CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-022290
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Interleukin-1 receptor-associated kinase 4 
Protein Synonyms/Alias
 IRAK-4; Renal carcinoma antigen NY-REN-64 
Gene Name
 IRAK4 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
3*****MNKPITPSTYacetylation[1]
3*****MNKPITPSTYubiquitination[2]
34DPQEGWKKLAVAIKKacetylation[1]
115TANTLPSKEAITVQQubiquitination[2]
313HHIHRDIKSANILLDubiquitination[2]
Reference
 [1] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 
Functional Description
 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. 
Sequence Annotation
 DOMAIN 20 104 Death.
 DOMAIN 186 454 Protein kinase.
 NP_BIND 192 200 ATP (By similarity).
 NP_BIND 313 316 ATP.
 ACT_SITE 311 311 Proton acceptor (By similarity).
 BINDING 213 213 ATP.
 BINDING 329 329 ATP.
 MOD_RES 34 34 N6-acetyllysine.
 MOD_RES 342 342 Phosphothreonine.
 MOD_RES 345 345 Phosphothreonine.
 MOD_RES 346 346 Phosphoserine.  
Keyword
 3D-structure; Acetylation; Alternative splicing; ATP-binding; Complete proteome; Cytoplasm; Immunity; Innate immunity; Kinase; Magnesium; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 460 AA 
Protein Sequence
MNKPITPSTY VRCLNVGLIR KLSDFIDPQE GWKKLAVAIK KPSGDDRYNQ FHIRRFEALL 60
QTGKSPTSEL LFDWGTTNCT VGDLVDLLIQ NEFFAPASLL LPDAVPKTAN TLPSKEAITV 120
QQKQMPFCDK DRTLMTPVQN LEQSYMPPDS SSPENKSLEV SDTRFHSFSF YELKNVTNNF 180
DERPISVGGN KMGEGGFGVV YKGYVNNTTV AVKKLAAMVD ITTEELKQQF DQEIKVMAKC 240
QHENLVELLG FSSDGDDLCL VYVYMPNGSL LDRLSCLDGT PPLSWHMRCK IAQGAANGIN 300
FLHENHHIHR DIKSANILLD EAFTAKISDF GLARASEKFA QTVMTSRIVG TTAYMAPEAL 360
RGEITPKSDI YSFGVVLLEI ITGLPAVDEH REPQLLLDIK EEIEDEEKTI EDYIDKKMND 420
ADSTSVEAMY SVASQCLHEK KNKRPDIKKV QQLLQEMTAS 460 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0010008; C:endosome membrane; TAS:Reactome.
 GO:0005886; C:plasma membrane; TAS:Reactome.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0000287; F:magnesium ion binding; IEA:InterPro.
 GO:0004674; F:protein serine/threonine kinase activity; EXP:Reactome.
 GO:0001816; P:cytokine production; IEA:Compara.
 GO:0019221; P:cytokine-mediated signaling pathway; IEA:Compara.
 GO:0045087; P:innate immune response; TAS:UniProtKB.
 GO:0007254; P:JNK cascade; IEA:Compara.
 GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:UniProtKB.
 GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Compara.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Compara.
 GO:0034166; P:toll-like receptor 10 signaling pathway; TAS:Reactome.
 GO:0034134; P:toll-like receptor 2 signaling pathway; TAS:Reactome.
 GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
 GO:0034146; P:toll-like receptor 5 signaling pathway; TAS:Reactome.
 GO:0034162; P:toll-like receptor 9 signaling pathway; TAS:Reactome.
 GO:0038123; P:toll-like receptor TLR1:TLR2 signaling pathway; TAS:Reactome.
 GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; TAS:Reactome. 
Interpro
 IPR011029; DEATH-like_dom.
 IPR017428; Interleukin-1_rcpt-assoc_kin4.
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom. 
Pfam
 PF00069; Pkinase 
SMART
  
PROSITE
 PS50017; DEATH_DOMAIN
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 
PRINTS