IL33_HUMAN
ID IL33_HUMAN Reviewed; 270 AA.
AC O95760; B2R8L1; B4DJ35; B4E1Q9; D3DRI5; E7EAX4; Q2YEJ5;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Interleukin-33;
DE Short=IL-33;
DE AltName: Full=Interleukin-1 family member 11;
DE Short=IL-1F11;
DE AltName: Full=Nuclear factor from high endothelial venules;
DE Short=NF-HEV;
DE Contains:
DE RecName: Full=Interleukin-33 (95-270);
DE Contains:
DE RecName: Full=Interleukin-33 (99-270);
DE Contains:
DE RecName: Full=Interleukin-33 (109-270);
DE Flags: Precursor;
GN Name=IL33 {ECO:0000312|HGNC:HGNC:16028}; Synonyms=C9orf26, IL1F11, NFHEV;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Endothelial cell;
RX PubMed=12819012; DOI=10.1016/s0002-9440(10)63631-0;
RA Baekkevold E.S., Roussigne M., Yamanaka T., Johansen F.-E., Jahnsen F.L.,
RA Amalric F., Brandtzaeg P., Erard M., Haraldsen G., Girard J.-P.;
RT "Molecular characterization of NF-HEV, a nuclear factor preferentially
RT expressed in human high endothelial venules.";
RL Am. J. Pathol. 163:69-79(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10566975; DOI=10.1097/00004647-199911000-00013;
RA Onda H., Kasuya H., Takakura K., Hori T., Imaizumi T., Takeuchi T.,
RA Inoue I., Takeda J.;
RT "Identification of genes differentially expressed in canine vasospastic
RT cerebral arteries after subarachnoid hemorrhage.";
RL J. Cereb. Blood Flow Metab. 19:1279-1288(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND PROTEOLYTIC
RP PROCESSING.
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RX PubMed=21454686; DOI=10.1074/jbc.m111.219089;
RA Hong J., Bae S., Jhun H., Lee S., Choi J., Kang T., Kwak A., Hong K.,
RA Kim E., Jo S., Kim S.;
RT "Identification of constitutively active interleukin 33 (IL-33) splice
RT variant.";
RL J. Biol. Chem. 286:20078-20086(2011).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 4).
RC TISSUE=Adrenal gland, and Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [10]
RP PROTEIN SEQUENCE OF 95-121, IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION,
RP PROTEOLYTIC CLEAVAGE AT PHE-94 AND LEU-108 BY CSTG, AND PROTEOLYTIC
RP CLEAVAGE AT ILE-98 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 [11]
RP FUNCTION.
RX PubMed=17853410; DOI=10.1002/eji.200737547;
RA Komai-Koma M., Xu D., Li Y., McKenzie A.N., McInnes I.B., Liew F.Y.;
RT "IL-33 is a chemoattractant for human Th2 cells.";
RL Eur. J. Immunol. 37:2779-2786(2007).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, AND NUCLEAR TARGETING DOMAIN.
RX PubMed=17185418; DOI=10.1073/pnas.0606854104;
RA Carriere V., Roussel L., Ortega N., Lacorre D.A., Americh L., Aguilar L.,
RA Bouche G., Girard J.P.;
RT "IL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-
RT associated nuclear factor in vivo.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:282-287(2007).
RN [13]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18787100; DOI=10.2353/ajpath.2008.080014;
RA Kuchler A.M., Pollheimer J., Balogh J., Sponheim J., Manley L.,
RA Sorensen D.R., De Angelis P.M., Scott H., Haraldsen G.;
RT "Nuclear interleukin-33 is generally expressed in resting endothelium but
RT rapidly lost upon angiogenic or proinflammatory activation.";
RL Am. J. Pathol. 173:1229-1242(2008).
RN [14]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18836528; DOI=10.1371/journal.pone.0003331;
RA Moussion C., Ortega N., Girard J.P.;
RT "The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of
RT endothelial cells and epithelial cells in vivo: a novel 'alarmin'?";
RL PLoS ONE 3:E3331-E3331(2008).
