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Aliases for IRAK4 Gene

Aliases for IRAK4 Gene

  • Interleukin 1 Receptor Associated Kinase 4 2 3 5
  • Renal Carcinoma Antigen NY-REN-64 3 4
  • EC 2.7.11.1 4 63
  • IRAK-4 3 4
  • NY-REN-64 3
  • EC 2.7.11 63
  • REN64 3
  • IPD1 3

External Ids for IRAK4 Gene

Previous GeneCards Identifiers for IRAK4 Gene

  • GC12P044231
  • GC12P044051
  • GC12P043869
  • GC12P042439
  • GC12P044152
  • GC12P041181

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 invasive pneumococcal disease, recurrent isolated, 1. Among its related pathways are Immune System and Interleukin-3, 5 and GM-CSF signaling. GO annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. 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.

Tocris Summary for IRAK4 Gene

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

Genomics for IRAK4 Gene

Regulatory Elements for IRAK4 Gene

Promoters for IRAK4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around IRAK4 on UCSC Golden Path with GeneCards custom track

Genomic Location for IRAK4 Gene

Chromosome:
12
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

Genes around IRAK4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
IRAK4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for IRAK4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence 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

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for IRAK4 (IRAK4)

Domains & Families for IRAK4 Gene

Gene Families for IRAK4 Gene

Graphical View of Domain Structure for InterPro Entry

Q9NWZ3

UniProtKB/Swiss-Prot:

IRAK4_HUMAN :
  • Contains 1 death domain.
  • Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Pelle subfamily.
Domain:
  • Contains 1 death domain.
  • Contains 1 protein kinase domain.
Family:
  • Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Pelle subfamily.
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:0004672 protein kinase activity EXP,IEA 11960013
genes like me logo Genes that share ontologies with IRAK4: view
genes like me logo Genes that share phenotypes with IRAK4: view

Human Phenotype Ontology for IRAK4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for IRAK4 Gene

MGI Knock Outs for IRAK4:

Animal Model Products

miRNA for IRAK4 Gene

miRTarBase miRNAs that target IRAK4

Inhibitory RNA Products

In Situ Assay Products

Flow Cytometry Products

No data available for Transcription Factor Targets 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 5
endosome 5
plasma membrane 5
nucleus 4
extracellular 3
cytoskeleton 2
mitochondrion 2

No data available for Gene Ontology (GO) - Cellular Components for IRAK4 Gene

Pathways & Interactions for IRAK4 Gene

SuperPathways for IRAK4 Gene

Superpath Contained pathways
1 MyD88 cascade initiated on plasma membrane
2 Diseases associated with the TLR signaling cascade
3 Toll Comparative Pathway
4 Toll-like receptor signaling pathway
5 Toll-Like receptor Signaling Pathways
genes like me logo Genes that share pathways with IRAK4: view

SIGNOR curated interactions for IRAK4 Gene

Activates:
Is activated by:
Is inactivated by:

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

Drugs & Compounds for IRAK4 Gene

(6) Drugs for IRAK4 Gene - From: HMDB, DGIdb, Novoseek, and DrugBank

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Adenosine triphosphate Approved Nutra 0
1-(3-HYDROXYPROPYL)-2-[(3-NITROBENZOYL)AMINO]-1H-BENZIMIDAZOL-5-YL PIVALATE Experimental Pharma Target 0
IRAK-1/4 INHIBITOR Pharma 0
Magnesium Nutra 0

(2) Additional Compounds for IRAK4 Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0
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 (x5.8).

Protein differential expression in normal tissues from HIPED for IRAK4 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (24.6), Platelet (6.7), and Lymph node (6.0).

Integrated Proteomics: protein expression in normal tissues and cell lines 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 expression patterns with IRAK4: view

