IL1RA_HUMAN
ID IL1RA_HUMAN Reviewed; 177 AA.
AC P18510; A8K4G1; Q14628; Q53SC2; Q7RTZ4; Q96GD6; Q9UPC0;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 1.
DT 03-AUG-2022, entry version 227.
DE RecName: Full=Interleukin-1 receptor antagonist protein;
DE Short=IL-1RN;
DE Short=IL-1ra;
DE Short=IRAP;
DE AltName: Full=ICIL-1RA;
DE AltName: Full=IL1 inhibitor;
DE AltName: INN=Anakinra;
DE Flags: Precursor;
GN Name=IL1RN; Synonyms=IL1F3, IL1RA;
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).
RX PubMed=2139180; DOI=10.1038/344633a0;
RA Carter D.B., Deibel M.R. Jr., Dunn C.J., Tomich C.S.C., Laborde A.L.,
RA Slightom J.L., Berger A.E., Bienkowski M.J., Sun F.F., McEwan R.N.,
RA Harris P.K.W., Yem A.W., Waszak G.A., Chosay J.G., Sieu L.C., Hardee M.M.,
RA Zurcher-Neely H.A., Reardon I.M., Heinrikson R.L., Truesdell S.E.,
RA Shelly J.A., Eessalu T.E., Taylor B.M., Tracey D.E.;
RT "Purification, cloning, expression and biological characterization of an
RT interleukin-1 receptor antagonist protein.";
RL Nature 344:633-638(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=2137201; DOI=10.1038/343341a0;
RA Eisenberg S.P., Evans R.J., Arend W.P., Verderber E., Brewer M.T.,
RA Hannum C.H., Thompson R.C.;
RT "Primary structure and functional expression from complementary DNA of a
RT human interleukin-1 receptor antagonist.";
RL Nature 343:341-346(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=1828896; DOI=10.1073/pnas.88.12.5232;
RA Eisenberg S.P., Brewer M.T., Verderber E., Heimdal P., Brandhuber B.J.,
RA Thompson R.C.;
RT "Interleukin 1 receptor antagonist is a member of the interleukin 1 gene
RT family: evolution of a cytokine control mechanism.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:5232-5236(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=1385987; DOI=10.1016/1043-4666(92)90041-o;
RA Lennard A., Gorman P., Carrier M., Griffiths S., Scotney H., Sheer D.,
RA Solari R.;
RT "Cloning and chromosome mapping of the human interleukin-1 receptor
RT antagonist gene.";
RL Cytokine 4:83-89(1992).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 3).
RX PubMed=8992991;
RA Jenkins J.K., Drong R.F., Shuck M.E., Bienkowski M.J., Slightom J.L.,
RA Arend W.P., Smith M.F. Jr.;
RT "Intracellular IL-1 receptor antagonist promoter: cell type-specific and
RT inducible regulatory regions.";
RL J. Immunol. 158:748-755(1997).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=1827201; DOI=10.1073/pnas.88.9.3681;
RA Haskill S., Martin G., van Le L., Morris J., Peace A., Bigler C.F.,
RA Jaffe G.J., Hammerberg C., Sporn S.A., Fong S., Arend W.P., Ralph P.;
RT "cDNA cloning of an intracellular form of the human interleukin 1 receptor
RT antagonist associated with epithelium.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:3681-3685(1991).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RX PubMed=7629520; DOI=10.1084/jem.182.2.623;
RA Muzio M., Polentarutti N., Sironi M., Poli G., De Gioia L., Introna M.,
RA Mantovani A., Colotta F.;
RT "Cloning and characterization of a new isoform of the interleukin 1
RT receptor antagonist.";
RL J. Exp. Med. 182:623-628(1995).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG SeattleSNPs variation discovery resource;
RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Esophagus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [10]
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 [11]
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 [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Pancreas;
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 [13]
RP PROTEIN SEQUENCE OF 26-45, AND GLYCOSYLATION AT ASN-109.
RX PubMed=2137200; DOI=10.1038/343336a0;
RA Hannum C.H., Wilcox C.J., Arend W.P., Joslin F.G., Dripps D.J.,
RA Heimdal P.L., Armes L.G., Sommer A., Eisenberg S.P., Thompson R.C.;
RT "Interleukin-1 receptor antagonist activity of a human interleukin-1
RT inhibitor.";
RL Nature 343:336-340(1990).
