Interleukin-1 receptor-associated kinase 4

Details

Name
Interleukin-1 receptor-associated kinase 4
Synonyms
  • 2.7.11.1
  • IRAK-4
  • Renal carcinoma antigen NY-REN-64
Gene Name
IRAK4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0008251|Interleukin-1 receptor-associated kinase 4 MNKPITPSTYVRCLNVGLIRKLSDFIDPQEGWKKLAVAIKKPSGDDRYNQFHIRRFEALL QTGKSPTSELLFDWGTTNCTVGDLVDLLIQNEFFAPASLLLPDAVPKTANTLPSKEAITV QQKQMPFCDKDRTLMTPVQNLEQSYMPPDSSSPENKSLEVSDTRFHSFSFYELKNVTNNF DERPISVGGNKMGEGGFGVVYKGYVNNTTVAVKKLAAMVDITTEELKQQFDQEIKVMAKC QHENLVELLGFSSDGDDLCLVYVYMPNGSLLDRLSCLDGTPPLSWHMRCKIAQGAANGIN FLHENHHIHRDIKSANILLDEAFTAKISDFGLARASEKFAQTVMTSRIVGTTAYMAPEAL RGEITPKSDIYSFGVVLLEIITGLPAVDEHREPQLLLDIKEEIEDEEKTIEDYIDKKMND ADSTSVEAMYSVASQCLHEKKNKRPDIKKVQQLLQEMTAS
Number of residues
460
分子量
51529.285
Theoretical pI
5.06
GO Classification
Functions
ATP binding/magnesium ion binding/protein kinase activity/protein serine/threonine kinase activity
Processes
cytokine production/cytokine-mediated signaling pathway/innate immune response/intracellular signal transduction/JNK cascade/MyD88-dependent toll-like receptor signaling pathway/neutrophil mediated immunity/neutrophil migration/positive regulation of I-kappaB kinase/NF-kappaB signaling/positive regulation of smooth muscle cell proliferation/toll-like receptor 10 signaling pathway/toll-like receptor 2 signaling pathway/toll-like receptor 4 signaling pathway/toll-like receptor 5 signaling pathway/toll-like receptor 9 signaling pathway/toll-like receptor signaling pathway/toll-like receptor TLR1/toll-like receptor TLR6
Components
cytoplasm/cytosol/endosome membrane/extracellular space/nucleus/plasma membrane
General Function
Protein serine/threonine kinase activity
Specific 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 (PubMed:17878374). 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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0020762|Interleukin-1 receptor-associated kinase 4 (IRAK4) ATGAACAAACCCATAACACCATCAACATATGTGCGCTGCCTCAATGTTGGACTAATTAGG AAGCTGTCAGATTTTATTGATCCTCAAGAAGGATGGAAGAAGTTAGCTGTAGCTATTAAA AAACCATCTGGTGATGATAGATACAATCAGTTTCACATAAGGAGATTTGAAGCATTACTT CAAACTGGAAAAAGTCCCACTTCTGAATTACTGTTTGACTGGGGCACCACAAATTGCACA GTTGGTGATCTTGTGGATCTTTTGATCCAAAATGAATTTTTTGCTCCTGCGAGTCTTTTG CTCCCAGATGCTGTTCCCAAAACTGCTAATACACTACCTTCTAAAGAAGCTATAACAGTT CAGCAAAAACAGATGCCTTTCTGTGACAAAGACAGGACATTGATGACACCTGTGCAGAAT CTTGAACAAAGCTATATGCCACCTGACTCCTCAAGTCCAGAAAATAAAAGTTTAGAAGTT AGTGATACACGTTTTCACAGTTTTTCATTTTATGAATTGAAGAATGTCACAAATAACTTT GATGAACGACCCATTTCTGTTGGTGGTAATAAAATGGGAGAGGGAGGATTTGGAGTTGTA TATAAAGGCTACGTAAATAACACAACTGTGGCAGTGAAGAAGCTTGCAGCAATGGTTGAC ATTACTACTGAAGAACTGAAACAGCAGTTTGATCAAGAAATAAAAGTAATGGCAAAGTGT CAACATGAAAACTTAGTAGAACTACTTGGTTTCTCAAGTGATGGAGATGACCTCTGCTTA GTATATGTTTACATGCCTAATGGTTCATTGCTAGACAGACTCTCTTGCTTGGATGGTACT CCACCACTTTCTTGGCACATGAGATGCAAGATTGCTCAGGGTGCAGCTAATGGCATCAAT TTTCTACATGAAAATCATCATATTCATAGAGATATTAAAAGTGCAAATATCTTACTGGAT GAAGCTTTTACTGCTAAAATATCTGACTTTGGCCTTGCACGGGCTTCTGAGAAGTTTGCC CAGACAGTCATGACTAGCAGAATTGTGGGAACAACAGCTTATATGGCACCAGAAGCTTTG CGTGGAGAAATAACACCCAAATCTGATATTTACAGCTTTGGTGTGGTTTTACTAGAAATA ATAACTGGACTTCCAGCTGTGGATGAACACCGTGAACCTCAGTTATTGCTAGATATTAAA GAAGAAATTGAAGATGAAGAAAAGACAATTGAAGATTATATTGATAAAAAGATGAATGAT GCTGATTCCACTTCAGTTGAAGCTATGTACTCTGTTGCTAGTCAATGTCTGCATGAAAAG AAAAATAAGAGACCAGACATTAAGAAGGTTCAACAGCTGCTGCAAGAGATGACAGCTTCT TAA
Chromosome Location
12
Locus
12q12
External Identifiers
Resource Link
UniProtKB ID Q9NWZ3
UniProtKB Entry Name IRAK4_HUMAN
GenBank Protein ID 20219010
GenBank Gene ID AF445802
HGNC ID HGNC:17967
General References
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Drug Relations

Drug Relations
DrugBank ID Name Drug group Pharmacological action? Actions Details
DB08590 1-(3-HYDROXYPROPYL)-2-[(3-NITROBENZOYL)AMINO]-1H-BENZIMIDAZOL-5-YL PIVALATE experimental unknown Details
DB12010 Fostamatinib approved, investigational unknown inhibitor Details