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Protein

Interleukin-1 receptor-associated kinase 4

Gene

IRAK4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.9 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Kineticsi

  1. KM=650 µM for ATP (at pH 7.5)1 Publication
  2. KM=1100 µM for substrate (at pH 7.5)1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei213ATP1
    Active sitei311Proton acceptorPROSITE-ProRule annotation1
    Binding sitei329ATP1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi192 – 200ATPPROSITE-ProRule annotation9
    Nucleotide bindingi313 – 316ATP4

    GO - Molecular functioni

    GO - Biological processi

    • cytokine-mediated signaling pathway Source: Ensembl
    • cytokine production Source: Ensembl
    • innate immune response Source: UniProtKB
    • JNK cascade Source: Ensembl
    • MyD88-dependent toll-like receptor signaling pathway Source: UniProtKB
    • neutrophil mediated immunity Source: UniProtKB
    • neutrophil migration Source: UniProtKB
    • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: MGI
    • positive regulation of smooth muscle cell proliferation Source: Ensembl
    • toll-like receptor 9 signaling pathway Source: Reactome
    • toll-like receptor signaling pathway Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Immunity, Innate immunity

    Keywords - Ligandi

    ATP-binding, Magnesium, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciZFISH:HS03405-MONOMER.
    ReactomeiR-HSA-166058. MyD88:Mal cascade initiated on plasma membrane.
    R-HSA-446652. Interleukin-1 signaling.
    R-HSA-5602498. MyD88 deficiency (TLR2/4).
    R-HSA-5602680. MyD88 deficiency (TLR5).
    R-HSA-5603037. IRAK4 deficiency (TLR5).
    R-HSA-5603041. IRAK4 deficiency (TLR2/4).
    R-HSA-975110. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
    R-HSA-975138. TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
    R-HSA-975155. MyD88 dependent cascade initiated on endosome.
    R-HSA-975871. MyD88 cascade initiated on plasma membrane.
    SignaLinkiQ9NWZ3.
    SIGNORiQ9NWZ3.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Interleukin-1 receptor-associated kinase 4 (EC:2.7.11.1)
    Short name:
    IRAK-4
    Alternative name(s):
    Renal carcinoma antigen NY-REN-64
    Gene namesi
    Name:IRAK4
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:17967. IRAK4.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Involvement in diseasei

    Recurrent isolated invasive pneumococcal disease 1 (IPD1)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionRecurrent 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.
    See also OMIM:610799
    IRAK4 deficiency (IRAK4D)6 Publications
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionCauses extracellular pyogenic bacterial and fungal infections in otherwise healthy children.
    See also OMIM:607676
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_07288812R → C in IRAK4D; no effect on inhibition of NF-kappa-B complex activation; loss of interaction with MYD88; decreases protein stability. 2 PublicationsCorresponds to variant rs377584435dbSNPEnsembl.1
    Natural variantiVAR_072892298G → D in IRAK4D; decreases inhibition of NF-kappa-B complex activation; impairs neutrophil migration and phagocytosis. 3 PublicationsCorresponds to variant rs568782766dbSNPEnsembl.1
    Natural variantiVAR_040590391R → H Found in a patient with IRAK4D in association with C-12; probable neutral polymorphism. 2 PublicationsCorresponds to variant rs55944915dbSNPEnsembl.1

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi213K → A: Loss of kinase activity. 1 Publication1

    Organism-specific databases

    DisGeNETi51135.
    MalaCardsiIRAK4.
    MIMi607676. phenotype.
    610799. phenotype.
    OpenTargetsiENSG00000198001.
    Orphaneti70592. Immunodeficiency due to interleukin-1 receptor-associated kinase-4 deficiency.
    PharmGKBiPA134914577.

    Chemistry databases

    ChEMBLiCHEMBL3778.
    GuidetoPHARMACOLOGYi2045.

    Polymorphism and mutation databases

    BioMutaiIRAK4.
    DMDMi50401181.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000860351 – 460Interleukin-1 receptor-associated kinase 4Add BLAST460

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei1N-acetylmethionineCombined sources1
    Modified residuei34N6-acetyllysineCombined sources1
    Modified residuei342Phosphothreonine2 Publications1
    Modified residuei345Phosphothreonine3 Publications1
    Modified residuei346Phosphoserine2 Publications1

    Post-translational modificationi

    Phosphorylated.By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    EPDiQ9NWZ3.
    MaxQBiQ9NWZ3.
    PaxDbiQ9NWZ3.
    PeptideAtlasiQ9NWZ3.
    PRIDEiQ9NWZ3.