RN [14]
RP PROTEIN SEQUENCE OF 26-52.
RX PubMed=2143761; DOI=10.1016/s0021-9258(18)77331-6;
RA Bienkowski M.J., Eessalu T.E., Berger A.E., Truesdell S.E., Shelly J.A.,
RA Laborde A.L., Zurcher-Neely H.A., Reardon I.M., Heinrikson R.L.,
RA Chosay J.G., Tracey D.E.;
RT "Purification and characterization of interleukin 1 receptor level
RT antagonist proteins from THP-1 cells.";
RL J. Biol. Chem. 265:14505-14511(1990).
RN [15]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 35-177 (ISOFORM 4).
RX PubMed=9514884; DOI=10.1006/bbrc.1998.8217;
RA Weissbach L., Tran K., Colquhoun S.A., Champliaud M.-F., Towle C.A.;
RT "Detection of an interleukin-1 intracellular receptor antagonist mRNA
RT variant.";
RL Biochem. Biophys. Res. Commun. 244:91-95(1998).
RN [16]
RP RECEPTOR-BINDING.
RX PubMed=7989776;
RA Giri J.G., Wells J., Dower S.K., McCall C.E., Guzman R.N., Slack J.,
RA Bird T.A., Shanebeck K., Grabstein K.H., Sims J.E., Alderson M.R.;
RT "Elevated levels of shed type II IL-1 receptor in sepsis. Potential role
RT for type II receptor in regulation of IL-1 responses.";
RL J. Immunol. 153:5802-5809(1994).
RN [17]
RP FUNCTION.
RX PubMed=7775431; DOI=10.1074/jbc.270.23.13757;
RA Greenfeder S.A., Nunes P., Kwee L., Labow M., Chizzonite R.A., Ju G.;
RT "Molecular cloning and characterization of a second subunit of the
RT interleukin 1 receptor complex.";
RL J. Biol. Chem. 270:13757-13765(1995).
RN [18]
RP IDENTIFICATION (ISOFORM 2).
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 [19]
RP INVOLVEMENT IN MVCD4.
RX PubMed=8786086; DOI=10.1007/bf02185776;
RA Blakemore A.I.F., Cox A., Gonzalez A.-M., Maskil J.K., Hughes M.E.,
RA Wilson R.M., Ward J.D., Duff G.W.;
RT "Interleukin-1 receptor antagonist allele (IL1RN*2) associated with
RT nephropathy in diabetes mellitus.";
RL Hum. Genet. 97:369-374(1996).
RN [20]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-109.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [21]
RP INVOLVEMENT IN DIRA.
RX PubMed=19494218; DOI=10.1056/nejmoa0807865;
RA Aksentijevich I., Masters S.L., Ferguson P.J., Dancey P., Frenkel J.,
RA van Royen-Kerkhoff A., Laxer R., Tedgard U., Cowen E.W., Pham T.H.,
RA Booty M., Estes J.D., Sandler N.G., Plass N., Stone D.L., Turner M.L.,
RA Hill S., Butman J.A., Schneider R., Babyn P., El-Shanti H.I., Pope E.,
RA Barron K., Bing X., Laurence A., Lee C.C., Chapelle D., Clarke G.I.,
RA Ohson K., Nicholson M., Gadina M., Yang B., Korman B.D., Gregersen P.K.,
RA van Hagen P.M., Hak A.E., Huizing M., Rahman P., Douek D.C., Remmers E.F.,
RA Kastner D.L., Goldbach-Mansky R.;
RT "An autoinflammatory disease with deficiency of the interleukin-1-receptor
RT antagonist.";
RL N. Engl. J. Med. 360:2426-2437(2009).
RN [22]
RP SUBCELLULAR LOCATION.
RX PubMed=32384874; DOI=10.1186/s12879-020-05047-x;
RA Zhang H., Cao X., Xin H., Liu J., Pan S., Guan L., Shen F., Liu Z.,
RA Wang D., Guan X., Yan J., Feng B., Li N., Jin Q., Gao L.;
RT "Serum level of IL-1ra was associated with the treatment of latent
RT tuberculosis infection in a Chinese population.";
RL BMC Infect. Dis. 20:330-330(2020).
RN [23]
RP STRUCTURE BY NMR.
