Affinage

IRAK2

Interleukin-1 receptor-associated kinase-like 2 · UniProt O43187

Length
625 aa
Mass
69.4 kDa
Annotated
2026-06-10
54 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IRAK2 is a death domain-containing signaling adapter that drives Toll-like receptor (TLR) and IL-1 receptor (IL-1R)–induced inflammatory gene expression by nucleating and sustaining the downstream signaling complex (PMID:9374458, PMID:18438411). It assembles into the Myddosome, a left-handed helical oligomer of six MyD88, four IRAK4, and four IRAK2 death domains in which MyD88 recruits IRAK4 and IRAK4 in turn recruits IRAK2 (PMID:20485341, PMID:42168171). Functionally, IRAK2 acts downstream of MyD88/Mal but upstream of TRIF and is required across multiple TLRs (TLR2/3/4/5/7/8/9) to promote TRAF6 K63-linked ubiquitination, the critical step for NF-κB activation (PMID:17878161). Whereas IRAK1 activity declines rapidly, IRAK2 specifically sustains the late phase of NF-κB activation, IKKβ activity, and cytokine output, such that cytokine production is only abolished when both IRAK1 and IRAK2 are lost (PMID:18438411, PMID:23918981). The IRAK2–TRAF6 interaction (via residue E525) and the extreme C-terminus are required to support TRAF6 auto-ubiquitination and full late-phase cytokine and ERK signaling (PMID:23918981, PMID:33799071). Beyond the cytoplasmic signaling complex, IRAK2 phosphorylates SRSF1 in the nucleus after LPS stimulation to promote nuclear export of a subset of inflammatory mRNAs following RanBP2-dependent sumoylation (PMID:28990926), and it translocates to mitochondria upon IL-1 stimulation where it binds PHB1 and OPA1 to suppress respiratory super-complex formation and oxidative metabolism (PMID:32778760). IRAK2 signaling is restrained by PELI1-mediated K63-linked ubiquitination and degradation (PMID:40986758). Human loss-of-function IRAK2 variants impair TRAF6 ubiquitination and cytokine induction and disrupt Myddosome assembly, causing impaired NF-κB/MAPK signaling with a paradoxical type I interferon signature and susceptibility to severe infection (PMID:26250868, PMID:42168171).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1997 High

    Established IRAK2 as a proximal IL-1R signaling component, answering whether it physically engages the receptor complex and contributes to NF-κB activation.

    Evidence Co-IP and dominant-negative overexpression with NF-κB reporters in the IL-1R complex

    PMID:9374458

    Open questions at the time
    • Did not resolve stoichiometry or hierarchy of complex assembly
    • Did not define the biochemical step IRAK2 catalyzes
  2. 2007 High

    Defined the core biochemical output of IRAK2 by showing it, not IRAK1, drives TRAF6 K63-linked ubiquitination required for NF-κB activation across most TLRs.

    Evidence siRNA knockdown, loss-of-function mutants, TRAF6 ubiquitination and NF-κB reporter assays in human cells

    PMID:17878161

    Open questions at the time
    • Did not establish whether IRAK2 acts as kinase, scaffold, or E3 cofactor in promoting ubiquitination
  3. 2008 High

    Resolved the temporal division of labor between IRAK1 and IRAK2, showing IRAK2 sustains late-phase NF-κB and cytokine output.

    Evidence IRAK1/IRAK2 knockout mouse macrophages with kinase activity and cytokine assays

    PMID:18438411

    Open questions at the time
    • Did not define the substrate of sustained IRAK2 kinase activity
    • Mechanism of late-phase specificity left open
  4. 2010 High

    Provided the structural basis for Myddosome assembly, defining IRAK2's 6:4:4 stoichiometry and hierarchical recruitment by IRAK4.

    Evidence X-ray crystallography of MyD88-IRAK4-IRAK2 death domains with mutagenesis

    PMID:20485341

    Open questions at the time
    • Did not capture full-length kinase domains or downstream signaling complexes
    • Order of kinase activation events inferred from proximity
  5. 2013 High

    Pinpointed the IRAK2-TRAF6 interaction (E525) as the determinant of late-phase but not early-phase cytokine production.

