Il1rl1
Domain
The TIR domain mediates NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is required for NADase activity.
Function
Receptor for interleukin-33 (IL-33) which plays crucial roles in innate and adaptive immunity, contributing to tissue homeostasis and responses to environmental stresses together with coreceptor IL1RAP. Its stimulation recruits MYD88, IRAK1, IRAK4, and TRAF6, followed by phosphorylation of MAPK3/ERK1 and/or MAPK1/ERK2, MAPK14, and MAPK8. Possibly involved in helper T-cell function (By similarity). Upon tissue injury, induces UCP2-dependent mitochondrial rewiring that attenuates the generation of reactive oxygen species and preserves the integrity of Krebs cycle required for persistent production of itaconate and subsequent GATA3-dependent differentiation of inflammation-resolving alternatively activated macrophages.
Isoform B
Inhibits IL-33 signaling.
Post-translational modifications
Phosphorylated by GSK3B at Ser-441; leading to proteasomal degradation.
Ubiquitinated at Lys-325 in a FBXL19-mediated manner; leading to proteasomal degradation. Ubiquitination by TRAF6 via 'Lys-27'-linked polyubiquitination and deubiquitination by USP38 serves as a critical regulatory mechanism for fine-tuning IL1RL1-mediated inflammatory response.
Sequence Similarities
Belongs to the interleukin-1 receptor family.
Tissue Specificity
Isoform A is detected in spleen, lung, bone marrow and lymh node. Isoform B is predominant in fibroblasts.
Cellular localization
- Cell membrane
- Single-pass type I membrane protein
- Isoform B
- Secreted
Alternative names
Fit1, Interleukin-1 receptor-like 1, Fit-1, Fos-responsive gene 1 protein
Database links
Other research areas
- Immuno-oncology