RX PubMed=1534997; DOI=10.1021/bi00138a001;
RA Stockman B.J., Scahill T.A., Roy M., Ulrich E.L., Strakalaitis N.A.,
RA Brunner D.P., Yem A.W., Deibel M.R. Jr.;
RT "Secondary structure and topology of interleukin-1 receptor antagonist
RT protein determined by heteronuclear three-dimensional NMR spectroscopy.";
RL Biochemistry 31:5237-5244(1992).
RN [24]
RP STRUCTURE BY NMR.
RX PubMed=8045306; DOI=10.1016/0014-5793(94)00643-1;
RA Stockman B.J., Scahill T.A., Strakalaitis N.A., Brunner D.P., Yem A.W.,
RA Deibel M.R. Jr.;
RT "Solution structure of human interleukin-1 receptor antagonist protein.";
RL FEBS Lett. 349:79-83(1994).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=8175703; DOI=10.1016/s0021-9258(18)99957-6;
RA Vigers G.P.A., Caffes P., Evans R.J., Thompson R.C., Eisenberg S.P.,
RA Brandhuber B.J.;
RT "X-ray structure of interleukin-1 receptor antagonist at 2.0-A
RT resolution.";
RL J. Biol. Chem. 269:12874-12879(1994).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
RX PubMed=7867645; DOI=10.1111/j.1432-1033.1995.tb20209.x;
RA Schreuder H.A., Rondeau J.-M., Tardif C., Soffientini A., Sarubbi E.,
RA Akeson A., Bowlin T.L., Yanofsky S., Barrett R.W.;
RT "Refined crystal structure of the interleukin-1 receptor antagonist.
RT Presence of a disulfide link and a cis-proline.";
RL Eur. J. Biochem. 227:838-847(1995).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 32-177 IN COMPLEX WITH IL1R.
RX PubMed=9062194; DOI=10.1038/386194a0;
RA Schreuder H., Tardif C., Trump-Kallmeyer S., Soffientini A., Sarubbi E.,
RA Akeson A., Bowlin T., Yanofsky S., Barrett R.W.;
RT "A new cytokine-receptor binding mode revealed by the crystal structure of
RT the IL-1 receptor with an antagonist.";
RL Nature 386:194-200(1997).
RN [28]
RP VARIANT [LARGE SCALE ANALYSIS] THR-124.
RX PubMed=18987736; DOI=10.1038/nature07485;
RA Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K.,
RA Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L.,
RA Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A.,
RA Abbott S., Locke D., Hillier L.W., Miner T., Fulton L., Magrini V.,
RA Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R.,
RA Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E.,
RA Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S.,
RA Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A.,
RA DiPersio J.F., Wilson R.K.;
RT "DNA sequencing of a cytogenetically normal acute myeloid leukaemia
RT genome.";
RL Nature 456:66-72(2008).
CC -!- FUNCTION: Anti-inflammatory antagonist of interleukin-1 family of
CC proinflammatory cytokines such as interleukin-1beta/IL1B and
CC interleukin-1alpha/IL1A. Protects from immune dysregulation and
CC uncontrolled systemic inflammation triggered by IL1 for a range of
CC innate stimulatory agents such as pathogens.
CC {ECO:0000250|UniProtKB:P25085, ECO:0000269|PubMed:7775431}.
CC -!- INTERACTION:
CC P18510; Q9NYB0: TERF2IP; NbExp=2; IntAct=EBI-1026330, EBI-750109;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Secreted
CC {ECO:0000269|PubMed:32384874}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Cytoplasm.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P18510-1; Sequence=Displayed;
CC Name=2; Synonyms=icIL-1ra;
CC IsoId=P18510-2; Sequence=VSP_002649;
CC Name=3; Synonyms=icIL-1ra type II;
CC IsoId=P18510-3; Sequence=VSP_002650;
CC Name=4;
CC IsoId=P18510-4; Sequence=VSP_002651;
CC -!- TISSUE SPECIFICITY: The intracellular form of IL1RN is predominantly
CC expressed in epithelial cells.
CC -!- DISEASE: Microvascular complications of diabetes 4 (MVCD4)
CC [MIM:612628]: Pathological conditions that develop in numerous tissues
CC and organs as a consequence of diabetes mellitus. They include diabetic
CC retinopathy, diabetic nephropathy leading to end-stage renal disease,
CC and diabetic neuropathy. Diabetic retinopathy remains the major cause
CC of new-onset blindness among diabetic adults. It is characterized by
CC vascular permeability and increased tissue ischemia and angiogenesis.
CC {ECO:0000269|PubMed:8786086}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry.