    Evidence IRAK2[E525A] knock-in mice with BMDM and pDC cytokine and IKKβ activity assays

    PMID:23918981

    Open questions at the time
    • Did not address non-TRAF6 IRAK2 functions
    • Cell-type differences in IFN dependence not fully explained
  6. 2017 High

    Revealed an unexpected nuclear function in which IRAK2 controls export of inflammatory mRNAs via SRSF1 phosphorylation.

    Evidence Nuclear fractionation, sumoylation assays, in vitro SRSF1 phosphorylation, mRNA export assays in murine macrophages

    PMID:28990926

    Open questions at the time
    • Catalytic competence of IRAK2 as a protein kinase not biochemically reconciled with prior pseudokinase data
    • Generality across cell types untested
  7. 2020 High

    Identified a mitochondrial role linking IRAK2 to metabolic suppression, distinct from its NF-κB signaling function.

    Evidence Mitochondrial fractionation, Co-IP with TOM20/TIMM50/PHB1/OPA1, conditional KO and kinase-dead knock-in mice, Seahorse assays

    PMID:32778760

    Open questions at the time
    • Mechanism by which IRAK2 disrupts super-complexes molecularly undefined
    • Switch between signaling and mitochondrial pools unresolved
  8. 2021 Medium

    Mapped a C-terminal element required for IRAK2 to support TRAF6 auto-ubiquitination independent of TRAF6 binding.

    Evidence C-terminal deletion mutagenesis with NF-κB/ERK2 and TRAF6 ubiquitination assays in macrophages

    PMID:33799071

    Open questions at the time
    • Molecular partner engaged by the C-terminal 55 residues not identified
    • Single lab, no structural validation
  9. 2025 Medium

    Established a negative-regulatory mechanism by which PELI1 ubiquitinates and degrades IRAK2 to limit inflammation.

    Evidence Peli1 overexpression/knockout, K63-ubiquitination assays and IRAK2 rescue in airway inflammation models

    PMID:40986758

    Open questions at the time
    • Single lab
    • Ubiquitination linkage-to-degradation coupling not fully dissected
  10. 2026 High

    Linked IRAK2 loss-of-function in patients to disrupted Myddosome assembly and a paradoxical type I interferon phenotype, defining a human disease connection.

    Evidence Patient variant characterization, Co-IP, signaling assays, knockout cells and knock-in mouse BMDMs with baricitinib rescue

    PMID:42168171

    Open questions at the time
    • Mechanism redirecting signaling to TRIF-dependent IFN not fully resolved
    • Penetrance and clinical spectrum incompletely defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved whether IRAK2 functions as a catalytically active kinase or scaffold across its cytoplasmic, nuclear, and mitochondrial roles, and how a single protein is partitioned among these distinct compartments.
  • No unified structural/biochemical model of IRAK2 catalysis
  • Regulation of subcellular pool selection unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005739 mitochondrion 2 GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-168256 Immune System 3 R-HSA-162582 Signal Transduction 2 R-HSA-8953897 Cellular responses to stimuli 1
Partners
FADDIRAK4MYD88OPA1PELI1PHB1SRSF1TRAF6
Complex memberships
Myddosome (MyD88-IRAK4-IRAK2)

