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Protein

Interleukin-33

Gene

IL33

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 Publications
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).2 Publications

GO - Molecular functioni

  • cytokine activity Source: BHF-UCL

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Keywords - Biological processi

Transcription

Enzyme and pathway databases

BioCyciZFISH:ENSG00000137033-MONOMER.
ReactomeiR-HSA-449147. Signaling by Interleukins.
R-HSA-5689880. Ub-specific processing proteases.

Names & Taxonomyi

Protein namesi
Recommended name:
Interleukin-33
Short 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
Name:IL33
Synonyms:C9orf26, IL1F11, NFHEV
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:16028. IL33.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Cytoplasmic vesicle, Nucleus, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi144E → K: Decreases affinity for IL1RL1. 1 Publication1
Mutagenesisi148E → K: 7-fold decrease in affinity for IL1RL1. 1 Publication1
Mutagenesisi149D → K: Almost abolishes binding to IL1RL1. 1 Publication1
Mutagenesisi165E → K: 8-fold decrease in affinity for IL1RL1. 1 Publication1
Mutagenesisi244D → K: Decreases affinity for IL1RL1. 1 Publication1

Organism-specific databases

DisGeNETi90865.
OpenTargetsiENSG00000137033.
PharmGKBiPA162392005.

Polymorphism and mutation databases

BioMutaiIL33.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000967901 – 270Interleukin-33Add BLAST270
PropeptideiPRO_00004300831 – 941 PublicationAdd BLAST94
ChainiPRO_000043008495 – 270Interleukin-33 (95-270)Add BLAST176
ChainiPRO_000043008599 – 270Interleukin-33 (99-270)Add BLAST172
ChainiPRO_0000430086109 – 270Interleukin-33 (109-270)Add BLAST162

Post-translational modificationi

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.6 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei94 – 95Cleavage; by CTSG2
Sitei98 – 99Cleavage; by ELANE2
Sitei108 – 109Cleavage; by CTSG2

Proteomic databases

PaxDbiO95760.
PeptideAtlasiO95760.
PRIDEiO95760.

PTM databases

iPTMnetiO95760.
PhosphoSitePlusiO95760.

Expressioni

Tissue specificityi

Expressed at high level in high endothelial venules found in tonsils, Peyer patches and mesenteric lymph nodes. Almost undetectable in placenta.1 Publication

Gene expression databases

BgeeiENSG00000137033.
CleanExiHS_IL33.
GenevisibleiO95760. HS.

Organism-specific databases

HPAiCAB007057.
HPA024426.

Interactioni

Subunit structurei

Forms a 1:1:1 heterotrimeric complex with its primary high-affinity receptor IL1RL1 and the coreceptor IL1RAP.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
HIST1H2AMP0C0S83EBI-724057,EBI-1390628
IL1RL1Q016382EBI-724057,EBI-993762

GO - Molecular functioni

  • cytokine activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi124776. 6 interactors.
DIPiDIP-37862N.
IntActiO95760. 5 interactors.
MINTiMINT-1423224.
STRINGi9606.ENSP00000370842.

Structurei

Secondary structure

1270
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi112 – 115Combined sources4
Beta strandi119 – 127Combined sources9
Turni129 – 131Combined sources3
Beta strandi133 – 138Combined sources6
Beta strandi140 – 148Combined sources9
Beta strandi158 – 169Combined sources12
Turni170 – 172Combined sources3
Beta strandi180 – 189Combined sources10
Beta strandi193 – 197Combined sources5
Turni198 – 201Combined sources4
Beta strandi202 – 206Combined sources5
Helixi214 – 216Combined sources3
Beta strandi218 – 224Combined sources7
Beta strandi228 – 235Combined sources8
Beta strandi238 – 243Combined sources6
Beta strandi246 – 251Combined sources6
Helixi261 – 263Combined sources3
Beta strandi265 – 267Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KLLNMR-A111-270[»]
4KC3X-ray3.27A112-270[»]
ProteinModelPortaliO95760.
SMRiO95760.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO95760.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 65Homeodomain-like HTH domainAdd BLAST65
Regioni66 – 111Interaction with RELABy similarityAdd BLAST46

Domaini

The homeodomain-like HTH domain mediates nuclear localization and heterochromatin association.

Sequence similaritiesi

Belongs to the IL-1 family. Highly divergent.Curated

Phylogenomic databases

eggNOGiENOG410J11H. Eukaryota.
ENOG41118MB. LUCA.
GeneTreeiENSGT00390000005185.
HOGENOMiHOG000070215.
HOVERGENiHBG081791.
InParanoidiO95760.
KOiK12967.
OMAiSPTKDFW.
OrthoDBiEOG091G0F5I.
PhylomeDBiO95760.
TreeFamiTF338120.

Family and domain databases

InterProiIPR026145. IL-33.
[Graphical view]
PANTHERiPTHR21114. PTHR21114. 1 hit.
PfamiPF15095. IL33. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O95760-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Length:270
Mass (Da):30,759
Last modified:May 1, 1999 - v1
Checksum:i7C158069196EF636
GO
Isoform 2 (identifier: O95760-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     115-156: Missing.

