ID   IL33_CANLF              Reviewed;         263 AA.
AC   O97863;
DT   05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   25-MAY-2022, entry version 77.
DE   RecName: Full=Interleukin-33;
DE            Short=IL-33;
DE   AltName: Full=Protein DVS27;
DE   Flags: Precursor;
GN   Name=IL33;
OS   Canis lupus familiaris (Dog) (Canis familiaris).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX   NCBI_TaxID=9615;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC   TISSUE=Cerebral artery;
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).
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. Involved in the maturation of Th2 cells inducing the
CC       secretion of T-helper type 2-associated cytokines. Also involved in
CC       activation of mast cells, basophils, eosinophils and natural killer
CC       cells. Acts as a chemoattractant for Th2 cells, and may function as an
CC       'alarmin', that amplifies immune responses during tissue injury (By
CC       similarity). {ECO:0000250}.
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 (By
CC       similarity). {ECO:0000250}.
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:10566975}. Chromosome
CC       {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   -!- TISSUE SPECIFICITY: Expressed in cultured umbilical artery smooth
CC       muscle cells after stimulation with IL1A and IL1B, and to a lesser
CC       extent with IFNG. Expressed in vasospastic cerebral arteries after
CC       subarachnoid hemorrhage. {ECO:0000269|PubMed:10566975}.
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       but could not be confirmed in vivo suggesting that IL33 is probably not
CC       a direct substrate for that caspase (By similarity). {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the IL-1 family. Highly divergent.
CC       {ECO:0000305}.
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DR   EMBL; AB024517; BAA75891.1; -; mRNA.
DR   RefSeq; NP_001003180.1; NM_001003180.1.
DR   AlphaFoldDB; O97863; -.
DR   SMR; O97863; -.
DR   STRING; 9615.ENSCAFP00000001950; -.
DR   Ensembl; ENSCAFT00040018732; ENSCAFP00040016253; ENSCAFG00040010108.
DR   GeneID; 403810; -.
DR   KEGG; cfa:403810; -.
DR   CTD; 90865; -.
DR   InParanoid; O97863; -.
DR   OrthoDB; 1062809at2759; -.
DR   Proteomes; UP000002254; Unplaced.
DR   GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR   GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR   GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR   GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR   GO; GO:0032722; P:positive regulation of chemokine production; IEA:Ensembl.
DR   GO; GO:0001819; P:positive regulation of cytokine production; IBA:GO_Central.
DR   GO; GO:0050729; P:positive regulation of inflammatory response; IBA:GO_Central.
DR   GO; GO:0043032; P:positive regulation of macrophage activation; IEA:Ensembl.
DR   InterPro; IPR026145; IL-33.
DR   PANTHER; PTHR21114; PTHR21114; 1.
DR   Pfam; PF15095; IL33; 1.
PE   2: Evidence at transcript level;
KW   Chromosome; Cytokine; Cytoplasm; Cytoplasmic vesicle; Nucleus;
KW   Reference proteome; Secreted; Transcription.
FT   CHAIN           1..263
FT                   /note="Interleukin-33"
FT                   /id="PRO_0000096789"
FT   PROPEP          1..?
FT                   /id="PRO_0000430082"
FT   REGION          1..65
FT                   /note="Homeodomain-like HTH domain"
FT                   /evidence="ECO:0000250"
FT   REGION          1..28
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          66..109
FT                   /note="Interaction with RELA"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   263 AA;  30179 MW;  25647EC7E50824F2 CRC64;
     MKYSTTKIPP AKMNSSADKA LVKSPKLRKS QQKPEGVCQM YFMQLRSGLI IEKTSCYFRK
     EITKRYSPRT AEKCRKQCLV FTACHQQLNK DFTSDVPMLQ KCFGRANVPS IQEYSASLST
     YNDQSITFVF EDGSYEIYVE DLRKGQEKDK VLFRYYDSQS PSHETGDDVD GQTLLVNLSP
     TKDKDFLLHA NNEEHSVELQ KCENQLPDQA FFLLHRKSSE CVSFECKNNP GVFIGVKDNH
     LALIKVGDQT KDSYIEKTIF KLS