ID   IL6RB_HUMAN             Reviewed;         918 AA.
AC   P40189; A0N0L4; Q5FC04; Q9UQ41;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   25-NOV-2008, sequence version 2.
DT   12-AUG-2020, entry version 227.
DE   RecName: Full=Interleukin-6 receptor subunit beta {ECO:0000305};
DE            Short=IL-6 receptor subunit beta;
DE            Short=IL-6R subunit beta;
DE            Short=IL-6R-beta;
DE            Short=IL-6RB;
DE   AltName: Full=CDw130;
DE   AltName: Full=Interleukin-6 signal transducer;
DE   AltName: Full=Membrane glycoprotein 130;
DE            Short=gp130 {ECO:0000303|PubMed:12829785};
DE   AltName: Full=Oncostatin-M receptor subunit alpha;
DE   AltName: CD_antigen=CD130;
DE   Flags: Precursor;
GN   Name=IL6ST {ECO:0000312|HGNC:HGNC:6021};
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), FUNCTION, TISSUE SPECIFICITY,
RP   VARIANT VAL-8, AND SUBUNIT.
RC   TISSUE=Myeloma, and Placenta;
RX   PubMed=2261637; DOI=10.1016/0092-8674(90)90411-7;
RA   Hibi M., Murakami M., Saito M., Hirano T., Taga T., Kishimoto T.;
RT   "Molecular cloning and expression of an IL-6 signal transducer, gp130.";
RL   Cell 63:1149-1157(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT VAL-8, AND TISSUE
RP   SPECIFICITY.
RC   TISSUE=Synovium;
RX   PubMed=10880057; DOI=10.1172/jci7479;
RA   Tanaka M., Kishimura M., Ozaki S., Osakada F., Hashimoto H., Okubo M.,
RA   Murakami M., Nakao K.;
RT   "Cloning of novel soluble gp130 and detection of its neutralizing
RT   autoantibodies in rheumatoid arthritis.";
RL   J. Clin. Invest. 106:137-144(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA   Hayashi A., Sameshima E., Tabata Y., Iida K., Mitsuyama M., Kanai S.,
RA   Furuya T., Saito T.;
RT   "IL6ST mRNA, nirs splice variant 4.";
RL   Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B.,
RA   Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O.,
RA   Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I.,
RA   Nickerson D.A.;
RL   Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15372022; DOI=10.1038/nature02919;
RA   Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA   Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA   She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA   Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA   Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA   Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA   Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA   Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA   Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA   Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA   Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA   Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA   Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT   "The DNA sequence and comparative analysis of human chromosome 5.";
RL   Nature 431:268-274(2004).
RN   [6]
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   [7]
RP   PARTIAL PROTEIN SEQUENCE, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-43;
RP   ASN-83; ASN-131; ASN-157; ASN-227; ASN-379; ASN-383; ASN-553 AND ASN-564.
RX   PubMed=11098061; DOI=10.1074/jbc.m009979200;
RA   Moritz R.L., Hall N.E., Connolly L.M., Simpson R.J.;
RT   "Determination of the disulfide structure and N-glycosylation sites of the
RT   extracellular domain of the human signal transducer gp130.";
RL   J. Biol. Chem. 276:8244-8253(2001).
RN   [8]
RP   SUBUNIT, AND INDUCTION.
RX   PubMed=8999038; DOI=10.1074/jbc.271.51.32635;
RA   Mosley B., De Imus C., Friend D., Boiani N., Thoma B., Park L.S.,
RA   Cosman D.;
RT   "Dual oncostatin M (OSM) receptors. Cloning and characterization of an
RT   alternative signaling subunit conferring OSM-specific receptor
RT   activation.";
RL   J. Biol. Chem. 271:32635-32643(1996).
RN   [9]
RP   INTERACTION WITH HCK.
RX   PubMed=9406996;
RA   Hallek M., Neumann C., Schaffer M., Danhauser-Riedl S., von Bubnoff N.,
RA   de Vos G., Druker B.J., Yasukawa K., Griffin J.D., Emmerich B.;
RT   "Signal transduction of interleukin-6 involves tyrosine phosphorylation of
RT   multiple cytosolic proteins and activation of Src-family kinases Fyn, Hck,
RT   and Lyn in multiple myeloma cell lines.";
RL   Exp. Hematol. 25:1367-1377(1997).
