ID I36RA_HUMAN Reviewed; 155 AA. AC Q9UBH0; A8K2I4; Q56AT9; Q7RTZ6; DT 08-NOV-2002, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 27-MAR-2024, entry version 190. DE RecName: Full=Interleukin-36 receptor antagonist protein; DE Short=IL-36Ra {ECO:0000303|PubMed:21965679}; DE AltName: Full=FIL1 delta; DE AltName: Full=IL-1-related protein 3; DE Short=IL-1RP3; DE AltName: Full=Interleukin-1 HY1; DE Short=IL-1HY1; DE AltName: Full=Interleukin-1 delta; DE Short=IL-1 delta; DE AltName: Full=Interleukin-1 family member 5; DE Short=IL-1F5; DE AltName: Full=Interleukin-1 receptor antagonist homolog 1; DE Short=IL-1ra homolog 1; DE AltName: Full=Interleukin-1-like protein 1; DE Short=IL-1L1; GN Name=IL36RN {ECO:0000312|HGNC:HGNC:15561}; GN Synonyms=FIL1D, IL1F5, IL1HY1, IL1L1, IL1RP3; GN ORFNames=UNQ1896/PRO4342; 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]. RC TISSUE=Placenta; 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 [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Fetal skin; RX PubMed=10512743; DOI=10.1006/bbrc.1999.1440; RA Mulero J.J., Pace A.M., Nelken S.T., Loeb D.B., Correa T.R., Drmanac R., RA Ford J.E.; RT "IL1HY1: a novel interleukin-1 receptor antagonist gene."; RL Biochem. Biophys. Res. Commun. 263:702-706(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Placenta; RX PubMed=11093146; RX DOI=10.1002/1521-4141(200011)30:11<3299::aid-immu3299>3.0.co;2-s; RA Barton J.L., Herbst R., Bosisio D., Higgins L., Nicklin M.J.H.; RT "A tissue specific IL-1 receptor antagonist homolog from the IL-1 cluster RT lacks IL-1, IL-1ra, IL-18 and IL-18 antagonist activities."; RL Eur. J. Immunol. 30:3299-3308(2000). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=11466363; DOI=10.4049/jimmunol.167.3.1440; RA Debets R., Timans J.C., Homey B., Zurawski S., Sana T.R., Lo S., Wagner J., RA Edwards G., Clifford T., Menon S., Bazan J.F., Kastelein R.A.; RT "Two novel IL-1 family members, IL-1 delta and IL-1 epsilon, function as an RT antagonist and agonist of NF-kappa B activation through the orphan IL-1 RT receptor-related protein 2."; RL J. Immunol. 167:1440-1446(2001). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=10860666; DOI=10.1006/geno.2000.6184; RA Busfield S.J., Comrack C.A., Yu G., Chickering T.W., Smutko J.S., Zhou H., RA Leiby K.R., Holmgren L.M., Gearing D.P., Pan Y.; RT "Identification and gene organization of three novel members of the IL-1 RT family on human chromosome 2."; RL Genomics 66:213-216(2000). RN [6] 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Cervix; 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 [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-47. RG SeattleSNPs variation discovery resource; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. 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]. 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 [13] RP FUNCTION, AND CLEAVAGE OF INITIATOR METHIONINE. 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 [14] RP FUNCTION, AND INDUCTION. RX PubMed=23147407; DOI=10.1002/eji.201242711; RA Gresnigt M.S., Roesler B., Jacobs C.W., Becker K.L., Joosten L.A., RA van der Meer J.W., Netea M.G., Dinarello C.A., van de Veerdonk F.L.; RT "The IL-36 receptor pathway regulates Aspergillus fumigatus-induced Th1 and RT Th17 responses."; RL Eur. J. Immunol. 43:416-426(2013). RN [15] 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 [16] RP VARIANTS PSORS14 TRP-48 AND LEU-113. RX PubMed=21839423; DOI=10.1016/j.ajhg.2011.07.022; RA Onoufriadis A., Simpson M.A., Pink A.E., Di Meglio P., Smith C.H., RA Pullabhatla V., Knight J., Spain S.L., Nestle F.O., Burden A.D., Capon F., RA Trembath R.C., Barker J.N.; RT "Mutations in IL36RN/IL1F5 are associated with the severe episodic RT inflammatory skin disease known as generalized pustular psoriasis."; RL Am. J. Hum. Genet. 