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 IRAK-2 and MyD88 are proximal mediators of IL-1R signaling that both associate with the IL-1R signaling complex; dominant negative forms of either attenuate IL-1R-mediated NF-κB activation. Co-immunoprecipitation, dominant-negative overexpression, NF-κB reporter assay Science High 9374458
2010 Crystal structure of the MyD88-IRAK4-IRAK2 death domain (Myddosome) complex reveals a left-handed helical oligomer of 6 MyD88, 4 IRAK4, and 4 IRAK2 DDs; assembly is hierarchical (MyD88 recruits IRAK4, then IRAK4 recruits IRAK2/IRAK1); composite binding sites are required, confirmed by mutagenesis; proximity of kinase domains enables phosphorylation/activation. X-ray crystallography, site-directed mutagenesis, functional signaling assays Nature High 20485341
2008 IRAK2 is essential for sustaining late-phase (peaking ~8 h) TLR-induced NF-κB activation and cytokine gene expression downstream of IRAK4; its kinase activity is sustained whereas IRAK1 kinase activity and protein levels decline within 1 h. TLR-induced cytokine production is abolished only in cells lacking both IRAK1 and IRAK2. IRAK1/IRAK2 knockout mouse macrophages, kinase activity assays, cytokine production measurements, NF-κB reporter assays Nature immunology High 18438411
2007 IRAK-2 is critical for TLR-mediated NF-κB activation across multiple TLRs (TLR2, 3, 4, 5, 7, 8, 9); IRAK-2 acts downstream of MyD88/Mal but upstream of TRIF; expression of IRAK-2 (but not IRAK-1) drives TRAF6 K63-linked ubiquitination, a critical step for NF-κB activation; loss-of-function IRAK-2 mutants that cannot activate NF-κB also fail to promote TRAF6 ubiquitination. siRNA knockdown in human cell lines and primary cells, overexpression assays, TRAF6 ubiquitination assay, NF-κB reporter assay, poxviral antagonist A52 interaction studies The Journal of biological chemistry High 17878161
2013 The IRAK2-TRAF6 interaction (via IRAK2 E525) is required for the late phase (2–8 h) but not early phase (0–2 h) of IL-6 and TNF-α mRNA production and secretion in bone marrow-derived macrophages stimulated via MyD88-dependent TLRs; the IRAK2-TRAF6 interaction sustains IKKβ activity during prolonged MyD88 network activation; in plasmacytoid dendritic cells, IRAK2-TRAF6 interaction is needed for IFN-α (but not IFN-β) production. IRAK2[E525A] and IRAK1[D359A] knock-in mice, BMDM and pDC cytokine assays, IKKβ activity assays Journal of immunology High 23918981
2020 IL-1 induces IRAK2 Myddosome recruitment to mitochondrial outer membranes via TOM20 recognition, followed by TIMM50-guided translocation into mitochondrial inner membranes; mitochondrial IRAK2 suppresses oxidative phosphorylation and fatty acid oxidation by interacting with PHB1 and OPA1, thereby disrupting respiratory super-complex formation. Adipocyte-specific MyD88 or IRAK2 deficiency reduces high-fat diet-induced weight gain and improves insulin resistance. Mitochondrial fractionation, co-immunoprecipitation (IRAK2 with TOM20, TIMM50, PHB1, OPA1), adipocyte-specific conditional KO mice, IRAK2 kinase-inactive knockin mice, metabolic phenotyping, Seahorse assay Nature immunology High 32778760
2017 LPS/TLR4 engagement promotes nuclear localization of IRAK2; IRAK2 kinase activity is required for RanBP2-mediated IRAK2 sumoylation and subsequent nuclear translocation; nuclear IRAK2 phosphorylates SRSF1 to reduce its binding to target mRNAs, promoting ALYREF binding and Nxf1 loading for nuclear export of a specific subset of inflammatory mRNAs (enriched for SRSF1-binding motifs) in murine macrophages. Nuclear fractionation/localization assays, IRAK2 kinase mutant analysis, sumoylation assays, RNA-binding and nuclear export assays, mRNA array analysis, phosphorylation of SRSF1 in vitro eLife High 28990926
2013 IRAK2 contributes to ER stress-mediated unfolded protein response signaling specifically through the IRE1 pathway; knockdown of IRAK2 suppresses ER stress-induced CHOP expression and stress kinase activation; ER stress induces IRAK2 gene expression in an IRE1/XBP1-dependent manner, creating a positive amplification loop; Irak2 knockout mice show defects in ER stress-induced CHOP expression and IRE1 signaling. siRNA kinome screen, RNAi knockdown in mammalian and Drosophila cells, Irak2 knockout mice, ER stress induction assays, UPR pathway analysis PloS one Medium 23724040
