I18BP_HUMAN
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 03-AUG-2022, entry version 175.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 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; 39-45;
RP 48-54; 57-60; 63-74; 91-95; 107-144 AND 151-169, AND TISSUE 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., Ushio S.,
RA 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 family of
RT secreted glycoproteins encoded by the Molluscum contagiosum poxvirus.";
RL Virology 257:297-302(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM D), FUNCTION, AND ALTERNATIVE SPLICING
RP (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 IL-18
RT 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., 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 [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., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., 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., 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 [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 project:
RT 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 verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [10]
RP GLYCOSYLATION AT SER-53; ASN-103 AND ASN-147, STRUCTURE OF CARBOHYDRATES,
RP 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 N- and
RT O-linked glycosylations by CID and ECD.";
RL Mol. Cell. Proteomics 11:1-17(2012).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND INVOLVEMENT IN FVH.
RX PubMed=31213488; DOI=10.1084/jem.20190669;
RA Belkaya S., Michailidis E., Korol C.B., Kabbani M., Cobat A., Bastard P.,
RA Lee Y.S., Hernandez N., Drutman S., de Jong Y.P., Vivier E., Bruneau J.,
RA Beziat V., Boisson B., Lorenzo-Diaz L., Boucherit S., Sebagh M.,
RA Jacquemin E., Emile J.F., Abel L., Rice C.M., Jouanguy E., Casanova J.L.;
RT "Inherited IL-18BP deficiency in human fulminant viral hepatitis.";
RL J. Exp. Med. 216:1777-1790(2019).
CC -!- FUNCTION: Isoform A binds to IL-18 and inhibits its activity. Functions
CC as an inhibitor of the early TH1 cytokine response.
CC {ECO:0000269|PubMed:10023777, ECO:0000269|PubMed:10655506,
CC ECO:0000269|PubMed:31213488}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:31213488}.
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 and
CC spleen. {ECO:0000269|PubMed:10023777, ECO:0000269|PubMed:10094485}.
CC -!- PTM: N- and O-glycosylated. O-glycosylated with core 1-like and core 2-
CC like glycans. O-glycan heterogeneity at Ser-53: HexHexNAc (major) and
CC Hex2HexNAc2 (minor). N-glycan heterogeneity at Asn-103: Hex5HexNAc4
CC (minor), dHex1Hex5HexNAc4 (major) and Hex6HexNAc5 (minor); N-glycan at
CC Asn-147: dHex1Hex5HexNAc4. {ECO:0000269|PubMed:22171320}.
CC -!- DISEASE: Hepatitis, fulminant viral (FVH) [MIM:618549]: An autosomal
CC recessive form of fulminant viral hepatitis, a disease that strikes
CC otherwise healthy individuals during primary infection with common
CC liver-tropic viruses. FVH is characterized by severe liver destruction
CC in the absence of a preexisting liver disorder, leading to
CC encephalopathy within 8 weeks of the onset of the first symptoms.
CC {ECO:0000269|PubMed:31213488}. Note=Disease susceptibility may be
CC associated with variants affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD17187.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAD17188.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAD17189.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
CC Sequence=AAD17190.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAD17191.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAD17192.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
CC Sequence=AAF31697.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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; 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 AlphaFoldDB; O95998; -.
DR SMR; O95998; -.
DR BioGRID; 115379; 1.
DR IntAct; O95998; 3.
DR STRING; 9606.ENSP00000384212; -.
DR GlyConnect; 669; 4 N-Linked glycans (2 sites), 2 O-Linked glycans (1 site).
DR GlyGen; O95998; 7 sites, 6 N-linked glycans (2 sites), 5 O-linked glycans (3 sites).
DR iPTMnet; O95998; -.
DR PhosphoSitePlus; O95998; -.
DR BioMuta; IL18BP; -.
DR jPOST; O95998; -.
DR MassIVE; O95998; -.
DR PaxDb; O95998; -.
DR PeptideAtlas; O95998; -.
DR PRIDE; O95998; -.
DR ProteomicsDB; 51175; -. [O95998-2]
DR ProteomicsDB; 51176; -. [O95998-3]
DR ProteomicsDB; 51177; -. [O95998-4]
DR Antibodypedia; 30767; 464 antibodies from 34 providers.
DR DNASU; 10068; -.
