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Protein

Interleukin-33

Gene

Il33

Organism
Mus musculus (Mouse)
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. 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.
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. This form is rapidely lost upon angiogenic or proinflammatory activation.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei101 – 1022Cleavage; by CTSG and ELANECurated
Sitei108 – 1092Cleavage; by ELANECurated

GO - Molecular functioni

  • cytokine activity Source: BHF-UCL

GO - Biological processi

  • defense response to virus Source: MGI
  • extrinsic apoptotic signaling pathway Source: MGI
  • negative regulation of immunoglobulin secretion Source: BHF-UCL
  • negative regulation of interferon-gamma production Source: BHF-UCL
  • negative regulation of leukocyte migration Source: BHF-UCL
  • negative regulation of T-helper 1 type immune response Source: BHF-UCL
  • positive regulation of chemokine secretion Source: BHF-UCL
  • positive regulation of gene expression Source: MGI
  • positive regulation of immunoglobulin secretion Source: BHF-UCL
  • positive regulation of inflammatory response Source: BHF-UCL
  • positive regulation of interleukin-13 production Source: BHF-UCL
  • positive regulation of interleukin-4 production Source: BHF-UCL
  • positive regulation of interleukin-5 production Source: BHF-UCL
  • positive regulation of interleukin-6 production Source: BHF-UCL
  • positive regulation of macrophage activation Source: BHF-UCL
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of type 2 immune response Source: BHF-UCL
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Keywords - Biological processi

Transcription

Names & Taxonomyi

Protein namesi
Recommended name:
Interleukin-33
Short name:
IL-33
Cleaved into the following 2 chains:
Gene namesi
Name:Il33
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:1924375. Il33.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Cytoplasmic vesicle, Nucleus, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 266266Interleukin-33PRO_0000096791Add
BLAST
Propeptidei1 – 101101CuratedPRO_0000430087Add
BLAST
Chaini102 – 266165Interleukin-33(102-266)CuratedPRO_0000430088Add
BLAST
Chaini109 – 266158Interleukin-33(109-266)CuratedPRO_0000430089Add
BLAST

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. Proteolytic cleavage mediated by apoptotic caspases including CASP3 and CASP7 results in IL33 inactivation. 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.3 Publications

Proteomic databases

PRIDEiQ8BVZ5.

PTM databases

PhosphoSiteiQ8BVZ5.

Expressioni

Gene expression databases

BgeeiQ8BVZ5.
CleanExiMM_IL33.
ExpressionAtlasiQ8BVZ5. baseline and differential.
GenevisibleiQ8BVZ5. MM.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi218533. 1 interaction.
IntActiQ8BVZ5. 1 interaction.
STRINGi10090.ENSMUSP00000025724.

Structurei

3D structure databases

ProteinModelPortaliQ8BVZ5.
SMRiQ8BVZ5. Positions 109-265.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 6565Homeodomain-like HTH domainBy similarityAdd
BLAST
Regioni66 – 10843Interaction with RELAAdd
BLAST

Domaini

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

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiNOG41297.
GeneTreeiENSGT00390000005185.
HOGENOMiHOG000070215.
HOVERGENiHBG081791.
InParanoidiQ8BVZ5.
KOiK12967.
OMAiSPTKDFW.
OrthoDBiEOG7TQV1R.
PhylomeDBiQ8BVZ5.
TreeFamiTF338120.

Family and domain databases

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

Sequencei

Sequence statusi: Complete.

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

Q8BVZ5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRPRMKYSNS KISPAKFSST AGEALVPPCK IRRSQQKTKE FCHVYCMRLR
60 70 80 90 100
SGLTIRKETS YFRKEPTKRY SLKSGTKHEE NFSAYPRDSR KRSLLGSIQA
110 120 130 140 150
FAASVDTLSI QGTSLLTQSP ASLSTYNDQS VSFVLENGCY VINVDDSGKD
160 170 180 190 200
QEQDQVLLRY YESPCPASQS GDGVDGKKLM VNMSPIKDTD IWLHANDKDY
210 220 230 240 250
SVELQRGDVS PPEQAFFVLH KKSSDFVSFE CKNLPGTYIG VKDNQLALVE
260
EKDESCNNIM FKLSKI
Length:266
Mass (Da):29,991
Last modified:March 1, 2003 - v1
Checksum:iE03C2C297EB43E23
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti24 – 252AL → RS in AAX86999 (PubMed:16286016).Curated
Sequence conflicti179 – 1791L → V in AAH03847 (PubMed:15489334).Curated
Sequence conflicti185 – 1851P → S in AAX86999 (PubMed:16286016).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY905582 mRNA. Translation: AAX86999.1.
AK075849 mRNA. Translation: BAC36003.1.
AK163464 mRNA. Translation: BAE37352.1.
BC003847 mRNA. Translation: AAH03847.1.
CCDSiCCDS29740.1.
RefSeqiNP_001158196.1. NM_001164724.1.
NP_598536.2. NM_133775.2.
XP_006527526.1. XM_006527463.2.
XP_011245701.1. XM_011247399.1.
UniGeneiMm.182359.