CC -!- DISEASE: Interleukin 1 receptor antagonist deficiency (DIRA)
CC [MIM:612852]: A rare autoinflammatory disease of skin and bone
CC resulting in sterile multifocal osteomyelitis, periostitis, and
CC pustulosis from birth. The term autoinflammatory disease describes a
CC group of disorders characterized by attacks of seemingly unprovoked
CC inflammation without significant levels of autoantibodies and
CC autoreactive T-cells. {ECO:0000269|PubMed:19494218}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
CC -!- PHARMACEUTICAL: Available under the name Kineret (Amgen). Used for the
CC reduction in signs and symptoms and slowing the progression of
CC structural damage in moderately to severely active rheumatoid
CC arthritis.
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/il1rn/";
CC -!- WEB RESOURCE: Name=Kineret professional medical information;
CC URL="https://www.rxlist.com/kineret-drug.htm";
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DR EMBL; X53296; CAA37386.1; -; mRNA.
DR EMBL; X52015; CAA36262.1; -; mRNA.
DR EMBL; M63099; AAB41943.1; -; Genomic_DNA.
DR EMBL; X64532; CAA45832.1; -; Genomic_DNA.
DR EMBL; U65590; AAB92270.1; -; Genomic_DNA.
DR EMBL; U65590; AAB92268.1; -; Genomic_DNA.
DR EMBL; U65590; AAB92269.1; -; Genomic_DNA.
DR EMBL; M55646; AAA59138.1; -; mRNA.
DR EMBL; X84348; CAA59087.1; -; mRNA.
DR EMBL; AY196903; AAN87150.1; -; Genomic_DNA.
DR EMBL; AK290898; BAF83587.1; -; mRNA.
DR EMBL; AK290926; BAF83615.1; -; mRNA.
DR EMBL; AC024704; AAX93278.1; -; Genomic_DNA.
DR EMBL; CH471217; EAW73625.1; -; Genomic_DNA.
DR EMBL; BC009745; AAH09745.1; -; mRNA.
DR EMBL; AF043143; AAC39672.1; -; mRNA.
DR EMBL; BN000002; CAD29879.1; -; Genomic_DNA.
DR CCDS; CCDS2113.1; -. [P18510-2]
DR CCDS; CCDS2114.1; -. [P18510-3]
DR CCDS; CCDS2115.1; -. [P18510-4]
DR CCDS; CCDS46396.1; -. [P18510-1]
DR PIR; A40956; A30368.
DR PIR; I37893; A39386.
DR RefSeq; NP_000568.1; NM_000577.4. [P18510-2]
DR RefSeq; NP_001305843.1; NM_001318914.1. [P18510-4]
DR RefSeq; NP_776213.1; NM_173841.2. [P18510-3]
DR RefSeq; NP_776214.1; NM_173842.2. [P18510-1]
DR RefSeq; NP_776215.1; NM_173843.2. [P18510-4]
DR RefSeq; XP_005263718.1; XM_005263661.4.
DR RefSeq; XP_011509423.1; XM_011511121.1. [P18510-4]
DR PDB; 1ILR; X-ray; 2.10 A; 1/2=26-177.
DR PDB; 1ILT; X-ray; 2.00 A; A/B=26-177.
DR PDB; 1IRA; X-ray; 2.70 A; X=26-177.
DR PDB; 1IRP; NMR; -; A=26-177.
DR PDB; 2IRT; X-ray; 3.20 A; A/B=26-177.
DR PDBsum; 1ILR; -.
DR PDBsum; 1ILT; -.
DR PDBsum; 1IRA; -.
DR PDBsum; 1IRP; -.
DR PDBsum; 2IRT; -.
DR AlphaFoldDB; P18510; -.
DR SMR; P18510; -.
DR BioGRID; 109772; 56.
DR IntAct; P18510; 8.
DR STRING; 9606.ENSP00000259206; -.
DR BindingDB; P18510; -.
DR ChEMBL; CHEMBL4523191; -.
DR DrugBank; DB06372; Rilonacept.
DR DrugCentral; P18510; -.
DR Allergome; 11858; Hom s Anakinra.
DR GlyConnect; 1947; 2 N-Linked glycans (1 site).
DR GlyGen; P18510; 1 site, 2 N-linked glycans (1 site).
DR iPTMnet; P18510; -.
DR PhosphoSitePlus; P18510; -.
DR BioMuta; IL1RN; -.
