| Tag | Content |
|---|
| EKPD ID | EKS-HOS-00414 |
| Classification | | Group/Family | Score | E-Value | Start | End | Domain Length |
|---|
| TKL/IRAK | 386.2 | 4.7E-115 | 65 | 330 | 266 |
|
| Status | Reviewed |
| Ensembl Protein | ENSP00000390327 |
| UniProt Accession | Q9NWZ3; Q69FE1; Q8TDF7; Q9Y589; |
| 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 | IRAK4; |
| Ensembl Information | |
| Organism | Homo sapiens |
| Functional Description | Serine/threonine-protein kinase that plays a criticalrole 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. |
| Protein Length | 336 |
Protein Sequence
(FASTA) | | MPFCDKDRTL MTPVQNLEQS YMPPDSSSPE NKSLEVSDTR FHSFSFYELK NVTNNFDERP 60 | | ISVGGNKMGE GGFGVVYKGY VNNTTVAVKK LAAMVDITTE ELKQQFDQEI KVMAKCQHEN 120 | | LVELLGFSSD GDDLCLVYVY MPNGSLLDRL SCLDGTPPLS WHMRCKIAQG AANGINFLHE 180 | | NHHIHRDIKS ANILLDEAFT AKISDFGLAR ASEKFAQTVM TSRIVGTTAY MAPEALRGEI 240 | | TPKSDIYSFG VVLLEIITGL PAVDEHREPQ LLLDIKEEIE DEEKTIEDYI DKKMNDADST 300 | | SVEAMYSVAS QCLHEKKNKR PDIKKVQQLL QEMTAS 336 |
|
Nucleotide Sequence
(FASTA) | | ATGCCTTTCT GTGACAAAGA CAGGACATTG ATGACACCTG TGCAGAATCT TGAACAAAGC 60 | | TATATGCCAC CTGACTCCTC AAGTCCAGAA AATAAAAGTT TAGAAGTTAG TGATACACGT 120 | | TTTCACAGTT TTTCATTTTA TGAATTGAAG AATGTCACAA ATAACTTTGA TGAACGACCC 180 | | ATTTCTGTTG GTGGTAATAA AATGGGAGAG GGAGGATTTG GAGTTGTATA TAAAGGCTAC 240 | | GTAAATAACA CAACTGTGGC AGTGAAGAAG CTTGCAGCAA TGGTTGACAT TACTACTGAA 300 | | GAACTGAAAC AGCAGTTTGA TCAAGAAATA AAAGTAATGG CAAAGTGTCA ACATGAAAAC 360 | | TTAGTAGAAC TACTTGGTTT CTCAAGTGAT GGAGATGACC TCTGCTTAGT ATATGTTTAC 420 | | ATGCCTAATG GTTCATTGCT AGACAGACTC TCTTGCTTGG ATGGTACTCC ACCACTTTCT 480 | | TGGCACATGA GATGCAAGAT TGCTCAGGGT GCAGCTAATG GCATCAATTT TCTACATGAA 540 | | AATCATCATA TTCATAGAGA TATTAAAAGT GCAAATATCT TACTGGATGA AGCTTTTACT 600 | | GCTAAAATAT CTGACTTTGG CCTTGCACGG GCTTCTGAGA AGTTTGCCCA GACAGTCATG 660 | | ACTAGCAGAA TTGTGGGAAC AACAGCTTAT ATGGCACCAG AAGCTTTGCG TGGAGAAATA 720 | | ACACCCAAAT CTGATATTTA CAGCTTTGGT GTGGTTTTAC TAGAAATAAT AACTGGACTT 780 | | CCAGCTGTGG ATGAACACCG TGAACCTCAG TTATTGCTAG ATATTAAAGA AGAAATTGAA 840 | | GATGAAGAAA AGACAATTGA AGATTATATT GATAAAAAGA TGAATGATGC TGATTCCACT 900 | | TCAGTTGAAG CTATGTACTC TGTTGCTAGT CAATGTCTGC ATGAAAAGAA AAATAAGAGA 960 | | CCAGACATTA AGAAGGTTCA ACAGCTGCTG CAAGAGATGA CAGCTTCTTA A 1011 |
|
| Domain Profile | S: 4 dnrigeGgfgevyrgelkntavavkklkeeadlslkelkqsfltElkvlarfrHdnilel 63 | +n++geGgfg+vy+g ++nt+vavkkl++++d++++elkq+f++E+kv+a+++H+n++el | Q: 65 GNKMGEGGFGVVYKGYVNNTTVAVKKLAAMVDITTEELKQQFDQEIKVMAKCQHENLVEL 124 | 79********************************************************** |
| S: 64 lgysaeseklcLvYqymknGsLedrLqcqkgsepLsWpqRlsillGtaraiefLHeasps 123 | lg+s+++++lcLvY ym+nGsL drL+c +g++pLsW++R++i++G+a++i+fLHe+ + | Q: 125 LGFSSDGDDLCLVYVYMPNGSLLDRLSCLDGTPPLSWHMRCKIAQGAANGINFLHEN--H 182 | *********************************************************..* |
| S: 124 lihgdiksaNiLLDekltpKlgDfglarfapesekqsstvlrtskvrgtlaYlpeefirv 183 | +ih+diksaNiLLDe++t+K++Dfglar +sek ++tv+ ts+++gt+aY+++e++r | Q: 183 HIHRDIKSANILLDEAFTAKISDFGLAR---ASEKFAQTVM-TSRIVGTTAYMAPEALR- 237 | ****************************...9********9.*****************. |
| S: 184 gqltvkvDvySfGiVllEvltGlravdedrktkyLkdllkeeieeekveilekfldkkag 243 | g++t k+D+ySfG+VllE++tGl+avde+r+++ L+d+ keeie+e+ +++e+++dkk++ | Q: 238 GEITPKSDIYSFGVVLLEIITGLPAVDEHREPQLLLDI-KEEIEDEE-KTIEDYIDKKMN 295 | *************************************9.********.9*********** |
| S: 244 kleeellealielalaclaekakkrPtmsqvlell 278 | +++++++ea++++a++cl+ek++krP++++v++ll | Q: 296 DADSTSVEAMYSVASQCLHEKKNKRPDIKKVQQLL 330 | ********************************986 |
|
Domain Sequence
(FASTA) | | GNKMGEGGFG VVYKGYVNNT TVAVKKLAAM VDITTEELKQ QFDQEIKVMA KCQHENLVEL 60 | | LGFSSDGDDL CLVYVYMPNG SLLDRLSCLD GTPPLSWHMR CKIAQGAANG INFLHENHHI 120 | | HRDIKSANIL LDEAFTAKIS DFGLARASEK FAQTVMTSRI VGTTAYMAPE ALRGEITPKS 180 | | DIYSFGVVLL EIITGLPAVD EHREPQLLLD IKEEIEDEEK TIEDYIDKKM NDADSTSVEA 240 | | MYSVASQCLH EKKNKRPDIK KVQQLL 266 |
|
| 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 | Ensembl |
| Orthology | |
| Gene Ontology | |
| KEGG | |
| InterPros | |
| Pfam | |
| SMARTs | |
| Prosites | | PS50017 | ; DEATH_DOMAIN; FALSE_NEG. | | PS00107 | ; PROTEIN_KINASE_ATP; FALSE_NEG. | | PS50011 | ; PROTEIN_KINASE_DOM; 1. | | PS00108 | ; PROTEIN_KINASE_ST; FALSE_NEG. |
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| Prints | |
| Created Date | 20-Feb-2013 |