IRAK1 - Interleukin-1 receptor-associated kinase 1 - human protein (Function)
 
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IRAK1 »  Interleukin-1 receptor-associated kinase 1   [ EC 2.7.11.1 ]  (IRAK-1)
 
Gene name:  IRAK1
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 131 4
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. Association with MYD88 leads to IRAK1 phosphorylation by IRAK4 and subsequent autophosphorylation and kinase activation. 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 the interferon regulatory factor 7 (IRF7) to induce its activation and translocation to the nucleus, resulting in transcriptional activation of type I IFN genes, which drive the cell in an antiviral state. When sumoylated, translocates to the nucleus and phosphorylates STAT3.  
8
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Interleukin-1 receptor bindingdefinition[GO:0005149] silver  
  • IEAOrtholog Compara
Kinase activitydefinition[GO:0016301]  
1
  • IDAMGI
NF-kappaB-inducing kinase activitydefinition[GO:0004704]  
1
  • TASPINC
Protein bindingdefinition[GO:0005515]  
13
  • IPIIntAct
  • IPIUniProtKB
  • IPIHGNC
Protein heterodimerization activitydefinition[GO:0046982]  
1
  • IPIBHF-UCL
Protein homodimerization activitydefinition[GO:0042803]  
2
  • NASUniProtKB
  • IPIBHF-UCL
Protein kinase activitydefinition[GO:0004672]  
1
  • IDAMGI
Protein serine/threonine kinase activitydefinition[GO:0004674]  
1
  • NASUniProtKB
GO biological process 
Activation of NF-kappaB-inducing kinase activitydefinition[GO:0007250]  
1
  • IDAUniProtKB
Cellular response to hypoxiadefinition[GO:0071456] silver  
  • IEAOrtholog Compara
Interleukin-1-mediated signaling pathwaydefinition[GO:0070498]  
1
  • IMPBHF-UCL
Lipopolysaccharide-mediated signaling pathwaydefinition[GO:0031663]  
1
  • IMPBHF-UCL
MyD88-dependent toll-like receptor signaling pathwaydefinition[GO:0002755]  
1
  • TASBHF-UCL
Negative regulation of NF-kappaB transcription factor activitydefinition[GO:0032088]  
1
  • IMPBHF-UCL
Positive regulation of NF-kappaB transcription factor activitydefinition[GO:0051092]  
2
  • IDAUniProtKB
  • IDABHF-UCL
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
Positive regulation of transcription, DNA-templateddefinition[GO:0045893]  
1
  • NASUniProtKB
Protein autophosphorylationdefinition[GO:0046777]  
3
  • IDAMGI
  • NASUniProtKB
  • IDABHF-UCL
Protein oligomerizationdefinition[GO:0051259]  
1
  • IMPUniProtKB
Protein phosphorylationdefinition[GO:0006468]  
1
  • TASPINC
Regulation of cytokine-mediated signaling pathwaydefinition[GO:0001959]  
1
  • IMPBHF-UCL
Response to interleukin-1definition[GO:0070555]  
1
  • IMPBHF-UCL
Response to lipopolysaccharidedefinition[GO:0032496]  
1
  • IMPBHF-UCL
Response to peptidoglycandefinition[GO:0032494] silver  
  • IEAOrtholog Compara
Signal transductiondefinition[GO:0007165]  
1
  • NASUniProtKB
Toll-like receptor 2 signaling pathwaydefinition[GO:0034134]  
1
  • IMPBHF-UCL
Transmembrane receptor protein serine/threonine kinase signaling pathwaydefinition[GO:0007178]  
1
  • NASUniProtKB
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
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Apoptosis  hsa04210+3654  
Chagas disease (American trypanosomiasis)  hsa05142+3654  
Leishmaniasis  hsa05140+3654  
Measles  hsa05162+3654  
Neurotrophin signaling pathway  hsa04722+3654  
Pertussis  hsa05133+3654  
Toll-like receptor signaling pathway  hsa04620+3654  
Toxoplasmosis  hsa05145+3654  
Tuberculosis  hsa05152+3654  
According to Reactome, this protein belongs to the following pathways:
Immune System  REACT_6900  
Signal Transduction  REACT_111102  
TRAF6 Mediated Induction of proinflammatory cytokines  REACT_6782  
 

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
GeneWiki: IRAK1
GenomeRNAi: 3654
PRO: PR:P51617
Chemistry
GuidetoPHARMACOLOGY: 2042