ID IL37_HUMAN Reviewed; 218 AA. AC Q9NZH6; B5BU97; Q56AP9; Q8TD04; Q8TD05; Q9HBF2; Q9HBF3; Q9UHA6; DT 08-NOV-2002, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 24-JAN-2024, entry version 184. DE RecName: Full=Interleukin-37; DE Short=IL-37; DE AltName: Full=FIL1 zeta; DE AltName: Full=IL-1X; DE AltName: Full=Interleukin-1 family member 7; DE Short=IL-1F7; DE AltName: Full=Interleukin-1 homolog 4; DE Short=IL-1H; DE Short=IL-1H4; DE AltName: Full=Interleukin-1 zeta; DE Short=IL-1 zeta; DE AltName: Full=Interleukin-1-related protein; DE Short=IL-1RP1; DE Flags: Precursor; GN Name=IL37 {ECO:0000312|HGNC:HGNC:15563}; GN Synonyms=FIL1Z, IL1F7, IL1H4, IL1RP1; 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 B). RC TISSUE=Fetal B-cell, Fetal colon, Fetal lung, and Fetal testis; 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 B). RC TISSUE=Colon carcinoma; RA Manoj P.P., Mantovani A., Muzio M.; RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS B AND C), PROTEIN SEQUENCE OF 46-54, RP INTERACTION WITH IL18R1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND RP VARIANTS VAL-31 AND ALA-42. RX PubMed=11145836; DOI=10.1006/cyto.2000.0799; RA Pan G., Risser P., Mao W., Baldwin D.T., Zhong A.W., Filvaroff E., RA Yansura D., Lewis L., Eigenbrot C., Henzel W.J., Vandlen R.; RT "IL-1H, an interleukin 1-related protein that binds IL-18 receptor/IL- RT 1Rrp."; RL Cytokine 13:1-7(2001). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A). 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 [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS D AND E). RX PubMed=11991723; DOI=10.1006/geno.2002.6752; RA Taylor S.L., Renshaw B.R., Garka K.E., Smith D.E., Sims J.E.; RT "Genomic organization of the interleukin-1 locus."; RL Genomics 79:726-733(2002). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-31; ALA-42; LEU-108; RP TRP-152; ARG-164 AND ASN-218. RG SeattleSNPs variation discovery resource; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM D). RX PubMed=19054851; DOI=10.1038/nmeth.1273; RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B., RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., RA Nomura N.; RT "Human protein factory for converting the transcriptome into an in vitro- RT expressed proteome."; RL Nat. Methods 5:1011-1017(2008). RN [8] 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 [9] 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 [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B), AND VARIANTS VAL-31 AND RP ALA-42. RC TISSUE=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 [11] RP FUNCTION, SUBCELLULAR LOCATION, MATURATION BY CASP1, AND INDUCTION. RX PubMed=18390730; DOI=10.4049/jimmunol.180.8.5477; RA Sharma S., Kulk N., Nold M.F., Graf R., Kim S.H., Reinhardt D., RA Dinarello C.A., Bufler P.; RT "The IL-1 family member 7b translocates to the nucleus and down-regulates RT proinflammatory cytokines."; RL J. Immunol. 180:5477-5482(2008). RN [12] RP FUNCTION, INTERACTION WITH SMAD3, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, RP AND INDUCTION. RX PubMed=20935647; DOI=10.1038/ni.1944; RA Nold M.F., Nold-Petry C.A., Zepp J.A., Palmer B.E., Bufler P., RA Dinarello C.A.; RT "IL-37 is a fundamental inhibitor of innate immunity."; RL Nat. Immunol. 