RN   [10]
RP   PHOSPHORYLATION AT SER-782, MUTAGENESIS OF SER-782, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY.
RX   PubMed=10811661; DOI=10.1074/jbc.m907658199;
RA   Gibson R.M., Schiemann W.P., Prichard L.B., Reno J.M., Ericsson L.H.,
RA   Nathanson N.M.;
RT   "Phosphorylation of human gp130 at Ser-782 adjacent to the di-leucine
RT   internalization motif. Effects on expression and signaling.";
RL   J. Biol. Chem. 275:22574-22582(2000).
RN   [11]
RP   FUNCTION (ISOFORM 2), AND BIOTECHNOLOGY.
RX   PubMed=11121117; DOI=10.1046/j.1432-1327.2001.01867.x;
RA   Jostock T., Muellberg J., Ozbek S., Atreya R., Blinn G., Voltz N.,
RA   Fischer M., Neurath M.F., Rose-John S.;
RT   "Soluble gp130 is the natural inhibitor of soluble interleukin-6 receptor
RT   transsignaling responses.";
RL   Eur. J. Biochem. 268:160-167(2001).
RN   [12]
RP   INTERACTION WITH HERPES VIRUS-8/HHV-8 PROTEIN VIL6 (MICROBIAL INFECTION).
RX   PubMed=11238858; DOI=10.1128/jvi.75.7.3325-3334.2001;
RA   Li H., Wang H., Nicholas J.;
RT   "Detection of direct binding of human herpesvirus 8-encoded interleukin-6
RT   (vIL-6) to both gp130 and IL-6 receptor (IL-6R) and identification of amino
RT   acid residues of vIL-6 important for IL-6R-dependent and -independent
RT   signaling.";
RL   J. Virol. 75:3325-3334(2001).
RN   [13]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-379 AND ASN-383.
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   [14]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-829, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA   Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT   "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT   networks.";
RL   Cell 127:635-648(2006).
RN   [15]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-667, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Platelet;
RX   PubMed=18088087; DOI=10.1021/pr0704130;
RA   Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA   Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT   "Phosphoproteome of resting human platelets.";
RL   J. Proteome Res. 7:526-534(2008).
RN   [16]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [17]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-227 AND ASN-390.
RC   TISSUE=Liver;
RX   PubMed=19159218; DOI=10.1021/pr8008012;
RA   Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT   "Glycoproteomics analysis of human liver tissue by combination of multiple
RT   enzyme digestion and hydrazide chemistry.";
RL   J. Proteome Res. 8:651-661(2009).
RN   [18]
RP   GLYCOSYLATION AT ASN-390.
RX   PubMed=19139490; DOI=10.1074/mcp.m800504-mcp200;
RA   Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B.,
RA   Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L.,
RA   Ying W.T., He S.M., Qian X.H.;
RT   "A strategy for precise and large scale identification of core fucosylated
RT   glycoproteins.";
RL   Mol. Cell. Proteomics 8:913-923(2009).
RN   [19]
RP   FUNCTION, SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX   PubMed=19915009; DOI=10.1074/jbc.m109.075952;
RA   Waetzig G.H., Chalaris A., Rosenstiel P., Suthaus J., Holland C., Karl N.,
RA   Valles Uriarte L., Till A., Scheller J., Grotzinger J., Schreiber S.,
RA   Rose-John S., Seegert D.;
RT   "N-linked glycosylation is essential for the stability but not the
RT   signaling function of the interleukin-6 signal transducer glycoprotein
RT   130.";
RL   J. Biol. Chem. 285:1781-1789(2010).
RN   [20]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-667, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA   Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA   Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT   site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [21]
RP   FUNCTION (ISOFORM 2), AND BIOTECHNOLOGY.
RX   PubMed=21990364; DOI=10.1074/jbc.m111.295758;
RA   Garbers C., Thaiss W., Jones G.W., Waetzig G.H., Lorenzen I., Guilhot F.,
RA   Lissilaa R., Ferlin W.G., Groetzinger J., Jones S.A., Rose-John S.,
RA   Scheller J.;
RT   "Inhibition of classic signaling is a novel function of soluble
RT   glycoprotein 130 (sgp130), which is controlled by the ratio of interleukin
RT   6 and soluble interleukin 6 receptor.";
RL   J. Biol. Chem. 286:42959-42970(2011).
