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IRAK4 Gene

protein-coding   GIFtS: 68
GCID: GC12P044152

Interleukin-1 Receptor-Associated Kinase 4

  See IRAK4-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Interleukin-1 Receptor-Associated Kinase 41 2     IPD12 5
Renal Carcinoma Antigen NY-REN-642 3     REN642 5
IRAK-42 3     NY-REN-642
EC 2.7.11.13 8     EC 2.7.118

External Ids:    HGNC: 179671   Entrez Gene: 511352   Ensembl: ENSG000001980017   OMIM: 6068835   UniProtKB: Q9NWZ33   

Export aliases for IRAK4 gene to outside databases

Previous GC identifers: GC12P044231 GC12P044051 GC12P043869 GC12P042439 GC12P041181


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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 pneumococcal meningitis, and invasive pneumococcal disease, recurrent isolated, 1. 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: IRAK4_HUMAN, Q9NWZ3
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 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




(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000012.11  NT_029419.13  NC_018923.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the IRAK4 gene promoter:
         Elk-1   ATF-2   FOXO3   Pax-2   Pax-2a   FOXO3b   IRF-7A   FOXO3a   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidIRAK4 promoter sequence
   Search Chromatin IP Primers for IRAK4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat IRAK4


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 12q12   Ensembl cytogenetic band:  12q12   HGNC cytogenetic band: 12q12

IRAK4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
IRAK4 gene location

GeneLoc information about chromosome 12         GeneLoc Exon Structure

GeneLoc location for GC12P044152:  view genomic region     (about GC identifiers)

Start:
44,152,747 bp from pter      End:
44,183,346 bp from pter
Size:
30,600 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: IRAK4_HUMAN, Q9NWZ3 (See protein sequence)
Recommended Name: Interleukin-1 receptor-associated kinase 4  
Size: 460 amino acids; 51530 Da
Cofactor: Magnesium
Subunit: 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
Selected PDB 3D structures from and Proteopedia for IRAK4 (see all 7):
2NRU (3D)        2NRY (3D)        2O8Y (3D)        2OIB (3D)        2OIC (3D)        2OID (3D)    
Secondary accessions: Q69FE1 Q8TDF7 Q9Y589
Alternative splicing: 2 isoforms:  Q9NWZ3-1   Q9NWZ3-2   

Explore the universe of human proteins at neXtProt for IRAK4: NX_Q9NWZ3

Explore proteomics data for IRAK4 at MOPED

Post-translational modifications: 

  • Phosphorylated (By similarity)1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus
  • 3 DME Specific Peptides for IRAK4 (Q9NWZ3)
     TSRIVGT  DFGLARA  YMPNGSL 


    See IRAK4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (5 alternative transcripts): 
    NP_001107654.1  NP_001138728.1  NP_001138729.1  NP_001138730.1  NP_057207.2  

    ENSEMBL proteins: 
     ENSP00000408734   ENSP00000446571   ENSP00000449553   ENSP00000449693   ENSP00000390651  
     ENSP00000446490   ENSP00000449848   ENSP00000449317   ENSP00000448197   ENSP00000449859  
     ENSP00000390327  
    Reactome Protein details: Q9NWZ3

    IRAK4 Human Recombinant Protein Products:

    EMD Millipore Purified and/or Recombinant IRAK4 Protein
    Browse R&D Systems for human recombinant proteins
    Browse recombinant and purified proteins available from Enzo Life Sciences
    OriGene Purified Protein for IRAK4
    OriGene Protein Over-expression Lysate for IRAK4
    OriGene MassSpec for IRAK4
    OriGene Custom Protein Services for IRAK4
    GenScript Custom Purified and Recombinant Proteins Services for IRAK4
    Novus Biologicals IRAK4 Proteins
    Novus Biologicals IRAK4 Lysates
    Sino Biological Recombinant Protein for IRAK4
    Sino Biological Cell Lysate for IRAK4
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for IRAK4

     
    Search eBioscience for Proteins for IRAK4 

    IRAK4 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of IRAK4
    R&D Systems Antibodies for IRAK4
    Cell Signaling Technology (CST) Antibodies for IRAK4 
    OriGene Antibodies for IRAK4
    OriGene Custom Antibody Services for IRAK4
    Novus Biologicals IRAK4 Antibodies
    Abcam antibodies for IRAK4
    Cloud-Clone Corp. Antibodies for IRAK4
    ThermoFisher Antibody for IRAK4
    LSBio Antibodies in human, mouse, rat for IRAK4

