/note="DVS27-related protein;
nuclear factor for high endothelial venules;
nuclear factor from high endothelial venules;
interleukin-1 family member 11"
- Also known as
- DVS27; IL1F11; NF-HEV; NFEHEV; C9orf26
- Summary
- The protein encoded by this gene is a cytokine that binds to the IL1RL1/ST2 receptor. The encoded protein is involved in the maturation of Th2 cells and the activation of mast cells, basophils, eosinophils and natural killer cells. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]
- Expression
- Ubiquitous expression in urinary bladder (RPKM 34.7), lung (RPKM 27.3) and 23 other tissues See more
A new paradigm for understanding immune-surveillance and immune escape in cancer is described here. Metastatic carcinomas express reduced levels of IL-33 and diminished levels of antigen processing machinery (APM), compared to syngeneic primary tumours. Complementation of IL-33 expression in metastatic tumours upregulates APM expression and functionality of major histocompatibility complex (MHC)-molecules, resulting in reduced tumour growth rates and a lower frequency of circulating tumour cells. Parallel studies in humans demonstrate that low tumour expression of IL-33 is an immune biomarker associated with recurrent prostate and kidney renal clear cell carcinomas. Thus, IL-33 has a significant role in cancer immune-surveillance against primary tumours, which is lost during the metastatic transition that actuates immune escape in cancer.
- Artikkeleita PubMed
Interleukiini-33 signalointitien kartta (2018)
A network map of IL-33 signaling pathway.
Pinto SM1,2, Subbannayya Y3, Rex DAB3, Raju R4, Chatterjee O5, Advani J5,6, Radhakrishnan A5, Keshava Prasad TS5,3, Wani MR7, Pandey A8,9,10,11,12,13.Abstract
Interleukin-33
(IL-33) is a member of the IL-1 family of cytokines that play a central
role in the regulation of immune responses. Its release from epithelial
and endothelial cells is mediated by pro-inflammatory cytokines, cell
damage and by recognition of pathogen-associated molecular patterns
(PAMPs). The activity of IL-33 is mediated by binding to the IL-33
receptor complex (IL-33R) and activation of NF-κB signaling via the
classical MyD88/IRAK/TRAF6 module. IL-33 also induces the
phosphorylation and activation of ERK1/2, JNK, p38 and PI3K/AKT
signaling modules resulting in the production and release of
pro-inflammatory cytokines. Aberrant signaling by IL-33 has been
implicated in the pathogenesis of several acute and chronic inflammatory
diseases, including asthma, atopic dermatitis, rheumatoid arthritis and
ulcerative colitis among others. Considering the biomedical importance
of IL-33, we developed a pathway resource of signaling events mediated
by IL-33/IL-33R in this study. Using data mined from the published
literature, we describe an integrated pathway reaction map of
IL-33/IL-33R consisting of 681 proteins and 765 reactions. These include
information pertaining to 19 physical interaction events, 740 enzyme
catalysis events, 6 protein translocation events, 4
activation/inhibition events, 9 transcriptional regulators and 2492 gene
regulation events. The pathway map is publicly available through
NetPath ( http://www.netpath.org /), a resource of human signaling
pathways developed previously by our group. This resource will provide a
platform to the scientific community in facilitating identification of
novel therapeutic targets for diseases associated with dysregulated
IL-33 signaling. Database URL:
http://www.netpath.org/pathways?path_id=NetPath_120
KEYWORDS:
Immune response; Inflammation; NetSlim; Post-translational modifications; Pro-inflammatory cytokine; Protein-protein interactions- PMID:
- 29705949
- DOI:
- 10.1007/s12079-018-0464-4
Tietoa Interleukiinsita IL-33 Pubmed hakulaiteella
- Preferred Names
- interleukin-33
- Names
- DVS27-related protein
- interleukin-1 family member 11
- nuclear factor for high endothelial venules
- nuclear factor from high endothelial venules
- Conserved Domains (1) summary pfam15095
- Location:5 → 226 IL33; Interleukin 33
- interleukin-33 isoform b [Homo sapiens]
- NCBI Reference Sequence: NP_001186569.1
- Identical Proteins FASTA Graphics
- Go to:
LOCUS NP_001186569 228 aa linear PRI 05-APR-2018 DEFINITION interleukin-33 isoform b [Homo sapiens]. ACCESSION NP_001186569 VERSION NP_001186569.1 DBSOURCE REFSEQ: accession NM_001199640.1 KEYWORDS RefSeq. SOURCE Homo sapiens (human) ORGANISM Homo sapiens Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. REFERENCE 1 (residues 1 to 228) AUTHORS Xu Z, Zhao C, Wang Z, Tao J, Han Z, Zhang W, Tan R and Gu M. TITLE Interleukin-33 levels are elevated in chronic allograft dysfunction of kidney transplant recipients and promotes epithelial to mesenchymal transition of human kidney (HK-2) cells JOURNAL Gene 644, 113-121 (2018) PUBMED 29122645 REMARK GeneRIF: IL-33 could induce EMT. REFERENCE 2 (residues 1 to 228) AUTHORS Umebashi K, Tokito A, Yamamoto M and Jougasaki M. TITLE Interleukin-33 induces interleukin-8 expression via JNK/c-Jun/AP-1 pathway in human umbilical vein endothelial cells JOURNAL PLoS ONE 13 (1), e0191659 (2018) PUBMED 29373608 REMARK GeneRIF: IL-33 induces IL-8 expression via JNK/c-Jun/AP-1 pathway in human vascular endothelial cells, and provides a new insight into the role of IL-33-induced IL-8 in the pathophysiology of atherosclerosis and vascular inflammation Publication Status: Online-Only REFERENCE 3 (residues 1 to 228) AUTHORS Yamamoto M, Umebashi K, Tokito A, Imamura J and Jougasaki M. TITLE Interleukin-33 induces growth-regulated oncogene-alpha expression and secretion in human umbilical vein endothelial cells JOURNAL Am. J. Physiol. Regul. Integr. Comp. Physiol. 313 (3), R272-R279 (2017) PUBMED 28637660 REMARK GeneRIF: Taken together, the present study indicates that IL-33 localized in the human atherosclerotic plaque increases GRO-alpha mRNA expression and protein secretion via activation of ERK1/2, JNK, and NF-kappaB in HUVECs, suggesting that IL-33 plays an important role in the pathophysiology and development of atherosclerosis. REFERENCE 4 (residues 1 to 228) AUTHORS Ndaw VS, Abebayehu D, Spence AJ, Paez PA, Kolawole EM, Taruselli MT, Caslin HL, Chumanevich AP, Paranjape A, Baker B, Barnstein BO, Haque TT, Kiwanuka KN, Oskeritzian CA and Ryan JJ. TITLE TGF-beta1 Suppresses IL-33-Induced Mast Cell Function JOURNAL J. Immunol. 199 (3), 866-873 (2017) PUBMED 28637902 REMARK GeneRIF: TGF-beta1 also suppressed the combined effects of IL-33 and IgE-mediated activation on mouse and human mast cells. The role of IL-33 in the pathogenesis of allergic diseases is incompletely understood. These findings, demonstrate that TGF-beta1 can provide broad inhibitory signals to activated mast cells. REFERENCE 5 (residues 1 to 228) AUTHORS Lock FE, Babaian A, Zhang Y, Gagnier L, Kuah S, Weberling A, Karimi MM and Mager DL. TITLE A novel isoform of IL-33 revealed by screening for transposable element promoted genes in human colorectal cancer JOURNAL PLoS ONE 12 (7), e0180659 (2017) PUBMED 28715472 REMARK GeneRIF: LTR-IL-33 expression is required for optimal CRC cell line growth Publication Status: Online-Only REFERENCE 6 (residues 1 to 228) AUTHORS Tada H, Shimizu T, Matsushita K and Takada H. TITLE Porphyromonas gingivalis-induced