    PTM databases

    iPTMnetiQ9NWZ3.
    PhosphoSitePlusiQ9NWZ3.

    Expressioni

    Gene expression databases

    BgeeiENSG00000198001.
    CleanExiHS_IRAK4.
    ExpressionAtlasiQ9NWZ3. baseline and differential.
    GenevisibleiQ9NWZ3. HS.

    Organism-specific databases

    HPAiCAB016685.
    CAB022077.
    HPA000924.

    Interactioni

    Subunit structurei

    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 IL1RL1.7 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    Irak3Q8K4B24EBI-448378,EBI-646179From a different organism.
    MYD88Q998365EBI-448378,EBI-447677
    PELI2Q9HAT83EBI-448378,EBI-448407
    TIRAPP587532EBI-448378,EBI-528644

    Protein-protein interaction databases

    BioGridi119322. 26 interactors.
    DIPiDIP-31351N.
    IntActiQ9NWZ3. 14 interactors.
    MINTiMINT-1383671.
    STRINGi9606.ENSP00000390651.

    Chemistry databases

    BindingDBiQ9NWZ3.

    Structurei

    Secondary structure

    1460
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi11 – 13Combined sources3
    Helixi16 – 26Combined sources11
    Helixi31 – 38Combined sources8
    Beta strandi42 – 48Combined sources7
    Helixi50 – 57Combined sources8
    Helixi58 – 60Combined sources3
    Turni61 – 63Combined sources3
    Helixi66 – 73Combined sources8
    Turni74 – 77Combined sources4
    Helixi81 – 89Combined sources9
    Turni90 – 92Combined sources3
    Helixi94 – 100Combined sources7
    Beta strandi102 – 104Combined sources3
    Beta strandi166 – 168Combined sources3
    Helixi170 – 176Combined sources7
    Turni177 – 180Combined sources4
    Turni185 – 188Combined sources4
    Beta strandi191 – 194Combined sources4
    Beta strandi196 – 207Combined sources12
    Beta strandi209 – 215Combined sources7
    Beta strandi218 – 220Combined sources3
    Turni223 – 225Combined sources3
    Helixi226 – 239Combined sources14
    Beta strandi248 – 252Combined sources5
    Beta strandi254 – 257Combined sources4
    Beta strandi259 – 263Combined sources5
    Helixi270 – 275Combined sources6
    Helixi277 – 279Combined sources3
    Helixi285 – 304Combined sources20
    Helixi314 – 316Combined sources3
    Beta strandi317 – 319Combined sources3
    Beta strandi325 – 327Combined sources3
    Beta strandi349 – 351Combined sources3
    Helixi352 – 354Combined sources3
    Helixi357 – 360Combined sources4
    Helixi367 – 382Combined sources16
    Beta strandi391 – 395Combined sources5
    Helixi398 – 404Combined sources7
    Helixi410 – 413Combined sources4
    Helixi423 – 436Combined sources14
    Turni441 – 443Combined sources3
    Helixi447 – 457Combined sources11

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2NRUX-ray2.00A/B/C/D154-460[»]
    2NRYX-ray2.15A/B/C/D154-460[»]
    2O8YX-ray2.40A/B163-460[»]
    2OIBX-ray2.00A/B/C/D160-460[»]
    2OICX-ray2.40A/B/C/D160-460[»]
    2OIDX-ray2.30A/B/C/D160-460[»]
    3MOPX-ray3.40G/H/I/J4-106[»]
    4RMZX-ray2.20A/B154-460[»]
    4U97X-ray2.65A/B154-460[»]
    4U9AX-ray2.80A/B154-460[»]
    4XS2X-ray2.73A/B/C/D160-460[»]
    4Y73X-ray2.14A/B/C/D160-460[»]
    4YO6X-ray2.32A/B/C/D160-460[»]
    4YP8X-ray2.64A/B/C/D160-460[»]
    4ZTLX-ray2.39A/B/C/D160-460[»]
    4ZTMX-ray2.66A/B/C/D160-460[»]
    4ZTNX-ray2.23A/B/C/D160-460[»]
    5KX7X-ray2.80A/B160-460[»]
    5KX8X-ray2.67A/B/C/D160-460[»]
    ProteinModelPortaliQ9NWZ3.
    SMRiQ9NWZ3.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9NWZ3.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini20 – 104DeathAdd BLAST85
    Domaini186 – 454Protein kinasePROSITE-ProRule annotationAdd BLAST269

