Interleukin-33

Details

Name
Interleukin-33
Synonyms
  • C9orf26
  • IL-1F11
  • IL-33
  • IL1F11
  • Interleukin-1 family member 11
  • NF-HEV
  • NFHEV
  • Nuclear factor from high endothelial venules
Gene Name
IL33
Organism
Humans
Amino acid sequence
>lcl|BSEQ0052630|Interleukin-33
MKPKMKYSTNKISTAKWKNTASKALCFKLGKSQQKAKEVCPMYFMKLRSGLMIKKEACYF
RRETTKRPSLKTGRKHKRHLVLAACQQQSTVECFAFGISGVQKYTRALHDSSITGISPIT
EYLASLSTYNDQSITFALEDESYEIYVEDLKKDEKKDKVLLSYYESQHPSNESGDGVDGK
MLMVTLSPTKDFWLHANNKEHSVELHKCEKPLPDQAFFVLHNMHSNCVSFECKTDPGVFI
GVKDNHLALIKVDSSENLCTENILFKLSET
Number of residues
270
Molecular Weight
30759.145
Theoretical pI
Not Available
GO Classification
Functions
cytokine activity / interleukin-33 receptor binding
Processes
defense response to virus / extrinsic apoptotic signaling pathway / interleukin-33-mediated signaling pathway / microglial cell activation involved in immune response / microglial cell proliferation / negative regulation of immunoglobulin production / negative regulation of interferon-gamma production / negative regulation of leukocyte migration / negative regulation of macrophage proliferation / negative regulation of T-helper 1 type immune response / negative regulation of transcription by RNA polymerase II / positive regulation of CD80 production / positive regulation of CD86 production / positive regulation of cellular defense response / positive regulation of chemokine production / positive regulation of cytokine production / positive regulation of gene expression / positive regulation of immunoglobulin production / positive regulation of inflammatory response / positive regulation of interleukin-13 production / positive regulation of interleukin-4 production / positive regulation of interleukin-5 production / positive regulation of interleukin-6 production / positive regulation of macrophage activation / positive regulation of MHC class I biosynthetic process / positive regulation of MHC class II biosynthetic process / positive regulation of neuroinflammatory response / positive regulation of nitric-oxide synthase biosynthetic process / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / positive regulation of transcription by RNA polymerase II / positive regulation of tumor necrosis factor production / positive regulation of type 2 immune response / protein deubiquitination
Components
chromosome / cytoplasm / extracellular region / extracellular space / intracellular membrane-bounded organelle / nucleoplasm / nucleus / transport vesicle
General Function
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).
Specific Function
Cytokine activity
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0052631|Interleukin-33 (IL33)
ATGAAGCCTAAAATGAAGTATTCAACCAACAAAATTTCCACAGCAAAGTGGAAGAACACA
GCAAGCAAAGCCTTGTGTTTCAAGCTGGGAAAATCCCAACAGAAGGCCAAAGAAGTTTGC
CCCATGTACTTTATGAAGCTCCGCTCTGGCCTTATGATAAAAAAGGAGGCCTGTTACTTT
AGGAGAGAAACCACCAAAAGGCCTTCACTGAAAACAGGTAGAAAGCACAAAAGACATCTG
GTACTCGCTGCCTGTCAACAGCAGTCTACTGTGGAGTGCTTTGCCTTTGGTATATCAGGG
GTCCAGAAATATACTAGAGCACTTCATGATTCAAGTATCACAGGAATTTCACCTATTACA