Genome annotation databases

EnsembliENSMUST00000025724; ENSMUSP00000025724; ENSMUSG00000024810.
ENSMUST00000120388; ENSMUSP00000113829; ENSMUSG00000024810.
GeneIDi77125.
KEGGimmu:77125.
UCSCiuc008hec.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY905582 mRNA. Translation: AAX86999.1.
AK075849 mRNA. Translation: BAC36003.1.
AK163464 mRNA. Translation: BAE37352.1.
BC003847 mRNA. Translation: AAH03847.1.
CCDSiCCDS29740.1.
RefSeqiNP_001158196.1. NM_001164724.1.
NP_598536.2. NM_133775.2.
XP_006527526.1. XM_006527463.2.
XP_011245701.1. XM_011247399.1.
UniGeneiMm.182359.

3D structure databases

ProteinModelPortaliQ8BVZ5.
SMRiQ8BVZ5. Positions 109-265.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi218533. 1 interaction.
IntActiQ8BVZ5. 1 interaction.
STRINGi10090.ENSMUSP00000025724.

PTM databases

PhosphoSiteiQ8BVZ5.

Proteomic databases

PRIDEiQ8BVZ5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000025724; ENSMUSP00000025724; ENSMUSG00000024810.
ENSMUST00000120388; ENSMUSP00000113829; ENSMUSG00000024810.
GeneIDi77125.
KEGGimmu:77125.
UCSCiuc008hec.2. mouse.

Organism-specific databases

CTDi90865.
MGIiMGI:1924375. Il33.

Phylogenomic databases

eggNOGiNOG41297.
GeneTreeiENSGT00390000005185.
HOGENOMiHOG000070215.
HOVERGENiHBG081791.
InParanoidiQ8BVZ5.
KOiK12967.
OMAiSPTKDFW.
OrthoDBiEOG7TQV1R.
PhylomeDBiQ8BVZ5.
TreeFamiTF338120.

Miscellaneous databases

NextBioi346526.
PROiQ8BVZ5.
SOURCEiSearch...

Gene expression databases

BgeeiQ8BVZ5.
CleanExiMM_IL33.
ExpressionAtlasiQ8BVZ5. baseline and differential.
GenevisibleiQ8BVZ5. MM.

Family and domain databases

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

Publicationsi

« Hide 'large scale' publications
  1. "IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST 2 and induces T helper type 2-associated cytokines."
    Schmitz J., Owyang A., Oldham E., Song Y., Murphy E., McClanahan T.K., Zurawski G., Moshrefi M., Qin J., Li X., Gorman D.M., Bazan J.F., Kastelein R.A.
    Immunity 23:479-490(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
    Strain: BALB/c.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Corpora quadrigemina and Gastric mucosa.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Mammary gland.
  4. "Interleukin-33 is biologically active independently of caspase-1 cleavage."
    Talabot-Ayer D., Lamacchia C., Gabay C., Palmer G.
    J. Biol. Chem. 284:19420-19426(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PROTEOLYTIC PROCESSING, SUBCELLULAR LOCATION.
  5. "The dual function cytokine IL-33 interacts with the transcription factor NF-kappaB to dampen NF-kappaB-stimulated gene transcription."
    Ali S., Mohs A., Thomas M., Klare J., Ross R., Schmitz M.L., Martin M.U.
    J. Immunol. 187:1609-1616(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH NF-KAPPAB/RELA.
  6. "IL-33 is processed into mature bioactive forms by neutrophil elastase and cathepsin G."
    Lefrancais E., Roga S., Gautier V., Gonzalez-de-Peredo A., Monsarrat B., Girard J.P., Cayrol C.
    Proc. Natl. Acad. Sci. U.S.A. 109:1673-1678(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING, CLEAVAGE AT PHE-101 BY CSTG AND ELANE, CLEAVAGE AT LEU-108 BY ELANE.

Entry informationi

Entry nameiIL33_MOUSE
AccessioniPrimary (citable) accession number: Q8BVZ5
Secondary accession number(s): Q2YEJ4, Q3TQN0, Q99L46
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: March 1, 2003
Last modified: July 22, 2015
This is version 94 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Intraperitoneal injections of IL-33 induce the expression of IL-4, IL-5, and IL-13 and lead to severe pathological changes in mucosal organs.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.