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] See more...

Aliases for IL33 Gene

Aliases for IL33 Gene

  • Interleukin 33 2 3 5
  • IL1F11 2 3 4
  • NF-HEV 2 3 4
  • Nuclear Factor From High Endothelial Venules 3 4
  • Nuclear Factor For High Endothelial Venules 2 3
  • Interleukin-1 Family Member 11 3 4
  • DVS27-Related Protein 2 3
  • Interleukin-33 3 4
  • C9orf26 3 4
  • DVS27 2 3
  • Chromosome 9 Open Reading Frame 26 (NF-HEV) 2
  • Interleukin-1 Family, Member 11 2
  • DKFZp586H0523 2
  • IL-1F11 4
  • NFEHEV 3
  • NFHEV 4
  • IL-33 4
  • IL33 5

External Ids for IL33 Gene

Previous HGNC Symbols for IL33 Gene

  • C9orf26

Summaries for IL33 Gene

Entrez Gene Summary for IL33 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]

CIViC Summary for IL33 Gene

GeneCards Summary for IL33 Gene

IL33 (Interleukin 33) is a Protein Coding gene. Diseases associated with IL33 include Granulomatous Mastitis and Loeffler Syndrome. Among its related pathways are PEDF Induced Signaling and Metabolism of proteins. Gene Ontology (GO) annotations related to this gene include cytokine activity.

UniProtKB/Swiss-Prot Summary for IL33 Gene

  • 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 (PubMed:16286016). 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 (PubMed:17853410, PubMed:18836528).
  • In quiescent endothelia the uncleaved form is constitutively and abundantly expressed, and acts as a chromatin-associated nuclear factor with transcriptional repressor properties, it may sequester nuclear NF-kappaB/RELA, lowering expression of its targets (PubMed:21734074). This form is rapidely lost upon angiogenic or proinflammatory activation (PubMed:18787100).

No data available for Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for IL33 Gene

Genomics for IL33 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for IL33 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH09J006212 Enhancer 0.5 Ensembl 600.7 -1.4 -1390 0.8 NFE2 CEBPB ZNF316 MAFF MAFK MAFG NFE2L2 EMSY IL33 piR-37972-677 RANBP6 RF00017-7416
GH09J006216 Promoter 0.3 Ensembl 600.7 +1.9 1910 1.4 IL33 RF00017-7418 piR-37972-678 TPD52L3 RF00017-7416
GH09J006215 Promoter 0.3 EPDnew 600.7 +0.5 541 0.1 IL33 RF00017-7418 TPD52L3 RF00017-7416
GH09J006020 Promoter 0.3 EPDnew 600.1 -194.2 -194245 0.1 piR-33804-133 piR-35002-130 IL33 RANBP6 RF00017-7417 RF00017-7415 RF00017-7416
GH09J006238 Enhancer 1.1 FANTOM5 Ensembl ENCODE 14.9 +24.7 24702 1 GATAD2A TFE3 SOX13 SP1 MNT TCF7 ZBTB26 NFE2 ZKSCAN8 FOXA2 IL33 RF00017-7418 piR-37972-678 LOC107987046 TPD52L3 RF00017-7416
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around IL33 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for IL33

Top Transcription factor binding sites by QIAGEN in the IL33 gene promoter:
  • Cdc5
  • FOXD3
  • FOXI1
  • FOXJ2
  • FOXJ2 (long isoform)
  • HFH-1
  • HFH-3
  • HNF-3beta
  • IRF-2
  • LyF-1

Genomic Locations for IL33 Gene

Genomic Locations for IL33 Gene
chr9:6,214,591-6,257,983
(GRCh38/hg38)
Size:
43,393 bases
Orientation:
Plus strand
chr9:6,215,786-6,257,983
(GRCh37/hg19)
Size:
42,198 bases
Orientation:
Plus strand

Genomic View for IL33 Gene

Genes around IL33 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
IL33 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for IL33 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for IL33 Gene

Proteins for IL33 Gene

  • Protein details for IL33 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O95760-IL33_HUMAN
    Recommended name:
    Interleukin-33
    Protein Accession:
    O95760
    Secondary Accessions:
    • B2R8L1
    • B4DJ35
    • B4E1Q9
    • D3DRI5
    • E7EAX4
    • Q2YEJ5

    Protein attributes for IL33 Gene

    Size:
    270 amino acids
    Molecular mass:
    30759 Da
    Quaternary structure:
    • Forms a 1:1:1 heterotrimeric complex with its primary high-affinity receptor IL1RL1 and the coreceptor IL1RAP.
    • (Microbial infection) Interacts (in reduced form) with H.polygyrus ARI.
    Miscellaneous:
    • [Isoform 3]: Constitutively active.

