IRAK4

Protein identityUniProt · HPA

UniProt accession

Q9NWZ3

Gene

IRAK4

Ensembl

ENSG00000198001

Chromosome

12

Canonical length

460 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoli,Plasma membrane,Microtubules,Cytosol

OverviewNCBI Gene

This gene encodes a kinase that activates NF-kappaB in both the Toll-like receptor (TLR) and T-cell receptor (TCR) signaling pathways. The protein is essential for most innate immune responses. Mutations in this gene result in IRAK4 deficiency and recurrent invasive pneumococcal disease. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

Canonical amino-acid sequenceUniProt

460 residues, UniProt reviewed canonical sequence.

>Q9NWZ3|IRAK4
     1  MNKPITPSTY VRCLNVGLIR KLSDFIDPQE GWKKLAVAIK KPSGDDRYNQ FHIRRFEALL
    61  QTGKSPTSEL LFDWGTTNCT VGDLVDLLIQ NEFFAPASLL LPDAVPKTAN TLPSKEAITV
   121  QQKQMPFCDK DRTLMTPVQN LEQSYMPPDS SSPENKSLEV SDTRFHSFSF YELKNVTNNF
   181  DERPISVGGN KMGEGGFGVV YKGYVNNTTV AVKKLAAMVD ITTEELKQQF DQEIKVMAKC
   241  QHENLVELLG FSSDGDDLCL VYVYMPNGSL LDRLSCLDGT PPLSWHMRCK IAQGAANGIN
   301  FLHENHHIHR DIKSANILLD EAFTAKISDF GLARASEKFA QTVMTSRIVG TTAYMAPEAL
   361  RGEITPKSDI YSFGVVLLEI ITGLPAVDEH REPQLLLDIK EEIEDEEKTI EDYIDKKMND
   421  ADSTSVEAMY SVASQCLHEK KNKRPDIKKV QQLLQEMTAS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against IRAK4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.31

Highest tissue expression

18 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about IRAK4.

Disease | AllUniProt

Conditions IRAK4 is implicated in, by any mechanism.

• Immunodeficiency 67 (IMD67) MIM:607676

Disease | GeneticClinVar

35 pathogenic / likely-pathogenic of 380 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Immunodeficiency 67
• IRAK4-related disorder
• Invasive pneumococcal disease, recurrent isolated
• Congenital dyserythropoietic anemia

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.05

gnomAD pLI

0

gnomAD missense Z

0.22

DepMap mean gene effect

-0.02

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cytokine-mediated signaling pathway
• innate immune response
• interleukin-1-mediated signaling pathway
• interleukin-33-mediated signaling pathway
• intracellular signal transduction
• JNK cascade
• lipopolysaccharide-mediated signaling pathway
• MyD88-dependent toll-like receptor signaling pathway
• neutrophil mediated immunity
• neutrophil migration
• positive regulation of canonical NF-kappaB signal transduction
• positive regulation of smooth muscle cell proliferation
• Toll signaling pathway
• toll-like receptor 4 signaling pathway
• toll-like receptor 9 signaling pathway
• toll-like receptor signaling pathway

Molecular functions

• ATP binding
• interleukin-1 receptor binding
• kinase activity
• magnesium ion binding
• protein kinase binding
• protein serine kinase activity
• protein serine/threonine kinase activity

Cellular components

• cell surface
• cytoplasm
• cytosol
• endosome membrane
• extracellular space
• extrinsic component of plasma membrane
• nucleus
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Protein kinase domain
• Serine-threonine/tyrosine-protein kinase, catalytic domain
• Protein kinase-like domain superfamily
• Death-like domain superfamily
• Protein tyrosine and serine/threonine kinase
• Interleukin-1 receptor-associated kinase 4
• IRAK4, Death domain
• LRR Receptor-Like Ser/Thr Protein Kinase

KeywordsUniProt

• Acetylation
• ATP-binding
• Cytoplasm
• Immunity
• Innate immunity
• Kinase
• Magnesium
• Nucleotide-binding
• Phosphoprotein
• Serine/threonine-protein kinase
• Transferase

InteractionsUniProt · HPA

Protein binding partners of IRAK4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• IL1RL1
• TICAM2
• PELI2
• IRAK1
• MYD88
• PELI1
• TIRAP