11:1014-1022(2010). RN [13] 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). RN [14] RP INVOLVEMENT IN IBD31, VARIANT IBD31 THR-177, CHARACTERIZATION OF VARIANT RP IBD31 THR-177, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=33674380; DOI=10.1073/pnas.2009217118; RA Zhang Z.Z., Zhang Y., He T., Sweeney C.L., Baris S., Karakoc-Aydiner E., RA Yao Y., Ertem D., Matthews H.F., Gonzaga-Jauregui C., Malech H.L., Su H.C., RA Ozen A., Smith K.G.C., Lenardo M.J.; RT "Homozygous IL37 mutation associated with infantile inflammatory bowel RT disease."; RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021). CC -!- FUNCTION: Immune regulatory cytokine that acts as a suppressor of CC innate inflammatory and immune responses involved in curbing excessive CC inflammation. Signaling can occur via two mechanisms, intracellularly CC through nuclear translocation with SMAD3 and extracellularly after CC secretion and binding to its receptor composed of IL18R1 and IL18RAP. CC Suppresses, or reduces, pro-inflammatory cytokine production, including CC IL1A and IL6, as well as CCL12, CSF1, CSF2, CXCL13, IL1B, IL23A and CC IL1RN, but spares anti-inflammatory cytokines. Inhibits dendritic cell CC activation. {ECO:0000269|PubMed:18390730, ECO:0000269|PubMed:20935647, CC ECO:0000269|PubMed:33674380}. CC -!- SUBUNIT: Interacts with SMAD3. Binds IL18R1, but not to IL1R1, with CC lower affinity than IL18, and does not seem to act as a receptor CC antagonist for IL18. Interacts with cargo receptor TMED10; the CC interaction mediates the translocation from the cytoplasm into the CC ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and CC thereby secretion (PubMed:32272059). {ECO:0000269|PubMed:11145836, CC ECO:0000269|PubMed:20935647, ECO:0000269|PubMed:32272059}. CC -!- INTERACTION: CC Q9NZH6; P28329-3: CHAT; NbExp=3; IntAct=EBI-3862125, EBI-25837549; CC Q9NZH6; P22607: FGFR3; NbExp=3; IntAct=EBI-3862125, EBI-348399; CC Q9NZH6; Q14957: GRIN2C; NbExp=3; IntAct=EBI-3862125, EBI-8285963; CC Q9NZH6; P06396: GSN; NbExp=3; IntAct=EBI-3862125, EBI-351506; CC Q9NZH6; O43741: PRKAB2; NbExp=5; IntAct=EBI-3862125, EBI-1053424; CC Q9NZH6; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-3862125, EBI-741480; CC Q9NZH6; Q9Y649; NbExp=3; IntAct=EBI-3862125, EBI-25900580; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:18390730, CC ECO:0000269|PubMed:20935647}. Nucleus {ECO:0000269|PubMed:18390730, CC ECO:0000269|PubMed:20935647, ECO:0000269|PubMed:33674380}. Secreted CC {ECO:0000269|PubMed:11145836, ECO:0000269|PubMed:18390730, CC ECO:0000269|PubMed:32272059, ECO:0000269|PubMed:33674380}. CC Note=Stimulation with IL1B leads to colocalization with SMAD3 mostly in CC perinuclear regions (PubMed:20935647, PubMed:33674380). Only the CASP1- CC cleaved mature form translocates into the nucleus upon LPS stimulation CC (PubMed:18390730). The secretion is dependent on protein unfolding and CC facilitated by the cargo receptor TMED10; it results in protein CC translocation from the cytoplasm into the ERGIC (endoplasmic reticulum- CC Golgi intermediate compartment) followed by vesicle entry and secretion CC (PubMed:32272059, PubMed:33674380). {ECO:0000269|PubMed:18390730, CC ECO:0000269|PubMed:20935647, ECO:0000269|PubMed:32272059, CC ECO:0000269|PubMed:33674380}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=B; Synonyms=IL-1F7b, IL-HLa; CC IsoId=Q9NZH6-1; Sequence=Displayed; CC Name=A; CC IsoId=Q9NZH6-2; Sequence=VSP_002653; CC Name=C; Synonyms=IL-HS; CC IsoId=Q9NZH6-3; Sequence=VSP_002656; CC Name=D; Synonyms=IL1F7d; CC IsoId=Q9NZH6-4; Sequence=VSP_002654; CC Name=E; Synonyms=IL1F7e; CC IsoId=Q9NZH6-5; Sequence=VSP_002655; CC -!