RN   [22]
RP   FUNCTION, AND MUTAGENESIS OF CYS-172; 186-TYR--TYR-190; VAL-189; TYR-190;
RP   ASP-215 AND VAL-252.
RX   PubMed=23294003; DOI=10.1042/bj20121660;
RA   Schutt A., Zacharias M., Schneider N., Horn S., Grotzinger J.,
RA   Rose-John S., Schmidt-Arras D.;
RT   "gp130 activation is regulated by D2-D3 interdomain connectivity.";
RL   Biochem. J. 450:487-496(2013).
RN   [23]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-667 AND SER-839, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [24]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-661 AND SER-667, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [25]
RP   FUNCTION, MUTAGENESIS OF TYR-759, AND INTERACTION WITH SRC AND YES.
RX   PubMed=25731159; DOI=10.1038/nature14228;
RA   Taniguchi K., Wu L.W., Grivennikov S.I., de Jong P.R., Lian I., Yu F.X.,
RA   Wang K., Ho S.B., Boland B.S., Chang J.T., Sandborn W.J., Hardiman G.,
RA   Raz E., Maehara Y., Yoshimura A., Zucman-Rossi J., Guan K.L., Karin M.;
RT   "A gp130-Src-YAP module links inflammation to epithelial regeneration.";
RL   Nature 519:57-62(2015).
RN   [26]
RP   BIOTECHNOLOGY.
RX   PubMed=26876177; DOI=10.1016/j.celrep.2016.01.053;
RA   Lokau J., Nitz R., Agthe M., Monhasery N., Aparicio-Siegmund S.,
RA   Schumacher N., Wolf J., Moeller-Hackbarth K., Waetzig G.H., Groetzinger J.,
RA   Mueller-Newen G., Rose-John S., Scheller J., Garbers C.;
RT   "Proteolytic Cleavage Governs Interleukin-11 Trans-signaling.";
RL   Cell Rep. 14:1761-1773(2016).
RN   [27]
RP   FUNCTION (ISOFORM 2), AND BIOTECHNOLOGY.
RX   PubMed=30279168; DOI=10.1126/scisignal.aar7388;
RA   Lamertz L., Rummel F., Polz R., Baran P., Hansen S., Waetzig G.H.,
RA   Moll J.M., Floss D.M., Scheller J.;
RT   "Soluble gp130 prevents interleukin-6 and interleukin-11 cluster signaling
RT   but not intracellular autocrine responses.";
RL   Sci. Signal. 11:0-0(2018).
RN   [28]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 122-325.
RX   PubMed=9501088; DOI=10.1093/emboj/17.6.1665;
RA   Bravo J., Staunton D., Heath J.K., Jones E.Y.;
RT   "Crystal structure of a cytokine-binding region of gp130.";
RL   EMBO J. 17:1665-1674(1998).
RN   [29]
RP   X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 23-325 IN COMPLEX WITH HERPES
RP   VIRUS-8/HHV-8 PROTEIN VIL6 (MICROBIAL INFECTION), SUBUNIT, AND
RP   GLYCOSYLATION.
RX   PubMed=11251120; DOI=10.1126/science.1058308;
RA   Chow D.-C., He X.-L., Snow A.L., Rose-John S., Garcia K.C.;
RT   "Structure of an extracellular gp130 cytokine receptor signaling complex.";
RL   Science 291:2150-2155(2001).
RN   [30]
RP   X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 123-323 IN COMPLEX WITH LIF.
RX   PubMed=14527405; DOI=10.1016/s1097-2765(03)00365-4;
RA   Boulanger M.J., Bankovich A.J., Kortemme T., Baker D., Garcia K.C.;
RT   "Convergent mechanisms for recognition of divergent cytokines by the shared
RT   signaling receptor gp130.";
RL   Mol. Cell 12:577-589(2003).
RN   [31] {ECO:0000244|PDB:1P9M}
RP   X-RAY CRYSTALLOGRAPHY (3.65 ANGSTROMS) OF 23-321 IN COMPLEX WITH IL6 AND
RP   IL6R, AND SUBUNIT.