89:432-437(2011). RN [17] RP VARIANT PSORS14 PRO-27, AND CHARACTERIZATION OF VARIANT PSORS14 PRO-27. RX PubMed=21848462; DOI=10.1056/nejmoa1013068; RA Marrakchi S., Guigue P., Renshaw B.R., Puel A., Pei X.Y., Fraitag S., RA Zribi J., Bal E., Cluzeau C., Chrabieh M., Towne J.E., Douangpanya J., RA Pons C., Mansour S., Serre V., Makni H., Mahfoudh N., Fakhfakh F., RA Bodemer C., Feingold J., Hadj-Rabia S., Favre M., Genin E., Sahbatou M., RA Munnich A., Casanova J.L., Sims J.E., Turki H., Bachelez H., Smahi A.; RT "Interleukin-36-receptor antagonist deficiency and generalized pustular RT psoriasis."; RL N. Engl. J. Med. 365:620-628(2011). RN [18] RP VARIANT PSORS14 ARG-123, AND CHARACTERIZATION OF VARIANT PSORS14 ARG-123. RX PubMed=22903787; DOI=10.1002/humu.22203; RA Farooq M., Nakai H., Fujimoto A., Fujikawa H., Matsuyama A., Kariya N., RA Aizawa A., Fujiwara H., Ito M., Shimomura Y.; RT "Mutation analysis of the IL36RN gene in 14 Japanese patients with RT generalized pustular psoriasis."; RL Hum. Mutat. 34:176-183(2013). CC -!- FUNCTION: Inhibits the activity of interleukin-36 (IL36A,IL36B and CC IL36G) by binding to receptor IL1RL2 and preventing its association CC with the coreceptor IL1RAP for signaling. Part of the IL-36 signaling CC system that is thought to be present in epithelial barriers and to take CC part in local inflammatory response; similar to the IL-1 system with CC which it shares the coreceptor. Proposed to play a role in skin CC inflammation. May be involved in the innate immune response to fungal CC pathogens, such as Aspergillus fumigatus. May activate an anti- CC inflammatory signaling pathway by recruiting SIGIRR. CC {ECO:0000269|PubMed:11466363, ECO:0000269|PubMed:21965679, CC ECO:0000269|PubMed:23147407}. 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 -!- INTERACTION: CC Q9UBH0; O95994: AGR2; NbExp=3; IntAct=EBI-465156, EBI-712648; CC Q9UBH0; Q9Y2T2: AP3M1; NbExp=3; IntAct=EBI-465156, EBI-2371151; CC Q9UBH0; O95628-2: CNOT4; NbExp=5; IntAct=EBI-465156, EBI-12019444; CC Q9UBH0; Q8N4Y2-3: CRACR2B; NbExp=3; IntAct=EBI-465156, EBI-11982645; CC Q9UBH0; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-465156, EBI-742054; CC Q9UBH0; P84074: HPCA; NbExp=3; IntAct=EBI-465156, EBI-12197079; CC Q9UBH0; Q0VD86: INCA1; NbExp=3; IntAct=EBI-465156, EBI-6509505; CC Q9UBH0; Q9NWZ3: IRAK4; NbExp=3; IntAct=EBI-465156, EBI-448378; CC Q9UBH0; Q04864: REL; NbExp=3; IntAct=EBI-465156, EBI-307352; CC Q9UBH0; Q04864-2: REL; NbExp=3; IntAct=EBI-465156, EBI-10829018; CC Q9UBH0; O14492-2: SH2B2; NbExp=3; IntAct=EBI-465156, EBI-19952306; CC Q9UBH0; Q9BWW4: SSBP3; NbExp=8; IntAct=EBI-465156, EBI-2902395; CC Q9UBH0; Q9BWG4: SSBP4; NbExp=4; IntAct=EBI-465156, EBI-744719; CC Q9UBH0; Q8N7F7: UBL4B; NbExp=3; IntAct=EBI-465156, EBI-10267507; CC Q9UBH0; Q969J2: ZKSCAN4; NbExp=3; IntAct=EBI-465156, EBI-2818641; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:32272059}. Secreted CC {ECO:0000269|PubMed:32272059}. 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 -!- TISSUE SPECIFICITY: Predominantly expressed in skin keratinocytes but CC not in fibroblasts, endothelial cells or melanocytes. Detected also in CC the spleen, brain leukocyte and macrophage cell types. Increased in CC lesional psoriasis skin. {ECO:0000269|PubMed:11466363}. CC -!