    Three dimensional structures from OCA and Proteopedia for IL33 Gene

    Alternative splice isoforms for IL33 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for IL33 Gene

Post-translational modifications for IL33 Gene

  • The full-length protein can be released from cells and is able to signal via the IL1RL1/ST2 receptor. However, proteolytic processing by CSTG/cathepsin G and ELANE/neutrophil elastase produces C-terminal peptides that are more active than the unprocessed full length protein. May also be proteolytically processed by calpains (PubMed:19596270). Proteolytic cleavage mediated by apoptotic caspases including CASP3 and CASP7 results in IL33 inactivation (PubMed:19559631). In vitro proteolytic cleavage by CASP1 was reported (PubMed:16286016) but could not be confirmed in vivo (PubMed:19465481) suggesting that IL33 is probably not a direct substrate for that caspase.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Antibody Products

  • Abcam antibodies for IL33

No data available for DME Specific Peptides for IL33 Gene

Domains & Families for IL33 Gene

Gene Families for IL33 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Predicted secreted proteins

Protein Domains for IL33 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for IL33 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ51972, highly similar to Nuclear factor from high endothelial venules (B4DJ35_HUMAN)
  • cDNA FLJ50356, highly similar to Nuclear factor from high endothelial venules (B4E1Q9_HUMAN)
  • Interleukin 33 variant 2 (E7EAX4_HUMAN)
  • Nuclear factor from high endothelial venules (IL33_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O95760

UniProtKB/Swiss-Prot:

IL33_HUMAN :
  • The homeodomain-like HTH domain mediates nuclear localization and heterochromatin association.
  • Belongs to the IL-1 family. Highly divergent.
Domain:
  • The homeodomain-like HTH domain mediates nuclear localization and heterochromatin association.
Family:
  • Belongs to the IL-1 family. Highly divergent.
genes like me logo Genes that share domains with IL33: view

Function for IL33 Gene

Molecular function for IL33 Gene

UniProtKB/Swiss-Prot 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 (PubMed:16286016). 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 (PubMed:17853410, PubMed:18836528).
UniProtKB/Swiss-Prot Function:
In quiescent endothelia the uncleaved form is constitutively and abundantly expressed, and acts as a chromatin-associated nuclear factor with transcriptional repressor properties, it may sequester nuclear NF-kappaB/RELA, lowering expression of its targets (PubMed:21734074). This form is rapidely lost upon angiogenic or proinflammatory activation (PubMed:18787100).
UniProtKB/Swiss-Prot Induction:
By infection with the parasite H.polygyrus.

Phenotypes From GWAS Catalog for IL33 Gene

Gene Ontology (GO) - Molecular Function for IL33 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002112 interleukin-33 receptor binding IEA --
GO:0005125 cytokine activity IDA 19841166
GO:0005515 protein binding IPI 16286016
genes like me logo Genes that share ontologies with IL33: view
genes like me logo Genes that share phenotypes with IL33: view

Animal Models for IL33 Gene

MGI Knock Outs for IL33:
  • Il33 Il33<tm1(KOMP)Vlcg>
  • Il33 Il33<tm1Aki>
  • Il33 Il33<tm1Amgn>
  • Il33 Il33<tm1Snak>
  • Il33 Il33<tm1.1(KOMP)Vlcg>
  • Il33 Il33<tm1Anjm>

Animal Model Products

CRISPR Products

miRNA for IL33 Gene

miRTarBase miRNAs that target IL33

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for IL33

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for IL33 Gene

Localization for IL33 Gene

Subcellular locations from UniProtKB/Swiss-Prot for IL33 Gene

Nucleus. Chromosome. Cytoplasmic vesicle, secretory vesicle. Secreted. Note=Associates with heterochromatin and mitotic chromosomes (PubMed:17185418).

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for IL33 gene
Compartment Confidence
extracellular 5
nucleus 5
cytosol 4
plasma membrane 3
mitochondrion 3
cytoskeleton 2
endoplasmic reticulum 2
endosome 2
lysosome 2
peroxisome 1
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for IL33 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IEA --
GO:0005634 nucleus IDA 18787100
GO:0005654 nucleoplasm TAS --
GO:0005694 chromosome IEA --
genes like me logo Genes that share ontologies with IL33: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for IL33 Gene

Pathways & Interactions for IL33 Gene

genes like me logo Genes that share pathways with IL33: view

Gene Ontology (GO) - Biological Process for IL33 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IMP 17185418
GO:0001819 positive regulation of cytokine production IBA 21873635
GO:0002281 macrophage activation involved in immune response IEA --
GO:0002282 microglial cell activation involved in immune response IEA --
GO:0002686 negative regulation of leukocyte migration IEA --
genes like me logo Genes that share ontologies with IL33: view

No data available for SIGNOR curated interactions for IL33 Gene

Drugs & Compounds for IL33 Gene

No Compound Related Data Available

Transcripts for IL33 Gene

mRNA/cDNA for IL33 Gene

9 REFSEQ mRNAs :
19 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for IL33

Alternative Splicing Database (ASD) splice patterns (SP) for IL33 Gene

No ASD Table

Relevant External Links for IL33 Gene

GeneLoc Exon Structure for
IL33

Expression for IL33 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for IL33 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for IL33 Gene

This gene is overexpressed in Gallbladder (15.0), Lymph node (10.4), Uterus (8.7), and Pancreas (8.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for IL33 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for IL33

SOURCE GeneReport for Unigene cluster for IL33 Gene:

Hs.731660

mRNA Expression by UniProt/SwissProt for IL33 Gene:

O95760-IL33_HUMAN
Tissue specificity: Expressed at high level in high endothelial venules found in tonsils, Peyer patches and mesenteric lymph nodes. Almost undetectable in placenta.

