ID   I18BP_HUMAN             Reviewed;         194 AA.
AC   O95998; B3KUZ0; B7WPK4; O95993; O96027; Q9NZA9; Q9UBR7;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   07-JUL-2009, sequence version 2.
DT   13-FEB-2019, entry version 155.
DE   RecName: Full=Interleukin-18-binding protein;
DE            Short=IL-18BP;
DE   AltName: Full=Tadekinig-alfa;
DE   Flags: Precursor;
GN   Name=IL18BP;
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 [GENOMIC DNA / MRNA] (ISOFORMS A AND B), PROTEIN
RP   SEQUENCE OF 31-70, FUNCTION, ALTERNATIVE SPLICING, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=10023777; DOI=10.1016/S1074-7613(00)80013-8;
RA   Novick D., Kim S.-H., Fantuzzi G., Reznikov L.L., Dinarello C.A.,
RA   Rubinstein M.;
RT   "Interleukin-18 binding protein: a novel modulator of the Th1 cytokine
RT   response.";
RL   Immunity 10:127-136(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), PROTEIN SEQUENCE OF 31-35;
RP   39-45; 48-54; 57-60; 63-74; 91-95; 107-144 AND 151-169, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=10094485; DOI=10.1016/S0014-5793(99)00148-9;
RA   Aizawa Y., Akita K., Taniai M., Torigoe K., Mori T., Nishida Y.,
RA   Ushio S., Nukada Y., Tanimoto T., Ikegami H., Ikeda M., Kurimoto M.;
RT   "Cloning and expression of interleukin-18 binding protein.";
RL   FEBS Lett. 445:338-342(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RX   PubMed=10329540; DOI=10.1006/viro.1999.9676;
RA   Xiang Y., Moss B.;
RT   "Identification of human and mouse homologs of the MC51L-53L-54L
RT   family of secreted glycoproteins encoded by the Molluscum contagiosum
RT   poxvirus.";
RL   Virology 257:297-302(1999).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM D), FUNCTION, AND ALTERNATIVE
RP   SPLICING (ISOFORMS A AND B).
RC   TISSUE=T-cell;
RX   PubMed=10655506; DOI=10.1073/pnas.97.3.1190;
RA   Kim S.-H., Eisenstein M., Reznikov L., Fantuzzi G., Novick D.,
RA   Rubinstein M., Dinarello C.A.;
RT   "Structural requirements of six naturally occurring isoforms of the
RT   IL-18 binding protein to inhibit IL-18.";
RL   Proc. Natl. Acad. Sci. U.S.A. 97:1190-1195(2000).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC   TISSUE=Uterus;
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   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16554811; DOI=10.1038/nature04632;
RA   Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA   Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA   Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA   FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA   Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA   Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA   Sakaki Y.;
RT   "Human chromosome 11 DNA sequence and analysis including novel gene
RT   identification.";
RL   Nature 440:497-500(2006).
RN   [7]
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   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC   TISSUE=Leukocyte;
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   [9]
RP   PROTEIN SEQUENCE OF 31-45.
RX   PubMed=15340161; DOI=10.1110/ps.04682504;
RA   Zhang Z., Henzel W.J.;
RT   "Signal peptide prediction based on analysis of experimentally
RT   verified cleavage sites.";
RL   Protein Sci. 13:2819-2824(2004).
RN   [10]
RP   GLYCOSYLATION AT SER-53; ASN-103 AND ASN-147, STRUCTURE OF
RP   CARBOHYDRATES, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=22171320; DOI=10.1074/mcp.M111.013649;
RA   Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.;
RT   "Human urinary glycoproteomics; attachment site specific analysis of
RT   N-and O-linked glycosylations by CID and ECD.";
RL   Mol. Cell. Proteomics 11:1-17(2012).
CC   -!- FUNCTION: Isoform A binds to IL-18 and inhibits its activity.
CC       Functions as an inhibitor of the early TH1 cytokine response.
CC       {ECO:0000269|PubMed:10023777, ECO:0000269|PubMed:10655506}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=A; Synonyms=IL-18BPA;
CC         IsoId=O95998-2; Sequence=Displayed;
CC       Name=B; Synonyms=IL-18BPB;
CC         IsoId=O95998-3; Sequence=VSP_002515, VSP_002516;
CC       Name=D; Synonyms=IL-18BPD;
CC         IsoId=O95998-4; Sequence=VSP_037605, VSP_037606;
CC   -!- TISSUE SPECIFICITY: Strongly expressed in heart, lung, placenta
CC       and spleen. {ECO:0000269|PubMed:10023777,
CC       ECO:0000269|PubMed:10094485}.
CC   -!- PTM: N- and O-glycosylated. O-glycosylated with core 1-like and
CC       core 2-like glycans. O-glycan heterogeneity at Ser-53: HexHexNAc
CC       (major) and Hex2HexNAc2 (minor). N-glycan heterogeneity at Asn-
CC       103: Hex5HexNAc4 (minor), dHex1Hex5HexNAc4 (major) and Hex6HexNAc5
CC       (minor); N-glycan at Asn-147: dHex1Hex5HexNAc4.
