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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

IRAK4 Gene

protein-coding   GIFtS: 66
GCID: GC12P044152

interleukin-1 receptor-associated kinase 4

 Explore 41 diseases affiliated with
IRAK4 via our new
 Human Malady Compendium 
Biological research products
for IRAK4
    

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section

Aliases
Interleukin-1 Receptor-Associated Kinase 41 2     EC 2.7.11.13 8
NY-REN-641 2     IPD12 5
Renal Carcinoma Antigen NY-REN-642 3     REN642 5
IRAK-42 3     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, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for IRAK4:
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)

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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000012.11  NC_018923.1  NT_029419.12  
Regulatory elements:
   SABiosciences 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 SABiosciences Chromatin IP Primers for IRAK4

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays 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, neXtProt, Ensembl, and/or Reactome, Modification sites according to 2PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

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
Subcellular location: Cytoplasm
6/7 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

Post-translational modifications:

  • Phosphorylated (By similarity)1
  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_Q9NWZ3

  • 3 DME Specific Peptides for IRAK4 (Q9NWZ3)
     TSRIVGT  DFGLARA  YMPNGSL 

    IRAK4 Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

    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
    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: IRAK4
    OriGene Protein Over-expression Lysate (see all 2): IRAK4
    OriGene Custom Protein Services for IRAK4 
    GenScript Custom Purified and Recombinant Proteins Services for IRAK4
    Novus Biologicals IRAK4 Proteins
    Novus Biologicals IRAK4 Lysates
    Browse Sino Biological Recombinant Proteins
    Browse ProSpec Recombinant Proteins
    Uscn Proteins for IRAK4

    Gene Ontology (GO): 3 cellular component terms (GO ID links to tree view):    About this table

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


    IRAK4 for ontologies           About GeneDecksing



    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 (see all 3): IRAK4
    OriGene Custom Antibody Services for IRAK4 
    GenScript Custom Superior Antibodies Services for IRAK4
    Novus Biologicals IRAK4 Antibodies
    Abcam antibodies for IRAK4 
    Uscn Antibodies for IRAK4
    ThermoFisher Antibody for IRAK4

    Assay Products for IRAK4: 
    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Immunoassay Development
    Browse OriGene Fluorogenic Cell Assay Kits
    Browse R&D Systems for biochemical assays
    GenScript IRAK4-Activity-based Kinase Assay for Compound Screening
    Browse Enzo Life Sciences for kits & assays
    Uscn ELISAs and CLIAs for IRAK4


    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section

    IRAK4 for domains           About GeneDecksing

    4 InterPro domains/families:
     IPR017428 Interleukin-1_rcpt-assoc_kin4
     IPR011029 DEATH-like_dom
     IPR011009 Kinase-like_dom
     IPR000719 Prot_kinase_cat_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


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
    About This Section

    Function Summary:

         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
    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

    miRNA
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    OriGene 3'-UTR Clone (see all 5): IRAK4
    Browse MicroRNA Expression Plasmids
    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat IRAK4
    8/26 QIAGEN miScript miRNA 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:
        
    Browse for Gene Knock-down Tools from EMD Millipore
    OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for IRAK4 (see all 6)
    OriGene siRNA: IRAK4
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat IRAK4

    Gene Editing
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    DNA2.0 Custom Protein Engineering Service for IRAK4

    Clone
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    Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
    OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for IRAK4 (see all 7)
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    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)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for IRAK4
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat IRAK4 

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    Search LifeMap BioReagents cell lines for IRAK4

    In Situ Assay
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for IRAK4

    Gene Ontology (GO): 5/6 molecular function terms (GO ID links to tree view) (see all 6):    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:0005149interleukin-1 receptor binding IEA--
    GO:0005515protein binding IPI--


    IRAK4 for ontologies           About GeneDecksing


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

    Animal Models:
         Mouse knock-outs for IRAK4: Irak4tm1Yeh Irak4tm1Aki
         4 MGI mutant phenotypes (inferred from 6 alleles(MGI details for Irak4):
     cellular  hematopoietic system  homeostasis/metabolism  immune system 

    IRAK4 for phenotypes           About GeneDecksing


    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, 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 Mar 2013 via Entrez Gene).
    About This Section

    Unified GeneCards pathways - 5/26 super-pathways (see all 26About this table 
    See pathways by source

