IL33
Interleukin-33
Also known as: C9orf26, DKFZp586H0523, DVS27, IL1F11, IL33_HUMAN, NF-HEV
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- O95760
- Gene
- IL33
- Ensembl
- ENSG00000137033
- Chromosome
- 9
- Canonical length
- 270 aa
- Protein class
- Predicted intracellular proteins, Predicted secreted proteins
- Subcellular location
- Nucleoplasm,Vesicles
- Secretome location
- Secreted to blood
OverviewNCBI Gene
The protein encoded by this gene is a cytokine that binds to the IL1RL1/ST2 receptor. The encoded protein is involved in the maturation of Th2 cells and the activation of mast cells, basophils, eosinophils and natural killer cells. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]
Canonical amino-acid sequenceUniProt
270 residues, UniProt reviewed canonical sequence.
>O95760|IL33
1 MKPKMKYSTN KISTAKWKNT ASKALCFKLG KSQQKAKEVC PMYFMKLRSG LMIKKEACYF
61 RRETTKRPSL KTGRKHKRHL VLAACQQQST VECFAFGISG VQKYTRALHD SSITGISPIT
121 EYLASLSTYN DQSITFALED ESYEIYVEDL KKDEKKDKVL LSYYESQHPS NESGDGVDGK
181 MLMVTLSPTK DFWLHANNKE HSVELHKCEK PLPDQAFFVL HNMHSNCVSF ECKTDPGVFI
241 GVKDNHLALI KVDSSENLCT ENILFKLSETLocalizationUniProt · AlphaFold · HPA
Whether an antibody against IL33 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Secreted
- Secreted
- Yes
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.44
- Highest tissue expression
- 114 nTPM
Expression across tissuesHPA
Tissue
- urinary bladder: 114 nTPM
- placenta: 58 nTPM
- cervix: 54 nTPM
- lung: 51 nTPM
- smooth muscle: 49 nTPM
- endometrium: 47 nTPM
Single-cell type
- respiratory basal cells: 263 nCPM
- vascular endothelial cells: 186 nCPM
- lymphatic endothelial cells: 132 nCPM
- mucous neck cells: 128 nCPM
- medullary thymic epithelial cells: 127 nCPM
- fibroblasts: 100 nCPM
Immune cell
- basophil: 0 nTPM
- classical monocyte: 0 nTPM
- eosinophil: 0 nTPM
- gdT-cell: 0 nTPM
- intermediate monocyte: 0 nTPM
- MAIT T-cell: 0 nTPM
Brain region
- thalamus: 15 nTPM
- hypothalamus: 15 nTPM
- cerebral cortex: 11 nTPM
- basal ganglia: 11 nTPM
- amygdala: 11 nTPM
- hippocampal formation: 9.7 nTPM
ReferencesPubMed · IEDB
Publications for IL33 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
3 publications
- IL-33 blockade suppresses the development of experimental autoimmune encephalomyelitis in C57BL/6 mice.
2012 · J Neuroimmunol · RCR 2.2 · 85 citations - IL-33 neutralization suppresses lupus disease in lupus-prone mice.
2014 · Inflammation · RCR 1.8 · 58 citations - Selective production of IL-33-neutralizing autoantibody ameliorates asthma responses and severity.
2024 · Clin Immunol · RCR 1 · 5 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.75
- gnomAD pLI
- 0
- gnomAD missense Z
- -1.03
- DepMap mean gene effect
- 0.13
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- antibacterial innate immune response
- defense response to virus
- extrinsic apoptotic signaling pathway
- gene expression
- interleukin-33-mediated signaling pathway
- macrophage differentiation
- microglial cell activation involved in immune response
- microglial cell proliferation
- negative regulation of immunoglobulin production
- negative regulation of inflammatory response to wounding
- negative regulation of leukocyte migration
- negative regulation of T-helper 1 type immune response
- negative regulation of transcription by RNA polymerase II
- negative regulation of type II interferon production
- positive regulation of chemokine production
- positive regulation of cytokine production
- positive regulation of gene expression
- positive regulation of glycoprotein biosynthetic process
- positive regulation of immunoglobulin production
- positive regulation of inflammatory response
- positive regulation of interleukin-13 production
- positive regulation of interleukin-4 production
- positive regulation of interleukin-5 production
- positive regulation of interleukin-6 production
- positive regulation of macrophage activation
- positive regulation of MHC class I biosynthetic process
- positive regulation of MHC class II biosynthetic process
- positive regulation of neuroinflammatory response
- positive regulation of proteasomal ubiquitin-dependent protein catabolic process
- positive regulation of transcription by RNA polymerase II
- positive regulation of tumor necrosis factor production
- positive regulation of type 2 immune response
- protein import into nucleus
- response to wounding
- type 2 immune response
- negative regulation of macrophage proliferation
- positive regulation of cellular defense response
Molecular functions
- cytokine activity
- interleukin-33 receptor binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Interleukin-33
- Interleukin 33, C-terminal
- Interleukin 33
KeywordsUniProt
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads IL33 as an antibody target. Whether an autoantibody or antibody against IL33 could matter depends on whether native IL33 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
IL33 is annotated as secreted, so native IL33 circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.
Annotation status
The present source text does not explicitly label IL33 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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