IL33_MOUSE
ID IL33_MOUSE Reviewed; 266 AA.
AC Q8BVZ5; Q2YEJ4; Q3TQN0; Q99L46;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Interleukin-33;
DE Short=IL-33;
DE Contains:
DE RecName: Full=Interleukin-33(102-266);
DE Contains:
DE RecName: Full=Interleukin-33(109-266);
DE Flags: Precursor;
GN Name=Il33 {ECO:0000312|MGI:MGI:1924375};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC STRAIN=BALB/cJ;
RX PubMed=16286016; DOI=10.1016/j.immuni.2005.09.015;
RA Schmitz J., Owyang A., Oldham E., Song Y., Murphy E., McClanahan T.K.,
RA Zurawski G., Moshrefi M., Qin J., Li X., Gorman D.M., Bazan J.F.,
RA Kastelein R.A.;
RT "IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-
RT related protein ST 2 and induces T helper type 2-associated cytokines.";
RL Immunity 23:479-490(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Corpora quadrigemina, and Gastric mucosa;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, PROTEOLYTIC PROCESSING, AND SUBCELLULAR LOCATION.
RX PubMed=19465481; DOI=10.1074/jbc.m901744200;
RA Talabot-Ayer D., Lamacchia C., Gabay C., Palmer G.;
RT "Interleukin-33 is biologically active independently of caspase-1
RT cleavage.";
RL J. Biol. Chem. 284:19420-19426(2009).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH NF-KAPPAB/RELA.
RX PubMed=21734074; DOI=10.4049/jimmunol.1003080;
RA Ali S., Mohs A., Thomas M., Klare J., Ross R., Schmitz M.L., Martin M.U.;
RT "The dual function cytokine IL-33 interacts with the transcription factor
RT NF-kappaB to dampen NF-kappaB-stimulated gene transcription.";
RL J. Immunol. 187:1609-1616(2011).
RN [6]
RP PROTEOLYTIC CLEAVAGE AT PHE-101 BY CSTG AND ELANE, AND PROTEOLYTIC CLEAVAGE
RP AT LEU-108 BY ELANE.
RX PubMed=22307629; DOI=10.1073/pnas.1115884109;
RA Lefrancais E., Roga S., Gautier V., Gonzalez-de-Peredo A., Monsarrat B.,
RA Girard J.P., Cayrol C.;
RT "IL-33 is processed into mature bioactive forms by neutrophil elastase and
RT cathepsin G.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:1673-1678(2012).
RN [7]
RP FUNCTION, INTERACTION WITH H.POLYGYRUS ARI, SUBCELLULAR LOCATION, AND
RP INDUCTION BY A.ALTERNATA AND H.POLYGYRUS.
RX PubMed=29045903; DOI=10.1016/j.immuni.2017.09.015;
RA Osbourn M., Soares D.C., Vacca F., Cohen E.S., Scott I.C., Gregory W.F.,
RA Smyth D.J., Toivakka M., Kemter A.M., le Bihan T., Wear M., Hoving D.,
RA Filbey K.J., Hewitson J.P., Henderson H., Gonzalez-Ciscar A., Errington C.,
RA Vermeren S., Astier A.L., Wallace W.A., Schwarze J., Ivens A.C.,
RA Maizels R.M., McSorley H.J.;
RT "HpARI Protein Secreted by a Helminth Parasite Suppresses Interleukin-33.";
RL Immunity 47:739-751(2017).
CC -!- FUNCTION: Cytokine that binds to and signals through the IL1RL1/ST2
CC receptor which in turn activates NF-kappa-B and MAPK signaling pathways
CC in target cells (PubMed:29045903). Involved in the maturation of Th2
CC cells inducing the secretion of T-helper type 2-associated cytokines.
CC Also involved in activation of mast cells, basophils, eosinophils and
CC natural killer cells. Acts as a chemoattractant for Th2 cells, and may
CC function as an 'alarmin', that amplifies immune responses during tissue
CC injury. {ECO:0000269|PubMed:29045903}.
CC -!- FUNCTION: In quiescent endothelia the uncleaved form is constitutively
CC and abundantly expressed, and acts as a chromatin-associated nuclear
CC factor with transcriptional repressor properties, it may sequester
CC nuclear NF-kappaB/RELA, lowering expression of its targets. This form
CC is rapidely lost upon angiogenic or pro-inflammatory activation.
