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   25-JAN-2012, entry version 97.
DE   RecName: Full=Interleukin-36 receptor antagonist protein;
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; Synonyms=FIL1D, IL1F5, IL1HY1, IL1L1, IL1RP3;
GN   ORFNames=UNQ1896/PRO4342;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Placenta;
RX   MEDLINE=20092888; PubMed=10625660; DOI=10.1074/jbc.275.2.1169;
RA   Smith D.E., Renshaw B.R., Ketchem R.R., Kubin M., Garka K.E.,
RA   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   MEDLINE=99443727; PubMed=10512743; DOI=10.1006/bbrc.1999.1440;
RA   Mulero J.J., Pace A.M., Nelken S.T., Loeb D.B., Correa T.R.,
RA   Drmanac R., 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   MEDLINE=20545212; 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
RT   cluster 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].
RX   MEDLINE=21359532; PubMed=11466363;
RA   Debets R., Timans J.C., Homey B., Zurawski S., Sana T.R., Lo S.,
RA   Wagner J., Edwards G., Clifford T., Menon S., Bazan J.F.,
RA   Kastelein R.A.;
RT   "Two novel IL-1 family members, IL-1 delta and IL-1 epsilon, function
RT   as an antagonist and agonist of NF-kappa B activation through the
RT   orphan IL-1 receptor-related protein 2.";
RL   J. Immunol. 167:1440-1446(2001).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=20318623; PubMed=10860666; DOI=10.1006/geno.2000.6184;
RA   Busfield S.J., Comrack C.A., Yu G., Chickering T.W., Smutko J.S.,
RA   Zhou H., Leiby K.R., Holmgren L.M., Gearing D.P., Pan Y.;
RT   "Identification and gene organization of three novel members of the
RT   IL-1 family on human chromosome 2.";
RL   Genomics 66:213-216(2000).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   MEDLINE=21988050; 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   MEDLINE=22887296; 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.,
RA   Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
RA   Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
RA   Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
RA   Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
RA   Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
RA   Wood W.I., Godowski P.J., Gray A.M.;
RT   "The secreted protein discovery initiative (SPDI), a large-scale
RT   effort to identify novel human secreted and transmembrane proteins: a
RT   bioinformatics 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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA   Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA   Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA   Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA   Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA   Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA   Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA   Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA   Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA   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.,
RA   Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA   Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA   Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA   Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA   Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA   Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA   Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA   Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA   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.,
RA   Waterston R.H., Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2
RT   and 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.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [13]
RP   VARIANTS PSORP 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.,
RA   Capon F., 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   [14]
RP   VARIANT PSORP PRO-27, AND CHARACTERIZATION OF VARIANT PSORP 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.,
RA   Sahbatou M., Munnich A., Casanova J.L., Sims J.E., Turki H.,
RA   Bachelez H., Smahi A.;
RT   "Interleukin-36-receptor antagonist deficiency and generalized
RT   pustular psoriasis.";
RL   N. Engl. J. Med. 365:620-628(2011).
CC   -!- FUNCTION: Is a highly and a specific antagonist of the IL-1
CC       receptor-related protein 2-mediated response to interleukin 1
CC       family member 9 (IL1F9). Could constitute part of an independent
CC       signaling system analogous to interleukin-1 alpha (IL-1A), beta
CC       (IL-1B) receptor agonist and interleukin-1 receptor type I (IL-
CC       1R1), that is present in epithelial barriers and takes part in
CC       local inflammatory response.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Predominantly expressed in keratinocytes but
CC       not in fibroblasts, endothelial cells or melanocytes. Detected
CC       also in the spleen, brain leukocyte and macrophage cell types.
CC       Increased in lesional psoriasis skin.
CC   -!- INDUCTION: By phorbol ester (PMA) and bacterial
CC       lipopolysaccharides (LPS) treatment in macrophage cell line.
CC   -!- DISEASE: Defects in IL36RN are the cause of psoriasis generalized
CC       pustular (PSORP) [MIM:614204]. PSORP is a life-threatening disease
CC       defined by repeated flares of sudden onset consisting of diffuse
CC       erythematous skin eruption characterized by rapid coverage with
CC       pustules, high-grade fever, asthenia, marked leukocytosis, and
CC       elevated serum levels of C-reactive protein.
CC   -!- SIMILARITY: Belongs to the IL-1 family.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Interleukin-1 entry;
CC       URL="http://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 http://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution-NoDerivs 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   IPI; IPI00017500; -.
