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Aliases for IRAK4 Gene

Aliases for IRAK4 Gene

  • Interleukin-1 Receptor-Associated Kinase 4 2 3
  • Renal Carcinoma Antigen NY-REN-64 3 4
  • EC 2.7.11.1 4 64
  • IRAK-4 3 4
  • REN64 3 6
  • IPD1 3 6
  • NY-REN-64 3
  • EC 2.7.11 64

External Ids for IRAK4 Gene

Summaries for IRAK4 Gene

Entrez Gene Summary for IRAK4 Gene

  • This gene encodes a kinase that activates NF-kappaB in both the Toll-like receptor (TLR) and T-cell receptor (TCR) signaling pathways. The protein is essential for most innate immune responses. Mutations in this gene result in IRAK4 deficiency and recurrent invasive pneumococcal disease. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

GeneCards Summary for IRAK4 Gene

IRAK4 (Interleukin-1 Receptor-Associated Kinase 4) is a Protein Coding gene. Diseases associated with IRAK4 include irak4 deficiency and pneumococcal meningitis. Among its related pathways are NF-KappaB Family Pathway and NF-KappaB Family Pathway. GO annotations related to this gene include protein serine/threonine kinase activity and interleukin-1 receptor binding. An important paralog of this gene is IRAK1.

UniProtKB/Swiss-Prot for IRAK4 Gene

  • 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 (PubMed:17878374). Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. 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 NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections.

No data available for Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for IRAK4 Gene

Genomics for IRAK4 Gene

Genomic Location for IRAK4 Gene

Start:
43,758,944 bp from pter
End:
43,789,543 bp from pter
Size:
30,600 bases
Orientation:
Plus strand

Genomic View for IRAK4 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for IRAK4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for IRAK4 Gene

Regulatory Elements for IRAK4 Gene

Proteins for IRAK4 Gene

  • Protein details for IRAK4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NWZ3-IRAK4_HUMAN
    Recommended name:
    Interleukin-1 receptor-associated kinase 4
    Protein Accession:
    Q9NWZ3
    Secondary Accessions:
    • Q69FE1
    • Q8TDF7
    • Q9Y589

    Protein attributes for IRAK4 Gene

    Size:
    460 amino acids
    Molecular mass:
    51530 Da
    Cofactor:
    Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
    Quaternary structure:
    • Associates with MYD88 and IRAK2 to form a ternary complex called the Myddosome. Once phosphorylated, IRAK4 dissociates from the receptor complex and then associates with the TNF receptor-associated factor 6 (TRAF6), IRAK1, and PELI1; this intermediate complex is required for subsequent NF-kappa-B activation. Direct binding of SMAD6 to PELI1 prevents complex formation and hence negatively regulates IL1R-TLR signaling and eventually NF-kappa-B-mediated gene expression. Interacts with IL1RL1.

    Three dimensional structures from OCA and Proteopedia for IRAK4 Gene

    Alternative splice isoforms for IRAK4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for IRAK4 Gene

Proteomics data for IRAK4 Gene at MOPED

Selected DME Specific Peptides for IRAK4 Gene

Post-translational modifications for IRAK4 Gene

Domains for IRAK4 Gene

Protein Domains for IRAK4 Gene

UniProtKB/Swiss-Prot:

IRAK4_HUMAN
Domain:
  • Contains 1 death domain.:
    • Q9NWZ3
  • Contains 1 protein kinase domain.:
    • Q9NWZ3
Family:
  • Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Pelle subfamily.:
    • Q9NWZ3
genes like me logo Genes that share domains with IRAK4: view

Function for IRAK4 Gene

Molecular function for IRAK4 Gene

UniProtKB/Swiss-Prot BiophysicochemicalProperties: Kinetic parameters: KM=650 uM for ATP (at pH 7.5) {ECO:0000269 PubMed:17312103}; KM=1100 uM for substrate (at pH 7.5) {ECO:0000269 PubMed:17312103};
UniProtKB/Swiss-Prot CatalyticActivity: ATP + a protein = ADP + a phosphoprotein
UniProtKB/Swiss-Prot 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 (PubMed:17878374). Is rapidly recruited by MYD88 to the receptor-signaling complex upon TLR activation to form the Myddosome together with IRAK2. Phosphorylates initially IRAK1, thus stimulating the kinase activity and intensive autophosphorylation of IRAK1. 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 NCF1 and regulates NADPH oxidase activation after LPS stimulation suggesting a similar mechanism during microbial infections.