    IRAK4 Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for IRAK4
    Browse R&D Systems for biochemical assays
    GenScript IRAK4-Activity-based Kinase Assay for Compound Screening
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for IRAK4
    Cloud-Clone Corp. CLIAs for IRAK4
    Search eBioscience for ELISAs for IRAK4 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    IUPHAR Guide to PHARMACOLOGY protein family classification: interleukin-1 receptor-associated kinase 4
    Interleukin-1 receptor-associated kinase (IRAK) family

    4 InterPro protein domains:
     IPR017428 IL-1_rcpt-assoc_kin4
     IPR011029 DEATH-like_dom
     IPR011009 Kinase-like_dom
     IPR000719 Prot_kinase_dom

    Graphical View of Domain Structure for InterPro Entry Q9NWZ3

    ProtoNet protein and cluster: Q9NWZ3

    UniProtKB/Swiss-Prot: IRAK4_HUMAN, Q9NWZ3
    Similarity: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Pelle subfamily
    Similarity: Contains 1 death domain
    Similarity: Contains 1 protein kinase domain


    Find genes that share domains with IRAK4           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: IRAK4_HUMAN, Q9NWZ3
    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 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
    Catalytic activity: ATP + a protein = ADP + a phosphoprotein
    Biophysicochemical properties: Kinetic parameters: KM=650 uM for ATP (at pH 7.5); KM=1100 uM for substrate (at pH
    7.5);

         Enzyme Numbers (IUBMB): EC 2.7.11.11 2 EC 2.7.112

         Gene Ontology (GO): Selected molecular function terms (see all 8):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000287magnesium ion binding IEA--
    GO:0004672protein kinase activity EXP--
    GO:0004674protein serine/threonine kinase activity TAS--
    GO:0004713protein tyrosine kinase activity ----
    GO:0005149interleukin-1 receptor binding IEA--
         
    Find genes that share ontologies with IRAK4           About GenesLikeMe


    Phenotypes:
         3 GenomeRNAi human phenotypes for IRAK4:
     Decreased focal adhesion (FA)   Decreased substrate adherent c  Increased cell death HMECs cel 

         4 MGI mutant phenotypes (inferred from 6 alleles(MGI details for Irak4):
     cellular  hematopoietic system  homeostasis/metabolism  immune system 

    Find genes that share phenotypes with IRAK4           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for IRAK4: Irak4tm1Yeh Irak4tm1Aki

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for IRAK4
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for IRAK4

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for IRAK4
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for IRAK4

    miRNA
    Products:
        
    miRTarBase miRNAs that target IRAK4:
    hsa-mir-215-5p (MIRT024734), hsa-mir-192-5p (MIRT026168)

    Block miRNA regulation of human, mouse, rat IRAK4 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate IRAK4 (see all 26):
    hsa-miR-520e hsa-miR-302d hsa-miR-520f hsa-miR-520d-5p hsa-miR-106a hsa-miR-302e hsa-miR-548m hsa-miR-520a-3p
    SwitchGear 3'UTR luciferase reporter plasmidIRAK4 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for IRAK4
    Predesigned siRNA for gene silencing in human, mouse, rat IRAK4

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for IRAK4

    Clone
    Products:
         
    OriGene clones in human, mouse for IRAK4 (see all 31)
    OriGene ORF clones in mouse, rat for IRAK4
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 5): IRAK4 (NM_001145256)
    Sino Biological Human cDNA Clone for IRAK4
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for IRAK4
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat IRAK4
    Addgene plasmids for IRAK4 

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for IRAK4
    Browse ESI BIO Cell Lines and PureStem Progenitors for IRAK4 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for IRAK4


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    IRAK4_HUMAN, Q9NWZ3: Cytoplasm
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytosol4
    endosome4
    plasma membrane4
    cytoskeleton3
    nucleus3
    mitochondrion2

    Gene Ontology (GO): 3 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005829cytosol TAS--
    GO:0005886plasma membrane TAS--
    GO:0010008endosome membrane TAS--

    Find genes that share ontologies with IRAK4           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for IRAK4 About   (see all 23)  
    See pathways by source