- TISSUE SPECIFICITY: In general, low constitutive expression, if any, in CC healthy tissues; high expression in inflammatory counterparts, CC including in synovial tissues from individuals with active rheumatoid CC arthritis. Isoform A, isoform B and isoform C are expressed in testis, CC colon, placenta, lung and lymph node. Isoform D and isoform E were CC found only in testis and bone marrow. Whereas only isoform A is found CC in brain, only isoform B in kidney and only isoform C in heart. CC {ECO:0000269|PubMed:11145836, ECO:0000269|PubMed:20935647}. CC -!- INDUCTION: Highly induced by bacterial lipopolysaccharides (LPS) and CC TGFB1, more moderately by IFNG, IL18, IL1B, TNF and the dinucleotide CC CpG (at protein level). Constitutive expression in bone marrow CC macrophages is down-regulated in the presence of IL4 and CSF2. Induced CC by phorbol myristate acetate (PMA) in different cell lines. CC {ECO:0000269|PubMed:18390730, ECO:0000269|PubMed:20935647}. CC -!- PTM: Proteolytically converted to the mature form by CASP1. CC -!- DISEASE: Inflammatory bowel disease 31, autosomal recessive (IBD31) CC [MIM:619398]: A form of inflammatory bowel disease, a chronic, CC relapsing inflammation of the gastrointestinal tract with a complex CC etiology and a multifactorial inheritance pattern. It is subdivided CC into Crohn disease and ulcerative colitis phenotypes. Crohn disease may CC affect any part of the gastrointestinal tract from the mouth to the CC anus, but most frequently it involves the terminal ileum and colon. CC Bowel inflammation is transmural and discontinuous; it may contain CC granulomas or be associated with intestinal or perianal fistulas. In CC contrast, in ulcerative colitis, the inflammation is continuous and CC limited to rectal and colonic mucosal layers; fistulas and granulomas CC are not observed. Both diseases include extraintestinal inflammation of CC the skin, eyes, or joints. IBD31 patients suffer from infantile CC ulcerative colitis and present with recurrent bloody diarrhea with CC anemia and leukocytosis, extensive lymphoplasmocytic infiltration, CC cryptitis, and apoptotic crypt abcesses throughout the colon and CC rectum. {ECO:0000269|PubMed:33674380}. Note=The disease is caused by CC variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform B]: The name IL-HL refers to isoform B CC containing polymorphisms Val-31 and Ala-42. CC {ECO:0000305|PubMed:11145836}. 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/il1f7/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF200496; AAF69252.1; -; mRNA. DR EMBL; AF167368; AAG29344.1; -; mRNA. DR EMBL; AF251118; AAG14420.1; -; mRNA. DR EMBL; AF251119; AAG14421.1; -; mRNA. DR EMBL; AF251120; AAG14422.1; -; mRNA. DR EMBL; AF201832; AAF25212.1; -; mRNA. DR EMBL; AY071840; AAL67151.1; -; mRNA. DR EMBL; AY071841; AAL67154.1; -; mRNA. DR EMBL; AY973625; AAX59036.1; -; Genomic_DNA. DR EMBL; AB451333; BAG70147.1; -; mRNA. DR EMBL; AB451478; BAG70292.1; -; mRNA. DR EMBL; AC079753; AAX88889.1; -; Genomic_DNA. DR EMBL; CH471217; EAW73609.1; -; Genomic_DNA. DR EMBL; BC020637; AAH20637.1; -; mRNA. DR CCDS; CCDS2103.1; -. [Q9NZH6-1] DR CCDS; CCDS2104.1; -. [Q9NZH6-4] DR CCDS; CCDS2105.1; -. [Q9NZH6-5] DR CCDS; CCDS2106.1; -. [Q9NZH6-3] DR CCDS; CCDS2107.1; -. [Q9NZH6-2] DR RefSeq; NP_055254.2; NM_014439.3. [Q9NZH6-1] DR RefSeq; NP_775294.1; NM_173202.1. [Q9NZH6-4] DR RefSeq; NP_775295.1; NM_173203.1. [Q9NZH6-5] DR RefSeq; NP_775296.1; NM_173204.1. [Q9NZH6-3] DR RefSeq; NP_775297.1; NM_173205.1. [Q9NZH6-2] DR RefSeq; XP_011509265.1; XM_011510963.2. DR