IL36B_HUMAN
ID IL36B_HUMAN Reviewed; 164 AA.
AC Q9NZH7; Q3MIH0; Q53SR6; Q7RTZ7; Q9UHA5;
DT 08-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Interleukin-36 beta;
DE AltName: Full=FIL1 eta;
DE AltName: Full=Interleukin-1 eta;
DE Short=IL-1 eta;
DE AltName: Full=Interleukin-1 family member 8;
DE Short=IL-1F8;
DE AltName: Full=Interleukin-1 homolog 2;
DE Short=IL-1H2;
DE Flags: Precursor;
GN Name=IL36B {ECO:0000312|HGNC:HGNC:15564}; Synonyms=IL1F8, IL1H2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Osteoclastoma;
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] (ISOFORM 2).
RX PubMed=10625660; DOI=10.1074/jbc.275.2.1169;
RA Smith D.E., Renshaw B.R., Ketchem R.R., Kubin M., Garka K.E., Sims J.E.;
RT "Four new members expand the IL-1 superfamily.";
RL J. Biol. Chem. 275:1169-1175(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11991722; DOI=10.1006/geno.2002.6751;
RA Nicklin M.J.H., Barton J.L., Nguyen M., Fitzgerald M.G., Duff W.G.,
RA Kornman K.;
RT "A sequence-based map of the nine genes of the human interleukin-1
RT cluster.";
RL Genomics 79:718-725(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT CYS-36.
RG SeattleSNPs variation discovery resource;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lung, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP FUNCTION, INDUCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16646978; DOI=10.1186/ar1946;
RA Magne D., Palmer G., Barton J.L., Mezin F., Talabot-Ayer D., Bas S.,
RA Duffy T., Noger M., Guerne P.A., Nicklin M.J., Gabay C.;
RT "The new IL-1 family member IL-1F8 stimulates production of inflammatory
RT mediators by synovial fibroblasts and articular chondrocytes.";
RL Arthritis Res. Ther. 8:R80-R80(2006).
RN [9]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=20300079; DOI=10.1038/oby.2010.55;
RA van Asseldonk E.J., Stienstra R., Koenen T.B., van Tits L.J., Joosten L.A.,
RA Tack C.J., Netea M.G.;
RT "The effect of the interleukin-1 cytokine family members IL-1F6 and IL-1F8
RT on adipocyte differentiation.";
RL Obesity 18:2234-2236(2010).
RN [10]
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 [11]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=21242515; DOI=10.4049/jimmunol.1003162;
RA Johnston A., Xing X., Guzman A.M., Riblett M., Loyd C.M., Ward N.L.,
RA Wohn C., Prens E.P., Wang F., Maier L.E., Kang S., Voorhees J.J.,
RA Elder J.T., Gudjonsson J.E.;
RT "IL-1F5, -F6, -F8, and -F9: a novel IL-1 family signaling system that is
RT active in psoriasis and promotes keratinocyte antimicrobial peptide
RT expression.";
RL J. Immunol. 186:2613-2622(2011).
RN [12]
RP FUNCTION.
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 [13]
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).
RN [14]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH TMED10.
RX PubMed=32272059; DOI=10.1016/j.cell.2020.03.031;
RA Zhang M., Liu L., Lin X., Wang Y., Li Y., Guo Q., Li S., Sun Y., Tao X.,
RA Zhang D., Lv X., Zheng L., Ge L.;
RT "A Translocation Pathway for Vesicle-Mediated Unconventional Protein
RT Secretion.";
RL Cell 181:637-652(2020).
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-defensins 4 and 103 as
CC well as a number of matrix metalloproteases. Seems to be involved in
CC skin inflammatory response by acting on keratinocytes, dendritic cells
CC and indirectly on T-cells to drive tissue infiltration, cell maturation
CC and cell proliferation. In cultured keratinocytes induces the
CC expression of macrophage, T-cell, and neutrophil chemokines, such as
CC CCL3, CCL4, CCL5, CCL2, CCL17, CCL22, CL20, CCL5, CCL2, CCL17, CCL22,
CC CXCL8, CCL20 and CXCL1, and the production of pro-inflammatory
CC cytokines such as TNF-alpha, IL-8 and IL-6.
CC {ECO:0000269|PubMed:16646978, ECO:0000269|PubMed:20300079,
CC ECO:0000269|PubMed:21242515, ECO:0000269|PubMed:21881584,
CC ECO:0000269|PubMed:21965679, ECO:0000269|PubMed:24829417}.
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:0000269|PubMed:32272059}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:32272059}. Secreted
CC {ECO:0000269|PubMed:16646978}. Note=The secretion is dependent on
CC protein unfolding and facilitated by the cargo receptor TMED10; it
CC results in protein translocation from the cytoplasm into the ERGIC
CC (endoplasmic reticulum-Golgi intermediate compartment) followed by
CC vesicle entry and secretion. {ECO:0000269|PubMed:32272059}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NZH7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NZH7-2; Sequence=VSP_002657;
CC -!- TISSUE SPECIFICITY: Expression at low levels in tonsil, bone marrow,
CC heart, placenta, lung, testis and colon but not in any hematopoietic
CC cell lines. Not detected in adipose tissue. Expressed at higher levels
CC in psoriatic plaques than in symptomless psoriatic skin or healthy
CC control skin. Increased levels are not detected in inflamed joint
CC tissue. {ECO:0000269|PubMed:20300079, ECO:0000269|PubMed:21242515}.
CC -!- INDUCTION: By pro-inflammatory cytokines IL1A, IL1B and TNF in synovial
CC fibroblasts. By IL1A and TNF in keratinocytes. Constitutive in
CC articular chondrocytes. {ECO:0000269|PubMed:16646978}.