    Super-pathwaycontained gene-specific pathways
    1TRAF6 Mediated Induction of proinflammatory cytokines
    8/14 pathways (see all 14)
    Toll Like Receptor 10 (TLR10) Cascade0.86
    Toll Like Receptor TLR6:TLR2 Cascade0.78
    Toll Like Receptor 5 (TLR5) Cascade0.86
    Toll Like Receptor TLR1:TLR2 Cascade0.78
    MyD88 cascade initiated on plasma membrane0.86
    Toll Like Receptor 2 (TLR2) Cascade0.78
    TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation0.85
    MyD88:Mal cascade initiated on plasma membrane0.78
    2Toll Comparative Pathway
    Toll Comparative Pathway1.00
    Immune response MIF in innate immunity response0.46
    TLR-TRIF Pathway0.61
    IL-1 Pathway0.39
    Immune response_MIF in innate immunity response0.46
    iNOS Signaling0.34
    3Toll-like receptor signaling pathway
    Toll-like receptor signaling pathway1.00
    Toll-Like receptor Signaling Pathways0.51
    Toll-like receptor signaling pathway0.97
    Chagas disease (American trypanosomiasis)0.31
    4Immune response_Bacterial infections in normal airways
    Immune response_Bacterial infections in normal airways1.00
    IL-1 beta-dependent CFTR expression0.43
    Bacterial infections in CF airways0.78
    5Immune response_IL-1 signaling pathway
    Immune response_IL-1 signaling pathway1.00
    Immune response IL-1 signaling pathway0.98

    Pathway sources
    See GeneCards unified pathways
    Show all pathways

    3 EMD Millipore Pathways for IRAK4
        Immune response Toll-like receptor (TLR) ligands and common TLR signaling pathway leading to cell proinflammatory response
    Immune response MIF in innate immunity response
    Immune response IL-1 signaling pathway

    1 R&D Systems Pathway for IRAK4
        Toll-Like receptor Signaling Pathways

    5/12 Downloadable PowerPoint Slides of QIAGEN 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

    5/7 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

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

    5/21        Reactome Pathways for IRAK4 (see all 21)
        Toll Like Receptor 2 (TLR2) Cascade
    Toll Like Receptor TLR6:TLR2 Cascade
    TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling
    Toll-Like Receptors Cascades
    Toll Like Receptor 7/8 (TLR7/8) Cascade


    5/10         Kegg Pathways  (Kegg details for IRAK4) (see all 10):
        Apoptosis
    Toll-like receptor signaling pathway
    Neurotrophin signaling pathway
    Pertussis
    Leishmaniasis


    IRAK4 for pathways           About GeneDecksing

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for IRAK4

    5/24 Interacting proteins for IRAK4 (Q9NWZ31, 2, 3) via UniProtKB, MINT, STRING, and/or I2D (see all 24)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    PELI2Q9HAT81, 3EBI-448378,EBI-448407 I2D: score=5 
    TIRAPP587531, 3EBI-448378,EBI-528644 I2D: score=2 
    IRAK1P516173I2D: score=6 
    MYD88Q998363I2D: score=6 
    PELI1Q96FA33I2D: score=4 
    About this table

    Gene Ontology (GO): 5/13 biological process terms (GO ID links to tree view) (see all 13):    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:0007254JNK cascade IEA--


    IRAK4 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    IRAK4 for compounds           About GeneDecksing

    EMD Millipore small molecules for IRAK4:
    Small Molecule - inhibitor
    Browse drugs & compounds from Enzo Life Sciences

    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 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)

    Search CenterWatch for drugs/clinical trials and news about IRAK4 

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 235 Homo sapiens; Mar 10 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,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    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)


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    8/26 QIAGEN miScript miRNA 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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    Browse for Gene Knock-down Tools from EMD Millipore
    OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for IRAK4 (see all 6)
    OriGene siRNA: IRAK4
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat IRAK4
    Clone
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    OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for IRAK4 (see all 7)
    OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for IRAK4 (see all 8)
    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 
    Primer
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    OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for IRAK4
    Browse OriGene validated miRNA SYBR primer pairs
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      QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat IRAK4
      QIAGEN QuantiFast Probe-based Assays in human, mouse, rat IRAK4

    Additional cDNA 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 

    24/89 AceView cDNA sequences (see all 89):

    AA565017 AF445802 AA447173 BG696775 H78769 BM127285 AK000528 AY340965 
    AY340966 AY340962 AY340964 AY340967 AA480342 AA806159 CA941471 CA774834 
    AA489049 CA398253 CA941399 BQ020242 BG164491 AI401706 AY340963 CD654941 

    GeneLoc Exon Structure

    5/9 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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    IRAK4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: --

    Microarray
    RNAseq (Illumina Body Map)
    (100×FPKM)½
    SAGE (Serial Analysis of Gene Expression)

    About this image

    IRAK4 expression in embryonic tissues and stem cells
    Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine    About this table
    1 LifeMap In Vivo Development Anatomical Compartment/Cell 
    Tissue Anatomical Compartment CellCategory (developmental path)
    Yolk SacDefinitive Yolk SacDefinitive Hematopoietic Stem CellsBlood
    Expression: Positive    Negative     Selective marker
    Experimental details: Curated     Microarrays     In-situ hybridization
    Stem Cell Differentiation: 2 LifeMap Cells 
    NameCategory
    Human umbilical vein endothelial cells (HUVEC) (Primary Cell)Endothelium
    Fetal cardiomyocytes (20 weeks) (Primary Cell)Heart, Myocardium

    See IRAK4 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for IRAK4

    SOURCE GeneReport for Unigene cluster: Hs.138499
        SABiosciences Expression via Pathway-Focused 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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    (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

    This gene was present in the common ancestor of eukaryotes.

