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Q9NWZ3

- IRAK4_HUMAN

UniProt

Q9NWZ3 - IRAK4_HUMAN

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Protein

Interleukin-1 receptor-associated kinase 4

Gene
IRAK4
Organism
Homo sapiens (Human)
Status
Reviewed - 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. 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.7 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Magnesium.

Kineticsi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei213 – 2131ATP
Active sitei311 – 3111Proton acceptor By similarity
Binding sitei329 – 3291ATP

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi192 – 2009ATP By similarity
Nucleotide bindingi313 – 3164ATP

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. magnesium ion binding Source: InterPro
  3. protein binding Source: IntAct
  4. protein kinase activity Source: Reactome
  5. protein serine/threonine kinase activity Source: Reactome

GO - Biological processi

  1. cytokine-mediated signaling pathway Source: Ensembl
  2. cytokine production Source: Ensembl
  3. innate immune response Source: UniProtKB
  4. JNK cascade Source: Ensembl
  5. MyD88-dependent toll-like receptor signaling pathway Source: UniProtKB
  6. positive regulation of smooth muscle cell proliferation Source: Ensembl
  7. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  8. toll-like receptor 10 signaling pathway Source: Reactome
  9. toll-like receptor 2 signaling pathway Source: Reactome
  10. toll-like receptor 4 signaling pathway Source: Reactome
  11. toll-like receptor 5 signaling pathway Source: Reactome
  12. toll-like receptor 9 signaling pathway Source: Reactome
  13. toll-like receptor signaling pathway Source: UniProtKB
  14. toll-like receptor TLR1:TLR2 signaling pathway Source: Reactome
  15. toll-like receptor TLR6:TLR2 signaling pathway Source: Reactome
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

ReactomeiREACT_22442. Interleukin-1 signaling.
REACT_25024. TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
REACT_25120. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
REACT_25222. MyD88 dependent cascade initiated on endosome.
REACT_27215. MyD88 cascade initiated on plasma membrane.
REACT_6788. MyD88:Mal cascade initiated on plasma membrane.
SignaLinkiQ9NWZ3.

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
ProteomesiUP000005640: Chromosome 12

Organism-specific databases

HGNCiHGNC:17967. IRAK4.

Subcellular locationi

Cytoplasm 1 Publication

GO - Cellular componenti

  1. cytosol Source: Reactome
  2. endosome membrane Source: Reactome
  3. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

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.1 Publication
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.2 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi213 – 2131K → A: Loss of kinase activity. 1 Publication

Organism-specific databases

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 460460Interleukin-1 receptor-associated kinase 4PRO_0000086035Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionine1 Publication
Modified residuei34 – 341N6-acetyllysine1 Publication
Modified residuei342 – 3421Phosphothreonine2 Publications
Modified residuei345 – 3451Phosphothreonine3 Publications
Modified residuei346 – 3461Phosphoserine2 Publications

Post-translational modificationi

Phosphorylated By similarity.3 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ9NWZ3.
PaxDbiQ9NWZ3.
PRIDEiQ9NWZ3.

Expressioni

Gene expression databases

ArrayExpressiQ9NWZ3.
BgeeiQ9NWZ3.
CleanExiHS_IRAK4.
GenevestigatoriQ9NWZ3.

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 IL1RL1.4 Publications

Binary interactionsi

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

Protein-protein interaction databases

BioGridi119322. 26 interactions.
DIPiDIP-31351N.
IntActiQ9NWZ3. 11 interactions.
MINTiMINT-1383671.
STRINGi9606.ENSP00000349096.

Structurei

Secondary structure

1
460
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi11 – 133
Helixi16 – 2611
Helixi31 – 388
Beta strandi42 – 487
Helixi50 – 578
Helixi58 – 603
Turni61 – 633
Helixi66 – 738
Turni74 – 774
Helixi81 – 899
Turni90 – 923
Helixi94 – 1007
Beta strandi102 – 1043
Beta strandi166 – 1683
Helixi170 – 1767
Turni177 – 1804
Turni185 – 1884
Beta strandi191 – 1944
Beta strandi196 – 20712
Beta strandi209 – 2157
Turni223 – 2253
Helixi226 – 23914
Beta strandi248 – 2525
Beta strandi254 – 2574
Beta strandi259 – 2635
Helixi270 – 2756
Helixi277 – 2793
Helixi285 – 30420
Helixi314 – 3163
Beta strandi317 – 3193
Beta strandi325 – 3273
Helixi352 – 3543
Helixi357 – 3604
Helixi367 – 38216
Beta strandi391 – 3955
Helixi398 – 4047
Helixi410 – 4134
Helixi423 – 43614
Turni441 – 4433
Helixi447 – 45711

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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[»]
ProteinModelPortaliQ9NWZ3.
SMRiQ9NWZ3. Positions 4-458.

