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Interleukin-36 beta (FIL1 eta) (Interleukin-1 eta) (IL-1 eta) (Interleukin-1 family member 8) (IL-1F8) (Interleukin-1 homolog 2) (IL-1H2)

 IL36B_HUMAN             Reviewed;         164 AA.
Q9NZH7; Q3MIH0; Q53SR6; Q7RTZ7; Q9UHA5;
08-NOV-2002, integrated into UniProtKB/Swiss-Prot.
01-OCT-2000, sequence version 1.
17-JUN-2020, entry version 146.
RecName: Full=Interleukin-36 beta;
AltName: Full=FIL1 eta;
AltName: Full=Interleukin-1 eta;
Short=IL-1 eta;
AltName: Full=Interleukin-1 family member 8;
Short=IL-1F8;
AltName: Full=Interleukin-1 homolog 2;
Short=IL-1H2;
Flags: Precursor;
Name=IL36B; Synonyms=IL1F8, IL1H2;
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).
TISSUE=Osteoclastoma;
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 2).
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).
[3]
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).
[4]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT CYS-36.
SeattleSNPs variation discovery resource;
Submitted (SEP-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 GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
Hunkapiller M.W., Myers E.W., Venter J.C.;
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
TISSUE=Lung, and Placenta;
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).
[8]
FUNCTION, INDUCTION, AND SUBCELLULAR LOCATION.
PubMed=16646978; DOI=10.1186/ar1946;
Magne D., Palmer G., Barton J.L., Mezin F., Talabot-Ayer D., Bas S.,
Duffy T., Noger M., Guerne P.A., Nicklin M.J., Gabay C.;
"The new IL-1 family member IL-1F8 stimulates production of inflammatory
mediators by synovial fibroblasts and articular chondrocytes.";
Arthritis Res. Ther. 8:R80-R80(2006).
[9]
FUNCTION, AND TISSUE SPECIFICITY.
PubMed=20300079; DOI=10.1038/oby.2010.55;
van Asseldonk E.J., Stienstra R., Koenen T.B., van Tits L.J., Joosten L.A.,
Tack C.J., Netea M.G.;
"The effect of the interleukin-1 cytokine family members IL-1F6 and IL-1F8
on adipocyte differentiation.";
Obesity 18:2234-2236(2010).
[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=21242515; DOI=10.4049/jimmunol.1003162;
Johnston A., Xing X., Guzman A.M., Riblett M., Loyd C.M., Ward N.L.,
Wohn C., Prens E.P., Wang F., Maier L.E., Kang S., Voorhees J.J.,
Elder J.T., Gudjonsson J.E.;
"IL-1F5, -F6, -F8, and -F9: a novel IL-1 family signaling system that is
active in psoriasis and promotes keratinocyte antimicrobial peptide
expression.";
J. Immunol. 186:2613-2622(2011).
[12]
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).
[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 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. Stimulates
production of interleukin-6 and interleukin-8 in synovial fibrobasts,
articular chondrocytes and mature adipocytes. Induces expression of a
number of antimicrobial peptides including beta-defensins 4 and 103 as
well as a number of matrix metalloproteases. 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. {ECO:0000269|PubMed:16646978,
ECO:0000269|PubMed:20300079, ECO:0000269|PubMed:21242515,
ECO:0000269|PubMed:21881584, ECO:0000269|PubMed:21965679,
ECO:0000269|PubMed:24829417}.
-!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16646978}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=Q9NZH7-1; Sequence=Displayed;
Name=2;
IsoId=Q9NZH7-2; Sequence=VSP_002657;
-!- TISSUE SPECIFICITY: Expression at low levels in tonsil, bone marrow,
heart, placenta, lung, testis and colon but not in any hematopoietic
cell lines. Not detected in adipose tissue. Expressed at higher levels
in psoriatic plaques than in symptomless psoriatic skin or healthy
control skin. Increased levels are not detected in inflamed joint
tissue. {ECO:0000269|PubMed:20300079, ECO:0000269|PubMed:21242515}.
-!- INDUCTION: By proinflammatory cytokines IL1A, IL1B and TNF in synovial
fibroblasts. By IL1A and TNF in keratinocytes. Constitutive in
articular chondrocytes. {ECO:0000269|PubMed:16646978}.
-!- 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/il1f8/";
---------------------------------------------------------------------------
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Distributed under the Creative Commons Attribution (CC BY 4.0) License
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EMBL; AF200494; AAF69250.1; -; mRNA.
EMBL; AF201833; AAF25213.1; -; mRNA.
EMBL; CH471217; EAW73615.1; -; Genomic_DNA.
EMBL; BC101831; AAI01832.1; -; mRNA.
EMBL; BC101833; AAI01834.1; -; mRNA.
EMBL; BN000002; CAD29876.1; -; Genomic_DNA.
EMBL; DQ224343; ABA60896.1; -; Genomic_DNA.
EMBL; AC016724; AAY14989.1; -; Genomic_DNA.