RefSeq; XP_011509266.1; XM_011510964.2. DR PDB; 5HN1; X-ray; 2.25 A; A/B=46-218. DR PDB; 6NCU; X-ray; 3.50 A; A/B=53-206. DR PDBsum; 5HN1; -. DR PDBsum; 6NCU; -. DR AlphaFoldDB; Q9NZH6; -. DR SMR; Q9NZH6; -. DR BioGRID; 118054; 40. DR IntAct; Q9NZH6; 14. DR STRING; 9606.ENSP00000263326; -. DR iPTMnet; Q9NZH6; -. DR PhosphoSitePlus; Q9NZH6; -. DR BioMuta; IL37; -. DR DMDM; 25008593; -. DR MassIVE; Q9NZH6; -. DR PaxDb; 9606-ENSP00000263326; -. DR PeptideAtlas; Q9NZH6; -. DR ProteomicsDB; 83390; -. [Q9NZH6-1] DR ProteomicsDB; 83391; -. [Q9NZH6-2] DR ProteomicsDB; 83392; -. [Q9NZH6-3] DR ProteomicsDB; 83393; -. [Q9NZH6-4] DR ProteomicsDB; 83394; -. [Q9NZH6-5] DR Antibodypedia; 33300; 372 antibodies from 33 providers. DR DNASU; 27178; -. DR Ensembl; ENST00000263326.8; ENSP00000263326.3; ENSG00000125571.10. [Q9NZH6-1] DR Ensembl; ENST00000311328.2; ENSP00000309883.2; ENSG00000125571.10. [Q9NZH6-2] DR Ensembl; ENST00000349806.7; ENSP00000263328.3; ENSG00000125571.10. [Q9NZH6-5] DR Ensembl; ENST00000352179.7; ENSP00000263327.3; ENSG00000125571.10. [Q9NZH6-4] DR Ensembl; ENST00000353225.7; ENSP00000309208.3; ENSG00000125571.10. [Q9NZH6-3] DR GeneID; 27178; -. DR KEGG; hsa:27178; -. DR MANE-Select; ENST00000263326.8; ENSP00000263326.3; NM_014439.4; NP_055254.2. DR UCSC; uc002tij.4; human. [Q9NZH6-1] DR AGR; HGNC:15563; -. DR CTD; 27178; -. DR DisGeNET; 27178; -. DR GeneCards; IL37; -. DR HGNC; HGNC:15563; IL37. DR HPA; ENSG00000125571; Tissue enriched (skin). DR MalaCards; IL37; -. DR MIM; 605510; gene. DR MIM; 619398; phenotype. DR neXtProt; NX_Q9NZH6; -. DR OpenTargets; ENSG00000125571; -. DR PharmGKB; PA38390; -. DR VEuPathDB; HostDB:ENSG00000125571; -. DR eggNOG; ENOG502TCXA; Eukaryota. DR GeneTree; ENSGT00950000182943; -. DR HOGENOM; CLU_095373_0_0_1; -. DR InParanoid; Q9NZH6; -. DR OMA; HAGPRVK; -. DR OrthoDB; 5087445at2759; -. DR PhylomeDB; Q9NZH6; -. DR TreeFam; TF300203; -. DR PathwayCommons; Q9NZH6; -. DR Reactome; R-HSA-9008059; Interleukin-37 signaling. DR Reactome; R-HSA-9012546; Interleukin-18 signaling. DR SignaLink; Q9NZH6; -. DR BioGRID-ORCS; 27178; 8 hits in 1139 CRISPR screens. DR GeneWiki; IL1F7; -. DR GenomeRNAi; 27178; -. DR Pharos; Q9NZH6; Tbio. DR PRO; PR:Q9NZH6; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q9NZH6; Protein. DR Bgee; ENSG00000125571; Expressed in upper arm skin and 120 other cell types or tissues. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005576; C:extracellular region; TAS:UniProtKB. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central. DR GO; GO:0005149; F:interleukin-1 receptor binding; TAS:UniProtKB. 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:0002437; P:inflammatory response to antigenic stimulus; IBA:GO_Central. DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IGI:ARUK-UCL. DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IMP:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IBA:GO_Central. DR GO; GO:0050727; P:regulation of inflammatory response; IGI:ARUK-UCL. DR Gene3D; 2.80.10.50; -; 1. DR InterPro; IPR000975; IL-1_fam. DR InterPro; IPR003297; IL-1RA/IL-36. DR InterPro; IPR008996; IL1/FGF. DR PANTHER; PTHR10078; INTERLEUKIN-1 FAMILY MEMBER; 1. DR PANTHER; PTHR10078:SF31; INTERLEUKIN-37; 1. DR Pfam; PF00340; IL1; 1. DR PRINTS; PR00264; INTERLEUKIN1. DR PRINTS; PR01360; INTRLEUKIN1X. DR SMART; SM00125; IL1; 1. DR SUPFAM; SSF50353; Cytokine; 1. DR Genevisible; Q9NZH6; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytokine; Cytoplasm; KW Direct protein sequencing; Disease