Miscellaneous databases

EvolutionaryTraceiQ9NWZ3.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini20 – 10485DeathAdd
BLAST
Domaini186 – 454269Protein kinaseAdd
BLAST

Sequence similaritiesi

Contains 1 death domain.

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000116550.
HOVERGENiHBG066836.
InParanoidiQ9NWZ3.
KOiK04733.
OMAiYMPPDSS.
OrthoDBiEOG7MD4Q1.
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.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFiPIRSF038189. IRAK4. 1 hit.
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. Align

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

MNKPITPSTY VRCLNVGLIR KLSDFIDPQE GWKKLAVAIK KPSGDDRYNQ    50
FHIRRFEALL QTGKSPTSEL LFDWGTTNCT VGDLVDLLIQ NEFFAPASLL 100
LPDAVPKTAN TLPSKEAITV QQKQMPFCDK DRTLMTPVQN LEQSYMPPDS 150
SSPENKSLEV SDTRFHSFSF YELKNVTNNF DERPISVGGN KMGEGGFGVV 200
YKGYVNNTTV AVKKLAAMVD ITTEELKQQF DQEIKVMAKC QHENLVELLG 250
FSSDGDDLCL VYVYMPNGSL LDRLSCLDGT PPLSWHMRCK IAQGAANGIN 300
FLHENHHIHR DIKSANILLD EAFTAKISDF GLARASEKFA QTVMTSRIVG 350
TTAYMAPEAL RGEITPKSDI YSFGVVLLEI ITGLPAVDEH REPQLLLDIK 400
EEIEDEEKTI EDYIDKKMND ADSTSVEAMY SVASQCLHEK KNKRPDIKKV 450
QQLLQEMTAS 460
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

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti5 – 51I → V.1 Publication
Corresponds to variant rs56312115 [ dbSNP | Ensembl ].
VAR_040588
Natural varianti98 – 981S → R.1 Publication
Corresponds to variant rs4251469 [ dbSNP | Ensembl ].
VAR_019354
Natural varianti355 – 3551M → V.1 Publication
VAR_040589
Natural varianti390 – 3901H → R.1 Publication
Corresponds to variant rs4251583 [ dbSNP | Ensembl ].
VAR_019355
Natural varianti391 – 3911R → H.1 Publication
Corresponds to variant rs55944915 [ dbSNP | Ensembl ].
VAR_040590
Natural varianti428 – 4281A → T.2 Publications
Corresponds to variant rs4251545 [ dbSNP | Ensembl ].
VAR_019356

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 124124Missing in isoform 2. VSP_041556Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti81 – 811V → A in AAM15772. 1 Publication
Sequence conflicti432 – 4321V → G in AAD42884. 1 Publication
Sequence conflicti437 – 4371L → R in AAD42884. 1 Publication
Sequence conflicti444 – 4441R → S in AAD42884. 1 Publication
Sequence conflicti451 – 4511Q → H in AAD42884. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_005268943.2. [Q9NWZ3-1]
XP_005269001.1. XM_005268944.2. [Q9NWZ3-1]
XP_005269002.1. XM_005268945.2. [Q9NWZ3-1]
XP_005269003.1. XM_005268946.2. [Q9NWZ3-1]
XP_005269004.1. XM_005268947.2. [Q9NWZ3-2]
XP_005269005.1. XM_005268948.1. [Q9NWZ3-2]
XP_005269006.1. XM_005268949.1. [Q9NWZ3-2]
XP_006719501.1. XM_006719438.1. [Q9NWZ3-1]
XP_006719502.1. XM_006719439.1. [Q9NWZ3-2]
UniGeneiHs.138499.

Genome annotation databases

EnsembliENST00000431837; ENSP00000390327; ENSG00000198001. [Q9NWZ3-2]
ENST00000440781; ENSP00000408734; ENSG00000198001. [Q9NWZ3-2]
ENST00000448290; ENSP00000390651; ENSG00000198001. [Q9NWZ3-1]
ENST00000551736; ENSP00000446490; ENSG00000198001. [Q9NWZ3-1]
GeneIDi51135.
KEGGihsa:51135.
UCSCiuc001rnt.3. human. [Q9NWZ3-1]