DR DMDM; 124312; -.
DR EPD; P18510; -.
DR jPOST; P18510; -.
DR MassIVE; P18510; -.
DR MaxQB; P18510; -.
DR PaxDb; P18510; -.
DR PeptideAtlas; P18510; -.
DR PRIDE; P18510; -.
DR ProteomicsDB; 53572; -. [P18510-1]
DR ProteomicsDB; 53573; -. [P18510-2]
DR ProteomicsDB; 53574; -. [P18510-3]
DR ProteomicsDB; 53575; -. [P18510-4]
DR Antibodypedia; 806; 893 antibodies from 43 providers.
DR CPTC; P18510; 1 antibody.
DR DNASU; 3557; -.
DR Ensembl; ENST00000259206.9; ENSP00000259206.5; ENSG00000136689.19. [P18510-3]
DR Ensembl; ENST00000354115.6; ENSP00000329072.3; ENSG00000136689.19. [P18510-2]
DR Ensembl; ENST00000361779.7; ENSP00000354816.3; ENSG00000136689.19. [P18510-4]
DR Ensembl; ENST00000409052.5; ENSP00000387210.1; ENSG00000136689.19. [P18510-4]
DR Ensembl; ENST00000409930.4; ENSP00000387173.3; ENSG00000136689.19. [P18510-1]
DR GeneID; 3557; -.
DR KEGG; hsa:3557; -.
DR MANE-Select; ENST00000409930.4; ENSP00000387173.3; NM_173842.3; NP_776214.1.
DR UCSC; uc002tiy.3; human. [P18510-1]
DR CTD; 3557; -.
DR DisGeNET; 3557; -.
DR GeneCards; IL1RN; -.
DR HGNC; HGNC:6000; IL1RN.
DR HPA; ENSG00000136689; Tissue enriched (esophagus).
DR MalaCards; IL1RN; -.
DR MIM; 147679; gene.
DR MIM; 612628; phenotype.
DR MIM; 612852; phenotype.
DR neXtProt; NX_P18510; -.
DR OpenTargets; ENSG00000136689; -.
DR Orphanet; 210115; Sterile multifocal osteomyelitis with periostitis and pustulosis.
DR PharmGKB; PA29816; -.
DR VEuPathDB; HostDB:ENSG00000136689; -.
DR eggNOG; ENOG502S5F0; Eukaryota.
DR GeneTree; ENSGT00950000182943; -.
DR HOGENOM; CLU_095373_2_0_1; -.
DR InParanoid; P18510; -.
DR OMA; WYLCTAL; -.
DR OrthoDB; 1410755at2759; -.
DR PhylomeDB; P18510; -.
DR TreeFam; TF300203; -.
DR PathwayCommons; P18510; -.
DR Reactome; R-HSA-6783783; Interleukin-10 signaling.
DR Reactome; R-HSA-9020702; Interleukin-1 signaling.
DR SignaLink; P18510; -.
DR SIGNOR; P18510; -.
DR BioGRID-ORCS; 3557; 8 hits in 1081 CRISPR screens.
DR ChiTaRS; IL1RN; human.
DR EvolutionaryTrace; P18510; -.
DR GeneWiki; Interleukin_1_receptor_antagonist; -.
DR GenomeRNAi; 3557; -.
DR Pharos; P18510; Tchem.
DR PRO; PR:P18510; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P18510; protein.
DR Bgee; ENSG00000136689; Expressed in lower esophagus mucosa and 151 other tissues.
DR ExpressionAtlas; P18510; baseline and differential.
DR Genevisible; P18510; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005125; F:cytokine activity; IEA:InterPro.
DR GO; GO:0005152; F:interleukin-1 receptor antagonist activity; IDA:BHF-UCL.
DR GO; GO:0005149; F:interleukin-1 receptor binding; IDA:BHF-UCL.
DR GO; GO:0045352; F:interleukin-1 type I receptor antagonist activity; IDA:BHF-UCL.
DR GO; GO:0045353; F:interleukin-1 type II receptor antagonist activity; IDA:BHF-UCL.
DR GO; GO:0005150; F:interleukin-1, type I receptor binding; IPI:BHF-UCL.
DR GO; GO:0005151; F:interleukin-1, type II receptor binding; IPI:BHF-UCL.
DR GO; GO:0006953; P:acute-phase response; IDA:BHF-UCL.
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:0030073; P:insulin secretion; IEA:Ensembl.
