IRAK1

Gene Information

Official Symbol: IRAK1
Official Name: interleukin 1 receptor associated kinase 1
Aliases and Previous Symbols: N/A
Entrez ID: 3654
UniProt: P51617
Interactions: BioGRID
PubMed articles: Open PubMed
OMIM: Open OMIM

Function Summary

Entrez Summary: This gene encodes the interleukin-1 receptor-associated kinase 1, one of two putative serine/threonine kinases that become associated with the interleukin-1 receptor (IL1R) upon stimulation. This gene is partially responsible for IL1-induced upregulation of the transcription factor NF-kappa B. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008].
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. 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. {ECO:0000269|PubMed:11397809, ECO:0000269|PubMed:12860405, ECO:0000269|PubMed:14684752, ECO:0000269|PubMed:15084582, ECO:0000269|PubMed:15465816, ECO:0000269|PubMed:15767370, ECO:0000269|PubMed:17997719, ECO:0000269|PubMed:20400509}.

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: 0/694

Tissue	Fraction Of Cell Lines Where Essential
1290807.0	0/1
909776.0	0/1
bile duct	0/28
blood	0/26
bone	0/26
breast	0/30
central nervous system	0/49
cervix	0/4
colorectal	0/17
esophagus	0/11
fibroblast	0/1
gastric	0/14
kidney	0/18
liver	0/19
lung	0/72
lymphocyte	0/16
ovary	0/25
pancreas	0/22
peripheral nervous system	0/15
plasma cell	0/12
prostate	0/1
skin	0/20
soft tissue	0/9
thyroid	0/2
upper aerodigestive	0/22
urinary tract	0/28
uterus	0/5

Essentiality in NALM6

Essentiality Rank: 9303
Expression level (log2 read counts): 7.29

Expression Distribution

Screen	Score
LLY-283 2.6μM R06 exp290	-1.85
Pifithrin-alpha 20μM R07 exp390	-1.78
Ribavirin 10μM R01 exp52	-1.71
UM0125461 0.74μM R02 exp84	1.92

Pkinase Tyr
Death
Pkinase

interleukin-1 receptor complex
NF-kappaB-inducing kinase activity
toll-like receptor 2 signaling pathway
positive regulation of leukocyte adhesion to vascular endothelial cell
toll-like receptor 9 signaling pathway
activation of NF-kappaB-inducing kinase activity
regulation of leukocyte adhesion to vascular endothelial cell
toll-like receptor 4 signaling pathway
nucleotide-binding oligomerization domain containing signaling pathway
nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
MyD88-dependent toll-like receptor signaling pathway
lipopolysaccharide-mediated signaling pathway
cytoplasmic pattern recognition receptor signaling pathway
heat shock protein binding
cellular response to type I interferon
type I interferon signaling pathway
cellular response to heat
response to type I interferon
positive regulation of NIK/NF-kappaB signaling
positive regulation of type I interferon production
kinase activity
NIK/NF-kappaB signaling
JNK cascade
lipid droplet
negative regulation of NF-kappaB transcription factor activity
positive regulation of smooth muscle cell proliferation
interleukin-1-mediated signaling pathway
toll-like receptor signaling pathway
stress-activated MAPK cascade
regulation of NIK/NF-kappaB signaling
response to heat
regulation of type I interferon production
pattern recognition receptor signaling pathway
regulation of smooth muscle cell proliferation
stress-activated protein kinase signaling cascade
positive regulation of NF-kappaB transcription factor activity
activation of MAPK activity
negative regulation of DNA-binding transcription factor activity
regulation of cytokine-mediated signaling pathway
intracellular receptor signaling pathway