    SuperPathContained pathways About
    1NOD-like Receptor Signaling Pathways
    Toll-Like receptor Signaling Pathways0.58
    Mucin expression in CF via TLRs, EGFR signaling pathways0.42
    IL-1 Family Signaling Pathways0.44
    Immune response IL 1 signaling pathway0.42
    2Interleukin-1 signaling
    Interleukin-1 signaling0.45
    IL-1 Signaling Pathway0.00
    IL1-mediated signaling events0.45
    3Toll Comparative Pathway
    Toll Comparative Pathway0.61
    IL-1 Pathway0.39
    TLR-TRIF Pathway0.61
    iNOS Signaling0.34
    Immune response MIF in innate immunity response0.46
    4Immune response Bacterial infections in normal airways
    Immune response Bacterial infections in normal airways0.78
    Immune response Toll like receptor TLR ligands and common TLR signaling pathway leading to cell proinflammatory response0.47
    Bacterial infections in CF airways0.78
    IL 1 beta dependent CFTR expression0.43
    5Toll-like receptor signaling pathway
    Toll-like receptor signaling pathway0.94
    Regulation of toll-like receptor signaling pathway0.93
    Toll-like receptor signaling pathway0.94
    Chagas disease (American trypanosomiasis)0.32


    Find genes that share SuperPaths with IRAK4           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    2 R&D Systems Pathways for IRAK4
        IL-1 Family Signaling Pathways
    Toll-Like receptor Signaling Pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for IRAK4 (see all 12)
        MAPK Signaling
    14-3-3 Induced Apoptosis
    NF-KappaB (p50-p65) Pathway
    Toll-Like Receptors Pathway
    TRAF Pathway

    1 Cell Signaling Technology (CST) Pathway for IRAK4
        NF-kappaB Signaling

    Selected GeneGo (Thomson Reuters) Pathways for IRAK4 (see all 7)
        Mucin expression in CF via TLRs, EGFR signaling pathways
    Immune response Bacterial infections in normal airways
    Immune response MIF in innate immunity response
    Immune response TLR signaling pathways
    Bacterial infections in CF airways

    5 BioSystems Pathways for IRAK4
        IL-1 Signaling Pathway
    AGE/RAGE pathway
    Toll-like receptor signaling pathway
    IL1-mediated signaling events
    Regulation of toll-like receptor signaling pathway

    1 Sino Biological Pathway for IRAK4
        NF-kB (NFkB) Pathway

    Selected Reactome Pathways for IRAK4 (see all 6)
        Interleukin-1 signaling
    TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
    TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling
    MyD88:Mal cascade initiated on plasma membrane
    MyD88 cascade initiated on plasma membrane


    Selected Kegg Pathways  (Kegg details for IRAK4) (see all 11):
        NF-kappa B signaling pathway
    Apoptosis
    Toll-like receptor signaling pathway
    Neurotrophin signaling pathway
    Pertussis

        Pathway & Disease-focused RT2 Profiler PCR Arrays including IRAK4: 
              Antiviral Response in human mouse rat
              Toll-Like Receptor Signaling Pathway in human mouse rat
              NFKB Signaling Pathway in human mouse rat
              Antifungal Response in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for IRAK4

    Selected Interacting proteins for IRAK4 (Q9NWZ31, 2, 3) via UniProtKB, MINT, STRING, and/or I2D (see all 30)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    PELI2Q9HAT81, 3EBI-448378,EBI-448407 I2D: score=5 
    TIRAPP587531, 3EBI-448378,EBI-528644 I2D: score=2 
    AGERQ151093I2D: score=1 
    ENSG00000206320Q151093I2D: score=1 
    ENSG00000229058Q151093I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 17):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001816cytokine production IEA--
    GO:0002224toll-like receptor signaling pathway TAS--
    GO:0002755MyD88-dependent toll-like receptor signaling pathway TAS--
    GO:0006468protein phosphorylation ----
    GO:0007165signal transduction ----

    Find genes that share ontologies with IRAK4           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for IRAK4

    3 HMDB Compounds for IRAK4    About this table
    CompoundSynonyms CAS #PubMed Ids
    ADPadenosindiphosphorsaeure (see all 8)58-64-0--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--
    MagnesiumMagnesium (see all 2)7439-95-4--

    1 DrugBank Compound for IRAK4    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    1-(3-HYDROXYPROPYL)-2-[(3-NITROBENZOYL)AMINO]-1H-BENZIMIDAZOL-5-YL PIVALATE-- --target--10592235

