IL36B_MOUSE
ID IL36B_MOUSE Reviewed; 183 AA.
AC Q9D6Z6; Q8R461;
DT 08-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Interleukin-36 beta;
DE AltName: Full=Interleukin-1 family member 8;
DE Short=IL-1F8;
DE Flags: Precursor;
GN Name=Il36b {ECO:0000312|MGI:MGI:1916927};
GN Synonyms=Fil1e {ECO:0000305}, Il1f8 {ECO:0000312|MGI:MGI:1916927};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Swiss Webster / NIH;
RX PubMed=11991723; DOI=10.1006/geno.2002.6752;
RA Taylor S.L., Renshaw B.R., Garka K.E., Smith D.E., Sims J.E.;
RT "Genomic organization of the interleukin-1 locus.";
RL Genomics 79:726-733(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Tongue;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=19717513; DOI=10.4049/jimmunol.0803301;
RA Martin U., Scholler J., Gurgel J., Renshaw B., Sims J.E., Gabel C.A.;
RT "Externalization of the leaderless cytokine IL-1F6 occurs in response to
RT lipopolysaccharide/ATP activation of transduced bone marrow macrophages.";
RL J. Immunol. 183:4021-4030(2009).
RN [4]
RP FUNCTION.
RX PubMed=21860022; DOI=10.1182/blood-2011-05-356873;
RA Vigne S., Palmer G., Lamacchia C., Martin P., Talabot-Ayer D.,
RA Rodriguez E., Ronchi F., Sallusto F., Dinh H., Sims J.E., Gabay C.;
RT "IL-36R ligands are potent regulators of dendritic and T cells.";
RL Blood 118:5813-5823(2011).
RN [5]
RP FUNCTION, AND PROCESSING.
RX PubMed=21965679; DOI=10.1074/jbc.m111.267922;
RA Towne J.E., Renshaw B.R., Douangpanya J., Lipsky B.P., Shen M., Gabel C.A.,
RA Sims J.E.;
RT "Interleukin-36 (IL-36) ligands require processing for full agonist (IL-
RT 36alpha, IL-36beta, and IL-36gamma) or antagonist (IL-36Ra) activity.";
RL J. Biol. Chem. 286:42594-42602(2011).
CC -!- FUNCTION: Cytokine that binds to and signals through the IL1RL2/IL-36R
CC receptor which in turn activates NF-kappa-B and MAPK signaling pathways
CC in target cells linked to a pro-inflammatory response. Part of the IL-
CC 36 signaling system that is thought to be present in epithelial
CC barriers and to take part in local inflammatory response; similar to
CC the IL-1 system with which it shares the coreceptor IL1RAP. Stimulates
CC production of interleukin-6 and interleukin-8 in synovial fibrobasts,
CC articular chondrocytes and mature adipocytes. Induces expression of a
CC number of antimicrobial peptides including beta-defensin 4 and beta-
CC defensin 103 as well as a number of matrix metalloproteases (By
CC similarity). Seems to be involved in skin inflammatory response by
CC acting on keratinocytes, dendritic cells and indirectly on T-cells to
CC drive tissue infiltration, cell maturation and cell proliferation.
CC Induces the production of pro-inflammatory cytokines in bone marrow-
CC derived dendritic cells (BMDCs), including IL-12, Il-1 beta, IL-6, TNF-
CC alpha and IL-23, and activates p38 MAPK phosphorylation in BMDCs.
CC Involved in dendritic cell maturation by stimulating the surface
CC expression of CD80, CD86 and MHC class II. Induces the production of
CC IFN-gamma, IL-4 and IL-17 by T-helper 1 (Th1) cells, cultured CD4(+) T-
CC cells and splenocytes. {ECO:0000250|UniProtKB:Q9NZH7,
CC ECO:0000269|PubMed:21860022, ECO:0000269|PubMed:21965679}.
CC -!- SUBUNIT: Interacts with cargo receptor TMED10; the interaction mediates
CC the translocation from the cytoplasm into the ERGIC (endoplasmic
CC reticulum-Golgi intermediate compartment) and thereby secretion.
CC {ECO:0000250|UniProtKB:Q9NZH7}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9NZH7}.
CC Secreted {ECO:0000269|PubMed:19717513}. Note=Secreted upon LPS
CC treatment followed by ATP-induced activation of P2rx7. The secretion is
CC dependent on protein unfolding and facilitated by the cargo receptor
CC TMED10; it results in protein translocation from the cytoplasm into the
CC ERGIC (endoplasmic reticulum-Golgi intermediate compartment) followed
CC by vesicle entry and secretion (By similarity).