GAGTATCTTGCTTCTCTAAGCACATACAATGATCAATCCATTACTTTTGCTTTGGAGGAT
GAAAGTTATGAGATATATGTTGAAGACTTGAAAAAAGATGAAAAGAAAGATAAGGTGTTA
CTGAGTTACTATGAGTCTCAACACCCCTCAAATGAATCAGGTGACGGTGTTGATGGTAAG
ATGTTAATGGTAACCCTGAGTCCTACAAAAGACTTCTGGTTGCATGCCAACAACAAGGAA
CACTCTGTGGAGCTCCATAAGTGTGAAAAACCACTGCCAGACCAGGCCTTCTTTGTCCTT
CATAATATGCACTCCAACTGTGTTTCATTTGAATGCAAGACTGATCCTGGAGTGTTTATA
GGTGTAAAGGATAATCATCTTGCTCTGATTAAAGTAGACTCTTCTGAGAATTTGTGTACT
GAAAATATCTTGTTTAAGCTCTCTGAAACTTAG
Chromosome Location
9
Locus
9p24.1
External Identifiers
ResourceLink
UniProtKB IDO95760
UniProtKB Entry NameIL33_HUMAN
HGNC IDHGNC:16028
General References
  1. Baekkevold ES, Roussigne M, Yamanaka T, Johansen FE, Jahnsen FL, Amalric F, Brandtzaeg P, Erard M, Haraldsen G, Girard JP: Molecular characterization of NF-HEV, a nuclear factor preferentially expressed in human high endothelial venules. Am J Pathol. 2003 Jul;163(1):69-79. doi: 10.1016/S0002-9440(10)63631-0. [Article]
  2. Onda H, Kasuya H, Takakura K, Hori T, Imaizumi T, Takeuchi T, Inoue I, Takeda J: Identification of genes differentially expressed in canine vasospastic cerebral arteries after subarachnoid hemorrhage. J Cereb Blood Flow Metab. 1999 Nov;19(11):1279-88. doi: 10.1097/00004647-199911000-00013. [Article]
  3. Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, Zurawski G, Moshrefi M, Qin J, Li X, Gorman DM, Bazan JF, Kastelein RA: IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity. 2005 Nov;23(5):479-90. [Article]
  4. Hong J, Bae S, Jhun H, Lee S, Choi J, Kang T, Kwak A, Hong K, Kim E, Jo S, Kim S: Identification of constitutively active interleukin 33 (IL-33) splice variant. J Biol Chem. 2011 Jun 3;286(22):20078-86. doi: 10.1074/jbc.M111.219089. Epub 2011 Mar 22. [Article]
  5. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  6. Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. [Article]
  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  8. Lefrancais E, Roga S, Gautier V, Gonzalez-de-Peredo A, Monsarrat B, Girard JP, Cayrol C: IL-33 is processed into mature bioactive forms by neutrophil elastase and cathepsin G. Proc Natl Acad Sci U S A. 2012 Jan 31;109(5):1673-8. doi: 10.1073/pnas.1115884109. Epub 2012 Jan 17. [Article]
  9. Komai-Koma M, Xu D, Li Y, McKenzie AN, McInnes IB, Liew FY: IL-33 is a chemoattractant for human Th2 cells. Eur J Immunol. 2007 Oct;37(10):2779-86. doi: 10.1002/eji.200737547. [Article]
  10. Carriere V, Roussel L, Ortega N, Lacorre DA, Americh L, Aguilar L, Bouche G, Girard JP: IL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-associated nuclear factor in vivo. Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):282-7. doi: 10.1073/pnas.0606854104. Epub 2006 Dec 21. [Article]
  11. Kuchler AM, Pollheimer J, Balogh J, Sponheim J, Manley L, Sorensen DR, De Angelis PM, Scott H, Haraldsen G: Nuclear interleukin-33 is generally expressed in resting endothelium but rapidly lost upon angiogenic or proinflammatory activation. Am J Pathol. 2008 Oct;173(4):1229-42. doi: 10.2353/ajpath.2008.080014. Epub 2008 Sep 11. [Article]