    3 Novoseek inferred chemical compound relationships for IRAK4 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    threonine 29.3 3 17161373 (1), 20400509 (1), 17217339 (1)
    serine 6.26 3 17161373 (1), 20400509 (1), 17217339 (1)
    oxygen 0 1 15622543 (1)



    Find genes that share compounds with IRAK4           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for IRAK4 gene (5 alternative transcripts): 
    NM_001114182.2  NM_001145256.1  NM_001145257.1  NM_001145258.1  NM_016123.3  

    Unigene Cluster for IRAK4:

    Interleukin-1 receptor-associated kinase 4
    Hs.138499  [show with all ESTs]
    Unigene Representative Sequence: NM_001114182
    13 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000440781 ENST00000550616 ENST00000550615 ENST00000547521 ENST00000448290
    ENST00000551736 ENST00000550386 ENST00000547101 ENST00000546780 ENST00000552309
    ENST00000550361 ENST00000547928 ENST00000431837(uc001rnu.3 uc001rnt.3 uc001rnx.3 uc001rny.3 uc010sky.1 uc001rnv.3 uc001rnw.3)

    miRNA
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    Block miRNA regulation of human, mouse, rat IRAK4 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate IRAK4 (see all 26):
    hsa-miR-520e hsa-miR-302d hsa-miR-520f hsa-miR-520d-5p hsa-miR-106a hsa-miR-302e hsa-miR-548m hsa-miR-520a-3p
    SwitchGear 3'UTR luciferase reporter plasmidIRAK4 3' UTR sequence
    Inhib. RNA
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    OriGene RNAi products in human, mouse, rat for IRAK4
    Predesigned siRNA for gene silencing in human, mouse, rat IRAK4
    Clone
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    OriGene clones in human, mouse for IRAK4 (see all 31)
    OriGene ORF clones in mouse, rat for IRAK4
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 5): IRAK4 (NM_001145256)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for IRAK4
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat IRAK4
    Addgene plasmids for IRAK4 
    Primer
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    OriGene qPCR primer pairs and template standards for IRAK4
    OriGene qSTAR qPCR primer pairs in human, mouse for IRAK4
    Pre-validated RT2 qPCR Primer Assay in human, mouse, rat IRAK4
      QuantiTect SYBR Green Assays in human, mouse, rat IRAK4
      QuantiFast Probe-based Assays in human, mouse, rat IRAK4

    Additional mRNA sequence: 

    AF155118.1 AF445802.1 AK000528.1 AK027301.2 AK299944.1 AK304583.1 AK314288.1 AY283670.1 
    AY283671.1 AY340962.1 AY340963.1 AY340964.1 AY340965.1 AY340966.1 AY340967.1 AY730682.1 
    BC013316.1 

    11 DOTS entries:

    DT.109169  DT.91678124  DT.40199684  DT.97861332  DT.121211137  DT.121211143  DT.100035594  DT.100737275 
    DT.91700262  DT.95343378  DT.121211146 

    Selected AceView cDNA sequences (see all 89):

    AA480342 H78769 CA941399 AY340963 AA447173 AY340967 CA774834 AY340966 
    AY340962 BQ020242 AF445802 AA489049 BM127285 BG696775 CA398253 BG164491 
    CA941471 AA565017 AA806159 AY340965 AI401706 AY340964 AK000528 AA488795 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for IRAK4 (see all 9)    About this scheme

    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:                                                                                                        -                                             


    ECgene alternative splicing isoforms for IRAK4

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    IRAK4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    IRAK4 Expression
    About this image


    IRAK4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 4) fully expand
     
     Endothelium (Cardiovascular System)
             Human umbilical vein endothelial cells (HUVEC)
     
     Inner Cell Mass (Early Embryonic Tissues)
             Blimp1- mVenus and stella-ECFP genetically modified stem cells
     
     Blood (Cardiovascular System)
             Definitive Hematopoietic Stem Cells Definitive Yolk Sac
     
     Yolk Sac (Extraembryonic Tissues)
             Definitive Hematopoietic Stem Cells Definitive Yolk Sac
    IRAK4 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    IRAK4 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.138499
        Pathway & Disease-focused RT2 Profiler PCR Arrays including IRAK4: 
              Antiviral Response in human mouse rat
              Toll-Like Receptor Signaling Pathway in human mouse rat
              NFKB Signaling Pathway in human mouse rat
              Antifungal Response in human mouse rat

    Primer
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    OriGene qPCR primer pairs and template standards for IRAK4
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    QuantiFast Probe-based Assays in human, mouse, rat IRAK4
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for IRAK4

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

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    This gene was present in the common ancestor of eukaryotes.

