IRAK1
IRAK1 (Interleukin-1 receptor-associated kinase 1) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target and a tumour suppressor, and an approved or late-stage drug is recorded against it. Tied to Myeloproliferative neoplasms and Multiple myeloma.
Overview
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 signalling pathways. Is rapidly recruited by MYD88 to the receptor-signalling complex upon TLR activation.
Open Targets scores its association with cancer at 0.66 (direct and indirect evidence; datatypes literature 0.98, genetic association 0.00, somatic mutation 0.61, clinical 0.91). IntOGen calls it a driver in 1 cohort (0 activating, 1 loss-of-function), covering Plasma Cell Myeloma. In OnCo, 1 product record names it (Pacritinib).
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · IRAK1 (Interleukin-1 receptor-associated kinase 1) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target and a tumour suppressor, and an approved or late-stage drug is recorded against it. Tied to Myeloproliferative neoplasms and Multiple myeloma.
- 1 · What it is
IRAK1 (Interleukin-1 receptor-associated kinase 1) is a protein kinase, an enzyme that switches other proteins on by adding phosphate groups. The public catalogues list it as a drug target and a tumour suppressor, and an approved or late-stage drug is recorded against it. Tied to Myeloproliferative neoplasms and Multiple myeloma.
- 2 · What goes wrong in cancer
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 signalling pathways.
- 3 · How drugs use it
No product in this corpus aims at IRAK1 yet. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
External identifiers
Sources: HGNC HGNC:6112 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P51617 (protein name, function text, keywords and locations (REST API)); Open Targets ENSG00000184216 (association with cancer (MONDO_0004992) 0.66; per-cancer scores at or above 0.5: myeloproliferative neoplasm 0.58 (GraphQL API, CC0)); IntOGen IRAK1 (driver in 1 cohort (Act 0, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
Biology
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 signalling pathways. Is rapidly recruited by MYD88 to the receptor-signalling complex upon TLR activation. Association with MYD88 leads to IRAK1 phosphorylation by IRAK4 and subsequent autophosphorylation and kinase activation. 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. Location: Cytoplasm; Nucleus; Lipid droplet (UniProt). Locus Xq28 (HGNC).
- Myeloproliferative neoplasms: Open Targets association 0.58 with myeloproliferative neoplasm (MONDO_0020076)
- Multiple myeloma: IntOGen driver in 1 cohort (PCM)
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: Open Targets known-drug datatype score 0.91; IntOGen calls it a loss-of-function (LoF) driver in 1 cohort. Evidence tier "approved-drug" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
Latest papers
topQuery for this target: (TITLE:"IRAK1" OR ABSTRACT:"IRAK1" OR TITLE:"interleukin 1 receptor associated kinase 1" OR ABSTRACT:"interleukin 1 receptor associated kinase 1" OR TITLE:"Interleukin-1 receptor-associated kinase 1" OR ABSTRACT:"Interleukin-1 receptor-associated kinase 1" OR TITLE:"pelle" OR ABSTRACT:"pelle") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about IRAK1, not a curated reading list.
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