RX   PubMed=12829785; DOI=10.1126/science.1083901;
RA   Boulanger M.J., Chow D.C., Brevnova E.E., Garcia K.C.;
RT   "Hexameric structure and assembly of the interleukin-6/IL-6 alpha-
RT   receptor/gp130 complex.";
RL   Science 300:2101-2104(2003).
RN   [32]
RP   X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 24-612, DISULFIDE BONDS, AND
RP   GLYCOSYLATION AT ASN-43; ASN-83; ASN-227; ASN-383 AND ASN-553.
RX   PubMed=20489211; DOI=10.1074/jbc.c110.129502;
RA   Xu Y., Kershaw N.J., Luo C.S., Soo P., Pocock M.J., Czabotar P.E.,
RA   Hilton D.J., Nicola N.A., Garrett T.P., Zhang J.G.;
RT   "Crystal structure of the entire ectodomain of gp130: insights into the
RT   molecular assembly of the tall cytokine receptor complexes.";
RL   J. Biol. Chem. 285:21214-21218(2010).
RN   [33]
RP   VARIANT [LARGE SCALE ANALYSIS] ILE-415.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
RN   [34]
RP   VARIANT GLY-200.
RX   PubMed=25242236; DOI=10.1016/j.cancergen.2014.07.003;
RA   Sun L., Sui L., Cong X., Ma K., Ma X., Huang Y., Fan C., Fu X., Ma K.;
RT   "Low incidence of IL6ST (gp130) mutations in exon 6 in lung cancer of a
RT   Chinese cohort.";
RL   Cancer Genet. 207:291-298(2014).
RN   [35]
RP   VARIANT ARG-148, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=24629561; DOI=10.1016/j.metabol.2014.02.005;
RA   Wonnerth A., Katsaros K.M., Krychtiuk K.A., Speidl W.S., Kaun C.,
RA   Thaler K., Huber K., Wojta J., Maurer G., Seljeflot I., Arnesen H.,
RA   Weiss T.W.;
RT   "Glycoprotein 130 polymorphism predicts soluble glycoprotein 130 levels.";
RL   Metabolism 63:647-653(2014).
RN   [36]
RP   VARIANT HIES4 TYR-404, INVOLVEMENT IN HIES4, FUNCTION, AND CHARACTERIZATION
RP   OF VARIANT HIES4 TYR-404.
RX   PubMed=28747427; DOI=10.1084/jem.20161810;
RA   Schwerd T., Twigg S.R.F., Aschenbrenner D., Manrique S., Miller K.A.,
RA   Taylor I.B., Capitani M., McGowan S.J., Sweeney E., Weber A., Chen L.,
RA   Bowness P., Riordan A., Cant A., Freeman A.F., Milner J.D., Holland S.M.,
RA   Frede N., Mueller M., Schmidt-Arras D., Grimbacher B., Wall S.A.,
RA   Jones E.Y., Wilkie A.O.M., Uhlig H.H.;
RT   "A biallelic mutation in IL6ST encoding the GP130 co-receptor causes
RT   immunodeficiency and craniosynostosis.";
RL   J. Exp. Med. 214:2547-2562(2017).
RN   [37]
RP   VARIANT HIES4 LEU-498, INVOLVEMENT IN HIES4, FUNCTION, AND CHARACTERIZATION
RP   OF VARIANT HIES4 LEU-498.
RX   PubMed=30309848; DOI=10.3324/haematol.2018.194233;
RA   Shahin T., Aschenbrenner D., Cagdas D., Bal S.K., Conde C.D., Garncarz W.,
RA   Medgyesi D., Schwerd T., Karaatmaca B., Cetinkaya P.G., Esenboga S.,
RA   Twigg S.R.F., Cant A., Wilkie A.O.M., Tezcan I., Uhlig H.H., Boztug K.;
RT   "Selective loss of function variants in IL6ST cause Hyper-IgE syndrome with
RT   distinct impairments of T-cell phenotype and function.";
RL   Haematologica 104:609-621(2019).
CC   -!- FUNCTION: Signal-transducing molecule (PubMed:2261637). The receptor
CC       systems for IL6, LIF, OSM, CNTF, IL11, CTF1 and BSF3 can utilize IL6ST
CC       for initiating signal transmission. Binding of IL6 to IL6R induces
CC       IL6ST homodimerization and formation of a high-affinity receptor
CC       complex, which activate the intracellular JAK-MAPK and JAK-STAT3
CC       signaling pathways (PubMed:2261637, PubMed:19915009, PubMed:23294003).
