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This gene encodes a member of the interleukin-1 receptor-associated kinase protein family. Members of this family are essential components of the Toll/IL-R immune signal transduction pathways. This protein is primarily expressed in monocytes and macrophages and functions as a negative regulator of Toll-like receptor signaling. Mutations in this gene are associated with a susceptibility to asthma. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]
IRAK3 (Interleukin 1 Receptor Associated Kinase 3) is a Protein Coding gene. Diseases associated with IRAK3 include Asthma-Related Traits 5 and Asthma. Among its related pathways are IL-1 signaling pathway and Diseases associated with the TLR signaling cascade. Gene Ontology (GO) annotations related to this gene include protein homodimerization activity and protein kinase activity. An important paralog of this gene is IRAK1.
The IRAKs (Interleukin-1 receptor-associated kinases) are serine-threonine kinases, EC 2.7.11.1, that are essential regulators of IL-1R and TLR-mediated signaling. Four IRAK isoforms have been identified to date, IRAK1, IRAK2, IRAK3 (IRAK-M) and IRAK4.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0000287 | magnesium ion binding | IDA | 10383454 |
GO:0004672 | protein kinase activity | IEA | -- |
GO:0004674 | protein serine/threonine kinase activity | IEA,IDA | 10383454 |
GO:0005515 | protein binding | IPI | 32296183 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005634 | nucleus | IBA,IDA | 17379480 |
GO:0005737 | cytoplasm | IBA,IDA | 17379480 |
GO:0005886 | plasma membrane | IBA | 21873635 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Activated TLR4 signalling | ||
2 | Toll Comparative Pathway |
TLR-TRIF Pathway
.61
Toll Comparative Pathway
.61
|
IL-1 Pathway
.39
iNOS Signaling
.34
|
3 | TRAF Pathway |
TRAF Pathway
.42
Toll-Like Receptors Pathway
.41
|
14-3-3 Induced Apoptosis
.33
|
4 | IL-1 signaling pathway | ||
5 | NF-KappaB Family Pathway |
NF-KappaB (p50-p65) Pathway
.72
|
NF-KappaB Family Pathway
.72
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0001960 | negative regulation of cytokine-mediated signaling pathway | IC | 12150927 |
GO:0002755 | MyD88-dependent toll-like receptor signaling pathway | TAS | 10383454 |
GO:0006468 | protein phosphorylation | IDA | 10383454 |
GO:0007165 | signal transduction | IEA | -- |
GO:0009615 | response to virus | IC | 12150927 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
58-64-0 |
|
Compound | Action | Cas Number |
---|---|---|
IRAK inhibitor 2 | 928333-30-6 | |
IRAK inhibitor 3 | 1012343-93-9 | |
IRAK inhibitor 4 | IRAK inhibitor | 1012104-68-5 |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | IRAK3 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | IRAK3 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | IRAK3 30 |
|
||
IRAKM 31 |
|
OneToOne | |||
Rat (Rattus norvegicus) |
Mammalia | Irak3 30 |
|
||
Mouse (Mus musculus) |
Mammalia | Irak3 30 17 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | IRAK3 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | IRAK3 31 |
|
OneToOne | |
Zebrafish (Danio rerio) |
Actinopterygii | irak3 30 31 |
|
OneToOne | |
Fruit Fly (Drosophila melanogaster) |
Insecta | pll 31 |
|
OneToMany | |
Worm (Caenorhabditis elegans) |
Secernentea | pik-1 31 |
|
OneToMany | |
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
OneToMany |
SNP ID | Clinical significance and condition | Chr 12 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
rs121912630 | Risk Factor: Asthma-related traits, susceptibility to, 5 | 66,203,804(+) |
G/A NM_007199.3(IRAK3):c.227G>A (p.Trp76Ter) |
NONSENSE,INTRON | |
rs138190862 | Benign: not provided | 66,211,477(+) |
A/G NM_007199.3(IRAK3):c.468A>G (p.Gln156=) |
SYNONYMOUS | |
rs149356099 | Likely Benign: not provided | 66,245,004(+) |
C/T NM_007199.3(IRAK3):c.1143C>T (p.Ile381=) |
SYNONYMOUS | |
rs150116809 | Risk Factor: Asthma-related traits, susceptibility to, 5 | 66,209,521(+) |
G/T NM_007199.3(IRAK3):c.381+1G>T |
SPLICE_DONOR | |
rs1555201779 | Uncertain Significance: not provided | 66,189,393(+) |
C/A NM_007199.3(IRAK3):c.94C>A (p.Leu32Met) |
MISSENSE |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
esv29230 | CNV | loss | 19812545 |
esv3629799 | CNV | loss | 21293372 |
esv3892211 | CNV | loss | 25118596 |
esv7862 | CNV | gain | 19470904 |
nsv976637 | CNV | duplication | 23825009 |
Disorder | Aliases | PubMed IDs |
---|---|---|
asthma-related traits 5 |
|
|
asthma |
|
|
dermatitis |
|
|
melioidosis |
|
|
lung mucoepidermoid carcinoma |
|
|