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Interleukin-36 gamma (IL-1-related protein 2) (IL-1RP2) (Interleukin-1 epsilon) (IL-1 epsilon) (Interleukin-1 family member 9) (IL-1F9) (Interleukin-1 homolog 1) (IL-1H1)

 IL36G_HUMAN             Reviewed;         169 AA.
Q9NZH8; Q56B91; Q6UVX7; Q7RTZ9;
08-NOV-2002, integrated into UniProtKB/Swiss-Prot.
01-OCT-2000, sequence version 1.
13-FEB-2019, entry version 146.
RecName: Full=Interleukin-36 gamma;
AltName: Full=IL-1-related protein 2;
Short=IL-1RP2;
AltName: Full=Interleukin-1 epsilon;
Short=IL-1 epsilon;
AltName: Full=Interleukin-1 family member 9;
Short=IL-1F9;
AltName: Full=Interleukin-1 homolog 1;
Short=IL-1H1;
Flags: Precursor;
Name=IL36G; Synonyms=IL1E, IL1F9, IL1H1, IL1RP2;
ORFNames=UNQ2456/PRO5737;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INDUCTION.
TISSUE=Keratinocyte;
PubMed=10744718; DOI=10.1074/jbc.275.14.10308;
Kumar S., McDonnell P.C., Lehr R., Tierney L., Tzimas M.N.,
Griswold D.E., Capper E.A., Tal-Singer R., Wells G.I., Doyle M.L.,
Young P.R.;
"Identification and initial characterization of four novel members of
the interleukin-1 family.";
J. Biol. Chem. 275:10308-10314(2000).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND CHARACTERIZATION.
TISSUE=Epithelium;
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).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=10860666; DOI=10.1006/geno.2000.6184;
Busfield S.J., Comrack C.A., Yu G., Chickering T.W., Smutko J.S.,
Zhou H., Leiby K.R., Holmgren L.M., Gearing D.P., Pan Y.;
"Identification and gene organization of three novel members of the
IL-1 family on human chromosome 2.";
Genomics 66:213-216(2000).
[4]
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).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
PubMed=12975309; DOI=10.1101/gr.1293003;
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S.,
Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
Wood W.I., Godowski P.J., Gray A.M.;
"The secreted protein discovery initiative (SPDI), a large-scale
effort to identify novel human secreted and transmembrane proteins: a
bioinformatics assessment.";
Genome Res. 13:2265-2270(2003).
[6]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
SeattleSNPs variation discovery resource;
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
[7]
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).
[8]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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).
[9]
FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
PubMed=20870894; DOI=10.1165/rcmb.2010-0075OC;
Chustz R.T., Nagarkar D.R., Poposki J.A., Favoreto S. Jr., Avila P.C.,
Schleimer R.P., Kato A.;
"Regulation and function of the IL-1 family cytokine IL-1F9 in human
bronchial epithelial cells.";
Am. J. Respir. Cell Mol. Biol. 45:145-153(2011).
[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, AND TISSUE SPECIFICITY.
PubMed=23095752; DOI=10.1074/jbc.M112.385443;
Bachmann M., Scheiermann P., Hardle L., Pfeilschifter J., Muhl H.;
"IL-36gamma/IL-1F9, an innate T-bet target in myeloid cells.";
J. Biol. Chem. 287:41684-41696(2012).
[12]
FUNCTION, AND INDUCTION.
PubMed=23147407; DOI=10.1002/eji.201242711;
Gresnigt M.S., Roesler B., Jacobs C.W., Becker K.L., Joosten L.A.,
van der Meer J.W., Netea M.G., Dinarello C.A., van de Veerdonk F.L.;
"The IL-36 receptor pathway regulates Aspergillus fumigatus-induced
Th1 and Th17 responses.";
Eur. J. Immunol. 43:416-426(2013).
[13]
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. 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;
also stimulates its own expression and that of the prototypic
cutaneous proinflammatory parameters TNF-alpha, S100A7/psoriasin
and inducible NOS. May play a role in proinflammatory responses
during particular neutrophilic airway inflammation: activates
mitogen-activated protein kinases and NF-kappa B in primary lung
fibroblasts, and stimulates the expression of IL-8 and CXCL3 and
Th17 chemokine CCL20 in lung fibroblasts. May be involved in the
innate immune response to fungal pathogens, such as Aspergillus
fumigatus. {ECO:0000269|PubMed:11466363,
ECO:0000269|PubMed:20870894, ECO:0000269|PubMed:21965679,
ECO:0000269|PubMed:23095752, ECO:0000269|PubMed:23147407,
ECO:0000269|PubMed:24829417}.