    Orthologs for IRAK4 gene from Selected species (see all 17)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Irak41 , 5 interleukin-1 receptor-associated kinase 41, 5 79.23(n)1
    83.88(a)1
      15 (48.55 cM)5
    2666321  NM_029926.51  NP_084202.21 
     945436435 
    chicken
    (Gallus gallus)
    Aves IRAK41 interleukin-1 receptor-associated kinase 4 69.33(n)
    67.09(a)
      417796  NM_001030738.1  NP_001025909.1 
    lizard
    (Anolis carolinensis)
    Reptilia IRAK46
    interleukin-1 receptor-associated kinase 4
    62(a)
    1 ↔ 1
    5(54610580-54625689)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia irak41 interleukin-1 receptor-associated kinase 4 66.52(n)
    63.09(a)
      733738  NM_001123405.1  NP_001116877.1 
    zebrafish
    (Danio rerio)
    Actinopterygii BC045381.12   -- 71.81(n)   393132  BC045381.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta pll3 antifungal humoral response (sensu
    Invertebrata) more
    28(a)   3 97E11   --
    worm
    (Caenorhabditis elegans)
    Secernentea pik-13   -- 35(a)   IV(13416966-13421694)   --
    thale cress
    (Arabidopsis thaliana)
    eudicotyledons APK2A1 APK2A 52.85(n)
    45.05(a)
      837999  NM_101304.3  NP_172889.1 
    rice
    (Oryza sativa)
    Liliopsida Os10g04051001 Os10g0405100 47.52(n)
    39.07(a)
      4348579  NM_001071092.1  NP_001064557.1 


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for IRAK4 gene
    IRAK12  IRAK22  IRAK32  

    Find genes that share paralogs with IRAK4           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for IRAK4 (see all 698)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 12 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1219080021,2
    Cpathogenic144012381(+) TTGCTC/TAGGGT 10 Q * stg10--------
    rs1454809181,2
    --43991100(+) AAGGAC/TATCTA 5 -- us2k10--------
    rs753045271,2
    F--43991152(+) TTACCC/TCATTA 5 -- us2k11Minor allele frequency- T:0.01NA 120
    rs1394375571,2
    C--43991154(+) ACCCCA/GTTACC 5 -- us2k10--------
    rs1916515671,2
    --43991224(+) TTAAAC/TTGTTC 5 -- us2k10--------
    rs732804361,2
    C,F--43991268(+) TCATTT/CCCTCA 5 -- us2k12Minor allele frequency- C:0.06WA 120
    rs1451602021,2
    --43991287(+) TTTCCC/TGACCA 5 -- us2k10--------
    rs2022140411,2
    --43991319(+) GTGAT-/TCTCTTT 5 -- us2k10--------
    rs42514181,2
    C,F--43991321(+) GATTCTCT/-TTTTT 5 -- us2k12Minor allele frequency- -:0.02NS 88
    rs114821791,2
    C--43991322(+) TTCTC-/TTTTTT 5 -- us2k1 trp30--------

    HapMap Linkage Disequilibrium report for IRAK4 (44152747 - 44183346 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 1 variation for IRAK4:    About this table    
    Variant IDTypeSubtypePubMed ID
    dgv285e199CNV Deletion23128226

    Human Gene Mutation Database (HGMD): IRAK4
    Locus Specific Mutation Databases (LSDB): IRAK4

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing IRAK4
    DNA2.0 Custom Variant and Variant Library Synthesis for IRAK4

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

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    OMIM gene information: 606883   
    OMIM disorders: 607676  610799  
    UniProtKB/Swiss-Prot: IRAK4_HUMAN, Q9NWZ3
  • 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. 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. Note=The disease is caused by mutations affecting the gene represented in this entry

  • 6 diseases for IRAK4:    
    About MalaCards
    pneumococcal meningitis    invasive pneumococcal disease, recurrent isolated, 1    irak-4 deficiency    baraitser-winter syndrome 2
    baraitser-winter syndrome    isovaleric acidemia