CC -!- SUBUNIT: (Microbial infection) Interacts (in reduced form) with
CC H.polygyrus ARI; the interaction abolishes the interaction with its
CC primary receptor IL1RL1. {ECO:0000269|PubMed:29045903}.
CC -!- SUBUNIT: Forms a 1:1:1 heterotrimeric complex with its primary high-
CC affinity receptor IL1RL1 and the coreceptor IL1RAP. Interacts with
CC cargo receptor TMED10; the interaction mediates the translocation from
CC the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate
CC compartment) and thereby secretion. {ECO:0000250|UniProtKB:O95760}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:29045903}.
CC Note=(Microbial infection) Upon infection with H.polygyrus, tethered to
CC the nucleus by the H.polygyrus parasitic protein ARI.
CC {ECO:0000269|PubMed:29045903}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O95760}.
CC Chromosome {ECO:0000250|UniProtKB:O95760}. Cytoplasm
CC {ECO:0000250|UniProtKB:O95760}. Cytoplasmic vesicle, secretory vesicle
CC {ECO:0000250|UniProtKB:O95760}. Secreted
CC {ECO:0000250|UniProtKB:O95760}. Note=Associates with heterochromatin
CC and mitotic chromosomes. The secretion is dependent on protein
CC unfolding and facilitated by the cargo receptor TMED10; it results in
CC protein translocation from the cytoplasm into the ERGIC (endoplasmic
CC reticulum-Golgi intermediate compartment) followed by vesicle entry and
CC secretion. {ECO:0000250|UniProtKB:O95760}.
CC -!- INDUCTION: By cold stress, and by infection with the fungus A.alternata
CC and the parasite H.polygyrus. {ECO:0000269|PubMed:29045903}.
CC -!- DOMAIN: The homeodomain-like HTH domain mediates nuclear localization
CC and heterochromatin association. {ECO:0000250}.
CC -!- PTM: The full-length protein can be released from cells and is able to
CC signal via the IL1RL1/ST2 receptor. However, proteolytic processing by
CC CSTG/cathepsin G and ELANE/neutrophil elastase produces C-terminal
CC peptides that are more active than the unprocessed full-length protein.
CC May also be proteolytically processed by calpains. Proteolytic cleavage
CC mediated by apoptotic caspases including CASP3 and CASP7 results in
CC IL33 inactivation. In vitro proteolytic cleavage by CASP1 was reported
CC (PubMed:16286016) but could not be confirmed in vivo (PubMed:19465481)
CC suggesting that IL33 is probably not a direct substrate for that
CC caspase. {ECO:0000269|PubMed:16286016, ECO:0000269|PubMed:19465481,
CC ECO:0000269|PubMed:22307629}.
CC -!- MISCELLANEOUS: Intraperitoneal injections of IL-33 induce the
CC expression of IL-4, IL-5, and IL-13 and lead to severe pathological
CC changes in mucosal organs.
CC -!- SIMILARITY: Belongs to the IL-1 family. Highly divergent.
CC {ECO:0000305}.
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DR EMBL; AY905582; AAX86999.1; -; mRNA.
DR EMBL; AK075849; BAC36003.1; -; mRNA.
DR EMBL; AK163464; BAE37352.1; -; mRNA.
DR EMBL; BC003847; AAH03847.1; -; mRNA.
DR CCDS; CCDS29740.1; -.
DR RefSeq; NP_001158196.1; NM_001164724.1.
DR RefSeq; NP_598536.2; NM_133775.2.
DR RefSeq; XP_006527526.1; XM_006527463.3.
DR RefSeq; XP_011245701.1; XM_011247399.2.
DR PDB; 5VI4; X-ray; 2.79 A; A/D=109-266.
DR PDBsum; 5VI4; -.
DR AlphaFoldDB; Q8BVZ5; -.
DR SMR; Q8BVZ5; -.
DR BioGRID; 218533; 1.
DR IntAct; Q8BVZ5; 1.
DR STRING; 10090.ENSMUSP00000025724; -.
DR iPTMnet; Q8BVZ5; -.
DR PhosphoSitePlus; Q8BVZ5; -.
