma-associated mutations, we identify an evolutionarily conserved surface on IRAK3 that could form an interaction interface with IRAK4, suggesting a model for the negative regulation of IRAK4 by IRAK3. PMID:17379480 IRAK-M is ubiquitously present in the cell, and becomes exclusively cytoplasmic upon bacterial lipoprotein Pam(3)CSK(4) challenge. |
| GO:0043122 regulation of canonical NF-kappaB signal transduction | IEA GO_REF:0000117 | ACCEPT | Summary: regulation of canonical NF-kappaB signal transduction: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0043123 positive regulation of canonical NF-kappaB signal transduction | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IRAK-M can promote selected inflammatory outputs in the IL-33/PIN1 context despite restraining canonical TLR responses. The positive signaling annotation should be interpreted as context dependent rather than as a universal activator role. Reason: IRAK-M can promote selected inflammatory outputs in the IL-33/PIN1 context despite restraining canonical TLR responses. The positive signaling annotation should be interpreted as context dependent rather than as a universal activator role. Supporting Evidence: PMID:29686383 Upon IL-33-induced airway inflammation, PIN1 is activated for binding with and isomerization of IRAK-M, resulting in IRAK-M nuclear translocation and induction of selected proinflammatory genes in dendritic cells. |
| GO:0043124 negative regulation of canonical NF-kappaB signal transduction | IMP PMID:10383454 IRAK-M is a novel member of the Pelle/interleukin-1 receptor... | ACCEPT | Summary: negative regulation of canonical NF-kappaB signal transduction: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0043242 negative regulation of protein-containing complex disassembly | IMP PMID:12150927 IRAK-M is a negative regulator of Toll-like receptor signali... | ACCEPT | Summary: negative regulation of protein-containing complex disassembly: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0043244 regulation of protein-containing complex disassembly | IEA GO_REF:0000120 | ACCEPT | Summary: regulation of protein-containing complex disassembly: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0043244 regulation of protein-containing complex disassembly | ISS GO_REF:0000024 | ACCEPT | Summary: regulation of protein-containing complex disassembly: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0043330 response to exogenous dsRNA | IEA GO_REF:0000107 | UNDECIDED | Summary: response to exogenous dsRNA: The available evidence examined for IRAK3 does not resolve the exact claim of response to exogenous dsRNA. The specific experiment or traced orthology/phylogenetic inference behind GO_REF:0000107 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper. Reason: The available evidence examined for IRAK3 does not resolve the exact claim of response to exogenous dsRNA. The specific experiment or traced orthology/phylogenetic inference behind GO_REF:0000107 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper. |
| GO:0043330 response to exogenous dsRNA | ISS PMID:12150927 IRAK-M is a negative regulator of Toll-like receptor signali... | UNDECIDED | Summary: response to exogenous dsRNA: The available evidence examined for IRAK3 does not resolve the exact claim of response to exogenous dsRNA. The specific experiment or traced orthology/phylogenetic inference behind PMID:12150927 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper. Reason: The available evidence examined for IRAK3 does not resolve the exact claim of response to exogenous dsRNA. The specific experiment or traced orthology/phylogenetic inference behind PMID:12150927 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper. |
| GO:0043409 negative regulation of MAPK cascade | IEA GO_REF:0000120 | ACCEPT | Summary: IRAK-M stabilizes MKP-1 and selectively attenuates p38 activation after bacterial lipopeptide challenge. This is a supported noncatalytic route for restraining MAPK signaling. Reason: IRAK-M stabilizes MKP-1 and selectively attenuates p38 activation after bacterial lipopeptide challenge. This is a supported noncatalytic route for restraining MAPK signaling. Supporting Evidence: PMID:17379480 Our findings indicate that IRAK-M selectively attenuates p38 activation and inhibits innate immunity through stabilizing MKP-1. |
| GO:0043409 negative regulation of MAPK cascade | IMP PMID:17379480 Differential regulation and role of interleukin-1 receptor a... | ACCEPT | Summary: IRAK-M stabilizes MKP-1 and selectively attenuates p38 activation after bacterial lipopeptide challenge. This is a supported noncatalytic route for restraining MAPK signaling. Reason: IRAK-M stabilizes MKP-1 and selectively attenuates p38 activation after bacterial lipopeptide challenge. This is a supported noncatalytic route for restraining MAPK signaling. Supporting Evidence: PMID:17379480 Our findings indicate that IRAK-M selectively attenuates p38 activation and inhibits innate immunity through stabilizing MKP-1. |
| GO:0045088 regulation of innate immune response | IEA GO_REF:0000117 | ACCEPT | Summary: regulation of innate immune response: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0045824 negative regulation of innate immune response | IEA GO_REF:0000107 | ACCEPT | Summary: negative regulation of innate immune response: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0045824 negative regulation of innate immune response | ISS PMID:12150927 IRAK-M is a negative regulator of Toll-like receptor signali... | ACCEPT | Summary: negative regulation of innate immune response: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0046982 protein heterodimerization activity | IPI PMID:10383454 IRAK-M is a novel member of the Pelle/interleukin-1 receptor... | UNDECIDED | Summary: protein heterodimerization activity: The available evidence examined for IRAK3 does not resolve the exact claim of protein heterodimerization activity. The specific experiment or traced orthology/phylogenetic inference behind PMID:10383454 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper. Reason: The available evidence examined for IRAK3 does not resolve the exact claim of protein heterodimerization activity. The specific experiment or traced orthology/phylogenetic inference behind PMID:10383454 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper. |
| GO:0046982 protein heterodimerization activity | IPI PMID:10383454 IRAK-M is a novel member of the Pelle/interleukin-1 receptor... | UNDECIDED | Summary: protein heterodimerization activity: The available evidence examined for IRAK3 does not resolve the exact claim of protein heterodimerization activity. The specific experiment or traced orthology/phylogenetic inference behind PMID:10383454 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper. Reason: The available evidence examined for IRAK3 does not resolve the exact claim of protein heterodimerization activity. The specific experiment or traced orthology/phylogenetic inference behind PMID:10383454 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper. |
| GO:0070498 interleukin-1-mediated signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: interleukin-1-mediated signaling pathway: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0070498 interleukin-1-mediated signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: interleukin-1-mediated signaling pathway: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0070498 interleukin-1-mediated signaling pathway | IMP PMID:10383454 IRAK-M is a novel member of the Pelle/interleukin-1 receptor... | ACCEPT | Summary: interleukin-1-mediated signaling pathway: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
| GO:0070555 response to interleukin-1 | IMP PMID:10383454 IRAK-M is a novel member of the Pelle/interleukin-1 receptor... | ACCEPT | Summary: response to interleukin-1: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Reason: IRAK3/IRAK-M regulates MyD88-associated TLR/IL-1 signaling and restrains cytokine production by preventing release of IRAK proteins and formation of activating IRAK–TRAF6 complexes. These signaling and tolerance roles are compatible with a noncatalytic pseudokinase. Supporting Evidence: PMID:12150927 We show here that IRAK-M is induced upon TLR stimulation and negatively regulates TLR signaling. IRAK-M prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes. |
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