IL36A_MOUSE
ID IL36A_MOUSE Reviewed; 160 AA.
AC Q9JLA2;
DT 08-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Interleukin-36 alpha;
DE AltName: Full=FIL1 epsilon;
DE AltName: Full=Interleukin-1 epsilon;
DE Short=IL-1 epsilon;
DE AltName: Full=Interleukin-1 family member 6;
DE Short=IL-1F6;
DE AltName: Full=Interleukin-1 homolog 1;
DE Short=IL-1H1;
DE Flags: Precursor;
GN Name=Il36a {ECO:0000312|MGI:MGI:1859324};
GN Synonyms=Fil1e {ECO:0000250|UniProtKB:Q9UHA7},
GN Il1e {ECO:0000303|PubMed:11466363}, Il1f6 {ECO:0000312|MGI:MGI:1859324},
GN Il1h1 {ECO:0000312|MGI:MGI:1859324};
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].
RX PubMed=10744718; DOI=10.1074/jbc.275.14.10308;
RA Kumar S., McDonnell P.C., Lehr R., Tierney L., Tzimas M.N., Griswold D.E.,
RA Capper E.A., Tal-Singer R., Wells G.I., Doyle M.L., Young P.R.;
RT "Identification and initial characterization of four novel members of the
RT interleukin-1 family.";
RL J. Biol. Chem. 275:10308-10314(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=11466363; DOI=10.4049/jimmunol.167.3.1440;
RA Debets R., Timans J.C., Homey B., Zurawski S., Sana T.R., Lo S., Wagner J.,
RA Edwards G., Clifford T., Menon S., Bazan J.F., Kastelein R.A.;
RT "Two novel IL-1 family members, IL-1 delta and IL-1 epsilon, function as an
RT antagonist and agonist of NF-kappa B activation through the orphan IL-1
RT receptor-related protein 2.";
RL J. Immunol. 167:1440-1446(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo;
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 [4]
RP TISSUE SPECIFICITY.
RX PubMed=20101239; DOI=10.1038/labinvest.2009.148;
RA Ichii O., Otsuka S., Sasaki N., Yabuki A., Ohta H., Takiguchi M.,
RA Hashimoto Y., Endoh D., Kon Y.;
RT "Local overexpression of interleukin-1 family, member 6 relates to the
RT development of tubulointerstitial lesions.";
RL Lab. Invest. 90:459-475(2010).
RN [5]
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 [6]
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).
RN [7]
RP INDUCTION.
RX PubMed=21881584; DOI=10.1038/jid.2011.234;
RA Carrier Y., Ma H.L., Ramon H.E., Napierata L., Small C., O'Toole M.,
RA Young D.A., Fouser L.A., Nickerson-Nutter C., Collins M.,
RA Dunussi-Joannopoulos K., Medley Q.G.;
RT "Inter-regulation of Th17 cytokines and the IL-36 cytokines in vitro and in
RT vivo: implications in psoriasis pathogenesis.";
RL J. Invest. Dermatol. 131:2428-2437(2011).
RN [8]
RP FUNCTION.
RX PubMed=23029241; DOI=10.1371/journal.pone.0045784;
RA Ramadas R.A., Ewart S.L., Iwakura Y., Medoff B.D., LeVine A.M.;
RT "IL-36alpha exerts pro-inflammatory effects in the lungs of mice.";
RL PLoS ONE 7:E45784-E45784(2012).
RN [9]
RP FUNCTION.
RX PubMed=24829417; DOI=10.4049/jimmunol.1301481;
RA Foster A.M., Baliwag J., Chen C.S., Guzman A.M., Stoll S.W.,
RA Gudjonsson J.E., Ward N.L., Johnston A.;
RT "IL-36 promotes myeloid cell infiltration, activation, and inflammatory
RT activity in skin.";
RL J. Immunol. 192:6053-6061(2014).
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. Seems to be
CC involved in skin inflammatory response by acting on keratinocytes,
CC dendritic cells and indirectly on T-cells to drive tissue infiltration,
CC cell maturation and cell proliferation. Induces the production of pro-
CC inflammatory cytokines, including IL-12, Il-1 beta, IL-6, TNF-alpha and
CC IL-23 in bone marrow-derived dendritic cells (BMDCs). Involved in
CC dendritic cell maturation by stimulating the surface expression of
CC CD80, CD86 and MHC class II. Induces the production of IFN-gamma, IL-4
CC and IL-17 by cultured CD4(+) T-cells and splenocytes. May play a role
CC in pro-inflammatory effects in the lung: induces the expression of
CC CXCL1 and CXCL2 in the lung, and the expression of TNF-alpha, IL-36c,
CC IL-1A, IL-1B, CXCL1 and CXCL2 in isolated splenic CD11c(+) alveolar
CC macrophages. May be involved in T-cell maturation by stimulating the
CC surface expression of CD40 and modestly CD80 and CD86 in splenic
CC CD11c(+) cells. May be involved in CD4(+) T-cell proliferation. Induces
CC NF-kappa B activation in macrophages. {ECO:0000269|PubMed:21860022,
CC ECO:0000269|PubMed:21965679, ECO:0000269|PubMed:23029241,
CC ECO:0000269|PubMed:24829417}.