DR MaxQB; Q8BVZ5; -.
DR PaxDb; Q8BVZ5; -.
DR PRIDE; Q8BVZ5; -.
DR ProteomicsDB; 269549; -.
DR Antibodypedia; 3362; 1283 antibodies from 44 providers.
DR DNASU; 77125; -.
DR Ensembl; ENSMUST00000025724; ENSMUSP00000025724; ENSMUSG00000024810.
DR Ensembl; ENSMUST00000120388; ENSMUSP00000113829; ENSMUSG00000024810.
DR GeneID; 77125; -.
DR KEGG; mmu:77125; -.
DR UCSC; uc008hec.2; mouse.
DR CTD; 90865; -.
DR MGI; MGI:1924375; Il33.
DR VEuPathDB; HostDB:ENSMUSG00000024810; -.
DR eggNOG; ENOG502RW83; Eukaryota.
DR GeneTree; ENSGT00390000005185; -.
DR InParanoid; Q8BVZ5; -.
DR OMA; HRKSSKC; -.
DR OrthoDB; 1062809at2759; -.
DR PhylomeDB; Q8BVZ5; -.
DR TreeFam; TF338120; -.
DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-MMU-9014843; Interleukin-33 signaling.
DR BioGRID-ORCS; 77125; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Il33; mouse.
DR PRO; PR:Q8BVZ5; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q8BVZ5; protein.
DR Bgee; ENSMUSG00000024810; Expressed in ciliary body and 212 other tissues.
DR ExpressionAtlas; Q8BVZ5; baseline and differential.
DR Genevisible; Q8BVZ5; MM.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0005125; F:cytokine activity; IDA:BHF-UCL.
DR GO; GO:0002112; F:interleukin-33 receptor binding; IPI:UniProtKB.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0051607; P:defense response to virus; IDA:MGI.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IGI:MGI.
DR GO; GO:0010467; P:gene expression; IDA:MGI.
DR GO; GO:0038172; P:interleukin-33-mediated signaling pathway; IDA:ARUK-UCL.
DR GO; GO:0002281; P:macrophage activation involved in immune response; IDA:UniProtKB.
DR GO; GO:0002282; P:microglial cell activation involved in immune response; IDA:UniProtKB.
DR GO; GO:0061518; P:microglial cell proliferation; IDA:UniProtKB.
DR GO; GO:0002638; P:negative regulation of immunoglobulin production; IGI:BHF-UCL.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; IGI:BHF-UCL.
DR GO; GO:0002686; P:negative regulation of leukocyte migration; IGI:BHF-UCL.
DR GO; GO:0120042; P:negative regulation of macrophage proliferation; IDA:ARUK-UCL.
DR GO; GO:0002826; P:negative regulation of T-helper 1 type immune response; IGI:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0150145; P:positive regulation of CD80 production; IDA:ARUK-UCL.
DR GO; GO:0150142; P:positive regulation of CD86 production; IDA:ARUK-UCL.
DR GO; GO:0010186; P:positive regulation of cellular defense response; IMP:ARUK-UCL.
DR GO; GO:0032722; P:positive regulation of chemokine production; IDA:BHF-UCL.
DR GO; GO:0001819; P:positive regulation of cytokine production; IBA:GO_Central.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:ARUK-UCL.
DR GO; GO:0002639; P:positive regulation of immunoglobulin production; IGI:BHF-UCL.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IDA:BHF-UCL.
DR GO; GO:0032736; P:positive regulation of interleukin-13 production; IGI:BHF-UCL.
DR GO; GO:0032753; P:positive regulation of interleukin-4 production; IGI:BHF-UCL.
DR GO; GO:0032754; P:positive regulation of interleukin-5 production; IGI:BHF-UCL.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:ARUK-UCL.
DR GO; GO:0043032; P:positive regulation of macrophage activation; IDA:BHF-UCL.
DR GO; GO:0045345; P:positive regulation of MHC class I biosynthetic process; IDA:ARUK-UCL.
DR GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; IDA:ARUK-UCL.
DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; IDA:ARUK-UCL.
DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; ISO:MGI.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IDA:ARUK-UCL.
DR GO; GO:0002830; P:positive regulation of type 2 immune response; IDA:MGI.