- INDUCTION: By phorbol ester (PMA) and bacterial lipopolysaccharides CC (LPS) treatment in macrophage cell line. By Aspergillus fumigatus CC conidia in peripheral blood mnonocytes. {ECO:0000269|PubMed:23147407}. CC -!- DISEASE: Psoriasis 14, pustular (PSORS14) [MIM:614204]: A life- CC threatening disease defined by repeated flares of sudden onset CC consisting of diffuse erythematous skin eruption characterized by rapid CC coverage with pustules, high-grade fever, asthenia, marked CC leukocytosis, and elevated serum levels of C-reactive protein. CC {ECO:0000269|PubMed:21839423, ECO:0000269|PubMed:21848462, CC ECO:0000269|PubMed:22903787}. Note=The disease is caused by variants CC affecting the gene represented in this entry. 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/il1f5/"; 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; AF201830; AAF25210.1; -; mRNA. DR EMBL; AF186094; AAF02757.1; -; mRNA. DR EMBL; AJ242737; CAB59822.1; -; mRNA. DR EMBL; AJ242738; CAB59823.1; -; mRNA. DR EMBL; AJ271338; CAB67704.1; -; Genomic_DNA. DR EMBL; AF216693; AAF76981.1; -; Genomic_DNA. DR EMBL; AF230377; AAF91274.1; -; mRNA. DR EMBL; BN000002; CAD29877.1; -; Genomic_DNA. DR EMBL; AY359117; AAQ89475.1; -; mRNA. DR EMBL; AK290249; BAF82938.1; -; mRNA. DR EMBL; AY972853; AAX59031.1; -; Genomic_DNA. DR EMBL; AC016724; AAY14990.1; -; Genomic_DNA. DR EMBL; CH471217; EAW73617.1; -; Genomic_DNA. DR EMBL; BC024747; AAH24747.1; -; mRNA. DR CCDS; CCDS2111.1; -. DR PIR; JC7104; JC7104. DR RefSeq; NP_036407.1; NM_012275.2. DR RefSeq; NP_775262.1; NM_173170.1. DR PDB; 4P0J; X-ray; 2.30 A; A/B=2-135, A/B=147-155. DR PDB; 4P0K; X-ray; 1.70 A; A=2-49, A=55-135, A=147-155. DR PDB; 4P0L; X-ray; 1.55 A; A=2-49, A=55-135, A=147-155. DR PDBsum; 4P0J; -. DR PDBsum; 4P0K; -. DR PDBsum; 4P0L; -. DR AlphaFoldDB; Q9UBH0; -. DR SMR; Q9UBH0; -. DR BioGRID; 117728; 54. DR IntAct; Q9UBH0; 26. DR MINT; Q9UBH0; -. DR STRING; 9606.ENSP00000259212; -. DR iPTMnet; Q9UBH0; -. DR PhosphoSitePlus; Q9UBH0; -. DR BioMuta; IL36RN; -. DR DMDM; 25008600; -. DR MassIVE; Q9UBH0; -. DR PaxDb; 9606-ENSP00000376896; -. DR PeptideAtlas; Q9UBH0; -. DR ProteomicsDB; 83968; -. DR Antibodypedia; 35211; 324 antibodies from 32 providers. DR DNASU; 26525; -. DR Ensembl; ENST00000346807.7; ENSP00000259212.3; ENSG00000136695.15. DR Ensembl; ENST00000393200.7; ENSP00000376896.2; ENSG00000136695.15. DR Ensembl; ENST00000437409.2; ENSP00000409262.2; ENSG00000136695.15. DR GeneID; 26525; -. DR KEGG; hsa:26525; -. DR MANE-Select; ENST00000393200.7; ENSP00000376896.2; NM_012275.3; NP_036407.1. DR UCSC; uc002tis.4; human. DR AGR; HGNC:15561; -. DR CTD; 26525; -. DR DisGeNET; 26525; -. DR GeneCards; IL36RN; -. DR HGNC; HGNC:15561; IL36RN. DR HPA; ENSG00000136695; Group enriched (esophagus, lymphoid tissue, skin). DR MalaCards; IL36RN; -. DR MIM; 605507; gene. DR MIM; 614204; phenotype. DR neXtProt; NX_Q9UBH0; -. DR OpenTargets; ENSG00000136695; -. DR Orphanet; 163931; Acrodermatitis continua of Hallopeau. DR Orphanet; 404546; DITRA. DR Orphanet; 247353; Generalized pustular psoriasis. DR Orphanet; 163927; Pustulosis palmaris et plantaris. DR PharmGKB; PA38388; -. DR VEuPathDB; HostDB:ENSG00000136695; -. DR eggNOG; ENOG502SRSC; Eukaryota. DR GeneTree; ENSGT00950000182943; -. DR HOGENOM; CLU_095373_2_1_1; -. DR InParanoid; Q9UBH0; -. DR OMA; DPITDFY; -. DR OrthoDB; 4292752at2759; -. DR PhylomeDB; Q9UBH0; -. DR TreeFam; TF300203; -. DR PathwayCommons; Q9UBH0; -. DR Reactome; R-HSA-9014826; Interleukin-36 pathway. DR SignaLink; Q9UBH0; -. DR BioGRID-ORCS; 26525; 14 hits in 1142 CRISPR screens. DR ChiTaRS; IL36RN; human. DR GeneWiki; IL1F5; -. DR GenomeRNAi; 26525; -. DR Pharos; Q9UBH0; Tbio. DR PRO; PR:Q9UBH0; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q9UBH0; Protein. DR Bgee; ENSG00000136695; Expressed in amniotic fluid and 86 other cell types or tissues. DR ExpressionAtlas; Q9UBH0; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW. DR GO; GO:0005152; F:interleukin-1 receptor antagonist activity; TAS:ProtInc. DR GO; GO:0005149; F:interleukin-1 receptor binding; IEA:InterPro. DR GO; GO:0019732; P:antifungal humoral response; IMP:UniProtKB. