Protein: Interleukin-33 (IL-33) (Q66H70)
Organism: Rattus norvegicus (Rat)
Function: Cytokine that binds to and signals through the IL1RL1/ST2 receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells. Involved in the maturation of Th2 cells inducing the secretion of T-helper type 2-associated cytokines. Also involved in activation of mast cells, basophils, eosinophils and natural killer cells. Acts as a chemoattractant for Th2 cells, and may function as an 'alarmin', that amplifies immune responses during tissue injury (By similarity). Induces rapid 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 (By similarity).
Subcellular location: Nucleus {ECO:0000250|UniProtKB:O95760}. Chromosome {ECO:0000250|UniProtKB:O95760}. Cytoplasm {ECO:0000250|UniProtKB:O95760}. Cytoplasmic vesicle, secretory vesicle {ECO:0000250|UniProtKB:O95760}. Secreted {ECO:0000250|UniProtKB:O95760}. Note=Associates with heterochromatin and mitotic chromosomes. The secretion is dependent on protein unfolding and facilitated by the cargo receptor TMED10; it results in protein translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) followed by vesicle entry and secretion. {ECO:0000250|UniProtKB:O95760}.
Sequence: MRPRMKYSNSKISPAKCDSTSGRALVPPCKITRSQQKTKDICHVYCMRLRSGLTIRKETCYFGKEPAKRYSLKSGSKHEGRLSTCLPDSRKRSLLGSIQAFAASVDTLSIQGTSLLTESCALSTYNDQSVSFVLENGCYVINVEDCGKNQEKDKVLLRYYESSFPAQSGDGVDGKKLMVNMSPIKDTDIWLNANDKDYSVELQKGDVSPPDQAFFVLHKKSSDFVSFECKNLPGTYIGVKDNQLALVEENDESCNNIMFKLSKM
InterPro domains: - IPR026145: Interleukin-33 (family) [1-264]
- IPR053902: Interleukin 33, C-terminal (domain) [114-262]
Interaction partners: - Interleukin-1 receptor accessory protein
- Interleukin-1 receptor-like 1
- Caspase-1
- Interleukin-1 receptor type 1
- Interleukin-13
- Cytokine receptor-like factor 2
- Thymic stromal lymphopoietin
- Myeloid differentiation primary response protein MyD88
- Interleukin-5
- T-cell surface glycoprotein CD4
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0098772 (molecular function regulator activity), GO:0005488 (binding), GO:0030545 (signaling receptor regulator activity), GO:0140677 (molecular function activator activity), GO:0005515 (protein binding), GO:0005102 (signaling receptor binding), GO:0030546 (signaling receptor activator activity), GO:0005126 (cytokine receptor binding), GO:0048018 (receptor ligand activity), GO:0005125 (cytokine activity)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0048518 (positive regulation of biological process), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0044419 (biological process involved in interspecies interaction between organisms), GO:0002376 (immune system process), GO:0009987 (cellular process), GO:0009605 (response to external stimulus), GO:0009628 (response to abiotic stimulus), GO:0042221 (response to chemical), GO:0019222 (regulation of metabolic process), GO:0006955 (immune response), GO:0009607 (response to biotic stimulus), GO:0051240 (positive regulation of multicellular organismal process), GO:0009893 (positive regulation of metabolic process), GO:0051716 (cellular response to stimulus), GO:0051239 (regulation of multicellular organismal process), GO:0006950 (response to stress), GO:0051707 (response to other organism), GO:0001666 (response to hypoxia), GO:0043207 (response to external biotic stimulus), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0070887 (cellular response to chemical stimulus), GO:0070482 (response to oxygen levels), GO:0009617 (response to bacterium), GO:0060255 (regulation of macromolecule metabolic process), GO:0001819 (positive regulation of cytokine production), GO:0001817 (regulation of cytokine production), GO:0009615 (response to virus), GO:0010033 (response to organic substance), GO:0045087 (innate immune response), GO:0098542 (defense response to other organism), GO:0034097 (response to cytokine), GO:0140546 (defense response to symbiont), GO:0032481 (positive regulation of type I interferon production), GO:0051607 (defense response to virus), GO:0071310 (cellular response to organic substance), GO:0036293 (response to decreased oxygen levels), GO:0032755 (positive regulation of interleukin-6 production), GO:0032675 (regulation of interleukin-6 production), GO:0010628 (positive regulation of gene expression), GO:0019221 (cytokine-mediated signaling pathway), GO:0010468 (regulation of gene expression), GO:0032727 (positive regulation of interferon-alpha production), GO:0036294 (cellular response to decreased oxygen levels)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0005634 (nucleus)