DR   PIR; JC7104; JC7104.
DR   RefSeq; NP_036407.1; NM_012275.2.
DR   RefSeq; NP_775262.1; NM_173170.1.
DR   UniGene; Hs.516301; -.
DR   ProteinModelPortal; Q9UBH0; -.
DR   SMR; Q9UBH0; 2-155.
DR   IntAct; Q9UBH0; 4.
DR   MINT; MINT-1194342; -.
DR   STRING; Q9UBH0; -.
DR   DMDM; 25008600; -.
DR   PRIDE; Q9UBH0; -.
DR   Ensembl; ENST00000346807; ENSP00000259212; ENSG00000136695.
DR   Ensembl; ENST00000393200; ENSP00000376896; ENSG00000136695.
DR   GeneID; 26525; -.
DR   KEGG; hsa:26525; -.
DR   UCSC; uc002tis.1; human.
DR   CTD; 26525; -.
DR   GeneCards; GC02P113817; -.
DR   H-InvDB; HIX0002388; -.
DR   HGNC; HGNC:15561; IL36RN.
DR   HPA; HPA034542; -.
DR   MIM; 605507; gene.
DR   MIM; 614204; phenotype.
DR   neXtProt; NX_Q9UBH0; -.
DR   PharmGKB; PA38388; -.
DR   eggNOG; prNOG18290; -.
DR   GeneTree; ENSGT00530000062899; -.
DR   HOGENOM; HBG282870; -.
DR   HOVERGEN; HBG052099; -.
DR   InParanoid; Q9UBH0; -.
DR   OMA; SVVPNRS; -.
DR   OrthoDB; EOG4MKNHG; -.
DR   PhylomeDB; Q9UBH0; -.
DR   NextBio; 48854; -.
DR   ArrayExpress; Q9UBH0; -.
DR   Bgee; Q9UBH0; -.
DR   CleanEx; HS_IL1F5; -.
DR   Genevestigator; Q9UBH0; -.
DR   GermOnline; ENSG00000136695; Homo sapiens.
DR   GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR   GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR   GO; GO:0005152; F:interleukin-1 receptor antagonist activity; TAS:ProtInc.
DR   InterPro; IPR008996; Cytokine_IL1-like.
DR   InterPro; IPR003297; IL_rcpt_IL1RA.
DR   InterPro; IPR020877; Interleukin-1_CS.
DR   InterPro; IPR000975; Interleukin_1.
DR   KO; K05483; -.
DR   Pfam; PF00340; IL1; 1.
DR   PRINTS; PR00264; INTERLEUKIN1.
DR   PRINTS; PR01360; INTRLEUKIN1X.
DR   SMART; SM00125; IL1; 1.
DR   SUPFAM; SSF50353; Cytok_IL1_like; 1.
DR   PROSITE; PS00253; INTERLEUKIN_1; 1.
PE   1: Evidence at protein level;
KW   Complete proteome; Cytokine; Disease mutation; Disulfide bond;
KW   Polymorphism; Reference proteome; Secreted.
FT   CHAIN         1    155       Interleukin-36 receptor antagonist
FT                                protein.
FT                                /FTId=PRO_0000153642.
FT   DISULFID      8    154       By similarity.
FT   VARIANT      27     27       L -> P (in PSORP; expression of the
FT                                protein is severely impaired compared to
FT                                wild-type; the mutant protein is
FT                                substantially less able to inhibit IL1RL2
FT                                signaling than wild-type).
FT                                /FTId=VAR_066646.
FT   VARIANT      47     47       N -> S (in dbSNP:rs28938777).
FT                                /FTId=VAR_023239.
FT   VARIANT      48     48       R -> W (in PSORP).
FT                                /FTId=VAR_066647.
FT   VARIANT     113    113       S -> L (in PSORP).
FT                                /FTId=VAR_066648.
SQ   SEQUENCE   155 AA;  16962 MW;  B96DB5EFA2612E25 CRC64;
     MVLSGALCFR MKDSALKVLY LHNNQLLAGG LHAGKVIKGE EISVVPNRWL DASLSPVILG
     VQGGSQCLSC GVGQEPTLTL EPVNIMELYL GAKESKSFTF YRRDMGLTSS FESAAYPGWF
     LCTVPEADQP VRLTQLPENG GWNAPITDFY FQQCD
//