RN [15]
RP PROTEOLYTIC PROCESSING.
RX PubMed=19596270; DOI=10.1016/j.bbrc.2009.07.018;
RA Hayakawa M., Hayakawa H., Matsuyama Y., Tamemoto H., Okazaki H.,
RA Tominaga S.;
RT "Mature interleukin-33 is produced by calpain-mediated cleavage in vivo.";
RL Biochem. Biophys. Res. Commun. 387:218-222(2009).
RN [16]
RP PROTEOLYTIC PROCESSING.
RX PubMed=19559631; DOI=10.1016/j.immuni.2009.05.007;
RA Luthi A.U., Cullen S.P., McNeela E.A., Duriez P.J., Afonina I.S.,
RA Sheridan C., Brumatti G., Taylor R.C., Kersse K., Vandenabeele P.,
RA Lavelle E.C., Martin S.J.;
RT "Suppression of interleukin-33 bioactivity through proteolysis by apoptotic
RT caspases.";
RL Immunity 31:84-98(2009).
RN [17]
RP 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 [18]
RP PROTEOLYTIC PROCESSING.
RX PubMed=19439663; DOI=10.1073/pnas.0812690106;
RA Cayrol C., Girard J.P.;
RT "The IL-1-like cytokine IL-33 is inactivated after maturation by caspase-
RT 1.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:9021-9026(2009).
RN [19]
RP FUNCTION, AND SUBCELLULAR LOCATION.
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 [20]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22215666; DOI=10.1074/jbc.m111.298703;
RA Kakkar R., Hei H., Dobner S., Lee R.T.;
RT "Interleukin 33 as a mechanically responsive cytokine secreted by living
RT cells.";
RL J. Biol. Chem. 287:6941-6948(2012).
RN [21]
RP INTERACTION WITH H.POLYGYRUS ARI, AND INDUCTION BY 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).
RN [22]
RP STRUCTURE BY NMR OF 111-270, INTERACTION WITH IL1RL1 AND IL1RAP, AND
RP SUBUNIT.
RX PubMed=19836339; DOI=10.1016/j.str.2009.08.009;
RA Lingel A., Weiss T.M., Niebuhr M., Pan B., Appleton B.A., Wiesmann C.,
RA Bazan J.F., Fairbrother W.J.;
RT "Structure of IL-33 and its interaction with the ST2 and IL-1RAcP
RT receptors--insight into heterotrimeric IL-1 signaling complexes.";
RL Structure 17:1398-1410(2009).
RN [23]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH TMED10.
RX PubMed=32272059; DOI=10.1016/j.cell.2020.03.031;
RA Zhang M., Liu L., Lin X., Wang Y., Li Y., Guo Q., Li S., Sun Y., Tao X.,
RA Zhang D., Lv X., Zheng L., Ge L.;
RT "A Translocation Pathway for Vesicle-Mediated Unconventional Protein
RT Secretion.";
RL Cell 181:637-652(2020).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (3.27 ANGSTROMS) OF 112-270 IN COMPLEX WITH
RP IL1RL1/ST2, AND MUTAGENESIS OF GLU-144; GLU-148; ASP-149; GLU-165 AND
RP ASP-244.
RX PubMed=23980170; DOI=10.1073/pnas.1308651110;
RA Liu X., Hammel M., He Y., Tainer J.A., Jeng U.S., Zhang L., Wang S.,
RA Wang X.;
RT "Structural insights into the interaction of IL-33 with its receptors.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:14918-14923(2013).
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:16286016). 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 (PubMed:17853410, PubMed:18836528).
CC {ECO:0000269|PubMed:16286016, ECO:0000269|PubMed:17853410,
CC ECO:0000269|PubMed:18836528}.
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
CC (PubMed:21734074). This form is rapidely lost upon angiogenic or pro-
CC inflammatory activation (PubMed:18787100).