Note: No experimental confirmation available.
Show »
Length:228
Mass (Da):25,930
Checksum:iD48B2E3078CFA6C8
GO
Isoform 3 (identifier: O95760-3) [UniParc]FASTAAdd to basket
Also known as: spIL-33

The sequence of this isoform differs from the canonical sequence as follows:
     72-113: Missing.

Note: Constitutively active.
Show »
Length:228
Mass (Da):26,104
Checksum:iA982BD564D8FEC0E
GO
Isoform 4 (identifier: O95760-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     31-157: KSQQKAKEVC...EDLKKDEKKD → N

Show »
Length:144
Mass (Da):16,250
Checksum:i1B73431981DFFF46
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti139E → G in BAG36208 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049576263I → M.Corresponds to variant rs16924241dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04544031 – 157KSQQK…DEKKD → N in isoform 4. 1 PublicationAdd BLAST127
Alternative sequenceiVSP_04494872 – 113Missing in isoform 3. 1 PublicationAdd BLAST42
Alternative sequenceiVSP_042728115 – 156Missing in isoform 2. 1 PublicationAdd BLAST42

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. Translation: CAI16003.1.
CH471071 Genomic DNA. Translation: EAW58748.1.
CH471071 Genomic DNA. Translation: EAW58750.1.
CH471071 Genomic DNA. Translation: EAW58751.1.
BC047085 mRNA. Translation: AAH47085.1.
CCDSiCCDS56563.1. [O95760-2]
CCDS56564.1. [O95760-4]
CCDS6468.1. [O95760-1]
CCDS83341.1. [O95760-3]
RefSeqiNP_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]
UniGeneiHs.731660.

Genome annotation databases

EnsembliENST00000381434; ENSP00000370842; ENSG00000137033. [O95760-1]
ENST00000417746; ENSP00000394039; ENSG00000137033. [O95760-4]
ENST00000456383; ENSP00000414238; ENSG00000137033. [O95760-2]
ENST00000611532; ENSP00000478858; ENSG00000137033. [O95760-3]
GeneIDi90865.
KEGGihsa:90865.
UCSCiuc011lmh.3. human. [O95760-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

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. Translation: CAI16003.1.
CH471071 Genomic DNA. Translation: EAW58748.1.
CH471071 Genomic DNA. Translation: EAW58750.1.
CH471071 Genomic DNA. Translation: EAW58751.1.
BC047085 mRNA. Translation: AAH47085.1.
CCDSiCCDS56563.1. [O95760-2]
CCDS56564.1. [O95760-4]
CCDS6468.1. [O95760-1]
CCDS83341.1. [O95760-3]
RefSeqiNP_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]
UniGeneiHs.731660.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KLLNMR-A111-270[»]
4KC3X-ray3.27A112-270[»]
ProteinModelPortaliO95760.
SMRiO95760.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124776. 6 interactors.
DIPiDIP-37862N.
IntActiO95760. 5 interactors.
MINTiMINT-1423224.
STRINGi9606.ENSP00000370842.

PTM databases

iPTMnetiO95760.
PhosphoSitePlusiO95760.

Polymorphism and mutation databases

BioMutaiIL33.

Proteomic databases

PaxDbiO95760.
PeptideAtlasiO95760.
PRIDEiO95760.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000381434; ENSP00000370842; ENSG00000137033. [O95760-1]
ENST00000417746; ENSP00000394039; ENSG00000137033. [O95760-4]
ENST00000456383; ENSP00000414238; ENSG00000137033. [O95760-2]
ENST00000611532; ENSP00000478858; ENSG00000137033. [O95760-3]
GeneIDi90865.
KEGGihsa:90865.
UCSCiuc011lmh.3. human. [O95760-1]

Organism-specific databases

CTDi90865.
DisGeNETi90865.
GeneCardsiIL33.
HGNCiHGNC:16028. IL33.
HPAiCAB007057.
HPA024426.
MIMi608678. gene.
neXtProtiNX_O95760.
OpenTargetsiENSG00000137033.
PharmGKBiPA162392005.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J11H. Eukaryota.
ENOG41118MB. LUCA.
GeneTreeiENSGT00390000005185.
HOGENOMiHOG000070215.
HOVERGENiHBG081791.
InParanoidiO95760.
KOiK12967.
OMAiSPTKDFW.
OrthoDBiEOG091G0F5I.
PhylomeDBiO95760.
TreeFamiTF338120.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000137033-MONOMER.
ReactomeiR-HSA-449147. Signaling by Interleukins.
R-HSA-5689880. Ub-specific processing proteases.

Miscellaneous databases

EvolutionaryTraceiO95760.
GenomeRNAii90865.
PROiO95760.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000137033.
CleanExiHS_IL33.
GenevisibleiO95760. HS.

Family and domain databases

InterProiIPR026145. IL-33.
[Graphical view]
PANTHERiPTHR21114. PTHR21114. 1 hit.
PfamiPF15095. IL33. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiIL33_HUMAN
AccessioniPrimary (citable) accession number: O95760
Secondary accession number(s): B2R8L1
, B4DJ35, B4E1Q9, D3DRI5, E7EAX4, Q2YEJ5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: May 1, 1999
Last modified: November 2, 2016
This is version 126 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.