InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: IRAK1

Summary

InnateDB Protein

IDBP-243103.7

Last Modified

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

Gene Symbol

IRAK1

Protein Name

interleukin-1 receptor-associated kinase 1

Synonyms

IRAK; pelle;

Species

Homo sapiens

Ensembl Protein

ENSP00000377291

InnateDB Gene

IDBG-90782 (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. {ECO:0000269PubMed:11397809, ECO:0000269PubMed:12860405, ECO:0000269PubMed:14684752, ECO:0000269PubMed:15084582, ECO:0000269PubMed:15465816, ECO:0000269PubMed:15767370, ECO:0000269PubMed:17997719, ECO:0000269PubMed:20400509}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:16690127}. Nucleus {ECO:0000269PubMed:16690127}. Lipid droplet {ECO:0000250}. Note=Translocates to the nucleus when sumoylated. RSAD2/viperin recruits it to the lipid droplet (By similarity). {ECO:0000250}.

Disease Associations

Tissue Specificity

Isoform 1 and isoform 2 are ubiquitously expressed in all tissues examined, with isoform 1 being more strongly expressed than isoform 2. {ECO:0000269PubMed:11397809}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 196 experimentally validated interaction(s) in this database.
They are also associated with 33 interaction(s) predicted by orthology.

Experimentally validated
Total	196 [view]
Protein-Protein	190 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	2 [view]
DNA-RNA	0

Predicted by orthology
Total	33 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004704	NF-kappaB-inducing kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0004842	ubiquitin-protein transferase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016301	kinase activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0042803	protein homodimerization activity
GO:0046982	protein heterodimerization activity

Biological Process

GO:0000187	activation of MAPK activity
GO:0001959	regulation of cytokine-mediated signaling pathway
GO:0002224	toll-like receptor signaling pathway
GO:0002755	MyD88-dependent toll-like receptor signaling pathway
GO:0002756	MyD88-independent toll-like receptor signaling pathway
GO:0006468	protein phosphorylation
GO:0007165	signal transduction
GO:0007178	transmembrane receptor protein serine/threonine kinase signaling pathway
GO:0007250	activation of NF-kappaB-inducing kinase activity
GO:0007254	JNK cascade
GO:0016567	protein ubiquitination
GO:0031663	lipopolysaccharide-mediated signaling pathway
GO:0032088	negative regulation of NF-kappaB transcription factor activity
GO:0032496	response to lipopolysaccharide
GO:0034134	toll-like receptor 2 signaling pathway
GO:0034138	toll-like receptor 3 signaling pathway
GO:0034142	toll-like receptor 4 signaling pathway
GO:0034146	toll-like receptor 5 signaling pathway
GO:0034162	toll-like receptor 9 signaling pathway
GO:0034166	toll-like receptor 10 signaling pathway
GO:0035666	TRIF-dependent toll-like receptor signaling pathway
GO:0035872	nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
GO:0038123	toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124	toll-like receptor TLR6:TLR2 signaling pathway
GO:0043066	negative regulation of apoptotic process
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0045087	innate immune response (InnateDB)
GO:0045893	positive regulation of transcription, DNA-templated
GO:0046777	protein autophosphorylation
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0051259	protein oligomerization
GO:0051403	stress-activated MAPK cascade
GO:0070423	nucleotide-binding oligomerization domain containing signaling pathway
GO:0070498	interleukin-1-mediated signaling pathway
GO:0070555	response to interleukin-1

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005811	lipid particle
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0010008	endosome membrane
GO:0045323	interleukin-1 receptor complex

Protein Structure and Domains

PDB ID

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