CC       That causes phosphorylation of IL6ST tyrosine residues which in turn
CC       activates STAT3 (PubMed:19915009, PubMed:23294003, PubMed:25731159). In
CC       parallel, the IL6 signaling pathway induces the expression of two
CC       cytokine receptor signaling inhibitors, SOCS1 and SOCS3, which inhibit
CC       JAK and terminate the activity of the IL6 signaling pathway as a
CC       negative feedback loop (By similarity). Also activates the yes-
CC       associated protein 1 (YAP) and NOTCH pathways to control inflammation-
CC       induced epithelial regeneration, independently of STAT3 (By
CC       similarity). Mediates signals which regulate immune response,
CC       hematopoiesis, pain control and bone metabolism (By similarity). Has a
CC       role in embryonic development (By similarity). Essential for survival
CC       of motor and sensory neurons and for differentiation of astrocytes (By
CC       similarity). Required for expression of TRPA1 in nociceptive neurons
CC       (By similarity). Required for the maintenance of PTH1R expression in
CC       the osteoblast lineage and for the stimulation of PTH-induced
CC       osteoblast differentiation (By similarity). Required for normal
CC       trabecular bone mass and cortical bone composition (By similarity).
CC       {ECO:0000250|UniProtKB:Q00560, ECO:0000269|PubMed:19915009,
CC       ECO:0000269|PubMed:2261637, ECO:0000269|PubMed:23294003,
CC       ECO:0000269|PubMed:25731159, ECO:0000269|PubMed:28747427,
CC       ECO:0000269|PubMed:30309848}.
CC   -!- FUNCTION: [Isoform 2]: Binds to the soluble IL6:sIL6R complex (hyper-
CC       IL6), thereby blocking IL6 trans-signaling. Inhibits sIL6R-dependent
CC       acute phase response (PubMed:11121117, PubMed:21990364,
CC       PubMed:30279168). Also blocks IL11 cluster signaling through IL11R
CC       (PubMed:30279168). {ECO:0000269|PubMed:11121117,
CC       ECO:0000269|PubMed:21990364, ECO:0000269|PubMed:30279168}.
CC   -!- SUBUNIT: Component of a hexamer of two molecules each of IL6, IL6R and
CC       IL6ST; associates with the complex IL6:IL6R but does not interact with
CC       IL6 (PubMed:12829785, PubMed:2261637). Forms heterodimers composed of
CC       LIFR and IL6ST (type I OSM receptor) which are activated by LIF and OSM
CC       (PubMed:8999038). Also forms heterodimers composed of OSMR and IL6ST
CC       (type II receptor) which are activated by OSM but not by LIF
CC       (PubMed:8999038). Interacts with HCK (PubMed:9406996). Interacts with
CC       INPP5D/SHIP1 (By similarity). Interacts with SRC and YES
CC       (PubMed:25731159). {ECO:0000250|UniProtKB:Q00560,
CC       ECO:0000269|PubMed:12829785, ECO:0000269|PubMed:14527405,
CC       ECO:0000269|PubMed:2261637, ECO:0000269|PubMed:25731159,
CC       ECO:0000269|PubMed:8999038, ECO:0000269|PubMed:9406996}.
CC   -!- SUBUNIT: (Microbial infection) The homodimer binds two molecules of
CC       herpes virus 8/HHV-8 protein vIL-6. {ECO:0000269|PubMed:11238858,
CC       ECO:0000269|PubMed:11251120}.