-!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:20870894}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=Q9NZH8-1; Sequence=Displayed;
Name=2;
IsoId=Q9NZH8-2; Sequence=VSP_013002;
Note=No experimental confirmation available.;
-!- TISSUE SPECIFICITY: Highly expressed in tissues containing
epithelial cells: skin, lung, stomach and esophagus. Expressed in
bronchial epithelial. In skin is expressed only in keratinocytes
but not in fibroblasts, endothelial cells or melanocytes. Up-
regulated in lesional psoriasis skin. Expressed in monocyte-
derived dendritic cells and M1 macrophages.
{ECO:0000269|PubMed:20870894, ECO:0000269|PubMed:23095752}.
-!- INDUCTION: By TNF and by IFNG/IFN-gamma in keratinocytes. By
Aspergillus fumigatus conidia in peripheral blood mnonocytes;
involves CLEC7A and SYK. {ECO:0000269|PubMed:10744718,
ECO:0000269|PubMed:23147407}.
-!- PTM: N-terminal truncation leads to a dramatic enhancement of its
activity (>1000-fold). {ECO:0000269|PubMed:21965679}.
-!- 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/il1f9/";
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EMBL; AF200492; AAF69248.1; -; mRNA.
EMBL; AF206696; AAG35670.1; -; mRNA.
EMBL; BN000002; CAD29874.1; -; Genomic_DNA.
EMBL; AY359111; AAQ89469.1; -; mRNA.
EMBL; AY968311; AAX59035.1; -; Genomic_DNA.
EMBL; AC016724; AAY14987.1; -; Genomic_DNA.
EMBL; BC096721; AAH96721.1; -; mRNA.
EMBL; BC098130; AAH98130.1; -; mRNA.
EMBL; BC098155; AAH98155.1; -; mRNA.
EMBL; BC098337; AAH98337.1; -; mRNA.
CCDS; CCDS2108.1; -. [Q9NZH8-1]
CCDS; CCDS62992.1; -. [Q9NZH8-2]
RefSeq; NP_001265497.1; NM_001278568.1. [Q9NZH8-2]
RefSeq; NP_062564.1; NM_019618.3. [Q9NZH8-1]
UniGene; Hs.211238; -.
PDB; 4IZE; X-ray; 2.00 A; A=18-169.
PDB; 4P0J; X-ray; 2.30 A; A/B=154-160.
PDB; 4P0K; X-ray; 1.70 A; A=64-72, A=154-160.
PDB; 4P0L; X-ray; 1.55 A; A=64-72, A=154-160.
PDBsum; 4IZE; -.
PDBsum; 4P0J; -.
PDBsum; 4P0K; -.
PDBsum; 4P0L; -.
ProteinModelPortal; Q9NZH8; -.
SMR; Q9NZH8; -.
BioGrid; 121135; 8.
STRING; 9606.ENSP00000259205; -.
iPTMnet; Q9NZH8; -.
PhosphoSitePlus; Q9NZH8; -.
BioMuta; IL36G; -.
EPD; Q9NZH8; -.
PaxDb; Q9NZH8; -.
PeptideAtlas; Q9NZH8; -.
PRIDE; Q9NZH8; -.
ProteomicsDB; 83397; -.
ProteomicsDB; 83398; -. [Q9NZH8-2]
Ensembl; ENST00000259205; ENSP00000259205; ENSG00000136688. [Q9NZH8-1]
Ensembl; ENST00000376489; ENSP00000365672; ENSG00000136688. [Q9NZH8-2]
GeneID; 56300; -.
KEGG; hsa:56300; -.
UCSC; uc002tio.3; human. [Q9NZH8-1]
CTD; 56300; -.
DisGeNET; 56300; -.
EuPathDB; HostDB:ENSG00000136688.10; -.
GeneCards; IL36G; -.
HGNC; HGNC:15741; IL36G.
MIM; 605542; gene.
neXtProt; NX_Q9NZH8; -.
OpenTargets; ENSG00000136688; -.
PharmGKB; PA38395; -.
eggNOG; ENOG410J1V3; Eukaryota.
eggNOG; ENOG4111C31; LUCA.
GeneTree; ENSGT00900000141014; -.
HOVERGEN; HBG052100; -.
InParanoid; Q9NZH8; -.
KO; K05487; -.
OMA; PFLFYRV; -.
OrthoDB; 1502484at2759; -.
PhylomeDB; Q9NZH8; -.
TreeFam; TF300203; -.
Reactome; R-HSA-9014826; Interleukin-36 pathway.
SignaLink; Q9NZH8; -.
GeneWiki; IL1F9; -.
GenomeRNAi; 56300; -.
PRO; PR:Q9NZH8; -.
Proteomes; UP000005640; Chromosome 2.
Bgee; ENSG00000136688; Expressed in 63 organ(s), highest expression level in periodontal ligament.
