IRAK4

Gene Information

Official Symbol: IRAK4
Official Name: interleukin 1 receptor associated kinase 4
Aliases and Previous Symbols: N/A
Entrez ID: 51135
UniProt: Q9NWZ3
Interactions: BioGRID
PubMed articles: Open PubMed
OMIM: Open OMIM

Function Summary

Entrez Summary: This gene encodes a kinase that activates NF-kappaB in both the Toll-like receptor (TLR) and T-cell receptor (TCR) signaling pathways. The protein is essential for most innate immune responses. Mutations in this gene result in IRAK4 deficiency and recurrent invasive pneumococcal disease. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011].
UniProt Summary: 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. {ECO:0000269|PubMed:11960013, ECO:0000269|PubMed:12538665, ECO:0000269|PubMed:15084582, ECO:0000269|PubMed:17217339, ECO:0000269|PubMed:17337443, ECO:0000269|PubMed:17878374, ECO:0000269|PubMed:17997719, ECO:0000269|PubMed:20400509, ECO:0000269|PubMed:24316379}.

Pfam Domains GO Terms

CRISPR Data

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Global Fraction of Cell Lines Where Essential: 0/739

Tissue	Fraction Of Cell Lines Where Essential
1290807.0	0/1
909776.0	0/1
bile duct	0/28
blood	0/28
bone	0/26
breast	0/33
central nervous system	0/56
cervix	0/4
colorectal	0/17
esophagus	0/13
fibroblast	0/1
gastric	0/16
kidney	0/21
liver	0/20
lung	0/75
lymphocyte	0/16
ovary	0/26
pancreas	0/24
peripheral nervous system	0/16
plasma cell	0/15
prostate	0/1
skin	0/24
soft tissue	0/9
thyroid	0/2
upper aerodigestive	0/22
urinary tract	0/29
uterus	0/5

Essentiality in NALM6

Essentiality Rank: 17890
Expression level (log2 read counts): 5.86

Expression Distribution

Pkinase Tyr
Pkinase

interleukin-1 receptor binding
toll-like receptor 9 signaling pathway
MyD88-dependent toll-like receptor signaling pathway
JNK cascade
positive regulation of smooth muscle cell proliferation
neutrophil migration
interleukin-1-mediated signaling pathway
toll-like receptor signaling pathway
granulocyte migration
stress-activated MAPK cascade
pattern recognition receptor signaling pathway
myeloid leukocyte migration
regulation of smooth muscle cell proliferation
stress-activated protein kinase signaling cascade
cytokine production
positive regulation of NF-kappaB transcription factor activity
cellular response to interleukin-1
positive regulation of I-kappaB kinase/NF-kappaB signaling
response to interleukin-1
endosome membrane
magnesium ion binding
innate immune response-activating signal transduction
regulation of I-kappaB kinase/NF-kappaB signaling
protein kinase activity
activation of innate immune response
positive regulation of DNA-binding transcription factor activity
positive regulation of innate immune response
positive regulation of response to biotic stimulus
protein serine/threonine kinase activity
MAPK cascade
leukocyte migration
signal transduction by protein phosphorylation
regulation of DNA-binding transcription factor activity
regulation of innate immune response
positive regulation of defense response
neutrophil mediated immunity
positive regulation of multi-organism process
myeloid leukocyte mediated immunity
regulation of response to biotic stimulus
immune response-activating signal transduction