Polymorphism databases

DMDMi50401181.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

IRAK4base

IRAK4 mutation db

SeattleSNPs

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS44862.1. [Q9NWZ3-2 ]
CCDS8744.1. [Q9NWZ3-1 ]
RefSeqi NP_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_005268943.2. [Q9NWZ3-1 ]
XP_005269001.1. XM_005268944.2. [Q9NWZ3-1 ]
XP_005269002.1. XM_005268945.2. [Q9NWZ3-1 ]
XP_005269003.1. XM_005268946.2. [Q9NWZ3-1 ]
XP_005269004.1. XM_005268947.2. [Q9NWZ3-2 ]
XP_005269005.1. XM_005268948.1. [Q9NWZ3-2 ]
XP_005269006.1. XM_005268949.1. [Q9NWZ3-2 ]
XP_006719501.1. XM_006719438.1. [Q9NWZ3-1 ]
XP_006719502.1. XM_006719439.1. [Q9NWZ3-2 ]
UniGenei Hs.138499.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2NRU X-ray 2.00 A/B/C/D 154-460 [» ]
2NRY X-ray 2.15 A/B/C/D 154-460 [» ]
2O8Y X-ray 2.40 A/B 163-460 [» ]
2OIB X-ray 2.00 A/B/C/D 160-460 [» ]
2OIC X-ray 2.40 A/B/C/D 160-460 [» ]
2OID X-ray 2.30 A/B/C/D 160-460 [» ]
3MOP X-ray 3.40 G/H/I/J 4-106 [» ]
ProteinModelPortali Q9NWZ3.
SMRi Q9NWZ3. Positions 4-458.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 119322. 26 interactions.
DIPi DIP-31351N.
IntActi Q9NWZ3. 11 interactions.
MINTi MINT-1383671.
STRINGi 9606.ENSP00000349096.

Chemistry

BindingDBi Q9NWZ3.
ChEMBLi CHEMBL3778.
GuidetoPHARMACOLOGYi 2045.

Polymorphism databases

DMDMi 50401181.

Proteomic databases

MaxQBi Q9NWZ3.
PaxDbi Q9NWZ3.
PRIDEi Q9NWZ3.

Protocols and materials databases

DNASUi 51135.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000431837 ; ENSP00000390327 ; ENSG00000198001 . [Q9NWZ3-2 ]
ENST00000440781 ; ENSP00000408734 ; ENSG00000198001 . [Q9NWZ3-2 ]
ENST00000448290 ; ENSP00000390651 ; ENSG00000198001 . [Q9NWZ3-1 ]
ENST00000551736 ; ENSP00000446490 ; ENSG00000198001 . [Q9NWZ3-1 ]
GeneIDi 51135.
KEGGi hsa:51135.
UCSCi uc001rnt.3. human. [Q9NWZ3-1 ]

Organism-specific databases

CTDi 51135.
GeneCardsi GC12P044152.
HGNCi HGNC:17967. IRAK4.
HPAi CAB016685.
CAB022077.
HPA000924.
MIMi 606883. gene.
607676. phenotype.
610799. phenotype.
neXtProti NX_Q9NWZ3.
Orphaneti 70592. Immunodeficiency due to interleukin-1 receptor-associated kinase-4 deficiency.
PharmGKBi PA134914577.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000116550.
HOVERGENi HBG066836.
InParanoidi Q9NWZ3.
KOi K04733.
OMAi YMPPDSS.
OrthoDBi EOG7MD4Q1.
PhylomeDBi Q9NWZ3.
TreeFami TF351380.

Enzyme and pathway databases

Reactomei REACT_22442. Interleukin-1 signaling.
REACT_25024. TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
REACT_25120. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
REACT_25222. MyD88 dependent cascade initiated on endosome.
REACT_27215. MyD88 cascade initiated on plasma membrane.
REACT_6788. MyD88:Mal cascade initiated on plasma membrane.
SignaLinki Q9NWZ3.

Miscellaneous databases

EvolutionaryTracei Q9NWZ3.
GenomeRNAii 51135.
NextBioi 53983.
PROi Q9NWZ3.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q9NWZ3.
Bgeei Q9NWZ3.
CleanExi HS_IRAK4.
Genevestigatori Q9NWZ3.

Family and domain databases

Gene3Di 1.10.533.10. 1 hit.
InterProi IPR011029. DEATH-like_dom.
IPR017428. IL-1_rcpt-assoc_kin4.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
[Graphical view ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
PIRSFi PIRSF038189. IRAK4. 1 hit.
SUPFAMi SSF47986. SSF47986. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEi PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.
    , 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.
    , 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. 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. 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. 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. 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. 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.
    , 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.

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: September 3, 2014
This is version 137 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

External Data

Dasty 3

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