CC {ECO:0000269|PubMed:18787100, ECO:0000269|PubMed:21734074}.
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 (PubMed:32272059).
CC {ECO:0000269|PubMed:19836339, ECO:0000269|PubMed:23980170,
CC ECO:0000269|PubMed:32272059}.
CC -!- SUBUNIT: (Microbial infection) Interacts (in reduced form) with
CC H.polygyrus ARI. {ECO:0000269|PubMed:29045903}.
CC -!- INTERACTION:
CC O95760; P0C0S8: H2AC17; NbExp=3; IntAct=EBI-724057, EBI-1390628;
CC O95760; Q01638: IL1RL1; NbExp=2; IntAct=EBI-724057, EBI-993762;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12819012,
CC ECO:0000269|PubMed:17185418, ECO:0000269|PubMed:18787100,
CC ECO:0000269|PubMed:18836528, ECO:0000269|PubMed:21734074}. Chromosome
CC {ECO:0000269|PubMed:17185418}. Cytoplasm {ECO:0000269|PubMed:32272059}.
CC Cytoplasmic vesicle, secretory vesicle {ECO:0000269|PubMed:22215666}.
CC Secreted {ECO:0000269|PubMed:19465481}. Note=Associates with
CC heterochromatin and mitotic chromosomes (PubMed:17185418). The
CC secretion is dependent on protein unfolding and facilitated by the
CC cargo receptor TMED10; it results in protein translocation from the
CC cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate
CC compartment) followed by vesicle entry and secretion (PubMed:32272059).
CC {ECO:0000269|PubMed:32272059}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=O95760-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95760-2; Sequence=VSP_042728;
CC Name=3; Synonyms=spIL-33;
CC IsoId=O95760-3; Sequence=VSP_044948;
CC Name=4;
CC IsoId=O95760-4; Sequence=VSP_045440;
CC -!- TISSUE SPECIFICITY: Expressed at high level in high endothelial venules
CC found in tonsils, Peyer patches and mesenteric lymph nodes. Almost
CC undetectable in placenta. {ECO:0000269|PubMed:12819012}.
CC -!- INDUCTION: By infection with the parasite H.polygyrus.
CC {ECO:0000269|PubMed:29045903}.
CC -!- DOMAIN: The homeodomain-like HTH domain mediates nuclear localization
CC and heterochromatin association.
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 (PubMed:19596270).
CC Proteolytic cleavage mediated by apoptotic caspases including CASP3 and
CC CASP7 results in IL33 inactivation (PubMed:19559631). In vitro
CC proteolytic cleavage by CASP1 was reported (PubMed:16286016) but could
CC not be confirmed in vivo (PubMed:19465481) suggesting that IL33 is
CC probably not a direct substrate for that caspase.
CC {ECO:0000269|PubMed:16286016, ECO:0000269|PubMed:19439663,
CC ECO:0000269|PubMed:19465481, ECO:0000269|PubMed:19559631,
CC ECO:0000269|PubMed:19596270, ECO:0000269|PubMed:22307629}.
CC -!- MISCELLANEOUS: [Isoform 3]: Constitutively active. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the IL-1 family. Highly divergent.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB024518; BAA75892.1; -; mRNA.
DR EMBL; AY905581; AAX86998.1; -; mRNA.
DR EMBL; HQ641439; ADR77828.1; -; mRNA.
DR EMBL; AK295908; BAG58697.1; -; mRNA.
DR EMBL; AK303943; BAG64871.1; -; mRNA.
DR EMBL; AK313414; BAG36208.1; -; mRNA.
DR EMBL; CR407619; CAG28547.1; -; mRNA.
DR EMBL; AL353741; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471071; EAW58748.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58750.1; -; Genomic_DNA.
DR EMBL; CH471071; EAW58751.1; -; Genomic_DNA.
DR EMBL; BC047085; AAH47085.1; -; mRNA.