DR GO; GO:0051930; P:regulation of sensory perception of pain; ISO:MGI.
DR GO; GO:0042092; P:type 2 immune response; IDA:MGI.
DR GO; GO:0042060; P:wound healing; IEA:Ensembl.
DR InterPro; IPR026145; IL-33.
DR PANTHER; PTHR21114; PTHR21114; 1.
DR Pfam; PF15095; IL33; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chromosome; Cytokine; Cytoplasm; Cytoplasmic vesicle;
KW Nucleus; Reference proteome; Secreted; Transcription.
FT CHAIN 1..266
FT /note="Interleukin-33"
FT /id="PRO_0000096791"
FT PROPEP 1..101
FT /evidence="ECO:0000305"
FT /id="PRO_0000430087"
FT CHAIN 102..266
FT /note="Interleukin-33(102-266)"
FT /evidence="ECO:0000305"
FT /id="PRO_0000430088"
FT CHAIN 109..266
FT /note="Interleukin-33(109-266)"
FT /evidence="ECO:0000305"
FT /id="PRO_0000430089"
FT REGION 1..65
FT /note="Homeodomain-like HTH domain"
FT /evidence="ECO:0000250"
FT REGION 66..108
FT /note="Interaction with RELA"
FT SITE 101..102
FT /note="Cleavage; by CTSG and ELANE"
FT /evidence="ECO:0000269|PubMed:22307629"
FT SITE 108..109
FT /note="Cleavage; by ELANE"
FT /evidence="ECO:0000269|PubMed:22307629"
FT CONFLICT 24..25
FT /note="AL -> RS (in Ref. 1; AAX86999)"
FT /evidence="ECO:0000305"
FT CONFLICT 179
FT /note="L -> V (in Ref. 3; AAH03847)"
FT /evidence="ECO:0000305"
FT CONFLICT 185
FT /note="P -> S (in Ref. 1; AAX86999)"
FT /evidence="ECO:0000305"
FT STRAND 117..125
FT /evidence="ECO:0007829|PDB:5VI4"
FT STRAND 130..134
FT /evidence="ECO:0007829|PDB:5VI4"
FT STRAND 141..145
FT /evidence="ECO:0007829|PDB:5VI4"
FT STRAND 156..166
FT /evidence="ECO:0007829|PDB:5VI4"
FT STRAND 177..187
FT /evidence="ECO:0007829|PDB:5VI4"
FT STRAND 192..195
FT /evidence="ECO:0007829|PDB:5VI4"
FT TURN 197..199
FT /evidence="ECO:0007829|PDB:5VI4"
FT STRAND 201..205
FT /evidence="ECO:0007829|PDB:5VI4"
FT HELIX 213..215
FT /evidence="ECO:0007829|PDB:5VI4"
FT STRAND 217..221
FT /evidence="ECO:0007829|PDB:5VI4"
FT STRAND 223..225
FT /evidence="ECO:0007829|PDB:5VI4"
FT STRAND 227..234
FT /evidence="ECO:0007829|PDB:5VI4"
FT STRAND 237..242
FT /evidence="ECO:0007829|PDB:5VI4"
FT STRAND 245..250
FT /evidence="ECO:0007829|PDB:5VI4"
FT TURN 253..255
FT /evidence="ECO:0007829|PDB:5VI4"
FT HELIX 256..259
FT /evidence="ECO:0007829|PDB:5VI4"
FT STRAND 261..264
FT /evidence="ECO:0007829|PDB:5VI4"
SQ SEQUENCE 266 AA; 29991 MW; E03C2C297EB43E23 CRC64;
MRPRMKYSNS KISPAKFSST AGEALVPPCK IRRSQQKTKE FCHVYCMRLR SGLTIRKETS
YFRKEPTKRY SLKSGTKHEE NFSAYPRDSR KRSLLGSIQA FAASVDTLSI QGTSLLTQSP
ASLSTYNDQS VSFVLENGCY VINVDDSGKD QEQDQVLLRY YESPCPASQS GDGVDGKKLM
VNMSPIKDTD IWLHANDKDY SVELQRGDVS PPEQAFFVLH KKSSDFVSFE CKNLPGTYIG
VKDNQLALVE EKDESCNNIM FKLSKI