2004 The murine Irak2 gene encodes four alternatively spliced isoforms (Irak2a–d); Irak2a and Irak2b (containing intact death domain) potentiate NF-κB activation; Irak2c and Irak2d are inhibitory; LPS induces Irak2c expression via an NF-κB-responsive promoter, suggesting a negative feedback mechanism. No equivalent alternative splicing was found for human IRAK2. Molecular cloning, alternative splicing analysis, NF-κB reporter overexpression assays, LPS stimulation, promoter analysis The Journal of biological chemistry Medium 15082713
2002 Murine IRAK-2 shares 67% sequence identity with human IRAK-2, is ubiquitously expressed, and both murine and human forms practically lack autophosphorylation kinase activity; unlike human IRAK-2, murine IRAK-2 has no stimulatory effect on IL-1-induced NF-κB activation when overexpressed. Molecular cloning, sequence analysis, autophosphorylation kinase assay, NF-κB reporter overexpression assay Biochemical and biophysical research communications Medium 12220507
2009 A deletion in the MOLF/Ei promoter of the inhibitory Irak2c isoform increases the ratio of pro- to anti-inflammatory IRAK-2 isoforms, leading to enhanced early NF-κB activity and p38 MAPK activation in TLR signaling; congenic mapping identified Irak2 as the causative gene at the Why1 locus. Genetic mapping (congenic mice), promoter deletion analysis, NF-κB and MAPK phosphorylation assays, LPS stimulation of primary macrophages The Journal of experimental medicine Medium 19564352
2001 Active Ras associates with IRAK, IRAK2, TRAF6, and TAK-1 in the IL-1 signaling complex; dominant-negative RasN17 blocks p38 MAPK activation downstream of TRAF6 but upstream of MKK3/MKK6; Ras likely aids assembly of the IRAK-TRAF6-TAK1 multiprotein complex required for IL-1-induced p38 MAPK activation. Co-immunoprecipitation of active RasVHa with signaling components, dominant-negative transfection epistasis, p38 MAPK activation assays The Journal of biological chemistry Medium 11744690
2003 IRAK2 and MyD88 (but not IRAK1) physically interact with Akt, as shown by co-immunoprecipitation and pull-down; the IRAK2-Akt association decreases upon IL-1 stimulation and is regulated by PTEN and PDK1; Akt kinase activity is required for IRAK2-dependent (but not IRAK1-dependent) NF-κB transactivation, acting at a step distinct from IκBα dissociation/p65 nuclear translocation. Co-immunoprecipitation, GST pull-down, NF-κB reporter assay with dominant-negative Akt, iNOS/IL-1β production assay The Biochemical journal Medium 12906710
2011 IRAK-2 mediates pathological Th17 cell development in a CD4 T cell-intrinsic manner by enhancing IL-1β-induced activation of transcription factors RORγt and BATF, as established by adoptive transfer of CD4 T cells from Why1 congenic (Irak2-variant) mice. Adoptive transfer of CD4 T cells, Schistosoma mansoni infection model, RORγt/BATF transcription factor activation assays, congenic mouse genetics PLoS pathogens Medium 21998578
2015 The IRAK2 coding variant L392V (rs3844283) shows intact binding to TRAF6 but impaired TRAF6 ubiquitination, resulting in reduced TLR-mediated cytokine and IFN-α induction in primary plasmacytoid dendritic cells; this hypofunctional variant is associated with reduced spontaneous HCV clearance. Co-immunoprecipitation (IRAK2-TRAF6 binding), ubiquitination assay, primary pDC cytokine/IFN assays, epidemiological cohort analysis Hepatology Medium 26250868
2014 The IRAK2 coding variant R214G (rs35060588) is hypofunctional for NF-κB signaling and TLR-mediated cytokine induction due to reduced TRAF6 ubiquitination. NF-κB reporter assay, cytokine induction assay, TRAF6 ubiquitination assay with variant IRAK2 The Journal of biological chemistry Medium 24973222