ExpressionAtlas; Q9NZH8; baseline and differential.
Genevisible; Q9NZH8; 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:0007267; P:cell-cell signaling; TAS:ProtInc.
GO; GO:0071222; P:cellular response to lipopolysaccharide; IBA:GO_Central.
GO; GO:0019221; P:cytokine-mediated signaling pathway; IBA:GO_Central.
GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
GO; GO:0030593; P:neutrophil chemotaxis; IBA:GO_Central.
GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
GO; GO:0032755; P:positive regulation of interleukin-6 production; IBA:GO_Central.
GO; GO:0046330; P:positive regulation of JNK cascade; IBA:GO_Central.
InterPro; IPR000975; IL-1_fam.
InterPro; IPR003297; IL-1RA/IL-36.
InterPro; IPR008996; IL1/FGF.
Pfam; PF00340; IL1; 1.
PRINTS; PR00264; INTERLEUKIN1.
PRINTS; PR01360; INTRLEUKIN1X.
SUPFAM; SSF50353; SSF50353; 1.
1: Evidence at protein level;
3D-structure; Alternative splicing; Complete proteome; Cytokine;
Immunity; Inflammatory response; Innate immunity; Polymorphism;
Reference proteome; Secreted.
PROPEP 1 17 {ECO:0000269|PubMed:21965679}.
/FTId=PRO_0000430549.
CHAIN 18 169 Interleukin-36 gamma.
/FTId=PRO_0000153648.
VAR_SEQ 19 54 MCKPITGTINDLNQQVWTLQGQNLVAVPRSDSVTPV -> I
(in isoform 2).
{ECO:0000303|PubMed:12975309}.
/FTId=VSP_013002.
VARIANT 69 69 Q -> K (in dbSNP:rs6707930).
/FTId=VAR_024505.
STRAND 23 29 {ECO:0000244|PDB:4IZE}.
STRAND 33 38 {ECO:0000244|PDB:4IZE}.
STRAND 41 46 {ECO:0000244|PDB:4IZE}.
HELIX 47 49 {ECO:0000244|PDB:4IZE}.
STRAND 55 60 {ECO:0000244|PDB:4IZE}.
HELIX 64 66 {ECO:0000244|PDB:4P0L}.
HELIX 69 71 {ECO:0000244|PDB:4P0L}.
STRAND 73 80 {ECO:0000244|PDB:4IZE}.
TURN 81 83 {ECO:0000244|PDB:4IZE}.
STRAND 84 89 {ECO:0000244|PDB:4IZE}.
STRAND 91 94 {ECO:0000244|PDB:4IZE}.
STRAND 96 101 {ECO:0000244|PDB:4IZE}.
HELIX 104 109 {ECO:0000244|PDB:4IZE}.
STRAND 110 112 {ECO:0000244|PDB:4IZE}.
HELIX 115 117 {ECO:0000244|PDB:4IZE}.
STRAND 118 124 {ECO:0000244|PDB:4IZE}.
STRAND 127 135 {ECO:0000244|PDB:4IZE}.
STRAND 139 142 {ECO:0000244|PDB:4IZE}.
STRAND 150 153 {ECO:0000244|PDB:4IZE}.
STRAND 156 160 {ECO:0000244|PDB:4P0L}.
STRAND 163 167 {ECO:0000244|PDB:4IZE}.
SEQUENCE 169 AA; 18721 MW; F00A9243706F4154 CRC64;
MRGTPGDADG GGRAVYQSMC KPITGTINDL NQQVWTLQGQ NLVAVPRSDS VTPVTVAVIT
CKYPEALEQG RGDPIYLGIQ NPEMCLYCEK VGEQPTLQLK EQKIMDLYGQ PEPVKPFLFY
RAKTGRTSTL ESVAFPDWFI ASSKRDQPII LTSELGKSYN TAFELNIND


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E2103h ELISA kit Cytokine Zcyto7,Homo sapiens,Human,IL17B,IL-17B,IL20,IL-20,Interleukin-17B,Interleukin-20,Neuronal interleukin-17-related factor,NIRF,UNQ516_PRO1031,ZCYTO7 96T
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U2103h CLIA Cytokine Zcyto7,Homo sapiens,Human,IL17B,IL-17B,IL20,IL-20,Interleukin-17B,Interleukin-20,Neuronal interleukin-17-related factor,NIRF,UNQ516_PRO1031,ZCYTO7 96T
U0066h CLIA CD121 antigen-like family member B,CDw121b,Homo sapiens,Human,IL1R2,IL-1R-2,IL1RB,IL-1R-beta,IL-1RT2,IL-1RT-2,Interleukin-1 receptor beta,Interleukin-1 receptor type 2,Interleukin-1 receptor type 96T

Kits Elisa; taq POLYMERASE

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