CC       {ECO:0000269|PubMed:22171320}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAD17187.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
CC       Sequence=AAD17188.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
CC       Sequence=AAD17189.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
CC       Sequence=AAD17190.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
CC       Sequence=AAD17191.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
CC       Sequence=AAD17192.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
CC       Sequence=AAF31697.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
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DR   EMBL; AF110798; AAD17187.1; ALT_INIT; Genomic_DNA.
DR   EMBL; AF110798; AAD17188.1; ALT_INIT; Genomic_DNA.
DR   EMBL; AF110798; AAD17189.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; AF110799; AAD17190.1; ALT_INIT; mRNA.
DR   EMBL; AF110800; AAD17191.1; ALT_INIT; mRNA.
DR   EMBL; AF110801; AAD17192.1; ALT_SEQ; mRNA.
DR   EMBL; AB019504; BAA76374.1; -; mRNA.
DR   EMBL; AF122906; AAD41051.1; -; mRNA.
DR   EMBL; AF215907; AAF31697.1; ALT_INIT; mRNA.
DR   EMBL; AK098255; BAG53602.1; -; mRNA.
DR   EMBL; AP002490; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471076; EAW74813.1; -; Genomic_DNA.
DR   EMBL; CH471076; EAW74816.1; -; Genomic_DNA.
DR   EMBL; BC044215; AAH44215.1; -; mRNA.
DR   CCDS; CCDS44666.1; -. [O95998-3]
DR   CCDS; CCDS8206.2; -. [O95998-2]
DR   RefSeq; NP_001034748.1; NM_001039659.1. [O95998-2]
DR   RefSeq; NP_001034749.1; NM_001039660.1. [O95998-2]
DR   RefSeq; NP_001138527.1; NM_001145055.1. [O95998-3]
DR   RefSeq; NP_001138529.1; NM_001145057.1. [O95998-2]
DR   RefSeq; NP_005690.2; NM_005699.3.
DR   RefSeq; NP_766630.2; NM_173042.2. [O95998-2]
DR   RefSeq; NP_766632.2; NM_173044.2. [O95998-4]
DR   RefSeq; XP_016872548.1; XM_017017059.1. [O95998-2]
DR   RefSeq; XP_016872549.1; XM_017017060.1. [O95998-2]
DR   RefSeq; XP_016872550.1; XM_017017061.1. [O95998-2]
DR   RefSeq; XP_016872551.1; XM_017017062.1. [O95998-2]
DR   RefSeq; XP_016872552.1; XM_017017063.1. [O95998-2]
DR   UniGene; Hs.591967; -.
DR   ProteinModelPortal; O95998; -.
DR   SMR; O95998; -.
DR   BioGrid; 115379; 1.
DR   IntAct; O95998; 3.
DR   STRING; 9606.ENSP00000260049; -.
DR   GlyConnect; 669; -.
DR   iPTMnet; O95998; -.
DR   PhosphoSitePlus; O95998; -.
DR   UniCarbKB; O95998; -.
DR   BioMuta; IL18BP; -.
DR   PaxDb; O95998; -.
DR   PeptideAtlas; O95998; -.
DR   PRIDE; O95998; -.
DR   ProteomicsDB; 51175; -.
DR   ProteomicsDB; 51176; -. [O95998-3]
DR   ProteomicsDB; 51177; -. [O95998-4]
DR   DNASU; 10068; -.
DR   Ensembl; ENST00000260049; ENSP00000260049; ENSG00000137496. [O95998-2]
DR   Ensembl; ENST00000337131; ENSP00000338723; ENSG00000137496. [O95998-2]
DR   Ensembl; ENST00000343898; ENSP00000343309; ENSG00000137496. [O95998-4]
DR   Ensembl; ENST00000393703; ENSP00000377306; ENSG00000137496. [O95998-2]
DR   Ensembl; ENST00000393705; ENSP00000377308; ENSG00000137496. [O95998-2]
DR   Ensembl; ENST00000393707; ENSP00000377310; ENSG00000137496. [O95998-3]
DR   Ensembl; ENST00000404792; ENSP00000384212; ENSG00000137496. [O95998-2]
DR   Ensembl; ENST00000534583; ENSP00000434376; ENSG00000137496. [O95998-2]
DR   Ensembl; ENST00000620017; ENSP00000480621; ENSG00000137496. [O95998-4]
DR   GeneID; 10068; -.
DR   KEGG; hsa:10068; -.
DR   UCSC; uc001ore.2; human. [O95998-2]
DR   CTD; 10068; -.
DR   DisGeNET; 10068; -.
DR   EuPathDB; HostDB:ENSG00000137496.17; -.
DR   GeneCards; IL18BP; -.
DR   H-InvDB; HIX0009903; -.
DR   HGNC; HGNC:5987; IL18BP.
DR   HPA; CAB025980; -.
DR   HPA; HPA041061; -.
DR   MIM; 604113; gene.
DR   neXtProt; NX_O95998; -.