2021 The extreme C-terminal 55 amino acids of IRAK2 (lacking known functional domains) are required for full TRAF6 auto-ubiquitination and optimal TLR4-induced NF-κB and ERK2 activation; the IRAK2Δ55 deletion mutant binds TRAF6 but fails to support TRAF6 auto-ubiquitination as an E3 ligase. IRAK2 C-terminal deletion mutagenesis, NF-κB and ERK2 activation assays, Co-IP (IRAK2-TRAF6), TRAF6 ubiquitination assay, CD40 expression, IL-6/NO production in macrophages Molecular immunology Medium 33799071
2018 IRAK2 phosphorylates Smurf1 at threonine residues to promote Smurf1 self-ubiquitination and degradation in response to ER stress, thereby altering the cascade of ER effectors to induce apoptosis. Co-immunoprecipitation, phosphorylation assay, ubiquitination assay, overexpression/knockdown in colorectal cancer cells Cellular signalling Low 29753111
2021 IRAK2 overexpression enhances radiosensitivity of oral squamous cell carcinoma cells by enhancing ionizing radiation-induced caspase-8/3-dependent apoptosis; low IRAK2 expression correlates with radioresistant phenotype. IRAK2 overexpression and knockdown in OSCC cell lines, clonogenic survival assay, caspase-8/3 activity assay, in vivo xenograft model Frontiers in oncology Low 34249686
2023 Adipsin directly interacts with IRAK2 (shown by LC-MS/MS, GST pull-down, Co-IP, immunofluorescence co-localization) and inhibits IRAK2 mitochondrial translocation in diabetic cardiomyopathy, thereby preventing IRAK2 interaction with PHB/OPA1 and preserving mitochondrial structure and fatty acid β-oxidation. Irak2 knockdown abolished the protective effects of Adipsin overexpression. LC-MS/MS interactome, GST pull-down, Co-IP, immunofluorescence co-localization, immunocolloidal gold electron microscopy, Western blot, IRAK2 knockdown epistasis, high-fat diet mouse model Military Medical Research Medium 38072993
2026 Loss-of-function mutation (IRAK2-Δex2, skipping exon 2) disrupts IRAK2 interaction with IRAK4, impairing Myddosome assembly, NF-κB and MAPK activation; IRAK2 deficiency leads to upregulated type I interferon responses via engagement of a TRIF-dependent interferon pathway in macrophages; Baricitinib attenuates elevated IFN signature in patient-derived cells. Patient loss-of-function variant characterization, Co-IP (IRAK2-IRAK4 interaction), NF-κB/MAPK signaling assays, IRAK2 knockout cell lines, knock-in mouse BMDMs, IFN signature analysis, baricitinib rescue experiment Nature communications High 42168171
2025 PELI1 (an E3 ubiquitin ligase) induces K63-linked ubiquitination and protein degradation of IRAK2; IRAK2 overexpression activates p38 MAPK/NF-κB signaling to exacerbate airway inflammation; PELI1-mediated IRAK2 degradation mitigates HDM-induced airway inflammation in pediatric asthma models. AAV6.2-mediated Peli1 overexpression in airway epithelium, CRISPR/Cas9 PELI1 knockout, ubiquitination assays (K63 linkage), Western blot, NF-κB/MAPK pathway analysis, HDM mouse model American journal of respiratory cell and molecular biology Medium 40986758
2024 Novel IRAK2 mutations in patients with severe invasive infections compromise IRAK2's capacity to ubiquitinate TRAF6, resulting in impaired TNF-α production. Patient variant characterization, TRAF6 ubiquitination assay International journal of infectious diseases Low 39299377
2009 miR-146a targets IRAK2 (in addition to TRAF6 and IRAK1) in macrophages, and IRAK1/IRAK2 participate in VSV-induced type I IFN production by associating with FADD (Fas-associated death domain protein) in a VSV infection-inducible manner. miRNA target validation, Co-IP (IRAK1/IRAK2 with FADD), VSV infection assay, IFN production measurement Journal of immunology Medium 19596990
2018 Small molecule mimetics of the α-helical domain of IRAK2 competitively disrupt the IRAK2-IRAK4 protein-protein interaction within the Myddosome, inhibiting IL-33-induced NF-κB activity and attenuating airway inflammation in mouse asthma models. NF-κB promoter assay (compound screening), protein-protein interaction disruption assay (Myddosome), in vivo IL-33-induced and OVA-induced mouse asthma models Journal of immunology Medium 29728508