    Sequence similaritiesi

    Contains 1 death domain.Curated
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiKOG1187. Eukaryota.
    COG0515. LUCA.
    GeneTreeiENSGT00530000063073.
    HOGENOMiHOG000116550.
    HOVERGENiHBG066836.
    InParanoidiQ9NWZ3.
    KOiK04733.
    OMAiLAKCQHE.
    OrthoDBiEOG091G0YKT.
    PhylomeDBiQ9NWZ3.
    TreeFamiTF351380.

    Family and domain databases

    Gene3Di1.10.533.10. 1 hit.
    InterProiIPR011029. DEATH-like_dom.
    IPR017428. IL-1_rcpt-assoc_kin4.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    [Graphical view]
    PfamiPF07714. Pkinase_Tyr. 1 hit.
    [Graphical view]
    PIRSFiPIRSF038189. IRAK4. 1 hit.
    SMARTiSM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF47986. SSF47986. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q9NWZ3-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MNKPITPSTY VRCLNVGLIR KLSDFIDPQE GWKKLAVAIK KPSGDDRYNQ
    60 70 80 90 100
    FHIRRFEALL QTGKSPTSEL LFDWGTTNCT VGDLVDLLIQ NEFFAPASLL
    110 120 130 140 150
    LPDAVPKTAN TLPSKEAITV QQKQMPFCDK DRTLMTPVQN LEQSYMPPDS
    160 170 180 190 200
    SSPENKSLEV SDTRFHSFSF YELKNVTNNF DERPISVGGN KMGEGGFGVV
    210 220 230 240 250
    YKGYVNNTTV AVKKLAAMVD ITTEELKQQF DQEIKVMAKC QHENLVELLG
    260 270 280 290 300
    FSSDGDDLCL VYVYMPNGSL LDRLSCLDGT PPLSWHMRCK IAQGAANGIN
    310 320 330 340 350
    FLHENHHIHR DIKSANILLD EAFTAKISDF GLARASEKFA QTVMTSRIVG
    360 370 380 390 400
    TTAYMAPEAL RGEITPKSDI YSFGVVLLEI ITGLPAVDEH REPQLLLDIK
    410 420 430 440 450
    EEIEDEEKTI EDYIDKKMND ADSTSVEAMY SVASQCLHEK KNKRPDIKKV
    460
    QQLLQEMTAS
    Length:460
    Mass (Da):51,530
    Last modified:October 1, 2000 - v1
    Checksum:i6C8156ADF25FF81E
    GO
    Isoform 2 (identifier: Q9NWZ3-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-124: Missing.

