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Interleukin-36 alpha (FIL1 epsilon) (Interleukin-1 epsilon) (IL-1 epsilon) (Interleukin-1 family member 6) (IL-1F6)

 IL36A_HUMAN             Reviewed;         158 AA.
Q9UHA7; B2RAD9; Q53SR7; Q5BLR4; Q7RTZ8;
08-NOV-2002, integrated into UniProtKB/Swiss-Prot.
01-MAY-2000, sequence version 1.
20-JUN-2018, entry version 138.
RecName: Full=Interleukin-36 alpha;
AltName: Full=FIL1 epsilon;
AltName: Full=Interleukin-1 epsilon;
Short=IL-1 epsilon;
AltName: Full=Interleukin-1 family member 6;
Short=IL-1F6;
Flags: Precursor;
Name=IL36A; Synonyms=FIL1E, IL1E, IL1F6;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=10625660; DOI=10.1074/jbc.275.2.1169;
Smith D.E., Renshaw B.R., Ketchem R.R., Kubin M., Garka K.E.,
Sims J.E.;
"Four new members expand the IL-1 superfamily.";
J. Biol. Chem. 275:1169-1175(2000).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=11991722; DOI=10.1006/geno.2002.6751;
Nicklin M.J.H., Barton J.L., Nguyen M., Fitzgerald M.G., Duff W.G.,
Kornman K.;
"A sequence-based map of the nine genes of the human interleukin-1
cluster.";
Genomics 79:718-725(2002).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-12.
TISSUE=Esophagus;
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-12; THR-63 AND
ARG-134.
SeattleSNPs variation discovery resource;
Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15815621; DOI=10.1038/nature03466;
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
Waterston R.H., Wilson R.K.;
"Generation and annotation of the DNA sequences of human chromosomes 2
and 4.";
Nature 434:724-731(2005).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
TISSUE SPECIFICITY, AND INDUCTION.
PubMed=11466363; DOI=10.4049/jimmunol.167.3.1440;
Debets R., Timans J.C., Homey B., Zurawski S., Sana T.R., Lo S.,
Wagner J., Edwards G., Clifford T., Menon S., Bazan J.F.,
Kastelein R.A.;
"Two novel IL-1 family members, IL-1 delta and IL-1 epsilon, function
as an antagonist and agonist of NF-kappa B activation through the
orphan IL-1 receptor-related protein 2.";
J. Immunol. 167:1440-1446(2001).
[8]
FUNCTION.
PubMed=14734551; DOI=10.1074/jbc.M400117200;
Towne J.E., Garka K.E., Renshaw B.R., Virca G.D., Sims J.E.;
"Interleukin (IL)-1F6, IL-1F8, and IL-1F9 signal through IL-1Rrp2 and
IL-1RAcP to activate the pathway leading to NF-kappaB and MAPKs.";
J. Biol. Chem. 279:13677-13688(2004).
[9]
NITRATION [LARGE SCALE ANALYSIS] AT TYR-96, AND IDENTIFICATION BY MASS
SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Pituitary adenoma;
PubMed=16777052; DOI=10.1016/j.ab.2006.05.024;
Zhan X., Desiderio D.M.;
"Nitroproteins from a human pituitary adenoma tissue discovered with a
nitrotyrosine affinity column and tandem mass spectrometry.";
Anal. Biochem. 354:279-289(2006).
[10]
FUNCTION, AND PROCESSING.
PubMed=21965679; DOI=10.1074/jbc.M111.267922;
Towne J.E., Renshaw B.R., Douangpanya J., Lipsky B.P., Shen M.,
Gabel C.A., Sims J.E.;
"Interleukin-36 (IL-36) ligands require processing for full agonist
(IL-36alpha, IL-36beta, and IL-36gamma) or antagonist (IL-36Ra)
activity.";
J. Biol. Chem. 286:42594-42602(2011).
[11]
FUNCTION.
PubMed=21881584; DOI=10.1038/jid.2011.234;
Carrier Y., Ma H.L., Ramon H.E., Napierata L., Small C., O'Toole M.,
Young D.A., Fouser L.A., Nickerson-Nutter C., Collins M.,
Dunussi-Joannopoulos K., Medley Q.G.;
"Inter-regulation of Th17 cytokines and the IL-36 cytokines in vitro
and in vivo: implications in psoriasis pathogenesis.";
J. Invest. Dermatol. 131:2428-2437(2011).
[12]
FUNCTION.