CCDS; CCDS2109.1; -. [Q9NZH7-1]
CCDS; CCDS2110.1; -. [Q9NZH7-2]
RefSeq; NP_055253.2; NM_014438.4. [Q9NZH7-1]
RefSeq; NP_775270.1; NM_173178.2. [Q9NZH7-2]
RefSeq; XP_011509264.1; XM_011510962.1. [Q9NZH7-2]
SMR; Q9NZH7; -.
BioGRID; 118053; 1.
STRING; 9606.ENSP00000259213; -.
iPTMnet; Q9NZH7; -.
PhosphoSitePlus; Q9NZH7; -.
BioMuta; IL36B; -.
DMDM; 25008595; -.
PaxDb; Q9NZH7; -.
PRIDE; Q9NZH7; -.
ProteomicsDB; 83395; -. [Q9NZH7-1]
ProteomicsDB; 83396; -. [Q9NZH7-2]
Antibodypedia; 33320; 186 antibodies.
Ensembl; ENST00000259213; ENSP00000259213; ENSG00000136696. [Q9NZH7-1]
Ensembl; ENST00000327407; ENSP00000328420; ENSG00000136696. [Q9NZH7-2]
GeneID; 27177; -.
KEGG; hsa:27177; -.
UCSC; uc002tiq.2; human. [Q9NZH7-1]
CTD; 27177; -.
DisGeNET; 27177; -.
EuPathDB; HostDB:ENSG00000136696.10; -.
GeneCards; IL36B; -.
HGNC; HGNC:15564; IL36B.
HPA; ENSG00000136696; Group enriched (esophagus, lymphoid tissue, skin).
MIM; 605508; gene.
neXtProt; NX_Q9NZH7; -.
OpenTargets; ENSG00000136696; -.
PharmGKB; PA38391; -.
eggNOG; ENOG410JCFD; Eukaryota.
eggNOG; ENOG41118F0; LUCA.
GeneTree; ENSGT00950000182943; -.
HOGENOM; CLU_137451_0_0_1; -.
InParanoid; Q9NZH7; -.
KO; K05486; -.
OMA; WFIATSK; -.
OrthoDB; 1270530at2759; -.
PhylomeDB; Q9NZH7; -.
Reactome; R-HSA-9014826; Interleukin-36 pathway.
BioGRID-ORCS; 27177; 7 hits in 780 CRISPR screens.
GeneWiki; IL1F8; -.
GenomeRNAi; 27177; -.
Pharos; Q9NZH7; Tbio.
PRO; PR:Q9NZH7; -.
Proteomes; UP000005640; Chromosome 2.
RNAct; Q9NZH7; protein.
Bgee; ENSG00000136696; Expressed in skin of leg and 21 other tissues.
Genevisible; Q9NZH7; HS.
GO; GO:0005576; C:extracellular region; TAS:UniProtKB.
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; 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:0006955; P:immune response; NAS:UniProtKB.
GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
GO; GO:0002437; P:inflammatory response to antigenic stimulus; IBA:GO_Central.
GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
GO; GO:0010628; P:positive regulation of gene expression; IBA:GO_Central.
GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
GO; GO:0045582; P:positive regulation of T cell differentiation; IBA:GO_Central.
InterPro; IPR000975; IL-1_fam.
InterPro; IPR027172; IL-36_beta.
InterPro; IPR008996; IL1/FGF.
PANTHER; PTHR10078; PTHR10078; 1.
PANTHER; PTHR10078:SF24; PTHR10078:SF24; 1.
SUPFAM; SSF50353; SSF50353; 1.
2: Evidence at transcript level;
Alternative splicing; Cytokine; Immunity; Inflammatory response;
Innate immunity; Polymorphism; Reference proteome; Secreted.
PROPEP 1..4
/evidence="ECO:0000269|PubMed:21965679"
/id="PRO_0000430547"
CHAIN 5..164
/note="Interleukin-36 beta"
/id="PRO_0000153646"
VAR_SEQ 88..164
/note="LQGSQDNIGKDTCWKLVGIHTCINLDVRESCFMGTLDQWGIGVGRKKWKSSF
QHHHLRKKDKDFSSMRTNIGMPGRM -> EKNIMDLYVEKKAQKPFLFFHNKEGSTSVF
QSVSYPGWFIATSTTSGQPIFLTKERGITNNTNFYLDSVE (in isoform 2)"
/evidence="ECO:0000303|PubMed:10625660,
ECO:0000303|PubMed:15489334"
/id="VSP_002657"
VARIANT 36
/note="R -> C (in dbSNP:rs34754959)"
/evidence="ECO:0000269|Ref.4"
/id="VAR_025057"
SEQUENCE 164 AA; 18522 MW; F0D2099F4A357A0A CRC64;
MNPQREAAPK SYAIRDSRQM VWVLSGNSLI AAPLSRSIKP VTLHLIACRD TEFSDKEKGN
MVYLGIKGKD LCLFCAEIQG KPTLQLKLQG SQDNIGKDTC WKLVGIHTCI NLDVRESCFM
GTLDQWGIGV GRKKWKSSFQ HHHLRKKDKD FSSMRTNIGM PGRM


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