DR GO; GO:0006629; P:lipid metabolic process; IEA:Ensembl.
DR GO; GO:0034115; P:negative regulation of heterotypic cell-cell adhesion; IDA:BHF-UCL.
DR GO; GO:2000660; P:negative regulation of interleukin-1-mediated signaling pathway; IDA:BHF-UCL.
DR GO; GO:0051384; P:response to glucocorticoid; IDA:BHF-UCL.
DR InterPro; IPR020877; IL-1_CS.
DR InterPro; IPR000975; IL-1_fam.
DR InterPro; IPR003297; IL-1RA/IL-36.
DR InterPro; IPR008996; IL1/FGF.
DR InterPro; IPR039348; IL1RA.
DR PANTHER; PTHR10078; PTHR10078; 1.
DR PANTHER; PTHR10078:SF28; PTHR10078:SF28; 1.
DR Pfam; PF00340; IL1; 1.
DR PRINTS; PR00264; INTERLEUKIN1.
DR PRINTS; PR01360; INTRLEUKIN1X.
DR SUPFAM; SSF50353; SSF50353; 1.
DR PROSITE; PS00253; INTERLEUKIN_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Pharmaceutical; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000269|PubMed:2137200,
FT ECO:0000269|PubMed:2143761"
FT CHAIN 26..177
FT /note="Interleukin-1 receptor antagonist protein"
FT /id="PRO_0000015328"
FT CARBOHYD 109
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:2137200"
FT DISULFID 91..141
FT VAR_SEQ 1..34
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:9514884"
FT /id="VSP_002651"
FT VAR_SEQ 1..21
FT /note="MEICRGLRSHLITLLLFLFHS -> MAL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:1827201"
FT /id="VSP_002649"
FT VAR_SEQ 1..21
FT /note="MEICRGLRSHLITLLLFLFHS -> MALADLYEEGGGGGGEGEDNADSK
FT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:7629520"
FT /id="VSP_002650"
FT VARIANT 124
FT /note="A -> T (in dbSNP:rs45507693)"
FT /evidence="ECO:0000269|PubMed:18987736"
FT /id="VAR_049573"
FT STRAND 36..42
FT /evidence="ECO:0007829|PDB:1ILR"
FT TURN 43..45
FT /evidence="ECO:0007829|PDB:1IRP"
FT STRAND 47..51
FT /evidence="ECO:0007829|PDB:1ILR"
FT STRAND 54..58
FT /evidence="ECO:0007829|PDB:1ILR"
FT HELIX 62..67
FT /evidence="ECO:0007829|PDB:1ILR"
FT STRAND 71..76
FT /evidence="ECO:0007829|PDB:1ILR"
FT TURN 77..79
FT /evidence="ECO:0007829|PDB:1ILR"
FT STRAND 80..85
FT /evidence="ECO:0007829|PDB:1ILR"
FT TURN 86..89
FT /evidence="ECO:0007829|PDB:1ILR"
FT STRAND 90..97
FT /evidence="ECO:0007829|PDB:1ILR"
FT STRAND 100..106
FT /evidence="ECO:0007829|PDB:1ILR"
FT HELIX 110..112
FT /evidence="ECO:0007829|PDB:1ILR"
FT HELIX 118..123
FT /evidence="ECO:0007829|PDB:1ILR"
FT STRAND 124..130
FT /evidence="ECO:0007829|PDB:1ILR"
FT STRAND 133..141
FT /evidence="ECO:0007829|PDB:1ILR"
FT STRAND 145..151
FT /evidence="ECO:0007829|PDB:1ILR"
FT STRAND 157..160
FT /evidence="ECO:0007829|PDB:1ILR"
FT STRAND 162..168
FT /evidence="ECO:0007829|PDB:1ILR"
FT STRAND 171..175
FT /evidence="ECO:0007829|PDB:1ILR"
SQ SEQUENCE 177 AA; 20055 MW; D1690776A7394057 CRC64;
MEICRGLRSH LITLLLFLFH SETICRPSGR KSSKMQAFRI WDVNQKTFYL RNNQLVAGYL
QGPNVNLEEK IDVVPIEPHA LFLGIHGGKM CLSCVKSGDE TRLQLEAVNI TDLSENRKQD
KRFAFIRSDS GPTTSFESAA CPGWFLCTAM EADQPVSLTN MPDEGVMVTK FYFQEDE
