Human Recombinant IRAK4 protein, His Tag-1 (V2LY-0526-LY5063)

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Basic Information

Expressed Host
Baculovirus-Insect Cells
Protein Species
Human
Tag
His Tag
Protein Construction
This product is Human Recombinant IRAK4 protein, His Tag consist of Amino Acid: 1-460 and predicts a molecular mass of 53.8 kDa.
Molecule Mass
53.8 kDa
Sequence
Amino Acid: 1-460
Species
Human

Formulations & Storage [For reference only, actual COA shall prevail!]

Purity
>92% as determined by SDS-PAGE
Endotoxin
Please contact us for more information.
Format
Liquid
Buffer
Tris, NaCl, Chaps, Trehalose, Arginine
Preservative
None
Storage
Samples are stable for up to twelve months from date of receipt at -20°C to -80°C. Store it under sterile conditions at -20°C to -80°C. It is recommended that the protein be aliquoted for optimal storage. Avoid repeated freeze-thaw cycles.
More Infomation

Target

Full Name
interleukin-1 receptor-associated kinase 4
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.
Biological Process
Cytokine-mediated signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Innate immune responseManual Assertion Based On ExperimentTAS:UniProtKB
Interleukin-1-mediated signaling pathwayTAS:Reactome
Intracellular signal transductionManual Assertion Based On ExperimentIBA:GO_Central
JNK cascadeIEA:Ensembl
MyD88-dependent toll-like receptor signaling pathwayManual Assertion Based On ExperimentTAS:UniProtKB
Neutrophil mediated immunityManual Assertion Based On ExperimentIMP:UniProtKB
Neutrophil migrationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of I-kappaB kinase/NF-kappaB signalingManual Assertion Based On ExperimentIMP:MGI
Positive regulation of smooth muscle cell proliferationIEA:Ensembl
Toll-like receptor 9 signaling pathwayTAS:Reactome
Toll-like receptor signaling pathwayManual Assertion Based On ExperimentTAS:UniProtKB
Cellular Location
Cytoplasm
Involvement in disease
Immunodeficiency 67 (IMD67):
An autosomal recessive primary immunodeficiency characterized by recurrent, life-threatening systemic and invasive bacterial infections beginning in infancy or early childhood.
PTM
Phosphorylated.

Lavazais, S., Jargosch, M., Dupont, S., Labéguère, F., Menet, C., Jagerschmidt, C., ... & Brys, R. (2023). IRAK4 inhibition dampens pathogenic processes driving inflammatory skin diseases. Science Translational Medicine, 15(683), eabj3289.

Bennett, J., & Starczynowski, D. T. (2022). IRAK1 and IRAK4 as emerging therapeutic targets in hematologic malignancies. Current Opinion in Hematology, 29(1), 8.

Pereira, M., Durso, D. F., Bryant, C. E., Kurt-Jones, E. A., Silverman, N., Golenbock, D. T., & Gazzinelli, R. T. (2022). The IRAK4 scaffold integrates TLR4-driven TRIF and MYD88 signaling pathways. Cell reports, 40(7).

Umar, S., Palasiewicz, K., Van Raemdonck, K., Volin, M. V., Romay, B., Amin, M. A., ... & Shahrara, S. (2021). IRAK4 inhibition: a promising strategy for treating RA joint inflammation and bone erosion. Cellular & Molecular Immunology, 18(9), 2199-2210.

Zhang, J., Fu, L., Shen, B., Liu, Y., Wang, W., Cai, X., ... & Dai, X. (2020). Assessing IRAK4 functions in ABC DLBCL by IRAK4 kinase inhibition and protein degradation. Cell Chemical Biology, 27(12), 1500-1509.

Wang, H., Zhou, H., Zhang, Q., Poulsen, K. L., Taylor, V., McMullen, M. R., ... & Li, X. (2020). Inhibition of IRAK4 kinase activity improves ethanol-induced liver injury in mice. Journal of hepatology, 73(6), 1470-1481.

Nunes, J., McGonagle, G. A., Eden, J., Kiritharan, G., Touzet, M., Lewell, X., ... & Anderson, N. A. (2019). Targeting IRAK4 for degradation with PROTACs. ACS medicinal chemistry letters, 10(7), 1081-1085.

Smith, M. A., Choudhary, G. S., Pellagatti, A., Choi, K., Bolanos, L. C., Bhagat, T. D., ... & Starczynowski, D. T. (2019). U2AF1 mutations induce oncogenic IRAK4 isoforms and activate innate immune pathways in myeloid malignancies. Nature cell biology, 21(5), 640-650.

Bryan, M. C., Drobnick, J., Gobbi, A., Kolesnikov, A., Chen, Y., Rajapaksa, N., ... & Kiefer, J. R. (2019). Development of potent and selective pyrazolopyrimidine IRAK4 inhibitors. Journal of Medicinal Chemistry, 62(13), 6223-6240.

Hjorton, K., Hagberg, N., Israelsson, E., Jinton, L., Berggren, O., Sandling, J. K., ... & Rönnblom, L. (2018). Cytokine production by activated plasmacytoid dendritic cells and natural killer cells is suppressed by an IRAK4 inhibitor. Arthritis research & therapy, 20, 1-11.

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For research use only. Not intended for any clinical use.

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