  12. Moussion C, Ortega N, Girard JP: The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel 'alarmin'? PLoS One. 2008 Oct 6;3(10):e3331. doi: 10.1371/journal.pone.0003331. [Article]
  13. Hayakawa M, Hayakawa H, Matsuyama Y, Tamemoto H, Okazaki H, Tominaga S: Mature interleukin-33 is produced by calpain-mediated cleavage in vivo. Biochem Biophys Res Commun. 2009 Sep 11;387(1):218-22. doi: 10.1016/j.bbrc.2009.07.018. Epub 2009 Jul 9. [Article]
  14. Luthi AU, Cullen SP, McNeela EA, Duriez PJ, Afonina IS, Sheridan C, Brumatti G, Taylor RC, Kersse K, Vandenabeele P, Lavelle EC, Martin SJ: Suppression of interleukin-33 bioactivity through proteolysis by apoptotic caspases. Immunity. 2009 Jul 17;31(1):84-98. doi: 10.1016/j.immuni.2009.05.007. Epub 2009 Jun 25. [Article]
  15. Talabot-Ayer D, Lamacchia C, Gabay C, Palmer G: Interleukin-33 is biologically active independently of caspase-1 cleavage. J Biol Chem. 2009 Jul 17;284(29):19420-6. doi: 10.1074/jbc.M901744200. Epub 2009 May 22. [Article]
  16. Cayrol C, Girard JP: The IL-1-like cytokine IL-33 is inactivated after maturation by caspase-1. Proc Natl Acad Sci U S A. 2009 Jun 2;106(22):9021-6. doi: 10.1073/pnas.0812690106. Epub 2009 May 13. [Article]
  17. Ali S, Mohs A, Thomas M, Klare J, Ross R, Schmitz ML, Martin MU: The dual function cytokine IL-33 interacts with the transcription factor NF-kappaB to dampen NF-kappaB-stimulated gene transcription. J Immunol. 2011 Aug 15;187(4):1609-16. doi: 10.4049/jimmunol.1003080. Epub 2011 Jul 6. [Article]
  18. Kakkar R, Hei H, Dobner S, Lee RT: Interleukin 33 as a mechanically responsive cytokine secreted by living cells. J Biol Chem. 2012 Feb 24;287(9):6941-8. doi: 10.1074/jbc.M111.298703. Epub 2012 Jan 3. [Article]
  19. Osbourn M, Soares DC, Vacca F, Cohen ES, Scott IC, Gregory WF, Smyth DJ, Toivakka M, Kemter AM, le Bihan T, Wear M, Hoving D, Filbey KJ, Hewitson JP, Henderson H, Gonzalez-Ciscar A, Errington C, Vermeren S, Astier AL, Wallace WA, Schwarze J, Ivens AC, Maizels RM, McSorley HJ: HpARI Protein Secreted by a Helminth Parasite Suppresses Interleukin-33. Immunity. 2017 Oct 17;47(4):739-751.e5. doi: 10.1016/j.immuni.2017.09.015. [Article]
  20. Lingel A, Weiss TM, Niebuhr M, Pan B, Appleton BA, Wiesmann C, Bazan JF, Fairbrother WJ: Structure of IL-33 and its interaction with the ST2 and IL-1RAcP receptors--insight into heterotrimeric IL-1 signaling complexes. Structure. 2009 Oct 14;17(10):1398-410. doi: 10.1016/j.str.2009.08.009. [Article]
  21. Zhang M, Liu L, Lin X, Wang Y, Li Y, Guo Q, Li S, Sun Y, Tao X, Zhang D, Lv X, Zheng L, Ge L: A Translocation Pathway for Vesicle-Mediated Unconventional Protein Secretion. Cell. 2020 Apr 30;181(3):637-652.e15. doi: 10.1016/j.cell.2020.03.031. Epub 2020 Apr 8. [Article]
  22. Liu X, Hammel M, He Y, Tainer JA, Jeng US, Zhang L, Wang S, Wang X: Structural insights into the interaction of IL-33 with its receptors. Proc Natl Acad Sci U S A. 2013 Sep 10;110(37):14918-23. doi: 10.1073/pnas.1308651110. Epub 2013 Aug 26. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails