UniProtKB - O95760 (IL33_HUMAN)
Interleukin-33
IL33
Functioni
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).
3 PublicationsIn 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).
2 PublicationsGO - Molecular functioni
- cytokine activity Source: BHF-UCL
GO - Biological processi
- interleukin-33-mediated signaling pathway Source: ARUK-UCL
- negative regulation of macrophage proliferation Source: ARUK-UCL
- negative regulation of transcription by RNA polymerase II Source: CACAO
- positive regulation of CD80 production Source: ARUK-UCL
- positive regulation of CD86 production Source: ARUK-UCL
- positive regulation of cellular defense response Source: ARUK-UCL
- positive regulation of chemokine production Source: BHF-UCL
- positive regulation of cytokine production Source: GO_Central
- positive regulation of gene expression Source: ARUK-UCL
- positive regulation of inflammatory response Source: BHF-UCL
- positive regulation of interleukin-6 production Source: ARUK-UCL
- positive regulation of macrophage activation Source: BHF-UCL
- positive regulation of neuroinflammatory response Source: ARUK-UCL
- positive regulation of nitric-oxide synthase biosynthetic process Source: ARUK-UCL
- positive regulation of transcription by RNA polymerase II Source: BHF-UCL
- positive regulation of tumor necrosis factor production Source: ARUK-UCL
Keywordsi
Molecular function | Cytokine |
Biological process | Transcription |
Enzyme and pathway databases
PathwayCommonsi | O95760 |
Reactomei | R-HSA-1257604, PIP3 activates AKT signaling R-HSA-5689880, Ub-specific processing proteases R-HSA-6811558, PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-HSA-9014843, Interleukin-33 signaling |
SignaLinki | O95760 |
Names & Taxonomyi
Protein namesi | Recommended name: Interleukin-33Short name: IL-33 Alternative name(s): Interleukin-1 family member 11 Short name: IL-1F11 Nuclear factor from high endothelial venules Short name: NF-HEV Cleaved into the following 3 chains: |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:16028, IL33 |
MIMi | 608678, gene |
neXtProti | NX_O95760 |
VEuPathDBi | HostDB:ENSG00000137033 |
Subcellular locationi
Nucleus
- Nucleus 5 Publications
Extracellular region or secreted
- Secreted 1 Publication
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Other locations
- Chromosome 1 Publication
- secretory vesicle 1 Publication
Note: Associates with heterochromatin and mitotic chromosomes (PubMed:17185418). 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 (PubMed:32272059).1 Publication
Extracellular region or secreted
- extracellular region Source: Reactome
- extracellular space Source: UniProtKB-KW
Nucleus
- nucleoplasm Source: HPA
- nucleus Source: CACAO
Other locations
- chromosome Source: UniProtKB-SubCell
- cytoplasm Source: CACAO
- intracellular membrane-bounded organelle Source: HPA
- transport vesicle Source: UniProtKB-SubCell
Keywords - Cellular componenti
Chromosome, Cytoplasm, Cytoplasmic vesicle, Nucleus, SecretedPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 144 | E → K: Decreases affinity for IL1RL1. 1 Publication | 1 | |
Mutagenesisi | 148 | E → K: 7-fold decrease in affinity for IL1RL1. 1 Publication | 1 | |
Mutagenesisi | 149 | D → K: Almost abolishes binding to IL1RL1. 1 Publication | 1 | |
Mutagenesisi | 165 | E → K: 8-fold decrease in affinity for IL1RL1. 1 Publication | 1 | |
Mutagenesisi | 244 | D → K: Decreases affinity for IL1RL1. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 90865 |
OpenTargetsi | ENSG00000137033 |
PharmGKBi | PA162392005 |
Miscellaneous databases
Pharosi | O95760, Tbio |
Chemistry databases
ChEMBLi | CHEMBL4630890 |
Genetic variation databases
BioMutai | IL33 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000096790 | 1 – 270 | Interleukin-33Add BLAST | 270 | |
PropeptideiPRO_0000430083 | 1 – 94 | 1 PublicationAdd BLAST | 94 | |
ChainiPRO_0000430084 | 95 – 270 | Interleukin-33 (95-270)Add BLAST | 176 | |
ChainiPRO_0000430085 | 99 – 270 | Interleukin-33 (99-270)Add BLAST | 172 | |
ChainiPRO_0000430086 | 109 – 270 | Interleukin-33 (109-270)Add BLAST | 162 |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 94 – 95 | Cleavage; by CTSG1 Publication | 2 | |
Sitei | 98 – 99 | Cleavage; by ELANE1 Publication | 2 | |
Sitei | 108 – 109 | Cleavage; by CTSG1 Publication | 2 |
Proteomic databases
MassIVEi | O95760 |
PaxDbi | O95760 |
PeptideAtlasi | O95760 |
PRIDEi | O95760 |
ProteomicsDBi | 4342 51036 [O95760-1] 51037 [O95760-2] |
PTM databases
iPTMneti | O95760 |
PhosphoSitePlusi | O95760 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000137033, Expressed in left coronary artery and 204 other tissues |
Genevisiblei | O95760, HS |
Organism-specific databases
HPAi | ENSG00000137033, Tissue enhanced (urinary) |
Interactioni
Subunit structurei
Forms a 1:1:1 heterotrimeric complex with its primary high-affinity receptor IL1RL1 and the coreceptor IL1RAP.
Interacts with cargo receptor TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion (PubMed:32272059).
3 Publications(Microbial infection) Interacts (in reduced form) with H.polygyrus ARI.
1 PublicationBinary interactionsi
GO - Molecular functioni
- cytokine activity Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 124776, 8 interactors |
DIPi | DIP-37862N |
IntActi | O95760, 6 interactors |
MINTi | O95760 |
STRINGi | 9606.ENSP00000370842 |
Miscellaneous databases
RNActi | O95760, protein |
Structurei
Secondary structure
3D structure databases
BMRBi | O95760 |
SMRi | O95760 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | O95760 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 65 | Homeodomain-like HTH domainAdd BLAST | 65 | |
Regioni | 66 – 111 | Interaction with RELABy similarityAdd BLAST | 46 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | ENOG502RW83, Eukaryota |
GeneTreei | ENSGT00390000005185 |
HOGENOMi | CLU_1795771_0_0_1 |
InParanoidi | O95760 |
OMAi | HRKSSKC |
OrthoDBi | 1062809at2759 |
PhylomeDBi | O95760 |
TreeFami | TF338120 |
Family and domain databases
InterProi | View protein in InterPro IPR026145, IL-33 |
PANTHERi | PTHR21114, PTHR21114, 1 hit |
Pfami | View protein in Pfam PF15095, IL33, 1 hit |
s (4)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MKPKMKYSTN KISTAKWKNT ASKALCFKLG KSQQKAKEVC PMYFMKLRSG
60 70 80 90 100
LMIKKEACYF RRETTKRPSL KTGRKHKRHL VLAACQQQST VECFAFGISG
110 120 130 140 150
VQKYTRALHD SSITGISPIT EYLASLSTYN DQSITFALED ESYEIYVEDL
160 170 180 190 200
KKDEKKDKVL LSYYESQHPS NESGDGVDGK MLMVTLSPTK DFWLHANNKE
210 220 230 240 250
HSVELHKCEK PLPDQAFFVL HNMHSNCVSF ECKTDPGVFI GVKDNHLALI
260 270
KVDSSENLCT ENILFKLSET
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 139 | E → G in BAG36208 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_049576 | 263 | I → M. Corresponds to variant dbSNP:rs16924241EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_045440 | 31 – 157 | KSQQK…DEKKD → N in isoform 4. 1 PublicationAdd BLAST | 127 | |
Alternative sequenceiVSP_044948 | 72 – 113 | Missing in isoform 3. 1 PublicationAdd BLAST | 42 | |
Alternative sequenceiVSP_042728 | 115 – 156 | Missing in isoform 2. 1 PublicationAdd BLAST | 42 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB024518 mRNA Translation: BAA75892.1 AY905581 mRNA Translation: AAX86998.1 HQ641439 mRNA Translation: ADR77828.1 AK295908 mRNA Translation: BAG58697.1 AK303943 mRNA Translation: BAG64871.1 AK313414 mRNA Translation: BAG36208.1 CR407619 mRNA Translation: CAG28547.1 AL353741 Genomic DNA No translation available. CH471071 Genomic DNA Translation: EAW58748.1 CH471071 Genomic DNA Translation: EAW58750.1 CH471071 Genomic DNA Translation: EAW58751.1 BC047085 mRNA Translation: AAH47085.1 |
CCDSi | CCDS56563.1 [O95760-2] CCDS56564.1 [O95760-4] CCDS6468.1 [O95760-1] CCDS83341.1 [O95760-3] |
RefSeqi | NP_001186569.1, NM_001199640.1 [O95760-2] NP_001186570.1, NM_001199641.1 [O95760-4] NP_001300973.1, NM_001314044.1 [O95760-1] NP_001300974.1, NM_001314045.1 [O95760-1] NP_001300975.1, NM_001314046.1 NP_001300976.1, NM_001314047.1 NP_001300977.1, NM_001314048.1 [O95760-3] NP_254274.1, NM_033439.3 [O95760-1] |
Genome annotation databases
Ensembli | ENST00000381434; ENSP00000370842; ENSG00000137033 ENST00000417746; ENSP00000394039; ENSG00000137033 [O95760-4] ENST00000456383; ENSP00000414238; ENSG00000137033 [O95760-2] ENST00000611532; ENSP00000478858; ENSG00000137033 [O95760-3] ENST00000682010; ENSP00000507310; ENSG00000137033 |
GeneIDi | 90865 |
KEGGi | hsa:90865 |
MANE-Selecti | ENST00000682010.1; ENSP00000507310.1; NM_033439.4; NP_254274.1 |
