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Q9NWZ3 (IRAK4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 133. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Interleukin-1 receptor-associated kinase 4

Short name=IRAK-4
EC=2.7.11.1
Alternative name(s):
Renal carcinoma antigen NY-REN-64
Gene names
Name:IRAK4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length460 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.1 Ref.9 Ref.11 Ref.15 Ref.16 Ref.18 Ref.23

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium.

Subunit structure

Associates with MYD88 and IRAK2 to form a ternary complex called the Myddosome. Once phosphorylated, IRAK4 dissociates from the receptor complex and then associates with the TNF receptor-associated factor 6 (TRAF6), IRAK1, and PELI1; this intermediate complex is required for subsequent NF-kappa-B activation. Direct binding of SMAD6 to PELI1 prevents complex formation and hence negatively regulates IL1R-TLR signaling and eventually NF-kappa-B-mediated gene expression. Interacts with IL1RL1. Ref.1 Ref.8 Ref.13 Ref.14

Subcellular location

Cytoplasm Ref.26.

Post-translational modification

Phosphorylated By similarity. Ref.29 Ref.30 Ref.31

Involvement in disease

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. Ref.17

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. Ref.10 Ref.12

Sequence similarities

Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Pelle subfamily.

Contains 1 death domain.

Contains 1 protein kinase domain.

Biophysicochemical properties

Kinetic parameters:

KM=650 µM for ATP (at pH 7.5) Ref.31

KM=1100 µM for substrate (at pH 7.5)

Ontologies

Keywords
   Biological processImmunity
Innate immunity
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandATP-binding
Magnesium
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processJNK cascade

Inferred from electronic annotation. Source: Ensembl

MyD88-dependent toll-like receptor signaling pathway

Traceable author statement Ref.27. Source: UniProtKB

cytokine production

Inferred from electronic annotation. Source: Ensembl

cytokine-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

innate immune response

Traceable author statement Ref.27. Source: UniProtKB

positive regulation of smooth muscle cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

toll-like receptor 10 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 5 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 9 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR1:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR6:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement Ref.27. Source: UniProtKB

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

endosome membrane

Traceable author statement. Source: Reactome

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

magnesium ion binding

Inferred from electronic annotation. Source: InterPro

protein kinase activity

Inferred from experiment. Source: Reactome

protein serine/threonine kinase activity

Inferred from experiment. Source: Reactome

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PELI2Q9HAT83EBI-448378,EBI-448407
TIRAPP587532EBI-448378,EBI-528644

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NWZ3-1)

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.
Isoform 2 (identifier: Q9NWZ3-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 460460Interleukin-1 receptor-associated kinase 4
PRO_0000086035

Regions

Domain20 – 10485Death
Domain186 – 454269Protein kinase
Nucleotide binding192 – 2009ATP By similarity
Nucleotide binding313 – 3164ATP

Sites

Active site3111Proton acceptor By similarity
Binding site2131ATP
Binding site3291ATP

Amino acid modifications

Modified residue11N-acetylmethionine Ref.28
Modified residue341N6-acetyllysine Ref.22
Modified residue3421Phosphothreonine Ref.30 Ref.31
Modified residue3451Phosphothreonine Ref.29 Ref.30 Ref.31
Modified residue3461Phosphoserine Ref.29 Ref.31

Natural variations

Alternative sequence1 – 124124Missing in isoform 2.
VSP_041556
Natural variant51I → V. Ref.33
Corresponds to variant rs56312115 [ dbSNP | Ensembl ].
VAR_040588
Natural variant981S → R. Ref.5
Corresponds to variant rs4251469 [ dbSNP | Ensembl ].
VAR_019354
Natural variant3551M → V. Ref.33
VAR_040589
Natural variant3901H → R. Ref.5
Corresponds to variant rs4251583 [ dbSNP | Ensembl ].
VAR_019355
Natural variant3911R → H. Ref.33
Corresponds to variant rs55944915 [ dbSNP | Ensembl ].
VAR_040590
Natural variant4281A → T. Ref.5 Ref.33
Corresponds to variant rs4251545 [ dbSNP | Ensembl ].
VAR_019356

