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Protein

Interleukin-1 receptor-associated kinase 4

Gene

IRAK4

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: -Experimental evidence at transcript 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 (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei214ATPPROSITE-ProRule annotation1
Active sitei312Proton acceptorPROSITE-ProRule annotation1
Binding sitei330ATPPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi193 – 201ATPPROSITE-ProRule annotation9
Nucleotide bindingi314 – 317ATPPROSITE-ProRule annotation4

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processImmunity, Innate immunity
LigandATP-binding, Magnesium, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-BTA-1257604 PIP3 activates AKT signaling
R-BTA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-BTA-9020702 Interleukin-1 signaling
R-BTA-975110 TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling
R-BTA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-BTA-975155 MyD88 dependent cascade initiated on endosome

Names & Taxonomyi

Protein namesi
Recommended name:
Interleukin-1 receptor-associated kinase 4 (EC:2.7.11.1)
Short name:
IRAK-4
Gene namesi
Name:IRAK4
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 5

Organism-specific databases

VGNCiVGNC:30268 IRAK4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002601581 – 461Interleukin-1 receptor-associated kinase 4Add BLAST461

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei34N6-acetyllysineBy similarity1
Modified residuei343PhosphothreonineBy similarity1
Modified residuei346PhosphothreonineBy similarity1
Modified residuei347PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiQ1RMT8
PRIDEiQ1RMT8

Expressioni

Gene expression databases

BgeeiENSBTAG00000021105

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 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000028115

Structurei

3D structure databases

ProteinModelPortaliQ1RMT8
SMRiQ1RMT8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini20 – 104DeathAdd BLAST85
Domaini187 – 455Protein kinasePROSITE-ProRule annotationAdd BLAST269

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1187 Eukaryota
COG0515 LUCA
GeneTreeiENSGT00530000063073
HOGENOMiHOG000116550
HOVERGENiHBG066836
InParanoidiQ1RMT8
KOiK04733
OMAiAQTVMTS
OrthoDBiEOG091G0YKT
TreeFamiTF351380

Family and domain databases

CDDicd08793 Death_IRAK4, 1 hit
InterProiView protein in InterPro
IPR011029 DEATH-like_dom_sf
IPR017428 IRAK4
IPR037970 IRAK4_Death
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
PfamiView protein in Pfam
PF07714 Pkinase_Tyr, 1 hit
PIRSFiPIRSF038189 IRAK4, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50011 PROTEIN_KINASE_DOM, 1 hit

Sequencei

Sequence statusi: Complete.

Q1RMT8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNKPITASTY VRCLSLGLIR KLSDFIDPQE GWKKLAVAIK KPSGDDRYNQ
60 70 80 90 100
FHIRRFEALL QIGKSPTCEL LFDWGTTNCT VGDLVDILVQ NEFFAPASLL
110 120 130 140 150
LPDAVPKNVN TLPSKVTVVA VQQKPKPLCG KDRTSVISDE NPEQNYVLPD
160 170 180 190 200
SSSPENTSLE FSDTRFHSFS FFELKDVTNN FDERPISVGG NKMGEGGFGV
210 220 230 240 250
VYKGYVNNRT VAVKKLAAMV DISTEELKQQ FDQEIKVMAK CQHENLVELL
260 270 280 290 300
GFSSDGDDLC LVYVYMPNGS LLDRLSCLDG TPPLSWNMRC KIAQGAANGL
310 320 330 340 350
SYLHENHHIH RDIKSANILL DEDFTAKISD FGLARASEKF AQTVMTSRIV
360 370 380 390 400
GTTAYMAPEA LRGEITPKSD IYSFGVVLLE IITGLPAVDE HREPQLLLDI
410 420 430 440 450
KEEIEDEEKT IEDYVDRKMN DIDSTSIETM YSVASQCLHE KKNKRPDIKK
460
VQQLLEEMTG S
Length:461
Mass (Da):51,575
Last modified:May 16, 2006 - v1
Checksum:iEF9DE6D50AD2D9CC
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC114720 mRNA Translation: AAI14721.1
RefSeqiNP_001069466.1, NM_001075998.1
XP_005206483.1, XM_005206426.3
UniGeneiBt.53276

Genome annotation databases

EnsembliENSBTAT00000028115; ENSBTAP00000028115; ENSBTAG00000021105
GeneIDi533692
KEGGibta:533692

Similar proteinsi

Entry informationi

Entry nameiIRAK4_BOVIN
AccessioniPrimary (citable) accession number: Q1RMT8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: May 16, 2006
Last modified: March 28, 2018
This is version 99 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health