DR CCDS; CCDS56563.1; -. [O95760-2]
DR CCDS; CCDS56564.1; -. [O95760-4]
DR CCDS; CCDS6468.1; -. [O95760-1]
DR CCDS; CCDS83341.1; -. [O95760-3]
DR RefSeq; NP_001186569.1; NM_001199640.1. [O95760-2]
DR RefSeq; NP_001186570.1; NM_001199641.1. [O95760-4]
DR RefSeq; NP_001300973.1; NM_001314044.1. [O95760-1]
DR RefSeq; NP_001300974.1; NM_001314045.1. [O95760-1]
DR RefSeq; NP_001300975.1; NM_001314046.1.
DR RefSeq; NP_001300976.1; NM_001314047.1.
DR RefSeq; NP_001300977.1; NM_001314048.1. [O95760-3]
DR RefSeq; NP_254274.1; NM_033439.3. [O95760-1]
DR PDB; 2KLL; NMR; -; A=111-270.
DR PDB; 4KC3; X-ray; 3.27 A; A=112-270.
DR PDBsum; 2KLL; -.
DR PDBsum; 4KC3; -.
DR AlphaFoldDB; O95760; -.
DR BMRB; O95760; -.
DR SMR; O95760; -.
DR BioGRID; 124776; 8.
DR DIP; DIP-37862N; -.
DR IntAct; O95760; 6.
DR MINT; O95760; -.
DR STRING; 9606.ENSP00000370842; -.
DR ChEMBL; CHEMBL4630890; -.
DR iPTMnet; O95760; -.
DR PhosphoSitePlus; O95760; -.
DR BioMuta; IL33; -.
DR MassIVE; O95760; -.
DR PaxDb; O95760; -.
DR PeptideAtlas; O95760; -.
DR PRIDE; O95760; -.
DR ProteomicsDB; 4342; -.
DR ProteomicsDB; 51036; -. [O95760-1]
DR ProteomicsDB; 51037; -. [O95760-2]
DR ABCD; O95760; 7 sequenced antibodies.
DR Antibodypedia; 3362; 1283 antibodies from 44 providers.
DR DNASU; 90865; -.
DR Ensembl; ENST00000381434.7; ENSP00000370842.3; ENSG00000137033.12. [O95760-1]
DR Ensembl; ENST00000417746.6; ENSP00000394039.2; ENSG00000137033.12. [O95760-4]
DR Ensembl; ENST00000456383.3; ENSP00000414238.2; ENSG00000137033.12. [O95760-2]
DR Ensembl; ENST00000611532.4; ENSP00000478858.1; ENSG00000137033.12. [O95760-3]
DR Ensembl; ENST00000682010.1; ENSP00000507310.1; ENSG00000137033.12. [O95760-1]
DR GeneID; 90865; -.
DR KEGG; hsa:90865; -.
DR MANE-Select; ENST00000682010.1; ENSP00000507310.1; NM_033439.4; NP_254274.1.
DR UCSC; uc011lmh.3; human. [O95760-1]
DR CTD; 90865; -.
DR DisGeNET; 90865; -.
DR GeneCards; IL33; -.
DR HGNC; HGNC:16028; IL33.
DR HPA; ENSG00000137033; Tissue enhanced (urinary).
DR MIM; 608678; gene.
DR neXtProt; NX_O95760; -.
DR OpenTargets; ENSG00000137033; -.
DR PharmGKB; PA162392005; -.
DR VEuPathDB; HostDB:ENSG00000137033; -.
DR eggNOG; ENOG502RW83; Eukaryota.
DR GeneTree; ENSGT00390000005185; -.
DR HOGENOM; CLU_1795771_0_0_1; -.
DR InParanoid; O95760; -.
DR OMA; HRKSSKC; -.
DR OrthoDB; 1062809at2759; -.
DR PhylomeDB; O95760; -.
DR TreeFam; TF338120; -.
DR PathwayCommons; O95760; -.
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-HSA-9014843; Interleukin-33 signaling.
DR SignaLink; O95760; -.
DR BioGRID-ORCS; 90865; 6 hits in 1064 CRISPR screens.
