Irak4 interleukin-1 receptor-associated kinase 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Irak4provided by MGI
Official Full Name: interleukin-1 receptor-associated kinase 4provided by MGI
Primary source: MGI:MGI:2182474
See related: Ensembl:ENSMUSG00000059883 AllianceGenome:MGI:2182474
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: IRAK-4; NY-REN-64; 8430405M07Rik; 9330209D03Rik
Summary: Enables interleukin-1 receptor binding activity. Acts upstream of or within cytokine-mediated signaling pathway. Predicted to be located in extracellular space. Predicted to be active in cytoplasm; nucleus; and plasma membrane. Is expressed in central nervous system; dorsal aorta; genitourinary system; liver; and retina. Human ortholog(s) of this gene implicated in primary immunodeficiency disease. Orthologous to human IRAK4 (interleukin 1 receptor associated kinase 4). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in large intestine adult (RPKM 7.0), colon adult (RPKM 5.3) and 25 other tissues See more
Orthologs: human all
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Genomic context

Location:: 15 E3; 15 48.55 cM

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	15	NC_000081.7 (94441495..94466198)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	15	NC_000081.6 (94543613..94568317)

Chromosome 15 - NC_000081.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

USP13-mediated IRAK4 deubiquitination disrupts the pathological symptoms of lipopolysaccharides-induced sepsis.
Title: USP13-mediated IRAK4 deubiquitination disrupts the pathological symptoms of lipopolysaccharides-induced sepsis.
Hypothalamic Irak4 is a genetically controlled regulator of hypoglycemia-induced glucagon secretion.
Title: Hypothalamic Irak4 is a genetically controlled regulator of hypoglycemia-induced glucagon secretion.
Eliminating chronic myeloid leukemia stem cells by IRAK1/4 inhibitors.
Title: Eliminating chronic myeloid leukemia stem cells by IRAK1/4 inhibitors.
The kinase IRAK4 promotes endosomal TLR and immune complex signaling in B cells and plasmacytoid dendritic cells.
Title: The kinase IRAK4 promotes endosomal TLR and immune complex signaling in B cells and plasmacytoid dendritic cells.
MyD88 oligomer size functions as a physical threshold to trigger IL1R Myddosome signaling.
Title: MyD88 oligomer size functions as a physical threshold to trigger IL1R Myddosome signaling.
IRAK4 mediates colitis-induced tumorigenesis and chemoresistance in colorectal cancer.
Title: IRAK4 mediates colitis-induced tumorigenesis and chemoresistance in colorectal cancer.
Pharmacological inhibition or siRNA mediated knockdown of IRAK1/4 attenuated Nod1-mediated activation of NF-kappaB, JNK, and the expression of proinflammatory cytokines. These results reveal that Nod1-mediated lipolysis promoted accumulation of DAG, which engaged PKCdelta and IRAK1/4 to augment inflammation in 3T3-L1 adipocytes.
Title: Nod1-mediated lipolysis promotes diacylglycerol accumulation and successive inflammation via PKCδ-IRAK axis in adipocytes.
IRAK4 kinase activity is prerequisite for regulating innate immunity during infections with intracellular bacteria. The loss of IRAK4 kinase activity underlies deficient cytokine and microbicidal responses during infection with intracellular bacteria L. monocytogenes or M. smegmatis via impaired activation of IRAK1, MAPKs, and NF-kappaB but increases bacterial burdens, correlating with decreased induction of NO.
Title: IRAK4 activity controls immune responses to intracellular bacteria Listeria monocytogenes and Mycobacterium smegmatis.
our results indicate that IRAK4 has a critical scaffold function in myddosome formation and that its kinase activity is dispensable for myddosome assembly and activation of the NF-kappaB and MAPK pathways but is essential for MyD88-dependent production of inflammatory cytokines. Our findings suggest that the scaffold function of IRAK4 may be an attractive target for treating inflammatory and autoimmune diseases.
Title: Interleukin-1 receptor-associated kinase 4 (IRAK4) plays a dual role in myddosome formation and Toll-like receptor signaling.
AMPK activation inhibited IL-1beta-stimulated CXCL10 secretion, associated with reduced interleukin-1 receptor associated kinase-4 (IRAK4) phosphorylation.
Title: Activation of AMP-activated protein kinase rapidly suppresses multiple pro-inflammatory pathways in adipocytes including IL-1 receptor-associated kinase-4 phosphorylation.

Submit: New GeneRIF Correction See all GeneRIFs (49)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (7) 1 citation
Chemically induced (ENU) (1)
Endonuclease-mediated (4)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Irak4 (e-PCR), detects polymorphism
- UniSTS:525671

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables interleukin-1 receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables kinase activity	ISO Inferred from Sequence Orthology more info
enables magnesium ion binding	IEA Inferred from Electronic Annotation more info
enables nucleotide binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	IEA Inferred from Electronic Annotation more info
enables protein kinase binding	ISO Inferred from Sequence Orthology more info
enables protein serine/threonine kinase activity	ISO Inferred from Sequence Orthology more info
enables transferase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in JNK cascade	ISO Inferred from Sequence Orthology more info
involved_in Toll signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to lipopolysaccharide	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within cytokine production	IDA Inferred from Direct Assay more info	PubMed
involved_in cytokine-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within cytokine-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in cytokine-mediated signaling pathway	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within immune system process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within innate immune response	IEA Inferred from Electronic Annotation more info
involved_in interleukin-1-mediated signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in interleukin-33-mediated signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in intracellular signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in neutrophil mediated immunity	ISO Inferred from Sequence Orthology more info
involved_in neutrophil migration	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of canonical NF-kappaB signal transduction	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within positive regulation of canonical NF-kappaB signal transduction	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of smooth muscle cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in protein phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cell surface	ISO Inferred from Sequence Orthology more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	ISO Inferred from Sequence Orthology more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: interleukin-1 receptor-associated kinase 4

NP_084202.2

EC 2.7.11.1

XP_011243947.1

EC 2.7.11.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_029926.5 → NP_084202.2 interleukin-1 receptor-associated kinase 4

See identical proteins and their annotated locations for NP_084202.2

Status: VALIDATED

Source sequence(s)

AK028837, AK029028, BC051676, BE635313

Consensus CDS

CCDS27772.1

UniProtKB/Swiss-Prot

Q80WW1, Q8R4K2

UniProtKB/TrEMBL

Q3USX5

Related

ENSMUSP00000074471.4, ENSMUST00000074936.10

Conserved Domains (3) summary

smart00221
Location:193 → 454

STYKc; Protein kinase; unclassified specificity

cd08793
Location:9 → 108

Death_IRAK4; Death domain of Interleukin-1 Receptor-Associated Kinase 4

cd14158
Location:170 → 457

STKc_IRAK4; Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000081.7 Reference GRCm39 C57BL/6J

Range

94441495..94466198

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011245645.3 → XP_011243947.1 interleukin-1 receptor-associated kinase 4 isoform X1

Conserved Domains (2) summary

cd08793
Location:9 → 108

Death_IRAK4; Death domain of Interleukin-1 Receptor-Associated Kinase 4

cl21453
Location:170 → 218

PKc_like; Protein Kinases, catalytic domain