    Orthologs for IRAK4 gene from 5/17 species (see all 17)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    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
    --
    66(a)
    1 ↔ 1
    5(54611984-54623083)
    zebrafish
    (Danio rerio)
    Actinopterygii BC045381.12   -- 71.81(n)   393132  BC045381.1 
    thale cress
    (Arabidopsis thaliana)
    eudicotyledons APK2B1 protein kinase 2B 48.79(n)
    38.74(a)
      814810  NM_126335.5  NP_178383.1 
    rice
    (Oryza sativa)
    Liliopsida Os10g04051001 hypothetical protein 47.62(n)
    39.36(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)
    About This Section
    Paralogs for IRAK4 gene
    IRAK12  IRAK22  IRAK32  

    IRAK4 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, UniProtKB, 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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/587 NCBI SNPs in IRAK4 are shown (see all 587    About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 12 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1219080021,2
    Cpathogenic44172041(+) TTGCTC/TAGGGT 10 Q * stg10--------
    rs1454809181,2
    --44150760(+) AAGGAC/TATCTA 8 -- us2k1 int10--------
    rs753045271,2
    --44150812(+) TTACCC/TCATTA 8 -- int1 us2k11Minor allele frequency- T:0.01NA 120
    rs1394375571,2
    --44150814(+) ACCCCA/GTTACC 8 -- int1 us2k10--------
    rs1916515671,2
    --44150884(+) TTAAAC/TTGTTC 8 -- int1 us2k10--------
    rs732804361,2
    C,--44150928(+) TCATTT/CCCTCA 8 -- us2k1 int12Minor allele frequency- C:0.06WA 120
    rs1451602021,2
    --44150947(+) TTTCCC/TGACCA 8 -- us2k1 int10--------
    rs2022140411,2
    --44150979(+) GTGAT-/TCTCTTT 8 -- int1 us2k10--------
    rs42514181,2
    C,F,--44150981(+) GATTCTCT/-TTTTT 8 -- us2k1 int12Minor allele frequency- -:0.02NS 88
    rs114821791,2
    C,--44150981(+) TTCTC-/TTTTTT 8 -- int1 us2k1 trp30--------

    HapMap Linkage Disequilibrium report for IRAK4 (44152747 - 44183346 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
    Database of Genomic Variants (DGV): 2 variations for IRAK4
         2 CNVs: 86348 86347
    Human Gene Mutation Database (HGMD): IRAK4

    Locus Specific Mutation Databases (LSDB): IRAK4

    SABiosciences Cancer Mutation PCR Assays
    QIAGEN SeqTarget long-range PCR primers in human, mouse, rat 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

    IRAK4 for disorders           About GeneDecksing

    OMIM gene information: 606883   
    OMIM disorders: 607676  610799  
    UniProtKB/Swiss-Prot: IRAK4_HUMAN, Q9NWZ3
  • Defects in IRAK4 are the cause of recurrent isolated invasive pneumococcal disease type 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
  • Defects in IRAK4 are the cause of IRAK4 deficiency (IRAK4D) [MIM:607676]. IRAK4 deficiency causes
  • extracellular pyogenic bacterial and fungal infections in otherwise healthy children

    20/41 diseases for IRAK4 (see all 41):    About MalaCards
    invasive pneumococcal disease, recurrent isolated, 1    renal carcinoma    ectodermal dysplasia    dengue hemorrhagic fever
    interleukin receptor    hemorrhagic fever    otitis media    carcinoma
    job's syndrome    systemic lupus erythematosus    allergic rhinitis    lupus erythematosus
    meningitis    chronic lymphocytic leukemia    pericarditis    lymphocytic leukemia
    rhinitis    bronchiolitis    renal cell carcinoma    kawasaki disease

    9 Novoseek 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)
    About This Section

    PubMed articles for IRAK4 gene, integrated from 9 sources (see all 158):
    (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. (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. (1999)
    3. Cross-talk between IRAK-4 and the NADPH oxidase. (PubMed id 17217339)1, 2, 9 Pacquelet S....Catz S.D. (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. (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. (2002)
    6. IRAK1 and IRAK4 promote phosphorylation, ubiquitinati on, and degradation of MyD88 adaptor-like (Mal). (PubMed id 20400509)1, 2, 9 Dunne A....O'Neill L.A. (2010)
    7. 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. (2006)
    8. 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. (2008)
    9. 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. (PubMed id 12496252)1, 2, 9 Jiang Z.... Li X. (2003)
    10. Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling. (PubMed id 20485341)1, 2 Lin S.C....Wu H. (2010)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     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)
    About This Section
    Entrez Gene: 51135 HGNC: 17967 AceView: IRAK4 Ensembl:ENSG00000198001 euGenes: HUgn51135
    ECgene: IRAK4 Kegg: 51135 H-InvDB: IRAK4

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    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.)
    About This Section
    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, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Uscn, Thermo Fisher Scientific, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences),
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    About This Section

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