Experimental info

Mutagenesis2131K → A: Loss of kinase activity. Ref.11
Sequence conflict811V → A in AAM15772. Ref.1
Sequence conflict4321V → G in AAD42884. Ref.2
Sequence conflict4371L → R in AAD42884. Ref.2
Sequence conflict4441R → S in AAD42884. Ref.2
Sequence conflict4511Q → H in AAD42884. Ref.2

Secondary structure

.......................................................................... 460
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: 6C8156ADF25FF81E

FASTA46051,530
        10         20         30         40         50         60 
MNKPITPSTY VRCLNVGLIR KLSDFIDPQE GWKKLAVAIK KPSGDDRYNQ FHIRRFEALL 

        70         80         90        100        110        120 
QTGKSPTSEL LFDWGTTNCT VGDLVDLLIQ NEFFAPASLL LPDAVPKTAN TLPSKEAITV 

       130        140        150        160        170        180 
QQKQMPFCDK DRTLMTPVQN LEQSYMPPDS SSPENKSLEV SDTRFHSFSF YELKNVTNNF 

       190        200        210        220        230        240 
DERPISVGGN KMGEGGFGVV YKGYVNNTTV AVKKLAAMVD ITTEELKQQF DQEIKVMAKC 

       250        260        270        280        290        300 
QHENLVELLG FSSDGDDLCL VYVYMPNGSL LDRLSCLDGT PPLSWHMRCK IAQGAANGIN 

       310        320        330        340        350        360 
FLHENHHIHR DIKSANILLD EAFTAKISDF GLARASEKFA QTVMTSRIVG TTAYMAPEAL 

       370        380        390        400        410        420 
RGEITPKSDI YSFGVVLLEI ITGLPAVDEH REPQLLLDIK EEIEDEEKTI EDYIDKKMND 

       430        440        450        460 
ADSTSVEAMY SVASQCLHEK KNKRPDIKKV QQLLQEMTAS 

« Hide

Isoform 2 [UniParc].

Checksum: 6608D68A2EE4138C
Show »