PubMed=24829417; DOI=10.4049/jimmunol.1301481;
Foster A.M., Baliwag J., Chen C.S., Guzman A.M., Stoll S.W.,
Gudjonsson J.E., Ward N.L., Johnston A.;
"IL-36 promotes myeloid cell infiltration, activation, and
inflammatory activity in skin.";
J. Immunol. 192:6053-6061(2014).
-!- FUNCTION: Cytokine that binds to and signals through the
IL1RL2/IL-36R receptor which in turn activates NF-kappa-B and MAPK
signaling pathways in target cells linked to a pro-inflammatory
response. Part of the IL-36 signaling system that is thought to be
present in epithelial barriers and to take part in local
inflammatory response; similar to the IL-1 system with which it
shares the coreceptor IL1RAP. Seems to be involved in skin
inflammatory response by acting on keratinocytes, dendritic cells
and indirectly on T-cells to drive tissue infiltration, cell
maturation and cell proliferation. In cultured keratinocytes
induces the expression of macrophage, T-cell, and neutrophil
chemokines, such as CCL3, CCL4, CCL5, CCL2, CCL17, CCL22, CL20,
CCL5, CCL2, CCL17, CCL22, CXCL8, CCL20 and CXCL1, and the
production of proinflammatory cytokines such as TNF-alpha, IL-8
and IL-6. In cultured monocytes upregulates expression of IL-1A,
IL-1B and IL-6. In myeloid dendritic cells involved in cell
maturation by upregulating surface expression of CD83, CD86 and
HLA-DR. In monocyte-derived dendritic cells facilitates dendritic
cell maturation and drives T-cell proliferation. May play a role
in proinflammatory effects in the lung.
{ECO:0000269|PubMed:14734551, ECO:0000269|PubMed:21881584,
ECO:0000269|PubMed:21965679, ECO:0000269|PubMed:24829417}.
-!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
-!- TISSUE SPECIFICITY: Expressed in immune system and fetal brain,
but not in other tissues tested or in multiple hematopoietic cell
lines. Predominantly expressed in skin keratinocytes but not in
fibroblasts, endothelial cells or melanocytes. Increased in
lesional psoriasis skin. {ECO:0000269|PubMed:11466363}.
-!- INDUCTION: By Il-1 and TNF-alpha. {ECO:0000269|PubMed:11466363}.
-!- PTM: N-terminal truncation leads to a dramatic enhancement of its
activity (>1000-fold). {ECO:0000269|PubMed:21965679}.
-!- MISCELLANEOUS: Initial experiments using non-processed full-length
protein found in vitro activity only in the ug range.
{ECO:0000269|PubMed:14734551}.
-!- SIMILARITY: Belongs to the IL-1 family. {ECO:0000305}.
-!- WEB RESOURCE: Name=Wikipedia; Note=Interleukin-1 entry;
URL="https://en.wikipedia.org/wiki/Interleukin_1";
-!- WEB RESOURCE: Name=SeattleSNPs;
URL="http://pga.gs.washington.edu/data/il1f6/";
-----------------------------------------------------------------------
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Distributed under the Creative Commons Attribution (CC BY 4.0) License
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EMBL; AF201831; AAF25211.1; -; mRNA.
EMBL; BN000002; CAD29875.1; -; Genomic_DNA.
EMBL; AK314149; BAG36836.1; -; mRNA.
EMBL; AY944686; AAX20113.1; -; Genomic_DNA.
EMBL; AC016724; AAY14988.1; -; Genomic_DNA.
EMBL; BC107042; AAI07043.1; -; mRNA.
EMBL; BC107043; AAI07044.1; -; mRNA.
CCDS; CCDS42734.1; -.
RefSeq; NP_055255.1; NM_014440.2.
RefSeq; XP_005263696.1; XM_005263639.2.
RefSeq; XP_011509267.1; XM_011510965.1.
RefSeq; XP_016859295.1; XM_017003806.1.
UniGene; Hs.278910; -.
ProteinModelPortal; Q9UHA7; -.
