UniProt ID | IRAK4_MOUSE | |
---|---|---|
UniProt AC | Q8R4K2 | |
Protein Name | Interleukin-1 receptor-associated kinase 4 | |
Gene Name | Irak4 | |
Organism | Mus musculus (Mouse). | |
Sequence Length | 459 | |
Subcellular Localization | Cytoplasm. | |
Protein 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 (By similarity).. | |
Protein Sequence | MNKPLTPSTYIRNLNVGILRKLSDFIDPQEGWKKLAVAIKKPSGDDRYNQFHIRRFEALLQTGKSPTCELLFDWGTTNCTVGDLVDLLVQIELFAPATLLLPDAVPQTVKSLPPREAATVAQTHGPCQEKDRTSVMPMPKLEHSCEPPDSSSPDNRSVESSDTRFHSFSFHELKSITNNFDEQPASAGGNRMGEGGFGVVYKGCVNNTIVAVKKLGAMVEISTEELKQQFDQEIKVMATCQHENLVELLGFSSDSDNLCLVYAYMPNGSLLDRLSCLDGTPPLSWHTRCKVAQGTANGIRFLHENHHIHRDIKSANILLDKDFTAKISDFGLARASARLAQTVMTSRIVGTTAYMAPEALRGEITPKSDIYSFGVVLLELITGLAAVDENREPQLLLDIKEEIEDEEKTIEDYTDEKMSDADPASVEAMYSAASQCLHEKKNRRPDIAKVQQLLQEMSA | |
Overview of Protein Modification Sites with Functional and Structural Information | ||
* ASA = Accessible Surface Area
Locations | Modification | Substrate Peptides & Secondary Structure |
ASA (%) | Reference | Orthologous Protein Cluster |
---|---|---|---|---|---|
1 | Acetylation | -------MNKPLTPS -------CCCCCCHH | 15.24 | - | |
6 | Phosphorylation | --MNKPLTPSTYIRN --CCCCCCHHHHHHH | 24.58 | 29472430 | |
8 | Phosphorylation | MNKPLTPSTYIRNLN CCCCCCHHHHHHHCC | 28.71 | 29472430 | |
9 | Phosphorylation | NKPLTPSTYIRNLNV CCCCCHHHHHHHCCH | 24.95 | 29472430 | |
34 | Acetylation | DPQEGWKKLAVAIKK CHHHCHHHHEEEEEC | 34.86 | - | |
43 | Phosphorylation | AVAIKKPSGDDRYNQ EEEEECCCCCCHHHH | 64.83 | 29109428 | |
144 | Phosphorylation | PMPKLEHSCEPPDSS CCCCCCCCCCCCCCC | 15.70 | 25619855 | |
145 | Glutathionylation | MPKLEHSCEPPDSSS CCCCCCCCCCCCCCC | 11.11 | 24333276 | |
150 | Phosphorylation | HSCEPPDSSSPDNRS CCCCCCCCCCCCCCC | 38.19 | 25619855 | |
151 | Phosphorylation | SCEPPDSSSPDNRSV CCCCCCCCCCCCCCC | 53.95 | 25619855 | |
152 | Phosphorylation | CEPPDSSSPDNRSVE CCCCCCCCCCCCCCC | 39.98 | 25619855 | |
342 | Phosphorylation | ASARLAQTVMTSRIV HHHHHHHHHHHHCCC | 13.46 | 30635358 | |
345 | Phosphorylation | RLAQTVMTSRIVGTT HHHHHHHHHCCCCCC | 15.54 | 30635358 | |
346 | Phosphorylation | LAQTVMTSRIVGTTA HHHHHHHHCCCCCCC | 11.25 | 30635358 | |
351 | Phosphorylation | MTSRIVGTTAYMAPE HHHCCCCCCCCCCHH | 9.43 | 30635358 | |
352 | Phosphorylation | TSRIVGTTAYMAPEA HHCCCCCCCCCCHHH | 15.17 | 30635358 | |
354 | Phosphorylation | RIVGTTAYMAPEALR CCCCCCCCCCHHHHC | 7.54 | 30635358 |
Modified Location | Modified Residue | Modification | Type of Upstream Proteins | Gene Name of Upstream Proteins | UniProt AC of Upstream Proteins | Sources |
---|---|---|---|---|---|---|
Oops, there are no upstream regulatory protein records of IRAK4_MOUSE !! |
Modified Location | Modified Residue | Modification | Function | Reference | ||
---|---|---|---|---|---|---|
Oops, there are no descriptions of PTM sites of IRAK4_MOUSE !! |
* Distance = the distance between SAP position and PTM sites.
Modified Location | Modification | Variant Position (Distance <= 10) |
Residue Change | SAP | Related Disease | Reference |
---|---|---|---|---|---|---|
Oops, there are no SNP-PTM records of IRAK4_MOUSE !! |
Interacting Protein | Gene Name | Interaction Type | PPI Reference | Domain-Domain Interactions |
---|---|---|---|---|
MYD88_MOUSE | Myd88 | physical | 19378012 | |
TIRAP_MOUSE | Tirap | physical | 19378012 | |
IRAK1_MOUSE | Irak1 | physical | 19378012 |
Kegg Drug | ||||||
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DrugBank | ||||||
There are no disease associations of PTM sites. |
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