FASTA33637,674

References

« Hide 'large scale' references
[1]"IRAK4: a novel member of the IRAK family with the properties of an IRAK-kinase."
Li S., Strelow A., Fontana E.J., Wesche H.
Proc. Natl. Acad. Sci. U.S.A. 99:5567-5572(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH IRAK1 AND TRAF6.
[2]"Antigens recognized by autologous antibody in patients with renal-cell carcinoma."
Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., Old L.J.
Int. J. Cancer 83:456-464(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), IDENTIFICATION AS A RENAL CANCER ANTIGEN.
[3]"Human interleukin-1 receptor associated kinase 4 cDNA sequences."
Chuang T.H., Ulevitch R.J.
Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Spleen.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
[5]SeattleSNPs variation discovery resource
Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-98; ARG-390 AND THR-428.
[6]"The finished DNA sequence of human chromosome 12."
Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. expand/collapse author list , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[8]"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."
Jiang Z., Johnson H.J., Nie H., Qin J., Bird T.A., Li X.
J. Biol. Chem. 278:10952-10956(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IRAK1; PELI1 AND TRAF6.
[9]"Inhibition of interleukin 1 receptor/Toll-like receptor signaling through the alternatively spliced, short form of MyD88 is due to its failure to recruit IRAK-4."
Burns K., Janssens S., Brissoni B., Olivos N., Beyaert R., Tschopp J.
J. Exp. Med. 197:263-268(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF IRAK1.
[10]"Distinct mutations in IRAK-4 confer hyporesponsiveness to lipopolysaccharide and interleukin-1 in a patient with recurrent bacterial infections."
Medvedev A.E., Lentschat A., Kuhns D.B., Blanco J.C.G., Salkowski C., Zhang S., Arditi M., Gallin J.I., Vogel S.N.
J. Exp. Med. 198:521-531(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN IRAK4D.
[11]"IRAK4 kinase activity is redundant for interleukin-1 (IL-1) receptor-associated kinase phosphorylation and IL-1 responsiveness."
Qin J., Jiang Z., Qian Y., Casanova J.-L., Li X.
J. Biol. Chem. 279:26748-26753(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF LYS-213.
[12]"Pyogenic bacterial infections in humans with IRAK-4 deficiency."
Picard C., Puel A., Bonnet M., Ku C.-L., Bustamante J., Yang K., Soudais C., Dupuis S., Feinberg J., Fieschi C., Elbim C., Hitchcock R., Lammas D., Davies G., Al-Ghonaium A., Al-Rayes H., Al-Jumaah S., Al-Hajjar S. expand/collapse author list , Al-Mohsen I.Z., Frayha H.H., Rucker R., Hawn T.R., Aderem A., Tufenkeji H., Haraguchi S., Day N.K., Good R.A., Gougerot-Pocidalo M.-A., Ozinsky A., Casanova J.-L.
Science 299:2076-2079(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN IRAK4D.
[13]"IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST 2 and induces T helper type 2-associated cytokines."
Schmitz J., Owyang A., Oldham E., Song Y., Murphy E., McClanahan T.K., Zurawski G., Moshrefi M., Qin J., Li X., Gorman D.M., Bazan J.F., Kastelein R.A.
Immunity 23:479-490(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH IL1RL1.
[14]"Smad6 negatively regulates interleukin 1-receptor-Toll-like receptor signaling through direct interaction with the adaptor Pellino-1."
Choi K.C., Lee Y.S., Lim S., Choi H.K., Lee C.H., Lee E.K., Hong S., Kim I.H., Kim S.J., Park S.H.
Nat. Immunol. 7:1057-1065(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN COMPLEX WITH IRAK1; MYD88; PELI1 AND TRAF6.
[15]"Cross-talk between IRAK-4 and the NADPH oxidase."
Pacquelet S., Johnson J.L., Ellis B.A., Brzezinska A.A., Lane W.S., Munafo D.B., Catz S.D.
Biochem. J. 403:451-461(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF NCF1.
[16]"IRAK-4 kinase activity is required for interleukin-1 (IL-1) receptor- and toll-like receptor 7-mediated signaling and gene expression."
Koziczak-Holbro M., Joyce C., Gluck A., Kinzel B., Muller M., Tschopp C., Mathison J.C., Davis C.N., Gram H.
J. Biol. Chem. 282:13552-13560(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN TLR7 SIGNALING PATHWAY.
[17]"IRAK4 and NEMO mutations in otherwise healthy children with recurrent invasive pneumococcal disease."
Ku C.-L., Picard C., Erdos M., Jeurissen A., Bustamante J., Puel A., von Bernuth H., Filipe-Santos O., Chang H.-H., Lawrence T., Raes M., Marodi L., Bossuyt X., Casanova J.-L.
J. Med. Genet. 44:16-23(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN IPD1.
[18]"The IRAK-catalysed activation of the E3 ligase function of Pellino isoforms induces the Lys63-linked polyubiquitination of IRAK1."
Ordureau A., Smith H., Windheim M., Peggie M., Carrick E., Morrice N., Cohen P.
Biochem. J. 409:43-52(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF PELI1.
[19]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[20]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[21]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[22]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-34, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]"IRAK1 and IRAK4 promote phosphorylation, ubiquitination, and degradation of MyD88 adaptor-like (Mal)."
Dunne A., Carpenter S., Brikos C., Gray P., Strelow A., Wesche H., Morrice N., O'Neill L.A.
J. Biol. Chem. 285:18276-18282(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF TIRAP.
[24]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[25]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[26]"Natural loss-of-function mutation of myeloid differentiation protein 88 disrupts its ability to form Myddosomes."
Nagpal K., Plantinga T.S., Sirois C.M., Monks B.G., Latz E., Netea M.G., Golenbock D.T.
J. Biol. Chem. 286:11875-11882(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[27]"What the Myddosome structure tells us about the initiation of innate immunity."
Gay N.J., Gangloff M., O'Neill L.A.
Trends Immunol. 32:104-109(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON MYDDOSOME.
[28]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[29]"Crystal structures of IRAK-4 kinase in complex with inhibitors: a serine/threonine kinase with tyrosine as a gatekeeper."
Wang Z., Liu J., Sudom A., Ayres M., Li S., Wesche H., Powers J.P., Walker N.P.C.
Structure 14:1835-1844(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 154-460 IN COMPLEX WITH INHIBITORS, PHOSPHORYLATION AT THR-345 AND SER-346.
[30]"Crystal structures of the apo and inhibited IRAK4 kinase domain."
Mol C.D., Arduini R.M., Baker D.P., Chien E.Y., Dougan D.R., Friedman J., Gibaja V., Hession C.A., Horne A.
Submitted (DEC-2006) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 163-460, PHOSPHORYLATION AT THR-342 AND THR-345.
[31]"Cutting Edge: IL-1 receptor-associated kinase 4 structures reveal novel features and multiple conformations."
Kuglstatter A., Villasenor A.G., Shaw D., Lee S.W., Tsing S., Niu L., Song K.W., Barnett J.W., Browner M.F.
J. Immunol. 178:2641-2645(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 160-460 IN COMPLEX WITH ATP ANALOGS, PHOSPHORYLATION AT THR-342; THR-345 AND SER-346, BIOPHYSICOCHEMICAL PROPERTIES.
[32]"Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling."
Lin S.-C., Lo Y.-C., Wu H.
Nature 465:885-890(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.40 ANGSTROMS) OF 4-106.
[33]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-5; VAL-355; HIS-391 AND THR-428.
+Additional computationally mapped references.