CC   -!- INTERACTION:
CC       P40189; P26441: CNTF; NbExp=10; IntAct=EBI-1030834, EBI-1050897;
CC       P40189; P40189: IL6ST; NbExp=2; IntAct=EBI-1030834, EBI-1030834;
CC       P40189; Q9NZI2-2: KCNIP1; NbExp=3; IntAct=EBI-1030834, EBI-22452746;
CC       P40189; Q9Y2W7: KCNIP3; NbExp=7; IntAct=EBI-1030834, EBI-751501;
CC       P40189; P15018: LIF; NbExp=2; IntAct=EBI-1030834, EBI-1037189;
CC       P40189; P43364: MAGEA11; NbExp=3; IntAct=EBI-1030834, EBI-739552;
CC       P40189; P13725: OSM; NbExp=2; IntAct=EBI-1030834, EBI-6595724;
CC       P40189; Q99650: OSMR; NbExp=2; IntAct=EBI-1030834, EBI-2804080;
CC       P40189; O43765: SGTA; NbExp=3; IntAct=EBI-1030834, EBI-347996;
CC       P40189; Q96EQ0: SGTB; NbExp=4; IntAct=EBI-1030834, EBI-744081;
CC       P40189; Q2HRC7: K2; Xeno; NbExp=2; IntAct=EBI-1030834, EBI-9007403;
CC       P40189; P42227: Stat3; Xeno; NbExp=4; IntAct=EBI-1030834, EBI-602878;
CC       P40189-1; P23458: JAK1; NbExp=3; IntAct=EBI-15742214, EBI-1383438;
CC   -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC       {ECO:0000269|PubMed:19915009}; Single-pass type I membrane protein
CC       {ECO:0000255}.
CC   -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted
CC       {ECO:0000269|PubMed:24629561}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=P40189-1; Sequence=Displayed;
CC       Name=2; Synonyms=GP130-RAPS {ECO:0000303|PubMed:10880057};
CC         IsoId=P40189-2; Sequence=VSP_001684, VSP_001685;
CC       Name=3;
CC         IsoId=P40189-3; Sequence=VSP_043716;
CC   -!- TISSUE SPECIFICITY: Found in all the tissues and cell lines examined
CC       (PubMed:2261637). Expression not restricted to IL6 responsive cells
CC       (PubMed:2261637). {ECO:0000269|PubMed:2261637}.
CC   -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed in blood serum (at protein
CC       level) (PubMed:24629561). {ECO:0000269|PubMed:24629561}.
CC   -!- INDUCTION: LIF and OSM activate the type I OSM receptor while only OSM
CC       can activate the type II OSM receptor. {ECO:0000269|PubMed:8999038}.
CC   -!- DOMAIN: The WSXWS motif appears to be necessary for proper protein
CC       folding and thereby efficient intracellular transport and cell-surface
CC       receptor binding.
CC   -!- DOMAIN: The box 1 motif is required for JAK interaction and/or
CC       activation.
CC   -!- PTM: Phosphorylation of Ser-782 down-regulates cell surface expression.
CC       {ECO:0000269|PubMed:10811661}.
CC   -!- PTM: Heavily N-glycosylated (PubMed:11098061, PubMed:16335952,
CC       PubMed:19159218, PubMed:19139490, PubMed:11251120). Glycosylation is
CC       required for protein stability and localization in plasma membrane but
CC       not for ligand binding (PubMed:19915009). {ECO:0000269|PubMed:11098061,
CC       ECO:0000269|PubMed:11251120, ECO:0000269|PubMed:16335952,
CC       ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218,
CC       ECO:0000269|PubMed:19915009}.
CC   -!- DISEASE: Hyper-IgE recurrent infection syndrome 4, autosomal recessive
CC       (HIES4) [MIM:618523]: An immunologic disorder characterized by
CC       recurrent infections, mainly affecting the respiratory tract, skin and
CC       eye, and skeletal abnormalities including craniosynostosis and
CC       scoliosis. Immunologic workup shows increased serum IgE, intermittent
CC       eosinophilia, impaired development of certain B- and T-cell
CC       populations, as well as impaired acute-phase response. Disease onset is
CC       in early childhood. {ECO:0000269|PubMed:28747427,
CC       ECO:0000269|PubMed:30309848}. Note=The disease is caused by mutations
CC       affecting the gene represented in this entry.
CC   -!- BIOTECHNOLOGY: Two extracellular parts of IL6ST/gp130 linked to the Fc-
CC       portions of a human IgG1 antibody (sgp130Fc) inhibit IL6 trans-
CC       signaling by the IL6:IL6R complex and has no affinity of IL6 or IL6R
CC       alone (PubMed:11121117, PubMed:21990364, PubMed:30279168). Also blocks
CC       IL11 cluster signaling through IL11R (PubMed:30279168,
CC       PubMed:26876177). {ECO:0000269|PubMed:11121117,
CC       ECO:0000269|PubMed:21990364, ECO:0000269|PubMed:26876177,
CC       ECO:0000269|PubMed:30279168}.
