InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Irak1

Summary

InnateDB Protein

IDBP-251916.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Irak1

Protein Name

interleukin-1 receptor-associated kinase 1

Synonyms

AA408924; Il1rak; IRAK; IRAK-1; IRAK1-S; mPLK; Plpk;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000110000

InnateDB Gene

IDBG-154747 (Irak1)

Protein Structure

UniProt Annotation

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. 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 (By similarity). {ECO:0000250}.

Subcellular Localization

Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. Lipid droplet {ECO:0000269PubMed:21435586}. Note=Translocates to the nucleus when sumoylated (By similarity). RSAD2/viperin recruits it to the lipid droplet. {ECO:0000250}.

Disease Associations

Tissue Specificity

Highly expressed in liver, followed by kidney and skeletal muscle. {ECO:0000269PubMed:8663605}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 51 experimentally validated interaction(s) in this database.
They are also associated with 112 interaction(s) predicted by orthology.

Experimentally validated
Total	51 [view]
Protein-Protein	49 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	112 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005149	interleukin-1 receptor binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups

Biological Process

GO:0006468	protein phosphorylation
GO:0007165	signal transduction
GO:0019221	cytokine-mediated signaling pathway
GO:0031663	lipopolysaccharide-mediated signaling pathway
GO:0032494	response to peptidoglycan
GO:0032496	response to lipopolysaccharide
GO:0034134	toll-like receptor 2 signaling pathway
GO:0034142	toll-like receptor 4 signaling pathway
GO:0043406	positive regulation of MAP kinase activity
GO:0043507	positive regulation of JUN kinase activity
GO:0045087	innate immune response (InnateDB)
GO:0045892	negative regulation of transcription, DNA-templated
GO:0046777	protein autophosphorylation
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0070498	interleukin-1-mediated signaling pathway
GO:0090370	negative regulation of cholesterol efflux

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005811	lipid particle
GO:0016020	membrane

Protein Structure and Domains

PDB ID

MGI:107420

InterPro

IPR000488 Death domain
IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine- /dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR011029 Death-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00531
PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00005
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt