Names & Taxonomy
- Uniprot ID:
- Q9NWZ3
- Entry Name:
- IRAK4_HUMAN
- Status:
- reviewed
- Protein Names:
- Interleukin-1 receptor-associated kinase 4 (IRAK-4) (EC 2.7.11.1) (Renal carcinoma antigen NY-REN-64)
- Gene Names:
- IRAK4
- Gene Names Primary:
- IRAK4
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 460
- Sequence:
- MNKPITPSTYVRCLNVGLIRKLSDFIDPQEGWKKLAVAIKKPSGDDRYNQFHIRRFEALLQTGKSPTSELLFDWGTTNCTVGDLVDLLIQNEFFAPASLLLPDAVPKTANTLPSKEAITVQQKQMPFCDKDRTLMTPVQNLEQSYMPPDSSSPENKSLEVSDTRFHSFSFYELKNVTNNFDERPISVGGNKMGEGGFGVVYKGYVNNTTVAVKKLAAMVDITTEELKQQFDQEIKVMAKCQHENLVELLGFSSDGDDLCLVYVYMPNGSLLDRLSCLDGTPPLSWHMRCKIAQGAANGINFLHENHHIHRDIKSANILLDEAFTAKISDFGLARASEKFAQTVMTSRIVGTTAYMAPEALRGEITPKSDIYSFGVVLLEIITGLPAVDEHREPQLLLDIKEEIEDEEKTIEDYIDKKMNDADSTSVEAMYSVASQCLHEKKNKRPDIKKVQQLLQEMTAS
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Cytoplasm
Function
- Function:
- Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens. Involved in Toll-like receptor (TLR) and IL-1R signaling pathways (PubMed:17878374). Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. Phosphorylates E3 ubiquitin ligases Pellino proteins (PELI1, PELI2 and PELI3) to promote pellino-mediated polyubiquitination of IRAK1. Then, the ubiquitin-binding domain of IKBKG/NEMO binds to polyubiquitinated IRAK1 bringing together the IRAK1-MAP3K7/TAK1-TRAF6 complex and the NEMO-IKKA-IKKB complex. In turn, MAP3K7/TAK1 activates IKKs (CHUK/IKKA and IKBKB/IKKB) leading to NF-kappa-B nuclear translocation and activation. Alternatively, phosphorylates TIRAP to promote its ubiquitination and subsequent degradation. Phosphorylates NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections.
- Catalytic Activity:
- ATP + a protein = ADP + a phosphoprotein.
- Cofactor:
- COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
- Kinetics:
- BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=650 uM for ATP (at pH 7.5)
- Active Site:
- ACT_SITE 311 311 Proton acceptor.
- Gene Ontology Go:
- cytoplasm
cytosol
endosome membrane
extracellular space
nucleus
plasma membrane
ATP binding
magnesium ion binding
protein kinase activity
protein serine/threonine kinase activity
cytokine production
cytokine-mediated signaling pathway
innate immune response
intracellular signal transduction
JNK cascade
MyD88-dependent toll-like receptor signaling pathway
neutrophil mediated immunity
neutrophil migration
positive regulation of I-kappaB kinase/NF-kappaB signaling
positive regulation of smooth muscle cell proliferation
toll-like receptor 10 signaling pathway
toll-like receptor 2 signaling pathway
toll-like receptor 4 signaling pathway
toll-like receptor 5 signaling pathway
toll-like receptor 9 signaling pathway
toll-like receptor signaling pathway
toll-like receptor TLR1:TLR2 signaling pathway
toll-like receptor TLR6:TLR2 signaling pathway - Gene Ontology Biological Process:
- cytokine-mediated signaling pathway
cytokine production
innate immune response
intracellular signal transduction
JNK cascade
MyD88-dependent toll-like receptor signaling pathway
neutrophil mediated immunity
neutrophil migration
positive regulation of I-kappaB kinase/NF-kappaB signaling
positive regulation of smooth muscle cell proliferation
toll-like receptor 10 signaling pathway
toll-like receptor 2 signaling pathway
toll-like receptor 4 signaling pathway
toll-like receptor 5 signaling pathway
toll-like receptor 9 signaling pathway
toll-like receptor signaling pathway
toll-like receptor TLR1:TLR2 signaling pathway
toll-like receptor TLR6:TLR2 signaling pathway - Gene Ontology Molecular Function:
- ATP binding
magnesium ion binding
protein kinase activity
protein serine/threonine kinase activity - Gene Ontology Cellular Component:
- cytoplasm
cytosol
endosome membrane
extracellular space
nucleus
plasma membrane - Keywords:
- 3D-structure
ATP-binding
Acetylation
Alternative splicing
Complete proteome
Cytoplasm
Immunity
Innate immunity
Kinase
Magnesium
Nucleotide-binding
Phosphoprotein
Polymorphism
Reference proteome
Serine/threonine-protein kinase
Transferase - Interacts With:
- Q8K4B2; Q9HAT8; P58753
Publication
- PubMed ID:
- 11960013 10508479 14702039 16541075 15489334 12496252 12538665 12925671 15084582 12637671 16286016 16951688 17217339 17337443 16950813 17997719 18691976 18669648 19690332 19608861 20400509 20068231 21269460 21325272 21269878 22814378 17161373 17312103 20485341 17878374 17344846 19663824 21057262 24316379