Web resources

IRAK4base

IRAK4 mutation db

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001107654.1. NM_001114182.2.
NP_001138728.1. NM_001145256.1.
NP_001138729.1. NM_001145257.1.
NP_001138730.1. NM_001145258.1.
NP_057207.2. NM_016123.3.
XP_005269000.1. XM_005268943.2.
XP_005269001.1. XM_005268944.2.
XP_005269002.1. XM_005268945.2.
XP_005269003.1. XM_005268946.2.
XP_005269004.1. XM_005268947.2.
XP_005269005.1. XM_005268948.1.
XP_005269006.1. XM_005268949.1.
UniGeneHs.138499.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalQ9NWZ3.
SMRQ9NWZ3. Positions 4-458.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119322. 26 interactions.
DIPDIP-31351N.
IntActQ9NWZ3. 11 interactions.
MINTMINT-1383671.
STRING9606.ENSP00000349096.

Chemistry

BindingDBQ9NWZ3.
ChEMBLCHEMBL3778.
GuidetoPHARMACOLOGY2045.

Polymorphism databases

DMDM50401181.

Proteomic databases

PaxDbQ9NWZ3.
PRIDEQ9NWZ3.

Protocols and materials databases

DNASU51135.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000431837; ENSP00000390327; ENSG00000198001. [Q9NWZ3-2]
ENST00000440781; ENSP00000408734; ENSG00000198001. [Q9NWZ3-2]
ENST00000448290; ENSP00000390651; ENSG00000198001. [Q9NWZ3-1]
ENST00000551736; ENSP00000446490; ENSG00000198001. [Q9NWZ3-1]
GeneID51135.
KEGGhsa:51135.
UCSCuc001rnt.3. human. [Q9NWZ3-1]

Organism-specific databases

CTD51135.
GeneCardsGC12P044152.
HGNCHGNC:17967. IRAK4.
HPACAB016685.
CAB022077.
HPA000924.
MIM606883. gene.
607676. phenotype.
610799. phenotype.
neXtProtNX_Q9NWZ3.
Orphanet70592. Immunodeficiency due to interleukin-1 receptor-associated kinase-4 deficiency.
PharmGKBPA134914577.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000116550.
HOVERGENHBG066836.
InParanoidQ9NWZ3.
KOK04733.
OMAYMPPDSS.
OrthoDBEOG7MD4Q1.
PhylomeDBQ9NWZ3.
TreeFamTF351380.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
SignaLinkQ9NWZ3.

Gene expression databases

ArrayExpressQ9NWZ3.
BgeeQ9NWZ3.
CleanExHS_IRAK4.
GenevestigatorQ9NWZ3.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
InterProIPR011029. DEATH-like_dom.
IPR017428. IL-1_rcpt-assoc_kin4.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFPIRSF038189. IRAK4. 1 hit.
SUPFAMSSF47986. SSF47986. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9NWZ3.
GenomeRNAi51135.
NextBio53983.
PROQ9NWZ3.
SOURCESearch...

Entry information

Entry nameIRAK4_HUMAN
AccessionPrimary (citable) accession number: Q9NWZ3
Secondary accession number(s): Q69FE1, Q8TDF7, Q9Y589
Entry history
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: October 1, 2000
Last modified: April 16, 2014
This is version 133 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM