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Protein

Interleukin-1 receptor-associated kinase 4

Gene

IRAK4

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei214 – 2141ATPPROSITE-ProRule annotation
Active sitei312 – 3121Proton acceptorPROSITE-ProRule annotation
Binding sitei330 – 3301ATPPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi193 – 2019ATPPROSITE-ProRule annotation
Nucleotide bindingi314 – 3174ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

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

ReactomeiR-BTA-446652. 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

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 461461Interleukin-1 receptor-associated kinase 4PRO_0000260158Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei34 – 341N6-acetyllysineBy similarity
Modified residuei343 – 3431PhosphothreonineBy similarity
Modified residuei346 – 3461PhosphothreonineBy similarity
Modified residuei347 – 3471PhosphoserineBy similarity

Post-translational modificationi

Phosphorylated.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiQ1RMT8.

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

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000028115.

Structurei

3D structure databases

ProteinModelPortaliQ1RMT8.
SMRiQ1RMT8. Positions 1-113, 164-459.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini20 – 10485DeathAdd
BLAST
Domaini187 – 455269Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG1187. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00530000063073.
HOGENOMiHOG000116550.
HOVERGENiHBG066836.
InParanoidiQ1RMT8.
KOiK04733.
OMAiVMALDHL.
OrthoDBiEOG7MD4Q1.
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]

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ1RMT8.
SMRiQ1RMT8. Positions 1-113, 164-459.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000028115.

Proteomic databases

PaxDbiQ1RMT8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000028115; ENSBTAP00000028115; ENSBTAG00000021105.
GeneIDi533692.
KEGGibta:533692.

Organism-specific databases

CTDi51135.

Phylogenomic databases

eggNOGiKOG1187. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00530000063073.
HOGENOMiHOG000116550.
HOVERGENiHBG066836.
InParanoidiQ1RMT8.
KOiK04733.
OMAiVMALDHL.
OrthoDBiEOG7MD4Q1.
TreeFamiTF351380.

Enzyme and pathway databases

ReactomeiR-BTA-446652. 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.

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...

Publicationsi

  1. NIH - Mammalian Gene Collection (MGC) project
    Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Hereford.
    Tissue: Uterus.

Entry informationi

Entry nameiIRAK4_BOVIN
AccessioniPrimary (citable) accession number: Q1RMT8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: May 16, 2006
Last modified: June 8, 2016
This is version 88 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.