IL-33 down-regulates hCAP-18/LL-37 production in human gingival epithelial cells JOURNAL Biomed. Res. 38 (3), 167-173 (2017) PUBMED 28637951 REMARK GeneRIF: IL-33 down-regulates the induction of hCAP-18/LL-37 production in human gingival epithelial cells. REFERENCE 7 (residues 1 to 228) AUTHORS Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, Zurawski G, Moshrefi M, Qin J, Li X, Gorman DM, Bazan JF and Kastelein RA. TITLE 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 JOURNAL Immunity 23 (5), 479-490 (2005) PUBMED 16286016 REMARK GeneRIF: IL-33, which mediates its biological effects via IL-1 receptor ST 2, activates NF-kappaB and MAP kinases, and drives production of T(H)2-associated cytokines from in vitro polarized T(H)2 cells REFERENCE 8 (residues 1 to 228) AUTHORS 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 and Dunham I. TITLE DNA sequence and analysis of human chromosome 9 JOURNAL Nature 429 (6990), 369-374 (2004) PUBMED 15164053 REFERENCE 9 (residues 1 to 228) AUTHORS Baekkevold ES, Roussigne M, Yamanaka T, Johansen FE, Jahnsen FL, Amalric F, Brandtzaeg P, Erard M, Haraldsen G and Girard JP. TITLE Molecular characterization of NF-HEV, a nuclear factor preferentially expressed in human high endothelial venules JOURNAL Am. J. Pathol. 163 (1), 69-79 (2003) PUBMED 12819012 REMARK GeneRIF: Results suggest that NF-HEV may be one of the key nuclear factors that controls the specialized phenotype of the lymphatic venule endothelium. REFERENCE 10 (residues 1 to 228) AUTHORS Onda H, Kasuya H, Takakura K, Hori T, Imaizumi T, Takeuchi T, Inoue I and Takeda J. TITLE Identification of genes differentially expressed in canine vasospastic cerebral arteries after subarachnoid hemorrhage JOURNAL J. Cereb. Blood Flow Metab. 19 (11), 1279-1288 (1999) PUBMED 10566975 COMMENT REVIEWED REFSEQ: This record has been curated by NCBI staff. The reference sequence was derived from DB477860.1, AK303943.1, BC047085.1, AB024518.1 and AI610794.1. Summary: The protein encoded by this gene is a cytokine that binds to the IL1RL1/ST2 receptor. The encoded protein is involved in the maturation of Th2 cells and the activation of mast cells, basophils, eosinophils and natural killer cells. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]. Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (b, also known as 2) has the same N- and C-termini but is shorter compared to isoform a. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: SRR1803616.212850.1, AK303943.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1968540, SAMEA1968968 [ECO:0000348] ##Evidence-Data-END## FEATURES Location/Qualifiers source 1..228 /organism="Homo sapiens" /db_xref="taxon:9606" /chromosome="9" /map="9p24.1" Protein 1..228 /product="interleukin-33 isoform b" /note="DVS27-related protein; nuclear factor for high endothelial venules; nuclear factor from high endothelial venules; interleukin-1 family member 11" /calculated_mol_wt=25799 Region 5..226 /region_name="IL33" /note="Interleukin 33; pfam15095" /db_xref="CDD:317507" CDS 1..228 /gene="IL33" /gene_synonym="C9orf26; DVS27; IL1F11; NF-HEV; NFEHEV" /coded_by="NM_001199640.1:79..765" /note="isoform b is encoded by transcript variant 2" /db_xref="CCDS:CCDS56563.1" /db_xref="GeneID:90865" /db_xref="HGNC:HGNC:16028" /db_xref="MIM:608678" ORIGIN 1 mkpkmkystn kistakwknt askalcfklg ksqqkakevc pmyfmklrsg lmikkeacyf 61 rrettkrpsl ktgrkhkrhl vlaacqqqst vecfafgisg vqkytralhd ssitdkvlls 121 yyesqhpsne sgdgvdgkml mvtlsptkdf wlhannkehs velhkcekpl pdqaffvlhn 181 mhsncvsfec ktdpgvfigv kdnhlalikv dssenlcten ilfklset //
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