Enzyme Numbers (IUBMB) for IRAK4 Gene

Gene Ontology (GO) - Molecular Function for IRAK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000287 magnesium ion binding IEA --
GO:0004672 protein kinase activity EXP --
GO:0004674 protein serine/threonine kinase activity TAS --
GO:0004713 protein tyrosine kinase activity --
GO:0005149 interleukin-1 receptor binding IEA --
genes like me logo Genes that share ontologies with IRAK4: view
genes like me logo Genes that share phenotypes with IRAK4: view

Animal Models for IRAK4 Gene

MGI Knock Outs for IRAK4:

miRNA for IRAK4 Gene

miRTarBase miRNAs that target IRAK4

No data available for Transcription Factor Targeting and HOMER Transcription for IRAK4 Gene

Localization for IRAK4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for IRAK4 Gene

Cytoplasm.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for IRAK4 Gene COMPARTMENTS Subcellular localization image for IRAK4 gene
Compartment Confidence
cytosol 4
endosome 4
plasma membrane 4
cytoskeleton 3
nucleus 3
mitochondrion 2

Gene Ontology (GO) - Cellular Components for IRAK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005615 extracellular space IEA --
GO:0005634 nucleus IBA --
GO:0005737 cytoplasm IBA --
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane TAS --
genes like me logo Genes that share ontologies with IRAK4: view

Pathways for IRAK4 Gene

genes like me logo Genes that share pathways with IRAK4: view

Gene Ontology (GO) - Biological Process for IRAK4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001816 cytokine production IEA --
GO:0002224 toll-like receptor signaling pathway TAS 21269878
GO:0002446 neutrophil mediated immunity IMP 19663824
GO:0002755 MyD88-dependent toll-like receptor signaling pathway TAS 21269878
GO:0006468 protein phosphorylation IEA --
genes like me logo Genes that share ontologies with IRAK4: view

Compounds for IRAK4 Gene

(3) HMDB Compounds for IRAK4 Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
ADP
  • adenosindiphosphorsaeure
58-64-0
Magnesium
  • Magnesium
7439-95-4

(1) Drugbank Compounds for IRAK4 Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
1-(3-HYDROXYPROPYL)-2-[(3-NITROBENZOYL)AMINO]-1H-BENZIMIDAZOL-5-YL PIVALATE
target

(3) Novoseek inferred chemical compound relationships for IRAK4 Gene

Compound -log(P) Hits PubMed IDs
threonine 29.3 3
serine 6.26 3
oxygen 0 1
genes like me logo Genes that share compounds with IRAK4: view

Transcripts for IRAK4 Gene

Unigene Clusters for IRAK4 Gene

Interleukin-1 receptor-associated kinase 4:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for IRAK4 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6a · 6b ^ 7a · 7b · 7c ^ 8a · 8b · 8c ^ 9a · 9b ^ 10 ^ 11a · 11b ^ 12 ^ 13 ^ 14
SP1: - -
SP2: - -
SP3: - - -
SP4: - - - -
SP5: -
SP6:
SP7: - - - -
SP8: - -
SP9:

Relevant External Links for IRAK4 Gene

GeneLoc Exon Structure for
IRAK4
ECgene alternative splicing isoforms for
IRAK4

Expression for IRAK4 Gene

mRNA expression in normal human tissues for IRAK4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for IRAK4 Gene

This gene is overexpressed in Whole Blood (5.8).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for IRAK4 Gene

SOURCE GeneReport for Unigene cluster for IRAK4 Gene Hs.138499

genes like me logo Genes that share expressions with IRAK4: view

Orthologs for IRAK4 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for IRAK4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia IRAK4 36
  • 99.57 (n)
  • 99.13 (a)
IRAK4 37
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia IRAK4 36
  • 92.25 (n)
  • 90.22 (a)
IRAK4 37
  • 90 (a)
OneToOne
dog
(Canis familiaris)
Mammalia IRAK4 36
  • 92.46 (n)
  • 92.83 (a)
IRAK4 37
  • 93 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Irak4 36
  • 79.23 (n)
  • 83.88 (a)
Irak4 16
Irak4 37
  • 84 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia IRAK4 37
  • 79 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 37
  • 80 (a)
OneToMany
-- 37
  • 75 (a)
OneToMany
rat
(Rattus norvegicus)
Mammalia Irak4 36
  • 80.54 (n)
  • 84.53 (a)
chicken
(Gallus gallus)
Aves IRAK4 36
  • 69.33 (n)
  • 67.09 (a)
IRAK4 37
  • 68 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia IRAK4 37
  • 62 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia irak4 36
  • 66.52 (n)
  • 63.09 (a)
zebrafish
(Danio rerio)
Actinopterygii -- 36
irak4 36
  • 52.25 (n)
  • 48.35 (a)
irak4 37
  • 45 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta pll 37
  • 24 (a)
OneToMany
pll 38
  • 28 (a)
worm
(Caenorhabditis elegans)
Secernentea pik-1 37
  • 26 (a)
OneToMany
pik-1 38
  • 35 (a)
thale cress
(Arabidopsis thaliana)
eudicotyledons APK2A 36
  • 52.85 (n)
  • 45.05 (a)
rice
(Oryza sativa)
Liliopsida Os10g0405100 36
  • 47.52 (n)
  • 39.07 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 37
  • 27 (a)
OneToOne
Species with no ortholog for IRAK4:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for IRAK4 Gene