variant; Nucleus; Reference proteome; KW Secreted. FT PROPEP 1..45 FT /note="Removed in mature form" FT /evidence="ECO:0000269|PubMed:11145836" FT /id="PRO_0000015335" FT CHAIN 46..218 FT /note="Interleukin-37" FT /id="PRO_0000015336" FT REGION 1..40 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 1..49 FT /note="MSFVGENSGVKMGSEDWEKDEPQCCLEDPAGSPLEPGPSLPTMNFVHTS -> FT MSGCDRRETETKGKNSFKKRLRG (in isoform A)" FT /evidence="ECO:0000303|PubMed:10625660" FT /id="VSP_002653" FT VAR_SEQ 28..88 FT /note="Missing (in isoform E)" FT /evidence="ECO:0000303|PubMed:11991723" FT /id="VSP_002655" FT VAR_SEQ 28..49 FT /note="DPAGSPLEPGPSLPTMNFVHTS -> G (in isoform D)" FT /evidence="ECO:0000303|PubMed:11991723, FT ECO:0000303|PubMed:19054851" FT /id="VSP_002654" FT VAR_SEQ 49..89 FT /note="SPKVKNLNPKKFSIHDQDHKVLVLDSGNLIAVPDKNYIRPE -> K (in FT isoform C)" FT /evidence="ECO:0000303|PubMed:11145836" FT /id="VSP_002656" FT VARIANT 31 FT /note="G -> V (in dbSNP:rs3811046)" FT /evidence="ECO:0000269|PubMed:11145836, FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.6" FT /id="VAR_014260" FT VARIANT 42 FT /note="T -> A (in dbSNP:rs3811047)" FT /evidence="ECO:0000269|PubMed:11145836, FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.6" FT /id="VAR_014261" FT VARIANT 50 FT /note="P -> R (in dbSNP:rs2708943)" FT /id="VAR_049574" FT VARIANT 54 FT /note="N -> S (in dbSNP:rs2723183)" FT /id="VAR_049575" FT VARIANT 108 FT /note="P -> L (in dbSNP:rs2723187)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_023334" FT VARIANT 152 FT /note="R -> W (in dbSNP:rs28947200)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_023335" FT VARIANT 164 FT /note="W -> R (in dbSNP:rs2708947)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_023336" FT VARIANT 177 FT /note="I -> T (in IBD31; decreased stability; increased FT degradation; decreased localization to the nucleus; FT decreased localization to the extracellular space; FT decreased function in regulation of inflammatory response; FT dbSNP:rs750833867)" FT /evidence="ECO:0000269|PubMed:33674380" FT /id="VAR_086000" FT VARIANT 218 FT /note="D -> N (in dbSNP:rs2723192)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_023337" FT STRAND 58..73 FT /evidence="ECO:0007829|PDB:5HN1" FT STRAND 76..81 FT /evidence="ECO:0007829|PDB:5HN1" FT STRAND 91..95 FT /evidence="ECO:0007829|PDB:5HN1" FT STRAND 103..105 FT /evidence="ECO:0007829|PDB:6NCU" FT STRAND 107..113 FT /evidence="ECO:0007829|PDB:5HN1" FT TURN 114..117 FT /evidence="ECO:0007829|PDB:5HN1" FT STRAND 118..123 FT /evidence="ECO:0007829|PDB:5HN1" FT STRAND 128..130 FT /evidence="ECO:0007829|PDB:6NCU" FT STRAND 132..137 FT /evidence="ECO:0007829|PDB:5HN1" FT HELIX 140..144 FT /evidence="ECO:0007829|PDB:5HN1" FT HELIX 148..151 FT /evidence="ECO:0007829|PDB:5HN1" FT HELIX 152..154 FT /evidence="ECO:0007829|PDB:5HN1" FT STRAND 156..161 FT /evidence="ECO:0007829|PDB:5HN1" FT STRAND 164..172 FT /evidence="ECO:0007829|PDB:5HN1" FT STRAND 176..178 FT /evidence="ECO:0007829|PDB:5HN1" FT STRAND 181..186 FT /evidence="ECO:0007829|PDB:5HN1" FT STRAND 188..191 FT /evidence="ECO:0007829|PDB:5HN1" FT HELIX 196..198 FT /evidence="ECO:0007829|PDB:5HN1" FT STRAND 201..205 FT /evidence="ECO:0007829|PDB:5HN1" SQ SEQUENCE 218 AA; 24126 MW; 96E089310D2CEA68 CRC64; MSFVGENSGV KMGSEDWEKD EPQCCLEDPA GSPLEPGPSL PTMNFVHTSP KVKNLNPKKF SIHDQDHKVL VLDSGNLIAV PDKNYIRPEI FFALASSLSS ASAEKGSPIL LGVSKGEFCL YCDKDKGQSH PSLQLKKEKL MKLAAQKESA RRPFIFYRAQ VGSWNMLESA AHPGWFICTS CNCNEPVGVT DKFENRKHIE FSFQPVCKAE MSPSEVSD //