DR ChiTaRS; IL33; human.
DR EvolutionaryTrace; O95760; -.
DR GenomeRNAi; 90865; -.
DR Pharos; O95760; Tbio.
DR PRO; PR:O95760; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; O95760; protein.
DR Bgee; ENSG00000137033; Expressed in calcaneal tendon and 161 other tissues.
DR Genevisible; O95760; HS.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:CACAO.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:CACAO.
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; IEA:Ensembl.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0051607; P:defense response to virus; IEA:Ensembl.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0038172; P:interleukin-33-mediated signaling pathway; ISS:ARUK-UCL.
DR GO; GO:0002282; P:microglial cell activation involved in immune response; IEA:Ensembl.
DR GO; GO:0061518; P:microglial cell proliferation; IEA:Ensembl.
DR GO; GO:0002638; P:negative regulation of immunoglobulin production; IEA:Ensembl.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; IEA:Ensembl.
DR GO; GO:0002686; P:negative regulation of leukocyte migration; IEA:Ensembl.
DR GO; GO:0120042; P:negative regulation of macrophage proliferation; ISS:ARUK-UCL.
DR GO; GO:0002826; P:negative regulation of T-helper 1 type immune response; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:CACAO.
DR GO; GO:0150145; P:positive regulation of CD80 production; ISS:ARUK-UCL.
DR GO; GO:0150142; P:positive regulation of CD86 production; ISS:ARUK-UCL.
DR GO; GO:0010186; P:positive regulation of cellular defense response; ISS: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; ISS:ARUK-UCL.
DR GO; GO:0002639; P:positive regulation of immunoglobulin production; IEA:Ensembl.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISS:BHF-UCL.
DR GO; GO:0032736; P:positive regulation of interleukin-13 production; IEA:Ensembl.
DR GO; GO:0032753; P:positive regulation of interleukin-4 production; IEA:Ensembl.
DR GO; GO:0032754; P:positive regulation of interleukin-5 production; IEA:Ensembl.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS: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; IEA:Ensembl.
DR GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; IEA:Ensembl.
DR GO; GO:0150078; P:positive regulation of neuroinflammatory response; TAS:ARUK-UCL.
DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; ISS:ARUK-UCL.
DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; IEA:Ensembl.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:BHF-UCL.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISS:ARUK-UCL.
DR GO; GO:0002830; P:positive regulation of type 2 immune response; IEA:Ensembl.
DR GO; GO:0051930; P:regulation of sensory perception of pain; IEA:Ensembl.
DR GO; GO:0042092; P:type 2 immune response; IEA:Ensembl.
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; Alternative splicing; Chromosome; Cytokine; Cytoplasm;
KW Cytoplasmic vesicle; Direct protein sequencing; Nucleus;
KW Reference proteome; Secreted; Transcription.
FT CHAIN 1..270
FT /note="Interleukin-33"
FT /id="PRO_0000096790"
FT PROPEP 1..94
FT /evidence="ECO:0000269|PubMed:22307629"
FT /id="PRO_0000430083"
FT CHAIN 95..270
FT /note="Interleukin-33 (95-270)"
FT /id="PRO_0000430084"
FT CHAIN 99..270
FT /note="Interleukin-33 (99-270)"
FT /id="PRO_0000430085"
FT CHAIN 109..270
FT /note="Interleukin-33 (109-270)"
FT /id="PRO_0000430086"
FT REGION 1..65
FT /note="Homeodomain-like HTH domain"
FT REGION 66..111
FT /note="Interaction with RELA"
FT /evidence="ECO:0000250"
FT SITE 94..95
FT /note="Cleavage; by CTSG"
FT /evidence="ECO:0000269|PubMed:22307629"
FT SITE 98..99
FT /note="Cleavage; by ELANE"
FT /evidence="ECO:0000269|PubMed:22307629"
FT SITE 108..109
FT /note="Cleavage; by CTSG"
FT /evidence="ECO:0000269|PubMed:22307629"
FT VAR_SEQ 31..157
FT /note="KSQQKAKEVCPMYFMKLRSGLMIKKEACYFRRETTKRPSLKTGRKHKRHLVL
FT AACQQQSTVECFAFGISGVQKYTRALHDSSITGISPITEYLASLSTYNDQSITFALEDE
FT SYEIYVEDLKKDEKKD -> N (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045440"
FT VAR_SEQ 72..113
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:21454686"
FT /id="VSP_044948"
FT VAR_SEQ 115..156
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042728"
FT VARIANT 263
FT /note="I -> M (in dbSNP:rs16924241)"
FT /id="VAR_049576"
FT MUTAGEN 144
FT /note="E->K: Decreases affinity for IL1RL1."
