IRAK4 - Interleukin-1 receptor-associated kinase 4 - human protein (Function)
 
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IRAK4 »  Interleukin-1 receptor-associated kinase 4   [ EC 2.7.11.1 ]  (IRAK-4)
 
Protein also known as:  Renal carcinoma antigen NY-REN-64.
Gene name:  IRAK4
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

 show evidences
Overview 
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.  
7
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Interleukin-1 receptor bindingdefinition[GO:0005149] silver  
  • IEAOrtholog Compara
Magnesium ion bindingdefinition[GO:0000287] silver  
  • IEAInterPro 2 GO
Protein bindingdefinition[GO:0005515]  
3
  • IPIIntAct
GO biological process 
Cytokine productiondefinition[GO:0001816] silver  
  • IEAOrtholog Compara
Cytokine-mediated signaling pathwaydefinition[GO:0019221] silver  
  • IEAOrtholog Compara
Innate immune responsedefinition[GO:0045087]  
1
  • TASUniProtKB
JNK cascadedefinition[GO:0007254] silver  
  • IEAOrtholog Compara
MyD88-dependent toll-like receptor signaling pathwaydefinition[GO:0002755]  
1
  • TASUniProtKB
Positive regulation of I-kappaB kinase/NF-kappaB signalingdefinition[GO:0043123]  
1
  • IMPMGI
Positive regulation of smooth muscle cell proliferationdefinition[GO:0048661] silver  
  • IEAOrtholog Compara
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944] silver  
  • IEAOrtholog Compara
Protein phosphorylationdefinition[GO:0006468] silver  
  • IEAInterPro 2 GO
Toll-like receptor signaling pathwaydefinition[GO:0002224]  
1
  • TASUniProtKB
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.1: ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
It requires the following cofactor
Magnesium.  
  • CuratedUniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathways:
Apoptosis  hsa04210+51135  
Chagas disease (American trypanosomiasis)  hsa05142+51135  
Influenza A  hsa05164+51135  
Leishmaniasis  hsa05140+51135  
Measles  hsa05162+51135  
Neurotrophin signaling pathway  hsa04722+51135  
Pertussis  hsa05133+51135  
Toll-like receptor signaling pathway  hsa04620+51135  
Toxoplasmosis  hsa05145+51135  
Tuberculosis  hsa05152+51135  
According to Reactome, this protein belongs to the following pathways:
Interleukin-1 signaling  REACT_22442  
MyD88 cascade initiated on plasma membrane  REACT_27215  
MyD88 dependent cascade initiated on endosome  REACT_25222  
MyD88:Mal cascade initiated on plasma membrane  REACT_6788  
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation  REACT_25024  
TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling  REACT_25120  
 

Biophysicochemical properties

Kinetic parameters
KM 1100 uM for substrate (at pH 7.5)
KM 650 uM for ATP (at pH 7.5)

Keywords

Biological process 
Immunity  definition   [KW-0391]
Innate immunity  definition   [KW-0399]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GenomeRNAi: 51135
PRO: PR:Q9NWZ3
Chemistry
GuidetoPHARMACOLOGY: 2045