ENSEMBL:
Gene Tree for IRAK4 (if available)
TreeFam:
Gene Tree for IRAK4 (if available)

Paralogs for IRAK4 Gene

Paralogs for IRAK4 Gene

genes like me logo Genes that share paralogs with IRAK4: view

Variants for IRAK4 Gene

Sequence variations from dbSNP and Humsavar for IRAK4 Gene

SNP ID Clin Chr 12 pos Sequence Context AA Info Type MAF
rs9849 -- 43,789,148(-) CATGA(A/G)ATTTG utr-variant-3-prime
rs1141168 -- 43,788,903(+) caaga(A/G)tgttt utr-variant-3-prime
rs1461567 -- 43,770,886(-) CATGA(C/T)GACAT intron-variant
rs1838341 -- 43,767,070(-) ACATT(C/G)TAAAA intron-variant
rs2407660 -- 43,761,865(+) TCTGA(A/G)TTGTC intron-variant, upstream-variant-2KB

Structural Variations from Database of Genomic Variants (DGV) for IRAK4 Gene

Variant ID Type Subtype PubMed ID
dgv285e199 CNV Deletion 23128226

Relevant External Links for IRAK4 Gene

HapMap Linkage Disequilibrium report
IRAK4
Human Gene Mutation Database (HGMD)
IRAK4
Locus Specific Mutation Databases (LSDB)
IRAK4

Disorders for IRAK4 Gene

(2) OMIM Diseases for IRAK4 Gene (606883)

UniProtKB/Swiss-Prot

IRAK4_HUMAN
  • Recurrent isolated invasive pneumococcal disease 1 (IPD1) [MIM:610799]: Recurrent invasive pneumococcal disease (IPD) is defined as two episodes of IPD occurring at least 1 month apart, whether caused by the same or different serotypes or strains. Recurrent IPD occurs in at least 2% of patients in most series, making IPD the most important known risk factor for subsequent IPD. {ECO:0000269 PubMed:16950813}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • IRAK4 deficiency (IRAK4D) [MIM:607676]: Causes extracellular pyogenic bacterial and fungal infections in otherwise healthy children. {ECO:0000269 PubMed:12637671, ECO:0000269 PubMed:12925671, ECO:0000269 PubMed:17878374, ECO:0000269 PubMed:19663824, ECO:0000269 PubMed:21057262, ECO:0000269 PubMed:24316379}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(9) Novoseek inferred disease relationships for IRAK4 Gene

Disease -log(P) Hits PubMed IDs
bacterial infections 63 12
ectodermal dysplasia, hypohidrotic 55.5 1
immunodeficiency 41.2 8
septicemia 33.7 1
meningitis 26.7 3

Relevant External Links for IRAK4

Genetic Association Database (GAD)
IRAK4
Human Genome Epidemiology (HuGE) Navigator
IRAK4
genes like me logo Genes that share disorders with IRAK4: view

Publications for IRAK4 Gene

  1. Distinct mutations in IRAK-4 confer hyporesponsiveness to lipopolysaccharide and interleukin-1 in a patient with recurrent bacterial infections. (PMID: 12925671) Medvedev A.E. … Vogel S.N. (J. Exp. Med. 2003) 3 4 23 49
  2. IRAK4: a novel member of the IRAK family with the properties of an IRAK-kinase. (PMID: 11960013) Li S. … Wesche H. (Proc. Natl. Acad. Sci. U.S.A. 2002) 3 4 23
  3. Pellino 1 is required for interleukin-1 (IL-1)-mediated signaling through its interaction with the IL-1 receptor-associated kinase 4 (IRAK4)-IRAK-tumor necrosis factor receptor-associated factor 6 (TRAF6) complex. (PMID: 12496252) Jiang Z. … Li X. (J. Biol. Chem. 2003) 3 4 23
  4. IRAK4 kinase activity is redundant for interleukin-1 (IL-1) receptor- associated kinase phosphorylation and IL-1 responsiveness. (PMID: 15084582) Qin J. … Li X. (J. Biol. Chem. 2004) 3 4 23
  5. Interactions of sequence variants in interleukin-1 receptor-associated kinase4 and the toll-like receptor 6-1-10 gene cluster increase prostate cancer risk. (PMID: 16537705) Sun J. … GrAPnberg H. (Cancer Epidemiol. Biomarkers Prev. 2006) 3 23 49

Products for IRAK4 Gene

  • Addgene plasmids for IRAK4

Sources for IRAK4 Gene

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