IL33_RAT
ID IL33_RAT Reviewed; 264 AA.
AC Q66H70;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Interleukin-33;
DE Short=IL-33;
DE Flags: Precursor;
GN Name=Il33 {ECO:0000312|RGD:1311155};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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).
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:0000250|UniProtKB:O95760}.
CC Chromosome {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 -!- 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; BC081993; AAH81993.1; -; mRNA.
DR RefSeq; NP_001014188.1; NM_001014166.1.
DR AlphaFoldDB; Q66H70; -.
DR SMR; Q66H70; -.
DR STRING; 10116.ENSRNOP00000022056; -.
DR iPTMnet; Q66H70; -.
DR PhosphoSitePlus; Q66H70; -.
DR PRIDE; Q66H70; -.
DR Ensembl; ENSRNOT00000022056; ENSRNOP00000022056; ENSRNOG00000016456.
DR GeneID; 361749; -.
DR KEGG; rno:361749; -.
DR UCSC; RGD:1311155; rat.
DR CTD; 90865; -.
DR RGD; 1311155; Il33.
DR eggNOG; ENOG502RW83; Eukaryota.
DR GeneTree; ENSGT00390000005185; -.
DR InParanoid; Q66H70; -.
DR OrthoDB; 1062809at2759; -.
DR PhylomeDB; Q66H70; -.
DR TreeFam; TF338120; -.
DR Reactome; R-RNO-1257604; PIP3 activates AKT signaling.
DR Reactome; R-RNO-5689880; Ub-specific processing proteases.
DR Reactome; R-RNO-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-RNO-9014843; Interleukin-33 signaling.
DR PRO; PR:Q66H70; -.
DR Proteomes; UP000002494; Chromosome 1.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0005125; F:cytokine activity; ISO:RGD.
DR GO; GO:0002112; F:interleukin-33 receptor binding; ISO:RGD.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:RGD.
DR GO; GO:0051607; P:defense response to virus; ISO:RGD.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0010467; P:gene expression; IEA:Ensembl.
DR GO; GO:0038172; P:interleukin-33-mediated signaling pathway; ISO:RGD.
DR GO; GO:0002281; P:macrophage activation involved in immune response; ISO:RGD.
DR GO; GO:0002282; P:microglial cell activation involved in immune response; ISO:RGD.
DR GO; GO:0061518; P:microglial cell proliferation; ISO:RGD.
DR GO; GO:0002638; P:negative regulation of immunoglobulin production; ISO:RGD.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; ISO:RGD.
DR GO; GO:0002686; P:negative regulation of leukocyte migration; ISO:RGD.
DR GO; GO:0120042; P:negative regulation of macrophage proliferation; ISO:RGD.
DR GO; GO:0002826; P:negative regulation of T-helper 1 type immune response; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0150145; P:positive regulation of CD80 production; ISO:RGD.
DR GO; GO:0150142; P:positive regulation of CD86 production; ISO:RGD.
DR GO; GO:0010186; P:positive regulation of cellular defense response; ISO:RGD.
DR GO; GO:0032722; P:positive regulation of chemokine production; ISO:RGD.
DR GO; GO:0001819; P:positive regulation of cytokine production; IBA:GO_Central.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0002639; P:positive regulation of immunoglobulin production; ISO:RGD.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISO:RGD.
DR GO; GO:0032736; P:positive regulation of interleukin-13 production; ISO:RGD.
DR GO; GO:0032753; P:positive regulation of interleukin-4 production; ISO:RGD.
DR GO; GO:0032754; P:positive regulation of interleukin-5 production; ISO:RGD.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISO:RGD.
DR GO; GO:0043032; P:positive regulation of macrophage activation; ISO:RGD.
DR GO; GO:0045345; P:positive regulation of MHC class I biosynthetic process; ISO:RGD.
DR GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; ISO:RGD.
DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; ISO:RGD.
DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; IMP:RGD.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:RGD.
DR GO; GO:0002830; P:positive regulation of type 2 immune response; ISO:RGD.
DR GO; GO:0051930; P:regulation of sensory perception of pain; IMP:RGD.
DR GO; GO:0042092; P:type 2 immune response; IEA:Ensembl.
DR GO; GO:0042060; P:wound healing; IEP:RGD.
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..264
FT /note="Interleukin-33"
FT /id="PRO_0000096793"
FT PROPEP 1..101
FT /evidence="ECO:0000250"
FT /id="PRO_0000430091"
FT REGION 1..65
FT /note="Homeodomain-like HTH domain"
FT /evidence="ECO:0000250"
FT REGION 66..108
FT /note="Interaction with RELA"
FT /evidence="ECO:0000250"
FT SITE 101..102
FT /note="Cleavage; by CTSG and ELANE"
FT /evidence="ECO:0000250"
FT SITE 108..109
FT /note="Cleavage; by ELANE"
FT /evidence="ECO:0000250"
SQ SEQUENCE 264 AA; 29486 MW; 91452ADC579B7BCC CRC64;
MRPRMKYSNS KISPAKCDST SGRALVPPCK ITRSQQKTKD ICHVYCMRLR SGLTIRKETC
YFGKEPAKRY SLKSGSKHEG RLSTCLPDSR KRSLLGSIQA FAASVDTLSI QGTSLLTESC
ALSTYNDQSV SFVLENGCYV INVEDCGKNQ EKDKVLLRYY ESSFPAQSGD GVDGKKLMVN
MSPIKDTDIW LNANDKDYSV ELQKGDVSPP DQAFFVLHKK SSDFVSFECK NLPGTYIGVK
DNQLALVEEN DESCNNIMFK LSKM