DR Ensembl; ENST00000260049.9; ENSP00000260049.5; ENSG00000137496.18. [O95998-2]
DR Ensembl; ENST00000337131.9; ENSP00000338723.5; ENSG00000137496.18. [O95998-2]
DR Ensembl; ENST00000343898.9; ENSP00000343309.5; ENSG00000137496.18. [O95998-4]
DR Ensembl; ENST00000393703.9; ENSP00000377306.4; ENSG00000137496.18. [O95998-2]
DR Ensembl; ENST00000393705.8; ENSP00000377308.4; ENSG00000137496.18. [O95998-2]
DR Ensembl; ENST00000393707.4; ENSP00000377310.4; ENSG00000137496.18. [O95998-3]
DR Ensembl; ENST00000404792.5; ENSP00000384212.1; ENSG00000137496.18. [O95998-2]
DR Ensembl; ENST00000534583.5; ENSP00000434376.1; ENSG00000137496.18. [O95998-2]
DR Ensembl; ENST00000620017.4; ENSP00000480621.1; ENSG00000137496.18. [O95998-4]
DR GeneID; 10068; -.
DR KEGG; hsa:10068; -.
DR MANE-Select; ENST00000393703.9; ENSP00000377306.4; NM_001039660.2; NP_001034749.1.
DR UCSC; uc001ore.2; human. [O95998-2]
DR CTD; 10068; -.
DR DisGeNET; 10068; -.
DR GeneCards; IL18BP; -.
DR HGNC; HGNC:5987; IL18BP.
DR HPA; ENSG00000137496; Tissue enhanced (lymphoid).
DR MalaCards; IL18BP; -.
DR MIM; 604113; gene.
DR MIM; 618549; phenotype.
DR neXtProt; NX_O95998; -.
DR OpenTargets; ENSG00000137496; -.
DR PharmGKB; PA29803; -.
DR VEuPathDB; HostDB:ENSG00000137496; -.
DR eggNOG; ENOG502SYZY; Eukaryota.
DR GeneTree; ENSGT00390000004026; -.
DR HOGENOM; CLU_131866_0_0_1; -.
DR InParanoid; O95998; -.
DR OMA; PTAKQCP; -.
DR OrthoDB; 1399939at2759; -.
DR PhylomeDB; O95998; -.
DR TreeFam; TF337962; -.
DR PathwayCommons; O95998; -.
DR Reactome; R-HSA-9008059; Interleukin-37 signaling.
DR Reactome; R-HSA-9012546; Interleukin-18 signaling.
DR SignaLink; O95998; -.
DR BioGRID-ORCS; 10068; 12 hits in 1079 CRISPR screens.
DR ChiTaRS; IL18BP; human.
DR GeneWiki; IL18BP; -.
DR GenomeRNAi; 10068; -.
DR Pharos; O95998; Tbio.
DR PRO; PR:O95998; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O95998; protein.
DR Bgee; ENSG00000137496; Expressed in spleen and 117 other tissues.
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: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: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; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Immunoglobulin domain; Reference proteome; Secreted; Signal.
FT SIGNAL 1..30
FT /evidence="ECO:0000269|PubMed:10023777,
FT ECO:0000269|PubMed:10094485, ECO:0000269|PubMed:15340161"
FT CHAIN 31..194
FT /note="Interleukin-18-binding protein"
FT /id="PRO_0000014778"
FT DOMAIN 65..166
FT /note="Ig-like C2-type"
FT CARBOHYD 53
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000269|PubMed:22171320"
FT CARBOHYD 79
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 94
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 103
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:22171320"
FT CARBOHYD 147
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:22171320"
FT DISULFID 86..150
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 79..115
FT /note="NGTLSLSCVACSRFPNFSILYWLGNGSFIEHLPGRLW -> SWAEGNLAPHP
FT RSPALQPQQSTAAGLRLSTGPAAAQP (in isoform B)"
FT /evidence="ECO:0000303|PubMed:10023777"
FT /id="VSP_002515"
FT VAR_SEQ 116..194
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000303|PubMed:10023777"
FT /id="VSP_002516"
FT VAR_SEQ 128..163
FT /note="TQLCKALVLEQLTPALHSTNFSCVLVDPEQVVQRHV -> WAEGNLAPHPRS
FT PALQPQQSTAAGLRLSTGPAAAQP (in isoform D)"
FT /evidence="ECO:0000303|PubMed:10655506"
FT /id="VSP_037605"
FT VAR_SEQ 164..194
FT /note="Missing (in isoform D)"
FT /evidence="ECO:0000303|PubMed:10655506"
FT /id="VSP_037606"
FT VARIANT 91
FT /note="R -> H (in dbSNP:rs5743672)"
FT /id="VAR_059393"
FT VARIANT 121
FT /note="R -> Q (in dbSNP:rs5743673)"
FT /id="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