    Find genes that share disorders with IRAK4           About GenesLikeMe

    9 Novoseek inferred disease relationships for IRAK4 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    bacterial infections 63 15 15905496 (2), 15069404 (1), 17878374 (1), 19430930 (1) (see all 11)
    ectodermal dysplasia, hypohidrotic 55.5 1 14612669 (1)
    immunodeficiency 41.2 8 15825022 (2), 17142536 (1), 18174872 (1), 17917042 (1) (see all 7)
    septicemia 33.7 1 15069404 (1)
    meningitis 26.7 3 15825022 (1), 19814626 (1), 18174872 (1)
    necrosis 24 12 18786322 (1), 12496252 (1), 18583235 (1)
    infectious disease 21.8 3 12297423 (1), 17646026 (1)
    inflammation 18.6 2 19689377 (2)
    tumors 0 14 19318560 (2), 18786322 (1), 12496252 (1), 18583235 (1)

    Genetic Association Database (GAD): IRAK4
    Human Genome Epidemiology (HuGE) Navigator: IRAK4 (24 documents)

    Export disorders for IRAK4 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for IRAK4 gene, integrated from 10 sources (see all 175):
    (articles sorted by number of sources associating them with IRAK4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Distinct mutations in IRAK-4 confer hyporesponsiveness to lipopolysaccharide and interleukin-1 in a patient with recurrent bacterial infections. (PubMed id 12925671)1, 2, 4, 9 Medvedev A.E.... Vogel S.N. (J. Exp. Med. 2003)
    2. Antigens recognized by autologous antibody in patients with renal- cell carcinoma. (PubMed id 10508479)1, 2, 3 Scanlan M.J....Old L.J. (Int. J. Cancer 1999)
    3. Cross-talk between IRAK-4 and the NADPH oxidase. (PubMed id 17217339)1, 2, 9 Pacquelet S.... Catz S.D. (Biochem. J. 2007)
    4. IRAK4 kinase activity is redundant for interleukin-1 (IL-1) receptor- associated kinase phosphorylation and IL-1 responsiveness. (PubMed id 15084582)1, 2, 9 Qin J.... Li X. (J. Biol. Chem. 2004)
    5. IRAK4: a novel member of the IRAK family with the properties of an IRAK-kinase. (PubMed id 11960013)1, 2, 9 Li S.... Wesche H. (Proc. Natl. Acad. Sci. U.S.A. 2002)
    6. IRAK1 and IRAK4 promote phosphorylation, ubiquitination, and degradation of MyD88 adaptor-like (Mal). (PubMed id 20400509)1, 2, 9 Dunne A.... O'Neill L.A. (J. Biol. Chem. 2010)
    7. Polymorphisms in interleukin-1 receptor-associated kinase 4 are associated with total serum IgE. (PubMed id 19254290)1, 4, 9 Tewfik M.A....Desrosiers M. (Allergy 2009)
    8. Interactions of sequence variants in interleukin-1 receptor-associated kinase4 and the toll-like receptor 6-1-10 gene cluster increase prostate cancer risk. (PubMed id 16537705)1, 4, 9 Sun J....GrAPnberg H. (amp 2006)
    9. Crystal structures of IRAK-4 kinase in complex with inhibitors: a serine/threonine kinase with tyrosine as a gatekeeper. (PubMed id 17161373)1, 2, 9 Wang Z....Walker N.P.C. (Structure 2006)
    10. The IRAK-catalysed activation of the E3 ligase function of Pellino isoforms induces the Lys63-linked polyubiquitination of IRAK1. (PubMed id 17997719)1, 2, 9 Ordureau A....Cohen P. (Biochem. J. 2008)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 51135 HGNC: 17967 AceView: IRAK4 Ensembl:ENSG00000198001 euGenes: HUgn51135
    ECgene: IRAK4 Kegg: 51135 H-InvDB: IRAK4

    (According to HUGE)
    About This Section

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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for IRAK4 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for IRAK4 Genetics and Cytogenetics in Oncology and Haematology
    IRAK4basehttp://bioinf.uta.fi/IRAK4base/
    SeattleSNPshttp://pga.gs.washington.edu/data/irak4/

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for IRAK4 gene:
    Search GeneIP for patents involving IRAK4

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, eBioscience, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
    Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
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