CC {ECO:0000250|UniProtKB:Q9NZH7, ECO:0000269|PubMed:19717513}.
CC -!- PTM: N-terminal truncation leads to a dramatic enhancement of its
CC activity (>1000-fold). {ECO:0000269|PubMed:21965679}.
CC -!- SIMILARITY: Belongs to the IL-1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL67152.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY071842; AAL67152.1; ALT_INIT; mRNA.
DR EMBL; AK009787; BAB26505.1; -; mRNA.
DR CCDS; CCDS38063.1; -.
DR RefSeq; NP_081439.1; NM_027163.4.
DR AlphaFoldDB; Q9D6Z6; -.
DR SMR; Q9D6Z6; -.
DR STRING; 10090.ENSMUSP00000028363; -.
DR PhosphoSitePlus; Q9D6Z6; -.
DR PaxDb; Q9D6Z6; -.
DR PRIDE; Q9D6Z6; -.
DR ProteomicsDB; 269550; -.
DR Antibodypedia; 33320; 219 antibodies from 30 providers.
DR DNASU; 69677; -.
DR Ensembl; ENSMUST00000028363; ENSMUSP00000028363; ENSMUSG00000026985.
DR GeneID; 69677; -.
DR KEGG; mmu:69677; -.
DR UCSC; uc008ion.1; mouse.
DR CTD; 27177; -.
DR MGI; MGI:1916927; Il36b.
DR VEuPathDB; HostDB:ENSMUSG00000026985; -.
DR eggNOG; ENOG502STX9; Eukaryota.
DR GeneTree; ENSGT00950000182943; -.
DR HOGENOM; CLU_095373_2_0_1; -.
DR InParanoid; Q9D6Z6; -.
DR OMA; WFIATSK; -.
DR OrthoDB; 1502484at2759; -.
DR PhylomeDB; Q9D6Z6; -.
DR TreeFam; TF300203; -.
DR Reactome; R-MMU-9014826; Interleukin-36 pathway.
DR BioGRID-ORCS; 69677; 3 hits in 72 CRISPR screens.
DR PRO; PR:Q9D6Z6; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9D6Z6; protein.
DR Bgee; ENSMUSG00000026985; Expressed in esophagus and 16 other tissues.
DR ExpressionAtlas; Q9D6Z6; baseline and differential.
DR Genevisible; Q9D6Z6; MM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0005125; F:cytokine activity; IGI:MGI.
DR GO; GO:0005149; F:interleukin-1 receptor binding; IEA:InterPro.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IBA:GO_Central.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0002437; P:inflammatory response to antigenic stimulus; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0001819; P:positive regulation of cytokine production; IDA:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IBA:GO_Central.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IGI:MGI.
DR GO; GO:0045582; P:positive regulation of T cell differentiation; IGI:MGI.
DR InterPro; IPR020877; IL-1_CS.
DR InterPro; IPR000975; IL-1_fam.
DR InterPro; IPR027172; IL-36_beta.
DR InterPro; IPR008996; IL1/FGF.
DR PANTHER; PTHR10078; PTHR10078; 1.
DR PANTHER; PTHR10078:SF24; PTHR10078:SF24; 1.
DR Pfam; PF00340; IL1; 1.
DR PRINTS; PR00264; INTERLEUKIN1.
DR SUPFAM; SSF50353; SSF50353; 1.
DR PROSITE; PS00253; INTERLEUKIN_1; 1.
PE 2: Evidence at transcript level;
KW Cytokine; Cytoplasm; Immunity; Inflammatory response; Innate immunity;
KW Reference proteome; Secreted.
FT PROPEP 1..30
FT /evidence="ECO:0000269|PubMed:21965679"
FT /id="PRO_0000430548"
FT CHAIN 31..183
FT /note="Interleukin-36 beta"
FT /id="PRO_0000153647"
SQ SEQUENCE 183 AA; 20878 MW; A3ACE339FB96F02F CRC64;
MMAFPPQSCV HVLPPKSIQM WEPNHNTMHG SSQSPRNYRV HDSQQMVWVL TGNTLTAVPA
SNNVKPVILS LIACRDTEFQ DVKKGNLVFL GIKNRNLCFC CVEMEGKPTL QLKEVDIMNL
YKERKAQKAF LFYHGIEGST SVFQSVLYPG WFIATSSIER QTIILTHQRG KLVNTNFYIE
SEK