Evidence on tissue expression from TISSUES for IL33 Gene

  • Heart(4.7)
  • Nervous system(4.6)
  • Adrenal gland(4.4)
  • Lung(3.6)
  • Lymph node(3.6)
  • Spleen(3.4)
  • Intestine(3.4)
  • Skin(3.2)
  • Muscle(3.2)
  • Blood(3.2)
  • Liver(3)
  • Bone marrow(2.8)
  • Stomach(2.6)
  • Kidney(2.4)
  • Pancreas(2.1)
  • Gall bladder(2)
  • Bone(2)
genes like me logo Genes that share expression patterns with IL33: view

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for IL33 Gene

Orthologs for IL33 Gene

This gene was present in the common ancestor of mammals.

Orthologs for IL33 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia IL33 30 31
  • 99.75 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia IL33 30 31
  • 77.69 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia IL33 30 31
  • 76.95 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Il33 30
  • 70.4 (n)
Mouse
(Mus musculus)
Mammalia Il33 30 17 31
  • 69.99 (n)
OneToOne
Species where no ortholog for IL33 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Lizard (Anolis carolinensis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Oppossum (Monodelphis domestica)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)
  • Zebrafish (Danio rerio)

Evolution for IL33 Gene

ENSEMBL:
Gene Tree for IL33 (if available)
TreeFam:
Gene Tree for IL33 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for IL33: view image

Paralogs for IL33 Gene

No data available for Paralogs for IL33 Gene

Variants for IL33 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for IL33 Gene

SNP ID Clinical significance and condition Chr 09 pos Variation AA Info Type
727097 Benign: not provided 6,251,195(+) G/C SYNONYMOUS_VARIANT,INTRON_VARIANT
776409 Benign: not provided 6,256,144(+) C/G MISSENSE_VARIANT
783540 Benign: not provided 6,252,979(+) G/T MISSENSE_VARIANT,INTRON_VARIANT
788062 Benign: not provided 6,250,532(+) C/A SYNONYMOUS_VARIANT,INTRON_VARIANT
792123 Benign: not provided 6,254,544(+) C/G MISSENSE_VARIANT

Additional dbSNP identifiers (rs#s) for IL33 Gene

Structural Variations from Database of Genomic Variants (DGV) for IL33 Gene

Variant ID Type Subtype PubMed ID
dgv7386n100 CNV gain 25217958
esv2674589 CNV deletion 23128226
esv2761483 CNV loss 21179565
esv3544466 CNV deletion 23714750
esv3619394 CNV gain 21293372
nsv1019912 CNV loss 25217958
nsv1029665 CNV gain 25217958
nsv521598 CNV loss 19592680
nsv613205 CNV loss 21841781
nsv831496 CNV gain 17160897

Variation tolerance for IL33 Gene

Residual Variation Intolerance Score: 40.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.83; 47.86% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for IL33 Gene

Human Gene Mutation Database (HGMD)
IL33
SNPedia medical, phenotypic, and genealogical associations of SNPs for
IL33

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for IL33 Gene

Disorders for IL33 Gene

MalaCards: The human disease database

(44) MalaCards diseases for IL33 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
granulomatous mastitis
  • idiopathic granulomatous mastitis
loeffler syndrome
  • loeffler's pneumonia
igg4-related disease
  • mediastinal fibrosis, familial
chronic apical periodontitis
allergic conjunctivitis
  • conjunctivitis allergic
- elite association - COSMIC cancer census association via MalaCards
Search IL33 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for IL33

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with IL33: view

No data available for UniProtKB/Swiss-Prot and Genatlas for IL33 Gene

Publications for IL33 Gene

  1. Molecular characterization of NF-HEV, a nuclear factor preferentially expressed in human high endothelial venules. (PMID: 12819012) Baekkevold ES … Girard JP (The American journal of pathology 2003) 2 3 4 23
  2. Interleukin-33 is biologically active independently of caspase-1 cleavage. (PMID: 19465481) Talabot-Ayer D … Palmer G (The Journal of biological chemistry 2009) 3 4 23
  3. Suppression of interleukin-33 bioactivity through proteolysis by apoptotic caspases. (PMID: 19559631) Lüthi AU … Martin SJ (Immunity 2009) 3 4 23
  4. Transcriptomic and genetic studies identify IL-33 as a candidate gene for Alzheimer's disease. (PMID: 19204726) Chapuis J … Lambert JC (Molecular psychiatry 2009) 3 23 41
  5. The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel 'alarmin'? (PMID: 18836528) Moussion C … Girard JP (PloS one 2008) 3 4 23

Products for IL33 Gene

Sources for IL33 Gene