Source papers

Stage 0 corpus · 54 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling. Science (New York, N.Y.) 944 9374458
2010 Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling. Nature 883 20485341
2009 MicroRNA-146a feedback inhibits RIG-I-dependent Type I IFN production in macrophages by targeting TRAF6, IRAK1, and IRAK2. Journal of immunology (Baltimore, Md. : 1950) 627 19596990
2008 Sequential control of Toll-like receptor-dependent responses by IRAK1 and IRAK2. Nature immunology 347 18438411
2010 Differential regulation of interleukin-1 receptor-associated kinase-1 (IRAK-1) and IRAK-2 by microRNA-146a and NF-kappaB in stressed human astroglial cells and in Alzheimer disease. The Journal of biological chemistry 244 20937840
2007 IRAK-2 participates in multiple toll-like receptor signaling pathways to NFkappaB via activation of TRAF6 ubiquitination. The Journal of biological chemistry 174 17878161
2001 Ras participates in the activation of p38 MAPK by interleukin-1 by associating with IRAK, IRAK2, TRAF6, and TAK-1. The Journal of biological chemistry 98 11744690
2004 The murine IRAK2 gene encodes four alternatively spliced isoforms, two of which are inhibitory. The Journal of biological chemistry 92 15082713
2013 Two phases of inflammatory mediator production defined by the study of IRAK2 and IRAK1 knock-in mice. Journal of immunology (Baltimore, Md. : 1950) 85 23918981
2014 Epigenetic silencing of microRNA-373 to epithelial-mesenchymal transition in non-small cell lung cancer through IRAK2 and LAMP1 axes. Cancer letters 59 25063738
2020 IL-1 induces mitochondrial translocation of IRAK2 to suppress oxidative metabolism in adipocytes. Nature immunology 52 32778760
2022 IRAK2-NF-κB signaling promotes glycolysis-dependent tumor growth in pancreatic cancer. Cellular oncology (Dordrecht, Netherlands) 29 35486320
2017 IRAK2 directs stimulus-dependent nuclear export of inflammatory mRNAs. eLife 29 28990926
2019 miR-497a-5p attenuates lipopolysaccharide-induced inflammatory injury by targeting IRAK2. Journal of cellular physiology 25 31148190
2023 Adipsin inhibits Irak2 mitochondrial translocation and improves fatty acid β-oxidation to alleviate diabetic cardiomyopathy. Military Medical Research 23 38072993
2015 A frequent hypofunctional IRAK2 variant is associated with reduced spontaneous hepatitis C virus clearance. Hepatology (Baltimore, Md.) 22 26250868
2013 Interleukin-1 receptor-associated kinase-2 (IRAK2) is a critical mediator of endoplasmic reticulum (ER) stress signaling. PloS one 22 23724040
2020 miR-205/IRAK2 signaling pathway is associated with urban airborne PM2.5-induced myocardial toxicity. Nanotoxicology 21 32880505
2009 A mutation in Irak2c identifies IRAK-2 as a central component of the TLR regulatory network of wild-derived mice. The Journal of experimental medicine 20 19564352
2018 miR-146a-5p promotes replication of infectious bronchitis virus by targeting IRAK2 and TNFRSF18. Microbial pathogenesis 19 29702211
2018 IRAK2 counterbalances oncogenic Smurf1 in colon cancer cells by dictating ER stress. Cellular signalling 19 29753111
2014 A coding IRAK2 protein variant compromises Toll-like receptor (TLR) signaling and is associated with colorectal cancer survival. The Journal of biological chemistry 19 24973222
2020 lncRNA NEAT1 mediates sepsis progression by regulating Irak2 via sponging miR-370-3p. Biology open 18 32414769
2021 miR-424-5p overexpression inhibits LPS-stimulated inflammatory response in bovine endometrial epithelial cells by targeting IRAK2. Journal of reproductive immunology 15 35032930
2018 Genetic variant of IRAK2 in the toll-like receptor signaling pathway and survival of non-small cell lung cancer. International journal of cancer 15 29978465
2022 Myc-mediated circular RNA circMcph1/miR-370-3p/Irak2 axis is a progressive regulator in hepatic fibrosis. Life sciences 14 36435226
2020 miR-497 induces apoptosis by the IRAK2/NF-κB axis in the canine mammary tumour. Veterinary and comparative oncology 14 32706167
2019 Screening candidate microR-15a- IRAK2 regulatory pairs for predicting the response to Staphylococcus aureus-induced mastitis in dairy cows. The Journal of dairy research 14 31722768