CC -!- SUBUNIT: Interacts with TMED10; the interaction mediates the
CC translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-
CC Golgi intermediate compartment) and thereby secretion.
CC {ECO:0000250|UniProtKB:Q9UHA7}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9UHA7}.
CC Secreted {ECO:0000250|UniProtKB:Q9UHA7}. Note=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. {ECO:0000250|UniProtKB:Q9UHA7}.
CC -!- TISSUE SPECIFICITY: Highly expressed in embryonic tissue and in tissues
CC containing epithelial cells. Elevated expression levels are detected in
CC chronic kidney disease; expressed inepithelia from the distal
CC convoluted tubules (DCTs) to the cortical collecting ducts (CCDs) in
CC single nephrons (at protein level). {ECO:0000269|PubMed:11466363,
CC ECO:0000269|PubMed:20101239}.
CC -!- INDUCTION: By IL-22 in normal and psoriasis-like skin.
CC {ECO:0000269|PubMed:21881584}.
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}.
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DR EMBL; AF200493; AAF69249.1; -; mRNA.
DR EMBL; AF206697; AAG35671.1; -; mRNA.
DR EMBL; AK004061; BAB23147.1; -; mRNA.
DR CCDS; CCDS15734.1; -.
DR RefSeq; NP_062323.1; NM_019450.3.
DR AlphaFoldDB; Q9JLA2; -.
DR SMR; Q9JLA2; -.
DR STRING; 10090.ENSMUSP00000028361; -.
DR PhosphoSitePlus; Q9JLA2; -.
DR PaxDb; Q9JLA2; -.
DR PRIDE; Q9JLA2; -.
DR ProteomicsDB; 301645; -.
DR Antibodypedia; 33315; 352 antibodies from 31 providers.
DR DNASU; 54448; -.
DR Ensembl; ENSMUST00000028361; ENSMUSP00000028361; ENSMUSG00000026984.
DR GeneID; 54448; -.
DR KEGG; mmu:54448; -.
DR UCSC; uc008ioq.1; mouse.
DR CTD; 27179; -.
DR MGI; MGI:1859324; Il36a.
DR VEuPathDB; HostDB:ENSMUSG00000026984; -.
DR eggNOG; ENOG502TDU1; Eukaryota.
DR GeneTree; ENSGT00950000182943; -.
DR HOGENOM; CLU_095373_1_0_1; -.
DR InParanoid; Q9JLA2; -.
DR OMA; PFLFYHN; -.
DR OrthoDB; 1502484at2759; -.
DR PhylomeDB; Q9JLA2; -.
DR TreeFam; TF300203; -.
DR Reactome; R-MMU-9014826; Interleukin-36 pathway.
DR BioGRID-ORCS; 54448; 2 hits in 73 CRISPR screens.
DR PRO; PR:Q9JLA2; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9JLA2; protein.
DR Bgee; ENSMUSG00000026984; Expressed in esophagus and 36 other tissues.
DR ExpressionAtlas; Q9JLA2; baseline and differential.
DR Genevisible; Q9JLA2; 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; ISS:MGI.
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 InterPro; IPR000975; IL-1_fam.
DR InterPro; IPR003297; IL-1RA/IL-36.
DR InterPro; IPR027163; IL-36_alpha.
DR InterPro; IPR008996; IL1/FGF.
DR PANTHER; PTHR10078; PTHR10078; 1.
DR PANTHER; PTHR10078:SF25; PTHR10078:SF25; 1.
DR Pfam; PF00340; IL1; 1.
DR PRINTS; PR01360; INTRLEUKIN1X.
DR SUPFAM; SSF50353; SSF50353; 1.
PE 1: Evidence at protein level;
KW Cytokine; Cytoplasm; Immunity; Inflammatory response; Innate immunity;
KW Nitration; Reference proteome; Secreted.
FT PROPEP 1..7
FT /evidence="ECO:0000269|PubMed:21965679"
FT /id="PRO_0000430546"
FT CHAIN 8..160
FT /note="Interleukin-36 alpha"
FT /id="PRO_0000153645"
FT MOD_RES 98
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9UHA7"
SQ SEQUENCE 160 AA; 18015 MW; AA0434D68FF62F4A CRC64;
MNKEKELRAA SPSLRHVQDL SSRVWILQNN ILTAVPRKEQ TVPVTITLLP CQYLDTLETN
RGDPTYMGVQ RPMSCLFCTK DGEQPVLQLG EGNIMEMYNK KEPVKASLFY HKKSGTTSTF
ESAAFPGWFI AVCSKGSCPL ILTQELGEIF ITDFEMIVVH
