Il1rl1
Developmental stage
Expressed first in the fetal liver and then in lung and hematopoietic tissues.
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 (PubMed:17675517, PubMed:18450470, PubMed:22660580, PubMed:29045903). Its stimulation recruits MYD88, IRAK1, IRAK4, and TRAF6, followed by phosphorylation of MAPK3/ERK1 and/or MAPK1/ERK2, MAPK14, and MAPK8 (By similarity). 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 (PubMed:34644537).
Isoform B
Inhibits IL-33 signaling.
Post-translational modifications
Phosphorylated by GSK3B at Ser-442; leading to proteasomal degradation.
Ubiquitinated at Lys-326 in a FBXL19-mediated manner; leading to proteasomal degradation (PubMed:22660580). 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 (By similarity).
Sequence Similarities
Belongs to the interleukin-1 receptor family.
Tissue Specificity
Predominantly expressed in hematopoietic tissues, and in macrophage, erythroid, epithelial and fibroblast cell lines. Isoform A is expressed in brain astrocytes and microglia. Isoform B is expressed in brain endothelial cells.
Cellular localization
- Cell membrane
- Single-pass type I membrane protein
- Isoform B
- Secreted
Alternative names
Ly84, St2, Ste2, Il1rl1, Interleukin-1 receptor-like 1, Interleukin-33 receptor alpha chain, Lymphocyte antigen 84, Protein ST2, Protein T1