CC   -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 2
CC       subfamily. {ECO:0000305}.
DR   EMBL; M57230; AAA59155.1; -; mRNA.
DR   EMBL; AB015706; BAA78112.1; -; mRNA.
DR   EMBL; AB102802; BAD89393.1; -; mRNA.
DR   EMBL; EF064722; ABK41905.1; -; Genomic_DNA.
DR   EMBL; AC008914; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC016596; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471123; EAW54936.1; -; Genomic_DNA.
DR   CCDS; CCDS3971.1; -. [P40189-1]
DR   CCDS; CCDS47209.1; -. [P40189-2]
DR   CCDS; CCDS54856.1; -. [P40189-3]
DR   PIR; A36337; A36337.
DR   RefSeq; NP_001177910.1; NM_001190981.1. [P40189-3]
DR   RefSeq; NP_002175.2; NM_002184.3. [P40189-1]
DR   RefSeq; NP_786943.1; NM_175767.2. [P40189-2]
DR   PDB; 1BJ8; NMR; -; A=219-325.
DR   PDB; 1BQU; X-ray; 2.00 A; A/B=122-333.
DR   PDB; 1I1R; X-ray; 2.40 A; A=23-325.
DR   PDB; 1N2Q; Model; -; A/B=23-324.
DR   PDB; 1P9M; X-ray; 3.65 A; A=23-321.
DR   PDB; 1PVH; X-ray; 2.50 A; A/C=123-323.
DR   PDB; 3L5H; X-ray; 3.60 A; A=24-612.
DR   PDB; 3L5I; X-ray; 1.90 A; A=323-612.
DR   PDB; 3L5J; X-ray; 3.04 A; A/B=323-610.
DR   PDBsum; 1BJ8; -.
DR   PDBsum; 1BQU; -.
DR   PDBsum; 1I1R; -.
DR   PDBsum; 1N2Q; -.
DR   PDBsum; 1P9M; -.
DR   PDBsum; 1PVH; -.
DR   PDBsum; 3L5H; -.
DR   PDBsum; 3L5I; -.
DR   PDBsum; 3L5J; -.
DR   SMR; P40189; -.
DR   BioGRID; 109786; 36.
DR   CORUM; P40189; -.
DR   DIP; DIP-95N; -.
DR   IntAct; P40189; 23.
DR   MINT; P40189; -.
DR   STRING; 9606.ENSP00000370698; -.
DR   BindingDB; P40189; -.
DR   ChEMBL; CHEMBL3124734; -.
DR   DrugCentral; P40189; -.
DR   GuidetoPHARMACOLOGY; 2317; -.
DR   GlyConnect; 649; 16 N-Linked glycans (9 sites).
DR   GlyGen; P40189; 13 sites, 3 N-linked glycans (3 sites).
DR   iPTMnet; P40189; -.
DR   PhosphoSitePlus; P40189; -.
DR   SwissPalm; P40189; -.
DR   UniCarbKB; P40189; -.
DR   BioMuta; IL6ST; -.
DR   DMDM; 215273999; -.
DR   EPD; P40189; -.
DR   jPOST; P40189; -.
DR   MassIVE; P40189; -.
DR   MaxQB; P40189; -.
DR   PaxDb; P40189; -.
DR   PeptideAtlas; P40189; -.
DR   PRIDE; P40189; -.
DR   ProteomicsDB; 55338; -. [P40189-1]
DR   ProteomicsDB; 55339; -. [P40189-2]
DR   ProteomicsDB; 55340; -. [P40189-3]
DR   Antibodypedia; 2448; 751 antibodies.
DR   DNASU; 3572; -.
DR   Ensembl; ENST00000336909; ENSP00000338799; ENSG00000134352. [P40189-1]
DR   Ensembl; ENST00000381287; ENSP00000370687; ENSG00000134352. [P40189-2]
DR   Ensembl; ENST00000381294; ENSP00000370694; ENSG00000134352. [P40189-3]
DR   Ensembl; ENST00000381298; ENSP00000370698; ENSG00000134352. [P40189-1]
DR   Ensembl; ENST00000502326; ENSP00000462158; ENSG00000134352. [P40189-1]
DR   Ensembl; ENST00000522633; ENSP00000435399; ENSG00000134352. [P40189-2]
DR   GeneID; 3572; -.