Protein tissue co-expression partners for IRAK4 Gene

- Elite partner

Primer Products

In Situ Assay Products

No data available for mRNA Expression by UniProt/SwissProt for IRAK4 Gene

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 (a)
OneToOne
IRAK4 35
  • 99.57 (n)
  • 99.13 (a)
cow
(Bos Taurus)
Mammalia IRAK4 36
  • 90 (a)
OneToOne
IRAK4 35
  • 92.25 (n)
  • 90.22 (a)
dog
(Canis familiaris)
Mammalia IRAK4 35
  • 92.46 (n)
  • 92.83 (a)
IRAK4 36
  • 93 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Irak4 36
  • 84 (a)
OneToOne
Irak4 16
Irak4 35
  • 79.23 (n)
  • 83.88 (a)
oppossum
(Monodelphis domestica)
Mammalia IRAK4 36
  • 79 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 80 (a)
OneToMany
-- 36
  • 75 (a)
OneToMany
rat
(Rattus norvegicus)
Mammalia Irak4 35
  • 80.54 (n)
  • 84.53 (a)
chicken
(Gallus gallus)
Aves IRAK4 35
  • 69.33 (n)
  • 67.09 (a)
IRAK4 36
  • 68 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia IRAK4 36
  • 62 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia irak4 35
  • 66.52 (n)
  • 63.09 (a)
zebrafish
(Danio rerio)
Actinopterygii -- 35
irak4 35
  • 52.25 (n)
  • 48.35 (a)
irak4 36
  • 45 (a)
OneToOne
fruit fly
(Drosophila melanogaster)
Insecta pll 36
  • 24 (a)
OneToMany
pll 37
  • 28 (a)
worm
(Caenorhabditis elegans)
Secernentea pik-1 37
  • 35 (a)
pik-1 36
  • 26 (a)
OneToMany
thale cress
(Arabidopsis thaliana)
eudicotyledons APK2A 35
  • 52.85 (n)
  • 45.05 (a)
rice
(Oryza sativa)
Liliopsida Os10g0405100 35
  • 47.52 (n)
  • 39.07 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 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
rs4251469 - 43,771,352(+) GCGAG(G/T)CTTTT intron-variant, reference, missense, utr-variant-5-prime
rs4251583 - 43,783,705(+) TGAAC(A/G)CCGTG reference, missense
rs4251545 - 43,786,492(+) TTGAA(A/G)CTATG reference, missense
rs56312115 - 43,768,124(+) AACCC(A/G)TAACA intron-variant, reference, missense, utr-variant-5-prime
VAR_040589 -

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

Variant ID Type Subtype PubMed ID
dgv285e199 CNV Deletion 23128226

Variation tolerance for IRAK4 Gene

Residual Variation Intolerance Score: 30.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.20; 69.79% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for IRAK4 Gene

HapMap Linkage Disequilibrium report
IRAK4
Human Gene Mutation Database (HGMD)
IRAK4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for IRAK4 Gene

Disorders for IRAK4 Gene

MalaCards: The human disease database

(15) MalaCards diseases for IRAK4 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
irak4 deficiency
  • irak-4 deficiency
invasive pneumococcal disease, recurrent isolated, 1
  • pneumococcal disease, invasive, protection against
immunodeficiency due to interleukin-1 receptor-associated kinase-4 deficiency
  • irak4 deficiency
cerebritis
myd88 deficiency
  • pyogenic bacterial infections due to myd88 deficiency
- elite association - COSMIC cancer census association via MalaCards
Search IRAK4 in MalaCards View complete list of genes associated with diseases

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.

Relevant External Links for IRAK4

Genetic Association Database (GAD)
IRAK4
Human Genome Epidemiology (HuGE) Navigator
IRAK4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
IRAK4
genes like me logo Genes that share disorders with IRAK4: view

No data available for Genatlas for IRAK4 Gene

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 48 67
  2. IRAK1 and IRAK4 promote phosphorylation, ubiquitination, and degradation of MyD88 adaptor-like (Mal). (PMID: 20400509) Dunne A. … O'Neill L.A. (J. Biol. Chem. 2010) 3 23
  3. Steady-state kinetic characterization of kinase activity and requirements for Mg2+ of interleukin-1 receptor-associated kinase-4. (PMID: 20104875) Hekmat-Nejad M. … Swinney D.C. (Biochemistry 2010) 3 23
  4. Regulation of IRAK-1 activation by its C-terminal domain. (PMID: 19166926) Nguyen T. … Scholz G.M. (Cell. Signal. 2009) 3 23
  5. The kinase activities of interleukin-1 receptor associated kinase (IRAK)-1 and 4 are redundant in the control of inflammatory cytokine expression in human cells. (PMID: 19181383) Song K.W. … Wong B.R. (Mol. Immunol. 2009) 3 23

Products for IRAK4 Gene

Sources for IRAK4 Gene

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