FT /evidence="ECO:0000269|PubMed:23980170"
FT MUTAGEN 148
FT /note="E->K: 7-fold decrease in affinity for IL1RL1."
FT /evidence="ECO:0000269|PubMed:23980170"
FT MUTAGEN 149
FT /note="D->K: Almost abolishes binding to IL1RL1."
FT /evidence="ECO:0000269|PubMed:23980170"
FT MUTAGEN 165
FT /note="E->K: 8-fold decrease in affinity for IL1RL1."
FT /evidence="ECO:0000269|PubMed:23980170"
FT MUTAGEN 244
FT /note="D->K: Decreases affinity for IL1RL1."
FT /evidence="ECO:0000269|PubMed:23980170"
FT CONFLICT 139
FT /note="E -> G (in Ref. 5; BAG36208)"
FT /evidence="ECO:0000305"
FT STRAND 112..115
FT /evidence="ECO:0007829|PDB:2KLL"
FT STRAND 119..127
FT /evidence="ECO:0007829|PDB:4KC3"
FT TURN 129..131
FT /evidence="ECO:0007829|PDB:2KLL"
FT STRAND 133..138
FT /evidence="ECO:0007829|PDB:4KC3"
FT STRAND 140..148
FT /evidence="ECO:0007829|PDB:4KC3"
FT STRAND 158..169
FT /evidence="ECO:0007829|PDB:4KC3"
FT TURN 170..172
FT /evidence="ECO:0007829|PDB:2KLL"
FT STRAND 180..189
FT /evidence="ECO:0007829|PDB:4KC3"
FT STRAND 193..197
FT /evidence="ECO:0007829|PDB:4KC3"
FT TURN 198..201
FT /evidence="ECO:0007829|PDB:4KC3"
FT STRAND 202..206
FT /evidence="ECO:0007829|PDB:4KC3"
FT HELIX 214..216
FT /evidence="ECO:0007829|PDB:4KC3"
FT STRAND 218..224
FT /evidence="ECO:0007829|PDB:4KC3"
FT STRAND 228..235
FT /evidence="ECO:0007829|PDB:4KC3"
FT STRAND 238..243
FT /evidence="ECO:0007829|PDB:4KC3"
FT STRAND 246..251
FT /evidence="ECO:0007829|PDB:4KC3"
FT HELIX 261..263
FT /evidence="ECO:0007829|PDB:2KLL"
FT STRAND 265..267
FT /evidence="ECO:0007829|PDB:4KC3"
SQ SEQUENCE 270 AA; 30759 MW; 7C158069196EF636 CRC64;
MKPKMKYSTN KISTAKWKNT ASKALCFKLG KSQQKAKEVC PMYFMKLRSG LMIKKEACYF
RRETTKRPSL KTGRKHKRHL VLAACQQQST VECFAFGISG VQKYTRALHD SSITGISPIT
EYLASLSTYN DQSITFALED ESYEIYVEDL KKDEKKDKVL LSYYESQHPS NESGDGVDGK
MLMVTLSPTK DFWLHANNKE HSVELHKCEK PLPDQAFFVL HNMHSNCVSF ECKTDPGVFI
GVKDNHLALI KVDSSENLCT ENILFKLSET
