IL37_HUMAN
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 03-AUG-2022, entry version 176.
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/";
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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. [Q9NZH6-1]
DR RefSeq; XP_011509266.1; XM_011510964.2. [Q9NZH6-3]
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; Q9NZH6; -.
DR PeptideAtlas; Q9NZH6; -.
DR PRIDE; 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; 327 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 CTD; 27178; -.
DR DisGeNET; 27178; -.
DR GeneCards; IL37; -.
DR HGNC; HGNC:15563; IL37.
DR HPA; ENSG00000125571; Tissue enriched (skin).
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; 1142952at2759; -.
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 1062 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 119 other tissues.
DR Genevisible; Q9NZH6; HS.
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:0006954; P:inflammatory response; IBA:GO_Central.
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 InterPro; IPR000975; IL-1_fam.
DR InterPro; IPR003297; IL-1RA/IL-36.
DR InterPro; IPR008996; IL1/FGF.
DR PANTHER; PTHR10078; PTHR10078; 1.
DR Pfam; PF00340; IL1; 1.
DR PRINTS; PR00264; INTERLEUKIN1.
DR PRINTS; PR01360; INTRLEUKIN1X.
DR SUPFAM; SSF50353; SSF50353; 1.
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 /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
