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UniProtKB - O95760 (IL33_HUMAN)

Protein

Interleukin-33

Gene

IL33

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionCytokine
Biological processTranscription

Enzyme and pathway databases

ReactomeiR-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

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:
Interleukin-33 (95-270)
Interleukin-33 (99-270)
Interleukin-33 (109-270)
Gene namesi
Name:IL33
Synonyms:C9orf26, IL1F11, NFHEV
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000137033.11
HGNCiHGNC:16028 IL33
MIMi608678 gene
neXtProtiNX_O95760

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 CTSG1 Publication2
Sitei98 – 99Cleavage; by ELANE1 Publication2
Sitei108 – 109Cleavage; by CTSG1 Publication2

Proteomic databases

PaxDbiO95760
PeptideAtlasiO95760
PRIDEiO95760
ProteomicsDBi51036
51037 [O95760-2]

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 Expressed in 193 organ(s), highest expression level in left coronary artery
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

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi124776, 7 interactors
DIPiDIP-37862N
IntActiO95760, 6 interactors
MINTiO95760
STRINGi9606.ENSP00000370842

Structurei

Secondary structure

1270
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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
OMAiKCVSFEC
OrthoDBiEOG091G0F5I
PhylomeDBiO95760
TreeFamiTF338120

Family and domain databases

InterProiView protein in InterPro
IPR026145 IL-33
PANTHERiPTHR21114 PTHR21114, 1 hit
PfamiView protein in Pfam
PF15095 IL33, 1 hit

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 dbSNP:rs16924241Ensembl.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 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
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

Similar 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
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, 7 interactors
DIPiDIP-37862N
IntActiO95760, 6 interactors
MINTiO95760
STRINGi9606.ENSP00000370842

PTM databases

iPTMnetiO95760
PhosphoSitePlusiO95760

Polymorphism and mutation databases

BioMutaiIL33

Proteomic databases

PaxDbiO95760
PeptideAtlasiO95760
PRIDEiO95760
ProteomicsDBi51036
51037 [O95760-2]

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
EuPathDBiHostDB:ENSG00000137033.11
GeneCardsiIL33
HGNCiHGNC:16028 IL33
HPAiCAB007057
HPA024426
MIMi608678 gene
neXtProtiNX_O95760
OpenTargetsiENSG00000137033
PharmGKBiPA162392005
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiR-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

Miscellaneous databases

EvolutionaryTraceiO95760
GenomeRNAii90865
PROiPR:O95760
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000137033 Expressed in 193 organ(s), highest expression level in left coronary artery
CleanExiHS_IL33
GenevisibleiO95760 HS

Family and domain databases

InterProiView protein in InterPro
IPR026145 IL-33
PANTHERiPTHR21114 PTHR21114, 1 hit
PfamiView protein in Pfam
PF15095 IL33, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiIL33_HUMAN
AccessioniPrimary (citable) accession number: O95760
Secondary accession number(s): B2R8L1
, B4DJ35, B4E1Q9, D3DRI5, E7EAX4, Q2YEJ5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: May 1, 1999
Last modified: November 7, 2018
This is version 139 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
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