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; 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:0001960; P:negative regulation of cytokine-mediated signaling pathway; IMP:UniProtKB. DR GO; GO:0032700; P:negative regulation of interleukin-17 production; IMP:UniProtKB. DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IEA:Ensembl. DR GO; GO:0032689; P:negative regulation of type II interferon production; IMP:UniProtKB. DR Gene3D; 2.80.10.50; -; 1. 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 PANTHER; PTHR10078; INTERLEUKIN-1 FAMILY MEMBER; 1. DR PANTHER; PTHR10078:SF32; INTERLEUKIN-36 RECEPTOR ANTAGONIST PROTEIN; 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 PROSITE; PS00253; INTERLEUKIN_1; 1. DR Genevisible; Q9UBH0; HS. PE 1: Evidence at protein level; KW 3D-structure; Cytokine; Cytoplasm; Disease variant; Disulfide bond; KW Immunity; Innate immunity; Reference proteome; Secreted. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:21965679" FT CHAIN 2..155 FT /note="Interleukin-36 receptor antagonist protein" FT /id="PRO_0000153642" FT DISULFID 8..154 FT /evidence="ECO:0000250" FT VARIANT 27 FT /note="L -> P (in PSORS14; expression of the protein is FT severely impaired compared to wild-type; the mutant protein FT is substantially less able to inhibit IL1RL2 signaling than FT wild-type; dbSNP:rs387906914)" FT /evidence="ECO:0000269|PubMed:21848462" FT /id="VAR_066646" FT VARIANT 47 FT /note="N -> S (in dbSNP:rs28938777)" FT /evidence="ECO:0000269|Ref.9" FT /id="VAR_023239" FT VARIANT 48 FT /note="R -> W (in PSORS14; dbSNP:rs151325121)" FT /evidence="ECO:0000269|PubMed:21839423" FT /id="VAR_066647" FT VARIANT 113 FT /note="S -> L (in PSORS14; dbSNP:rs144478519)" FT /evidence="ECO:0000269|PubMed:21839423" FT /id="VAR_066648" FT VARIANT 123 FT /note="T -> R (in PSORS14; shows impaired expression of the FT mutant protein which fails to antagonize the IL-36 FT signaling pathway; dbSNP:rs397514629)" FT /evidence="ECO:0000269|PubMed:22903787" FT /id="VAR_068972" FT STRAND 9..13 FT /evidence="ECO:0007829|PDB:4P0L" FT STRAND 18..22 FT /evidence="ECO:0007829|PDB:4P0L" FT STRAND 25..29 FT /evidence="ECO:0007829|PDB:4P0L" FT STRAND 42..46 FT /evidence="ECO:0007829|PDB:4P0L" FT HELIX 52..54 FT /evidence="ECO:0007829|PDB:4P0J" FT STRAND 55..61 FT /evidence="ECO:0007829|PDB:4P0L" FT TURN 62..65 FT /evidence="ECO:0007829|PDB:4P0L" FT STRAND 66..69 FT /evidence="ECO:0007829|PDB:4P0L" FT STRAND 72..75 FT /evidence="ECO:0007829|PDB:4P0L" FT STRAND 79..82 FT /evidence="ECO:0007829|PDB:4P0L" FT HELIX 85..89 FT /evidence="ECO:0007829|PDB:4P0L" FT HELIX 96..98 FT /evidence="ECO:0007829|PDB:4P0L" FT STRAND 99..102 FT /evidence="ECO:0007829|PDB:4P0L" FT STRAND 109..116 FT /evidence="ECO:0007829|PDB:4P0L" FT STRAND 120..123 FT /evidence="ECO:0007829|PDB:4P0L" FT STRAND 132..135 FT /evidence="ECO:0007829|PDB:4P0L" FT STRAND 149..153 FT /evidence="ECO:0007829|PDB:4P0L" SQ SEQUENCE 155 AA; 16962 MW; B96DB5EFA2612E25 CRC64; MVLSGALCFR MKDSALKVLY LHNNQLLAGG LHAGKVIKGE EISVVPNRWL DASLSPVILG VQGGSQCLSC GVGQEPTLTL EPVNIMELYL GAKESKSFTF YRRDMGLTSS FESAAYPGWF LCTVPEADQP VRLTQLPENG GWNAPITDFY FQQCD //