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 -!- WEB RESOURCE: Name=Wikipedia; Note=Interleukin-1 entry;
CC URL="https://en.wikipedia.org/wiki/Interleukin_1";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/il1f8/";
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DR EMBL; AF200494; AAF69250.1; -; mRNA.
DR EMBL; AF201833; AAF25213.1; -; mRNA.
DR EMBL; CH471217; EAW73615.1; -; Genomic_DNA.
DR EMBL; BC101831; AAI01832.1; -; mRNA.
DR EMBL; BC101833; AAI01834.1; -; mRNA.
DR EMBL; BN000002; CAD29876.1; -; Genomic_DNA.
DR EMBL; DQ224343; ABA60896.1; -; Genomic_DNA.
DR EMBL; AC016724; AAY14989.1; -; Genomic_DNA.
DR CCDS; CCDS2109.1; -. [Q9NZH7-1]
DR CCDS; CCDS2110.1; -. [Q9NZH7-2]
DR RefSeq; NP_055253.2; NM_014438.4. [Q9NZH7-1]
DR RefSeq; NP_775270.1; NM_173178.2. [Q9NZH7-2]
DR RefSeq; XP_011509264.1; XM_011510962.1. [Q9NZH7-2]
DR AlphaFoldDB; Q9NZH7; -.
DR SMR; Q9NZH7; -.
DR BioGRID; 118053; 3.
DR STRING; 9606.ENSP00000259213; -.
DR iPTMnet; Q9NZH7; -.
DR PhosphoSitePlus; Q9NZH7; -.
DR BioMuta; IL36B; -.
DR DMDM; 25008595; -.
DR MassIVE; Q9NZH7; -.
DR PaxDb; Q9NZH7; -.
DR PeptideAtlas; Q9NZH7; -.
DR PRIDE; Q9NZH7; -.
DR ProteomicsDB; 83396; -. [Q9NZH7-2]
DR Antibodypedia; 33320; 219 antibodies from 30 providers.
DR DNASU; 27177; -.
DR Ensembl; ENST00000259213.9; ENSP00000259213.4; ENSG00000136696.11. [Q9NZH7-1]
DR Ensembl; ENST00000327407.2; ENSP00000328420.2; ENSG00000136696.11. [Q9NZH7-2]
DR GeneID; 27177; -.
DR KEGG; hsa:27177; -.
DR MANE-Select; ENST00000259213.9; ENSP00000259213.4; NM_014438.5; NP_055253.2.
DR UCSC; uc002tiq.2; human. [Q9NZH7-1]
DR CTD; 27177; -.
DR DisGeNET; 27177; -.
DR GeneCards; IL36B; -.
DR HGNC; HGNC:15564; IL36B.
DR HPA; ENSG00000136696; Group enriched (esophagus, lymphoid tissue, skin).
DR MIM; 605508; gene.
DR neXtProt; NX_Q9NZH7; -.
DR OpenTargets; ENSG00000136696; -.
DR PharmGKB; PA38391; -.
DR VEuPathDB; HostDB:ENSG00000136696; -.
DR eggNOG; ENOG502STX9; Eukaryota.
DR GeneTree; ENSGT00950000182943; -.
DR HOGENOM; CLU_137451_0_0_1; -.
DR InParanoid; Q9NZH7; -.
DR OMA; WFIATSK; -.
DR OrthoDB; 1270530at2759; -.
DR PhylomeDB; Q9NZH7; -.
DR PathwayCommons; Q9NZH7; -.
DR Reactome; R-HSA-9014826; Interleukin-36 pathway.
DR BioGRID-ORCS; 27177; 12 hits in 1053 CRISPR screens.
DR GeneWiki; IL1F8; -.
DR GenomeRNAi; 27177; -.
DR Pharos; Q9NZH7; Tbio.
DR PRO; PR:Q9NZH7; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9NZH7; protein.
DR Bgee; ENSG00000136696; Expressed in skin of leg and 31 other tissues.
DR Genevisible; Q9NZH7; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; TAS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR GO; GO:0005149; F:interleukin-1 receptor binding; TAS:ProtInc.
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:0006955; P:immune response; NAS:UniProtKB.
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:0010628; P:positive regulation of gene expression; IBA:GO_Central.
DR GO; GO:0045582; P:positive regulation of T cell differentiation; IBA:GO_Central.
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 SUPFAM; SSF50353; SSF50353; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytokine; Cytoplasm; Immunity; Inflammatory response;
KW Innate immunity; Reference proteome; Secreted.
FT PROPEP 1..4
FT /evidence="ECO:0000269|PubMed:21965679"
FT /id="PRO_0000430547"
FT CHAIN 5..164
FT /note="Interleukin-36 beta"
FT /id="PRO_0000153646"
FT VAR_SEQ 88..164
FT /note="LQGSQDNIGKDTCWKLVGIHTCINLDVRESCFMGTLDQWGIGVGRKKWKSSF
FT QHHHLRKKDKDFSSMRTNIGMPGRM -> EKNIMDLYVEKKAQKPFLFFHNKEGSTSVF
FT QSVSYPGWFIATSTTSGQPIFLTKERGITNNTNFYLDSVE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10625660,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_002657"
FT VARIANT 36
FT /note="R -> C (in dbSNP:rs34754959)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_025057"
SQ SEQUENCE 164 AA; 18522 MW; F0D2099F4A357A0A CRC64;
MNPQREAAPK SYAIRDSRQM VWVLSGNSLI AAPLSRSIKP VTLHLIACRD TEFSDKEKGN
MVYLGIKGKD LCLFCAEIQG KPTLQLKLQG SQDNIGKDTC WKLVGIHTCI NLDVRESCFM
GTLDQWGIGV GRKKWKSSFQ HHHLRKKDKD FSSMRTNIGM PGRM