    Show »
    Length:336
    Mass (Da):37,674
    Checksum:i6608D68A2EE4138C
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti81V → A in AAM15772 (PubMed:11960013).Curated1
    Sequence conflicti432V → G in AAD42884 (PubMed:10508479).Curated1
    Sequence conflicti437L → R in AAD42884 (PubMed:10508479).Curated1
    Sequence conflicti444R → S in AAD42884 (PubMed:10508479).Curated1
    Sequence conflicti451Q → H in AAD42884 (PubMed:10508479).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_0405885I → V Polymorphism; no effect on inhibition of NF-kappa-B activation; no effect on interaction with MYD88. 2 PublicationsCorresponds to variant rs56312115dbSNPEnsembl.1
    Natural variantiVAR_07288812R → C in IRAK4D; no effect on inhibition of NF-kappa-B complex activation; loss of interaction with MYD88; decreases protein stability. 2 PublicationsCorresponds to variant rs377584435dbSNPEnsembl.1
    Natural variantiVAR_07288920R → W Polymorphism; increases inhibition of NF-kappa-B complex activation; decreases interaction with MYD88; decreases protein stability. 1 PublicationCorresponds to variant rs143625818dbSNPEnsembl.1
    Natural variantiVAR_07289026I → T Polymorphism; no effect on inhibition of NF-kappa-B activation; no effect on interaction with MYD88. 1 PublicationCorresponds to variant rs138116867dbSNPEnsembl.1
    Natural variantiVAR_07289139I → V Polymorphism; no effect on inhibition of NF-kappa-B activation; no effect on interaction with MYD88. 1 PublicationCorresponds to variant rs113588409dbSNPEnsembl.1
    Natural variantiVAR_01935498S → R Polymorphism; no effect on inhibition of NF-kappa-B activation; no effect on interaction with MYD88. 2 PublicationsCorresponds to variant rs4251469dbSNPEnsembl.1
    Natural variantiVAR_072892298G → D in IRAK4D; decreases inhibition of NF-kappa-B complex activation; impairs neutrophil migration and phagocytosis. 3 PublicationsCorresponds to variant rs568782766dbSNPEnsembl.1
    Natural variantiVAR_040589355M → V.1 PublicationCorresponds to variant rs142376871dbSNPEnsembl.1
    Natural variantiVAR_019355390H → R.1 PublicationCorresponds to variant rs4251583dbSNPEnsembl.1
    Natural variantiVAR_040590391R → H Found in a patient with IRAK4D in association with C-12; probable neutral polymorphism. 2 PublicationsCorresponds to variant rs55944915dbSNPEnsembl.1
    Natural variantiVAR_019356428A → T.2 PublicationsCorresponds to variant rs4251545dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0415561 – 124Missing in isoform 2. 2 PublicationsAdd BLAST124

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF445802 mRNA. Translation: AAM15772.1.
    AF155118 mRNA. Translation: AAD42884.1.
    AY340964 mRNA. Translation: AAR02360.1.
    AY340965 mRNA. Translation: AAR02361.1.
    AY340966 mRNA. Translation: AAR02362.1.
    AY340967 mRNA. Translation: AAR02363.1.
    AK000528 mRNA. Translation: BAA91232.1.
    AK299944 mRNA. Translation: BAG61774.1.
    AY186092 Genomic DNA. Translation: AAN75440.1.
    AC093012 Genomic DNA. No translation available.
    BC013316 mRNA. Translation: AAH13316.1.
    CCDSiCCDS44862.1. [Q9NWZ3-2]
    CCDS8744.1. [Q9NWZ3-1]
    RefSeqiNP_001107654.1. NM_001114182.2. [Q9NWZ3-1]
    NP_001138728.1. NM_001145256.1. [Q9NWZ3-2]
    NP_001138729.1. NM_001145257.1. [Q9NWZ3-2]
    NP_001138730.1. NM_001145258.1. [Q9NWZ3-2]
    NP_057207.2. NM_016123.3. [Q9NWZ3-1]
    XP_005269000.1. XM_005268943.3. [Q9NWZ3-1]
    XP_005269001.1. XM_005268944.4. [Q9NWZ3-1]
    XP_005269002.1. XM_005268945.4. [Q9NWZ3-1]
    XP_005269004.1. XM_005268947.4. [Q9NWZ3-2]
    XP_005269005.1. XM_005268948.2. [Q9NWZ3-2]
    XP_005269006.1. XM_005268949.2. [Q9NWZ3-2]
    XP_006719501.1. XM_006719438.3. [Q9NWZ3-1]
    XP_006719502.1. XM_006719439.2. [Q9NWZ3-2]
    XP_011536733.1. XM_011538431.2. [Q9NWZ3-1]
    XP_011536734.1. XM_011538432.1. [Q9NWZ3-1]
    XP_011536735.1. XM_011538433.2. [Q9NWZ3-1]
    XP_016874879.1. XM_017019390.1. [Q9NWZ3-1]
    XP_016874880.1. XM_017019391.1. [Q9NWZ3-2]
    UniGeneiHs.138499.

