Linked Life Data

Q9NWZ3

Source:http://identifiers.org/uniprot/Q9NWZ3

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
biopax3:comment
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. 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: Magnesium. BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=650 uM for ATP (at pH 7.5); KM=1100 uM for substrate (at pH 7.5); SUBUNIT: Associates with MYD88 and IRAK2 to form a ternary complex called the Myddosome. Once phosphorylated, IRAK4 dissociates from the receptor complex and then associates with the TNF receptor- associated factor 6 (TRAF6), IRAK1, and PELI1; this intermediate complex is required for subsequent NF-kappa-B activation. Interacts with IL1RL1. SUBCELLULAR LOCATION: Cytoplasm. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q9NWZ3-1; Sequence=Displayed; Name=2; IsoId=Q9NWZ3-2; Sequence=VSP_041556; PTM: Phosphorylated (By similarity). DISEASE: Defects in IRAK4 are the cause of recurrent isolated invasive pneumococcal disease type 1 (IPD1) [MIM:610799]. Recurrent invasive pneumococcal disease (IPD) is defined as two episodes of IPD occurring at least 1 month apart, whether caused by the same or different serotypes or strains. Recurrent IPD occurs in at least 2% of patients in most series, making IPD the most important known risk factor for subsequent IPD. DISEASE: Defects in IRAK4 are the cause of IRAK4 deficiency (IRAK4D) [MIM:607676]. IRAK4 deficiency causes extracellular pyogenic bacterial and fungal infections in otherwise healthy children. SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Pelle subfamily. SIMILARITY: Contains 1 death domain. SIMILARITY: Contains 1 protein kinase domain. WEB RESOURCE: Name=IRAK4base; Note=IRAK4 mutation db; URL="http://bioinf.uta.fi/IRAK4base/"; WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/irak4/"; GENE SYNONYMS:IRAK4. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License., SEQUENCE 460 AA; 51530 MW; 6C8156ADF25FF81E CRC64;
biopax3:xref
biopax3:displayName
IRAK4_HUMAN
biopax3:name
2.7.11.1, IRAK-4, IRAK4, Renal carcinoma antigen NY-REN-64
biopax3:entityFeature
biopax3:organism
biopax3:sequence
MNKPITPSTYVRCLNVGLIRKLSDFIDPQEGWKKLAVAIKKPSGDDRYNQFHIRRFEALLQTGKSPTSELLFDWGTTNCTVGDLVDLLIQNEFFAPASLLLPDAVPKTANTLPSKEAITVQQKQMPFCDKDRTLMTPVQNLEQSYMPPDSSSPENKSLEVSDTRFHSFSFYELKNVTNNFDERPISVGGNKMGEGGFGVVYKGYVNNTTVAVKKLAAMVDITTEELKQQFDQEIKVMAKCQHENLVELLGFSSDGDDLCLVYVYMPNGSLLDRLSCLDGTPPLSWHMRCKIAQGAANGINFLHENHHIHRDIKSANILLDEAFTAKISDFGLARASEKFAQTVMTSRIVGTTAYMAPEALRGEITPKSDIYSFGVVLLEIITGLPAVDEHREPQLLLDIKEEIEDEEKTIEDYIDKKMNDADSTSVEAMYSVASQCLHEKKNKRPDIKKVQQLLQEMTAS
biopax3:standardName
Interleukin-1 receptor-associated kinase 4