2002 Identification and characterization of murine IRAK-2. Biochemical and biophysical research communications 14 12220507
2021 IRAK2, an IL1R/TLR Immune Mediator, Enhances Radiosensitivity via Modulating Caspase 8/3-Mediated Apoptosis in Oral Squamous Cell Carcinoma. Frontiers in oncology 13 34249686
2011 IRAK-2 regulates IL-1-mediated pathogenic Th17 cell development in helminthic infection. PLoS pathogens 12 21998578
2018 Small Molecule Mimetics of α-Helical Domain of IRAK2 Attenuate the Proinflammatory Effects of IL-33 in Asthma-like Mouse Models. Journal of immunology (Baltimore, Md. : 1950) 11 29728508
2003 Interleukin-1-receptor-associated kinase 2 (IRAK2)-mediated interleukin-1-dependent nuclear factor kappaB transactivation in Saos2 cells requires the Akt/protein kinase B kinase. The Biochemical journal 10 12906710
2008 Insights from vaccinia virus into Toll-like receptor signalling proteins and their regulation by ubiquitin: role of IRAK-2. Biochemical Society transactions 9 18481979
2021 The extreme C-terminus of IRAK2 assures full TRAF6 ubiquitination and optimal TLR signaling. Molecular immunology 8 33799071
2000 IRAK-2 and PI 3-kinase synergistically activate NF-kappaB and AP-1. Inflammation 8 10850853
2023 IRAK2 Downregulation in Triple-Negative Breast Cancer Cells Decreases Cellular Growth In Vitro and Delays Tumour Progression in Murine Models. International journal of molecular sciences 7 36768848
2020 Mild hypothermia improves brain injury in rats with intracerebral hemorrhage by inhibiting IRAK2/NF-κB signaling pathway. Brain and behavior 7 33319491
2019 IRAK2 and TLR10 confer risk of Hashimoto's disease: a genetic association study based on the Han Chinese population. Journal of human genetics 7 31073143
2012 Upregulation of TLR1, TLR2, TLR4, and IRAK-2 Expression During ML-1 Cell Differentiation to Macrophages: Role in the Potentiation of Cellular Responses to LPS and LTA. ISRN oncology 7 22685674
1999 Antisense IRAK-2 oligonucleotide blocks IL-1-stimulated NF-kappaB activation and ICAM-1 expression in cultured endothelial cells. Inflammation 7 10565567
2025 Non-esterified fatty acids disrupt hepatic lipid metabolism and mitochondrial function via TLR4/MyD88/IRAK2 signaling in bovine hepatocytes. The Journal of steroid biochemistry and molecular biology 5 40518053
2017 IRAK2 is associated with susceptibility to rheumatoid arthritis. Clinical rheumatology 5 29129009
2023 IRAK2, an Immune and Radiation-Response Gene, Correlates with Advanced Disease Features but Predicts Higher Post-Irradiation Local Control in Non-Metastatic and Resected Oral Cancer Patients. International journal of molecular sciences 4 37108068
2010 Duplication of the VHL and IRAK2 genes in a patient with mental retardation/multiple congenital anomalies, epilepsy and ectomorphic habitus. Genetic counseling (Geneva, Switzerland) 4 20420027
2000 Effects of antisense IRAK-2 oligonucleotides on PGI2 release induced by IL-1 and TNF. Acta pharmacologica Sinica 4 11360675
2019 IRAK2 is associated with systemic lupus erythematosus risk. Clinical rheumatology 3 31650390
2018 Identification of a Constitutively Active Mutant Mouse IRAK2 by Retroviral Expression Screening. Molecular biotechnology 3 29468521
2025 PD-L1 autoregulation promotes the proliferation, migration and invasion of glioblastoma cells via GP130/JAK2/STAT3/IRAK2/IL6 signaling pathway. Scientific reports 2 41062811
2024 IRAK2 overexpression restrains prostate cancer progression by regulation of TRAF6 ubiquitination. Cellular signalling 2 39549822
2026 IRAK2 ubiquitination mediated by PELI1 regulates airway epithelial function and alleviates pediatric asthma. American journal of respiratory cell and molecular biology 1 40986758
2024 Severe invasive infections linked to IRAK2 immune variants. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 1 39299377
2000 Antisense IRAK-2 oligodeoxynucleotide inhibits interleukin-1-induced nuclear factor-kappa B activation in vitro. Acta pharmacologica Sinica 1 11324458
2026 IRAK2 deficiency causes immune dysregulation through defective Myddosome assembly and enhanced interferon responses. Nature communications 0 42168171

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