    Genome annotation databases

    EnsembliENST00000431837; ENSP00000390327; ENSG00000198001. [Q9NWZ3-2]
    ENST00000440781; ENSP00000408734; ENSG00000198001. [Q9NWZ3-2]
    ENST00000551736; ENSP00000446490; ENSG00000198001. [Q9NWZ3-1]
    ENST00000613694; ENSP00000479889; ENSG00000198001. [Q9NWZ3-1]
    GeneIDi51135.
    KEGGihsa:51135.
    UCSCiuc001rnt.4. human. [Q9NWZ3-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    IRAK4base

    IRAK4 mutation db

    SeattleSNPs

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF445802 mRNA. Translation: AAM15772.1.
    AF155118 mRNA. Translation: AAD42884.1.
    AY340964 mRNA. Translation: AAR02360.1.
    AY340965 mRNA. Translation: AAR02361.1.
    AY340966 mRNA. Translation: AAR02362.1.
    AY340967 mRNA. Translation: AAR02363.1.
    AK000528 mRNA. Translation: BAA91232.1.
    AK299944 mRNA. Translation: BAG61774.1.
    AY186092 Genomic DNA. Translation: AAN75440.1.
    AC093012 Genomic DNA. No translation available.
    BC013316 mRNA. Translation: AAH13316.1.
    CCDSiCCDS44862.1. [Q9NWZ3-2]
    CCDS8744.1. [Q9NWZ3-1]
    RefSeqiNP_001107654.1. NM_001114182.2. [Q9NWZ3-1]
    NP_001138728.1. NM_001145256.1. [Q9NWZ3-2]
    NP_001138729.1. NM_001145257.1. [Q9NWZ3-2]
    NP_001138730.1. NM_001145258.1. [Q9NWZ3-2]
    NP_057207.2. NM_016123.3. [Q9NWZ3-1]
    XP_005269000.1. XM_005268943.3. [Q9NWZ3-1]
    XP_005269001.1. XM_005268944.4. [Q9NWZ3-1]
    XP_005269002.1. XM_005268945.4. [Q9NWZ3-1]
    XP_005269004.1. XM_005268947.4. [Q9NWZ3-2]
    XP_005269005.1. XM_005268948.2. [Q9NWZ3-2]
    XP_005269006.1. XM_005268949.2. [Q9NWZ3-2]
    XP_006719501.1. XM_006719438.3. [Q9NWZ3-1]
    XP_006719502.1. XM_006719439.2. [Q9NWZ3-2]
    XP_011536733.1. XM_011538431.2. [Q9NWZ3-1]
    XP_011536734.1. XM_011538432.1. [Q9NWZ3-1]
    XP_011536735.1. XM_011538433.2. [Q9NWZ3-1]
    XP_016874879.1. XM_017019390.1. [Q9NWZ3-1]
    XP_016874880.1. XM_017019391.1. [Q9NWZ3-2]
    UniGeneiHs.138499.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2NRUX-ray2.00A/B/C/D154-460[»]
    2NRYX-ray2.15A/B/C/D154-460[»]
    2O8YX-ray2.40A/B163-460[»]
    2OIBX-ray2.00A/B/C/D160-460[»]
    2OICX-ray2.40A/B/C/D160-460[»]
    2OIDX-ray2.30A/B/C/D160-460[»]
    3MOPX-ray3.40G/H/I/J4-106[»]
    4RMZX-ray2.20A/B154-460[»]
    4U97X-ray2.65A/B154-460[»]
    4U9AX-ray2.80A/B154-460[»]
    4XS2X-ray2.73A/B/C/D160-460[»]
    4Y73X-ray2.14A/B/C/D160-460[»]
    4YO6X-ray2.32A/B/C/D160-460[»]
    4YP8X-ray2.64A/B/C/D160-460[»]
    4ZTLX-ray2.39A/B/C/D160-460[»]
    4ZTMX-ray2.66A/B/C/D160-460[»]
    4ZTNX-ray2.23A/B/C/D160-460[»]
    5KX7X-ray2.80A/B160-460[»]
    5KX8X-ray2.67A/B/C/D160-460[»]
    ProteinModelPortaliQ9NWZ3.
    SMRiQ9NWZ3.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi119322. 26 interactors.
    DIPiDIP-31351N.
    IntActiQ9NWZ3. 14 interactors.
    MINTiMINT-1383671.
    STRINGi9606.ENSP00000390651.