SMR; Q9UHA7; -.
BioGrid; 118055; 12.
IntAct; Q9UHA7; 1.
STRING; 9606.ENSP00000259211; -.
iPTMnet; Q9UHA7; -.
PhosphoSitePlus; Q9UHA7; -.
BioMuta; IL36A; -.
DMDM; 25008601; -.
PaxDb; Q9UHA7; -.
PeptideAtlas; Q9UHA7; -.
PRIDE; Q9UHA7; -.
ProteomicsDB; 84293; -.
Ensembl; ENST00000259211; ENSP00000259211; ENSG00000136694.
GeneID; 27179; -.
KEGG; hsa:27179; -.
UCSC; uc010yxr.3; human.
CTD; 27179; -.
DisGeNET; 27179; -.
EuPathDB; HostDB:ENSG00000136694.8; -.
GeneCards; IL36A; -.
HGNC; HGNC:15562; IL36A.
MIM; 605509; gene.
neXtProt; NX_Q9UHA7; -.
OpenTargets; ENSG00000136694; -.
PharmGKB; PA38389; -.
eggNOG; ENOG410JBMR; Eukaryota.
eggNOG; ENOG41118FS; LUCA.
GeneTree; ENSGT00900000141014; -.
HOVERGEN; HBG052100; -.
InParanoid; Q9UHA7; -.
KO; K05484; -.
OMA; PGWFIAV; -.
OrthoDB; EOG091G0V8E; -.
PhylomeDB; Q9UHA7; -.
TreeFam; TF300203; -.
Reactome; R-HSA-9014826; Interleukin-36 pathway.
GeneWiki; IL1F6; -.
GenomeRNAi; 27179; -.
PRO; PR:Q9UHA7; -.
Proteomes; UP000005640; Chromosome 2.
Bgee; ENSG00000136694; -.
CleanEx; HS_IL1F6; -.
Genevisible; Q9UHA7; HS.
GO; GO:0005576; C:extracellular region; TAS:Reactome.
GO; GO:0005615; C:extracellular space; IBA:GO_Central.
GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
GO; GO:0005149; F:interleukin-1 receptor binding; IBA:GO_Central.
GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
GO; GO:0006955; P:immune response; NAS:UniProtKB.
GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
GO; GO:0032755; P:positive regulation of interleukin-6 production; IEA:Ensembl.
InterPro; IPR000975; IL-1_fam.
InterPro; IPR027163; IL-36_alpha.
InterPro; IPR008996; IL1/FGF.
PANTHER; PTHR10078:SF25; PTHR10078:SF25; 1.
Pfam; PF00340; IL1; 1.
PRINTS; PR00264; INTERLEUKIN1.
SUPFAM; SSF50353; SSF50353; 1.
1: Evidence at protein level;
Complete proteome; Cytokine; Immunity; Inflammatory response;
Innate immunity; Nitration; Polymorphism; Reference proteome;
Secreted.
PROPEP 1 5 {ECO:0000269|PubMed:21965679}.
/FTId=PRO_0000430545.
CHAIN 6 158 Interleukin-36 alpha.
/FTId=PRO_0000153644.
MOD_RES 96 96 Nitrated tyrosine.
{ECO:0000244|PubMed:16777052}.
VARIANT 12 12 Q -> R (in dbSNP:rs895497).
{ECO:0000269|PubMed:14702039,
ECO:0000269|Ref.4}.
/FTId=VAR_024504.
VARIANT 63 63 I -> T (in dbSNP:rs28938798).
{ECO:0000269|Ref.4}.
/FTId=VAR_025055.
VARIANT 134 134 G -> R (in dbSNP:rs28947175).
{ECO:0000269|Ref.4}.
/FTId=VAR_025056.
SEQUENCE 158 AA; 17684 MW; 469AC84306B0E280 CRC64;
MEKALKIDTP QQGSIQDINH RVWVLQDQTL IAVPRKDRMS PVTIALISCR HVETLEKDRG
NPIYLGLNGL NLCLMCAKVG DQPTLQLKEK DIMDLYNQPE PVKSFLFYHS QSGRNSTFES
VAFPGWFIAV SSEGGCPLIL TQELGKANTT DFGLTMLF


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