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Q8BVZ5

- IL33_MOUSE

UniProt

Q8BVZ5 - IL33_MOUSE

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Protein
Interleukin-33
Gene
Il33
Organism
Mus musculus (Mouse)
Status
Reviewed - 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.2 Publications

Sites

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

GO - Molecular functioni

  1. cytokine activity Source: BHF-UCL

GO - Biological processi

  1. extrinsic apoptotic signaling pathway Source: MGI
  2. negative regulation of T-helper 1 type immune response Source: BHF-UCL
  3. negative regulation of immunoglobulin secretion Source: BHF-UCL
  4. negative regulation of interferon-gamma production Source: BHF-UCL
  5. negative regulation of leukocyte migration Source: BHF-UCL
  6. positive regulation of chemokine secretion Source: BHF-UCL
  7. positive regulation of gene expression Source: MGI
  8. positive regulation of immunoglobulin secretion Source: BHF-UCL
  9. positive regulation of inflammatory response Source: BHF-UCL
  10. positive regulation of interleukin-13 production Source: BHF-UCL
  11. positive regulation of interleukin-4 production Source: BHF-UCL
  12. positive regulation of interleukin-5 production Source: BHF-UCL
  13. positive regulation of interleukin-6 production Source: BHF-UCL
  14. positive regulation of macrophage activation Source: BHF-UCL
  15. positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: MGI
  16. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  17. positive regulation of type 2 immune response Source: BHF-UCL
  18. 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: Chromosome 19

Organism-specific databases

MGIiMGI:1924375. Il33.

Subcellular locationi

Nucleus. Chromosome. Cytoplasmic vesiclesecretory vesicle By similarity. Secreted
Note: Associates with heterochromatin and mitotic chromosomes. Translocation from the nucleus occurs upon biomechanical strain, depends on an intact microtubule network, and is ATP-dependent By similarity.1 Publication

GO - Cellular componenti

  1. chromosome Source: UniProtKB-SubCell
  2. extracellular space Source: UniProtKB-KW
  3. nucleus Source: MGI
  4. transport vesicle Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Cytoplasmic vesicle, Nucleus, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 266266Interleukin-33
PRO_0000096791Add
BLAST
Propeptidei1 – 101101 Inferred
PRO_0000430087Add
BLAST
Chaini102 – 266165Interleukin-33(102-266) Inferred
PRO_0000430088Add
BLAST
Chaini109 – 266158Interleukin-33(109-266) Inferred
PRO_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 (1 Publication) but could not be confirmed in vivo (1 Publication) suggesting that IL33 is probably not a direct substrate for that caspase.

Proteomic databases

PRIDEiQ8BVZ5.

PTM databases

PhosphoSiteiQ8BVZ5.

Expressioni

Gene expression databases

ArrayExpressiQ8BVZ5.
BgeeiQ8BVZ5.
CleanExiMM_IL33.
GenevestigatoriQ8BVZ5.

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.

Structurei

3D structure databases

ProteinModelPortaliQ8BVZ5.
SMRiQ8BVZ5. Positions 109-265.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 6565Homeodomain-like HTH domain By similarity
Add
BLAST
Regioni66 – 10843Interaction with RELA
Add
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.

Phylogenomic databases

eggNOGiNOG41297.
GeneTreeiENSGT00390000005185.
HOGENOMiHOG000070215.
HOVERGENiHBG081791.
InParanoidiQ8BVZ5.
KOiK12967.
OMAiDPGVFIG.
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

MRPRMKYSNS KISPAKFSST AGEALVPPCK IRRSQQKTKE FCHVYCMRLR    50
SGLTIRKETS YFRKEPTKRY SLKSGTKHEE NFSAYPRDSR KRSLLGSIQA 100
FAASVDTLSI QGTSLLTQSP ASLSTYNDQS VSFVLENGCY VINVDDSGKD 150
QEQDQVLLRY YESPCPASQS GDGVDGKKLM VNMSPIKDTD IWLHANDKDY 200
SVELQRGDVS PPEQAFFVLH KKSSDFVSFE CKNLPGTYIG VKDNQLALVE 250
EKDESCNNIM FKLSKI 266
Length:266
Mass (Da):29,991
Last modified:March 1, 2003 - v1
Checksum:iE03C2C297EB43E23
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti24 – 252AL → RS in AAX86999. 1 Publication
Sequence conflicti179 – 1791L → V in AAH03847. 1 Publication
Sequence conflicti185 – 1851P → S in AAX86999. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_006527463.1.
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:
EMBL
GenBank
DDBJ
Links Updated
AY905582 mRNA. Translation: AAX86999.1 .
AK075849 mRNA. Translation: BAC36003.1 .
AK163464 mRNA. Translation: BAE37352.1 .
BC003847 mRNA. Translation: AAH03847.1 .
CCDSi CCDS29740.1.
RefSeqi NP_001158196.1. NM_001164724.1.
NP_598536.2. NM_133775.2.
XP_006527526.1. XM_006527463.1.
UniGenei Mm.182359.

3D structure databases

ProteinModelPortali Q8BVZ5.
SMRi Q8BVZ5. Positions 109-265.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 218533. 1 interaction.
IntActi Q8BVZ5. 1 interaction.

PTM databases

PhosphoSitei Q8BVZ5.

Proteomic databases

PRIDEi Q8BVZ5.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000025724 ; ENSMUSP00000025724 ; ENSMUSG00000024810 .
ENSMUST00000120388 ; ENSMUSP00000113829 ; ENSMUSG00000024810 .
GeneIDi 77125.
KEGGi mmu:77125.
UCSCi uc008hec.2. mouse.

Organism-specific databases

CTDi 90865.
MGIi MGI:1924375. Il33.

Phylogenomic databases

eggNOGi NOG41297.
GeneTreei ENSGT00390000005185.
HOGENOMi HOG000070215.
HOVERGENi HBG081791.
InParanoidi Q8BVZ5.
KOi K12967.
OMAi DPGVFIG.
OrthoDBi EOG7TQV1R.
PhylomeDBi Q8BVZ5.
TreeFami TF338120.

Miscellaneous databases

NextBioi 346526.
PROi Q8BVZ5.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q8BVZ5.
Bgeei Q8BVZ5.
CleanExi MM_IL33.
Genevestigatori Q8BVZ5.

Family and domain databases

InterProi IPR026145. IL-33.
[Graphical view ]
PANTHERi PTHR21114. PTHR21114. 1 hit.
Pfami PF15095. IL33. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: September 3, 2014
This is version 88 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