    Chemistry databases

    BindingDBiQ9NWZ3.
    ChEMBLiCHEMBL3778.
    GuidetoPHARMACOLOGYi2045.

    PTM databases

    iPTMnetiQ9NWZ3.
    PhosphoSitePlusiQ9NWZ3.

    Polymorphism and mutation databases

    BioMutaiIRAK4.
    DMDMi50401181.

    Proteomic databases

    EPDiQ9NWZ3.
    MaxQBiQ9NWZ3.
    PaxDbiQ9NWZ3.
    PeptideAtlasiQ9NWZ3.
    PRIDEiQ9NWZ3.

    Protocols and materials databases

    DNASUi51135.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000431837; ENSP00000390327; ENSG00000198001. [Q9NWZ3-2]
    ENST00000440781; ENSP00000408734; ENSG00000198001. [Q9NWZ3-2]
    ENST00000551736; ENSP00000446490; ENSG00000198001. [Q9NWZ3-1]
    ENST00000613694; ENSP00000479889; ENSG00000198001. [Q9NWZ3-1]
    GeneIDi51135.
    KEGGihsa:51135.
    UCSCiuc001rnt.4. human. [Q9NWZ3-1]

    Organism-specific databases

    CTDi51135.
    DisGeNETi51135.
    GeneCardsiIRAK4.
    HGNCiHGNC:17967. IRAK4.
    HPAiCAB016685.
    CAB022077.
    HPA000924.
    MalaCardsiIRAK4.
    MIMi606883. gene.
    607676. phenotype.
    610799. phenotype.
    neXtProtiNX_Q9NWZ3.
    OpenTargetsiENSG00000198001.
    Orphaneti70592. Immunodeficiency due to interleukin-1 receptor-associated kinase-4 deficiency.
    PharmGKBiPA134914577.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG1187. Eukaryota.
    COG0515. LUCA.
    GeneTreeiENSGT00530000063073.
    HOGENOMiHOG000116550.
    HOVERGENiHBG066836.
    InParanoidiQ9NWZ3.
    KOiK04733.
    OMAiLAKCQHE.
    OrthoDBiEOG091G0YKT.
    PhylomeDBiQ9NWZ3.
    TreeFamiTF351380.

    Enzyme and pathway databases

    BioCyciZFISH:HS03405-MONOMER.
    ReactomeiR-HSA-166058. MyD88:Mal cascade initiated on plasma membrane.
    R-HSA-446652. Interleukin-1 signaling.
    R-HSA-5602498. MyD88 deficiency (TLR2/4).
    R-HSA-5602680. MyD88 deficiency (TLR5).
    R-HSA-5603037. IRAK4 deficiency (TLR5).
    R-HSA-5603041. IRAK4 deficiency (TLR2/4).
    R-HSA-975110. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
    R-HSA-975138. TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
    R-HSA-975155. MyD88 dependent cascade initiated on endosome.
    R-HSA-975871. MyD88 cascade initiated on plasma membrane.
    SignaLinkiQ9NWZ3.
    SIGNORiQ9NWZ3.

    Miscellaneous databases

    ChiTaRSiIRAK4. human.
    EvolutionaryTraceiQ9NWZ3.
    GenomeRNAii51135.
    PROiQ9NWZ3.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000198001.
    CleanExiHS_IRAK4.
    ExpressionAtlasiQ9NWZ3. baseline and differential.
    GenevisibleiQ9NWZ3. HS.

    Family and domain databases

    Gene3Di1.10.533.10. 1 hit.
    InterProiIPR011029. DEATH-like_dom.
    IPR017428. IL-1_rcpt-assoc_kin4.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    [Graphical view]
    PfamiPF07714. Pkinase_Tyr. 1 hit.
    [Graphical view]
    PIRSFiPIRSF038189. IRAK4. 1 hit.
    SMARTiSM00220. S_TKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF47986. SSF47986. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiIRAK4_HUMAN
    AccessioniPrimary (citable) accession number: Q9NWZ3
    Secondary accession number(s): Q69FE1, Q8TDF7, Q9Y589
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 19, 2004
    Last sequence update: October 1, 2000
    Last modified: November 30, 2016
    This is version 161 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 12
      Human chromosome 12: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    7. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.