DR   OpenTargets; ENSG00000137496; -.
DR   PharmGKB; PA29803; -.
DR   eggNOG; ENOG410J0UT; Eukaryota.
DR   eggNOG; ENOG4111EES; LUCA.
DR   GeneTree; ENSGT00390000004026; -.
DR   HOVERGEN; HBG052064; -.
DR   InParanoid; O95998; -.
DR   OMA; AKRCPAL; -.
DR   OrthoDB; 1399939at2759; -.
DR   PhylomeDB; O95998; -.
DR   TreeFam; TF337962; -.
DR   Reactome; R-HSA-9008059; Interleukin-37 signaling.
DR   Reactome; R-HSA-9012546; Interleukin-18 signaling.
DR   GeneWiki; IL18BP; -.
DR   GenomeRNAi; 10068; -.
DR   PRO; PR:O95998; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   Bgee; ENSG00000137496; Expressed in 138 organ(s), highest expression level in spleen.
DR   ExpressionAtlas; O95998; baseline and differential.
DR   Genevisible; O95998; HS.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; TAS:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0042007; F:interleukin-18 binding; IDA:UniProtKB.
DR   GO; GO:0048019; F:receptor antagonist activity; TAS:UniProtKB.
DR   GO; GO:0071345; P:cellular response to cytokine stimulus; TAS:Reactome.
DR   GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl.
DR   GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
DR   GO; GO:0035655; P:interleukin-18-mediated signaling pathway; TAS:Reactome.
DR   GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR   GO; GO:0042088; P:T-helper 1 type immune response; IDA:UniProtKB.
DR   Gene3D; 2.60.40.10; -; 1.
DR   InterPro; IPR007110; Ig-like_dom.
DR   InterPro; IPR036179; Ig-like_dom_sf.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR039681; IL18BP.
DR   PANTHER; PTHR14292; PTHR14292; 1.
DR   SUPFAM; SSF48726; SSF48726; 1.
DR   PROSITE; PS50835; IG_LIKE; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Complete proteome; Direct protein sequencing;
KW   Disulfide bond; Glycoprotein; Immunoglobulin domain; Polymorphism;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL        1     30       {ECO:0000269|PubMed:10023777,
FT                                ECO:0000269|PubMed:10094485,
FT                                ECO:0000269|PubMed:15340161}.
FT   CHAIN        31    194       Interleukin-18-binding protein.
FT                                /FTId=PRO_0000014778.
FT   DOMAIN       65    166       Ig-like C2-type.
FT   CARBOHYD     53     53       O-linked (GalNAc...) serine.
FT                                {ECO:0000269|PubMed:22171320}.
FT   CARBOHYD     79     79       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD     94     94       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    103    103       N-linked (GlcNAc...) (complex)
FT                                asparagine.
FT                                {ECO:0000269|PubMed:22171320}.
FT   CARBOHYD    147    147       N-linked (GlcNAc...) (complex)
FT                                asparagine.
FT                                {ECO:0000269|PubMed:22171320}.
FT   DISULFID     86    150       {ECO:0000255|PROSITE-ProRule:PRU00114}.
FT   VAR_SEQ      79    115       NGTLSLSCVACSRFPNFSILYWLGNGSFIEHLPGRLW ->
FT                                SWAEGNLAPHPRSPALQPQQSTAAGLRLSTGPAAAQP (in
FT                                isoform B).
FT                                {ECO:0000303|PubMed:10023777}.
FT                                /FTId=VSP_002515.
FT   VAR_SEQ     116    194       Missing (in isoform B).
FT                                {ECO:0000303|PubMed:10023777}.
FT                                /FTId=VSP_002516.
FT   VAR_SEQ     128    163       TQLCKALVLEQLTPALHSTNFSCVLVDPEQVVQRHV -> W
FT                                AEGNLAPHPRSPALQPQQSTAAGLRLSTGPAAAQP (in
FT                                isoform D).
FT                                {ECO:0000303|PubMed:10655506}.
FT                                /FTId=VSP_037605.
FT   VAR_SEQ     164    194       Missing (in isoform D).
FT                                {ECO:0000303|PubMed:10655506}.
FT                                /FTId=VSP_037606.
FT   VARIANT      91     91       R -> H (in dbSNP:rs5743672).
FT                                /FTId=VAR_059393.
FT   VARIANT     121    121       R -> Q (in dbSNP:rs5743673).
FT                                /FTId=VAR_024497.
SQ   SEQUENCE   194 AA;  21099 MW;  5E520D6E46AFA843 CRC64;
     MTMRHNWTPD LSPLWVLLLC AHVVTLLVRA TPVSQTTTAA TASVRSTKDP CPSQPPVFPA
     AKQCPALEVT WPEVEVPLNG TLSLSCVACS RFPNFSILYW LGNGSFIEHL PGRLWEGSTS
     RERGSTGTQL CKALVLEQLT PALHSTNFSC VLVDPEQVVQ RHVVLAQLWA GLRATLPPTQ
     EALPSSHSSP QQQG
//