UCSCi | uc011lmh.3, human [O95760-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB024518 mRNA Translation: BAA75892.1 AY905581 mRNA Translation: AAX86998.1 HQ641439 mRNA Translation: ADR77828.1 AK295908 mRNA Translation: BAG58697.1 AK303943 mRNA Translation: BAG64871.1 AK313414 mRNA Translation: BAG36208.1 CR407619 mRNA Translation: CAG28547.1 AL353741 Genomic DNA No translation available. CH471071 Genomic DNA Translation: EAW58748.1 CH471071 Genomic DNA Translation: EAW58750.1 CH471071 Genomic DNA Translation: EAW58751.1 BC047085 mRNA Translation: AAH47085.1 |
CCDSi | CCDS56563.1 [O95760-2] CCDS56564.1 [O95760-4] CCDS6468.1 [O95760-1] CCDS83341.1 [O95760-3] |
RefSeqi | NP_001186569.1, NM_001199640.1 [O95760-2] NP_001186570.1, NM_001199641.1 [O95760-4] NP_001300973.1, NM_001314044.1 [O95760-1] NP_001300974.1, NM_001314045.1 [O95760-1] NP_001300975.1, NM_001314046.1 NP_001300976.1, NM_001314047.1 NP_001300977.1, NM_001314048.1 [O95760-3] NP_254274.1, NM_033439.3 [O95760-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2KLL | NMR | - | A | 111-270 | [»] | |
4KC3 | X-ray | 3.27 | A | 112-270 | [»] | |
BMRBi | O95760 | |||||
SMRi | O95760 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 124776, 8 interactors |
DIPi | DIP-37862N |
IntActi | O95760, 6 interactors |
MINTi | O95760 |
STRINGi | 9606.ENSP00000370842 |
Chemistry databases
ChEMBLi | CHEMBL4630890 |
PTM databases
iPTMneti | O95760 |
PhosphoSitePlusi | O95760 |
Genetic variation databases
BioMutai | IL33 |
Proteomic databases
MassIVEi | O95760 |
PaxDbi | O95760 |
PeptideAtlasi | O95760 |
PRIDEi | O95760 |
ProteomicsDBi | 4342 51036 [O95760-1] 51037 [O95760-2] |
Protocols and materials databases
ABCDi | O95760, 7 sequenced antibodies |
Antibodypediai | 3362, 1385 antibodies from 44 providers |
DNASUi | 90865 |
Genome annotation databases
Ensembli | ENST00000381434; ENSP00000370842; ENSG00000137033 ENST00000417746; ENSP00000394039; ENSG00000137033 [O95760-4] ENST00000456383; ENSP00000414238; ENSG00000137033 [O95760-2] ENST00000611532; ENSP00000478858; ENSG00000137033 [O95760-3] ENST00000682010; ENSP00000507310; ENSG00000137033 |
GeneIDi | 90865 |
KEGGi | hsa:90865 |
MANE-Selecti | ENST00000682010.1; ENSP00000507310.1; NM_033439.4; NP_254274.1 |
UCSCi | uc011lmh.3, human [O95760-1] |
Organism-specific databases
CTDi | 90865 |
DisGeNETi | 90865 |
GeneCardsi | IL33 |
HGNCi | HGNC:16028, IL33 |
HPAi | ENSG00000137033, Tissue enhanced (urinary) |
MIMi | 608678, gene |
neXtProti | NX_O95760 |
OpenTargetsi | ENSG00000137033 |
PharmGKBi | PA162392005 |
VEuPathDBi | HostDB:ENSG00000137033 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502RW83, Eukaryota |
GeneTreei | ENSGT00390000005185 |
HOGENOMi | CLU_1795771_0_0_1 |
InParanoidi | O95760 |
OMAi | HRKSSKC |
OrthoDBi | 1062809at2759 |
PhylomeDBi | O95760 |
TreeFami | TF338120 |
Enzyme and pathway databases
PathwayCommonsi | O95760 |
Reactomei | R-HSA-1257604, PIP3 activates AKT signaling R-HSA-5689880, Ub-specific processing proteases R-HSA-6811558, PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling R-HSA-9014843, Interleukin-33 signaling |
SignaLinki | O95760 |
Miscellaneous databases
BioGRID-ORCSi | 90865, 4 hits in 1033 CRISPR screens |
ChiTaRSi | IL33, human |
EvolutionaryTracei | O95760 |
GenomeRNAii | 90865 |
Pharosi | O95760, Tbio |
PROi | PR:O95760 |
RNActi | O95760, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000137033, Expressed in left coronary artery and 204 other tissues |
Genevisiblei | O95760, HS |
Family and domain databases
InterProi | View protein in InterPro IPR026145, IL-33 |
PANTHERi | PTHR21114, PTHR21114, 1 hit |
Pfami | View protein in Pfam PF15095, IL33, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | IL33_HUMAN | |
Accessioni | O95760Primary (citable) accession number: O95760 Secondary accession number(s): B2R8L1 Q2YEJ5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 5, 2005 |
Last sequence update: | May 1, 1999 | |
Last modified: | February 23, 2022 | |
This is version 158 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 9
Human chromosome 9: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families