ID   IL33_HUMAN              Reviewed;         270 AA.
AC   O95760; D3DRI5; Q2YEJ5;
DT   05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   16-NOV-2011, entry version 79.
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   Flags: Precursor;
GN   Name=IL33; Synonyms=C9orf26, IL1F11, NFHEV;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, AND SUBCELLULAR
RP   LOCATION.
RC   TISSUE=Endothelial cell;
RX   MEDLINE=22702309; PubMed=12819012;
RA   Baekkevold E.S., Roussigne M., Yamanaka T., Johansen F.-E.,
RA   Jahnsen F.L., Amalric F., Brandtzaeg P., Erard M., Haraldsen G.,
RA   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].
RX   MEDLINE=20031251; PubMed=10566975;
RX   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
RT   vasospastic cerebral arteries after subarachnoid hemorrhage.";
RL   J. Cereb. Blood Flow Metab. 19:1279-1288(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, PROTEOLYTIC
RP   PROCESSING, AND FUNCTION.
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
RT   receptor-related protein ST 2 and induces T helper type 2-associated
RT   cytokines.";
RL   Immunity 23:479-490(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [5]
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.,
RA   Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA   Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA   Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA   Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA   Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA   Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA   Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA   Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA   Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA   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.,
RA   Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA   Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA   McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA   Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA   Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA   Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA   Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA   Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA   Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA   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.,
RA   Rogers J., Dunham I.;
RT   "DNA sequence and analysis of human chromosome 9.";
RL   Nature 429:369-374(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [8]
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
RT   vivo.";
RL   Biochem. Biophys. Res. Commun. 387:218-222(2009).
CC   -!- FUNCTION: Cytokine that binds to and signals through IL1RL1/ST2
CC       and its stimulation recruits MYD88, IRAK1, IRAK4, and TRAF6,
CC       followed by phosphorylation of MAPK3/ERK1 and/or MAPK1/ERK2,
CC       MAPK14, and MAPK8. Induces T helper type 2-associated cytokines.
CC   -!- INTERACTION:
CC       Q01638:IL1RL1; NbExp=2; IntAct=EBI-724057, EBI-993762;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Expressed at high level in high endothelial
CC       venules found in tonsils, Peyer patches and mesenteric lymph
CC       nodes. Almost undetectable in placenta.
CC   -!- PTM: Proteolytically converted to a mature form by CASP1 in vitro
CC       and calpains in vivo.
CC   -!- SIMILARITY: Belongs to the IL-1 family. Highly divergent.
CC   -!- CAUTION: Was originally (PubMed:12819012) thought to one of the
CC       key factors that controls the specialized post-capillary high
CC       endothelial venules (HEV) phenotype found in organized secondary
CC       lymphoid tissue and to be nuclear localized.
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DR   EMBL; AB024518; BAA75892.1; -; mRNA.
DR   EMBL; AY905581; AAX86998.1; -; mRNA.
DR   EMBL; CR407619; CAG28547.1; -; mRNA.
DR   EMBL; AL353741; CAI16003.1; -; 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   IPI; IPI00027628; -.
DR   RefSeq; NP_001186569.1; NM_001199640.1.
DR   RefSeq; NP_001186570.1; NM_001199641.1.
DR   RefSeq; NP_254274.1; NM_033439.3.
DR   UniGene; Hs.348390; -.
DR   PDB; 2KLL; NMR; -; A=111-270.
DR   PDBsum; 2KLL; -.
DR   ProteinModelPortal; O95760; -.
DR   SMR; O95760; 111-270.
DR   IntAct; O95760; 2.
DR   MINT; MINT-1423224; -.
DR   STRING; O95760; -.
DR   PRIDE; O95760; -.
DR   Ensembl; ENST00000381434; ENSP00000370842; ENSG00000137033.
DR   Ensembl; ENST00000429607; ENSP00000399586; ENSG00000137033.
DR   GeneID; 90865; -.
DR   KEGG; hsa:90865; -.
DR   UCSC; uc003zjt.2; human.
DR   CTD; 90865; -.
DR   GeneCards; GC09P006206; -.
DR   H-InvDB; HIX0007908; -.
DR   HGNC; HGNC:16028; IL33.
DR   HPA; CAB007057; -.
DR   HPA; HPA024426; -.
DR   MIM; 608678; gene.
DR   neXtProt; NX_O95760; -.
DR   PharmGKB; PA162392005; -.
DR   eggNOG; prNOG19288; -.
DR   GeneTree; ENSGT00390000005185; -.
DR   HOGENOM; HBG125786; -.
DR   HOVERGEN; HBG081791; -.
DR   InParanoid; O95760; -.
DR   OMA; GVKDNHL; -.
DR   OrthoDB; EOG4FXR8C; -.
DR   PhylomeDB; O95760; -.
DR   NextBio; 77016; -.
DR   ArrayExpress; O95760; -.
DR   Bgee; O95760; -.
DR   CleanEx; HS_IL33; -.
DR   Genevestigator; O95760; -.
DR   GermOnline; ENSG00000137033; Homo sapiens.
DR   GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR   GO; GO:0005125; F:cytokine activity; IDA:BHF-UCL.
DR   GO; GO:0090197; P:positive regulation of chemokine secretion; IDA:BHF-UCL.
DR   GO; GO:0050729; P:positive regulation of inflammatory response; ISS:BHF-UCL.
DR   GO; GO:0043032; P:positive regulation of macrophage activation; IDA:BHF-UCL.
DR   GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; ISS:BHF-UCL.
DR   KO; K12967; -.
PE   1: Evidence at protein level;
KW   3D-structure; Complete proteome; Cytokine; Polymorphism;
KW   Reference proteome; Secreted.
FT   PROPEP        1    111
FT                                /FTId=PRO_0000248845.
FT   CHAIN       112    270       Interleukin-33.
FT                                /FTId=PRO_0000096790.
FT   VARIANT     263    263       I -> M (in dbSNP:rs16924241).
FT                                /FTId=VAR_049576.
FT   STRAND      118    128
FT   TURN        129    131
FT   STRAND      132    138
FT   STRAND      143    149
FT   STRAND      159    165
FT   TURN        170    172
FT   STRAND      182    197
FT   TURN        198    201
FT   STRAND      202    207
FT   TURN        214    216
FT   STRAND      218    222
FT   STRAND      224    226
FT   STRAND      228    234
FT   STRAND      244    246
FT   HELIX       261    263
FT   STRAND      265    268
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
//