DR   KEGG; hsa:3572; -.
DR   UCSC; uc003jqq.4; human. [P40189-1]
DR   CTD; 3572; -.
DR   DisGeNET; 3572; -.
DR   EuPathDB; HostDB:ENSG00000134352.19; -.
DR   GeneCards; IL6ST; -.
DR   HGNC; HGNC:6021; IL6ST.
DR   HPA; ENSG00000134352; Low tissue specificity.
DR   MalaCards; IL6ST; -.
DR   MIM; 600694; gene.
DR   MIM; 618523; phenotype.
DR   neXtProt; NX_P40189; -.
DR   OpenTargets; ENSG00000134352; -.
DR   PharmGKB; PA29837; -.
DR   eggNOG; ENOG502QXEG; Eukaryota.
DR   GeneTree; ENSGT00940000159608; -.
DR   HOGENOM; CLU_017990_0_0_1; -.
DR   InParanoid; P40189; -.
DR   KO; K05060; -.
DR   OMA; YLITVYP; -.
DR   PhylomeDB; P40189; -.
DR   TreeFam; TF338122; -.
DR   PathwayCommons; P40189; -.
DR   Reactome; R-HSA-1059683; Interleukin-6 signaling.
DR   Reactome; R-HSA-110056; MAPK3 (ERK1) activation. [P40189-1]
DR   Reactome; R-HSA-112411; MAPK1 (ERK2) activation. [P40189-1]
DR   Reactome; R-HSA-6788467; IL-6-type cytokine receptor ligand interactions.
DR   Reactome; R-HSA-8984722; Interleukin-35 Signalling.
DR   Reactome; R-HSA-9020956; Interleukin-27 signaling.
DR   SignaLink; P40189; -.
DR   SIGNOR; P40189; -.
DR   BioGRID-ORCS; 3572; 26 hits in 888 CRISPR screens.
DR   ChiTaRS; IL6ST; human.
DR   EvolutionaryTrace; P40189; -.
DR   GeneWiki; Glycoprotein_130; -.
DR   GenomeRNAi; 3572; -.
DR   Pharos; P40189; Tclin.
DR   PRO; PR:P40189; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; P40189; protein.
DR   Bgee; ENSG00000134352; Expressed in female gonad and 259 other tissues.
DR   ExpressionAtlas; P40189; baseline and differential.
DR   Genevisible; P40189; HS.
DR   GO; GO:0070110; C:ciliary neurotrophic factor receptor complex; IDA:BHF-UCL.
DR   GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR   GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR   GO; GO:0005896; C:interleukin-6 receptor complex; IDA:BHF-UCL.
DR   GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR   GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR   GO; GO:0005900; C:oncostatin-M receptor complex; IDA:BHF-UCL.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR   GO; GO:0004897; F:ciliary neurotrophic factor receptor activity; IDA:BHF-UCL.
DR   GO; GO:0005127; F:ciliary neurotrophic factor receptor binding; IPI:BHF-UCL.
DR   GO; GO:0019955; F:cytokine binding; IBA:GO_Central.
DR   GO; GO:0004896; F:cytokine receptor activity; IBA:GO_Central.
DR   GO; GO:0019838; F:growth factor binding; IPI:BHF-UCL.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0019970; F:interleukin-11 binding; IEA:Ensembl.
DR   GO; GO:0004921; F:interleukin-11 receptor activity; IEA:Ensembl.
DR   GO; GO:0045509; F:interleukin-27 receptor activity; IC:BHF-UCL.
DR   GO; GO:0070120; P:ciliary neurotrophic factor-mediated signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0019221; P:cytokine-mediated signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0005977; P:glycogen metabolic process; IEA:Ensembl.
DR   GO; GO:0070106; P:interleukin-27-mediated signaling pathway; IMP:BHF-UCL.
DR   GO; GO:0070757; P:interleukin-35-mediated signaling pathway; TAS:Reactome.
DR   GO; GO:0070102; P:interleukin-6-mediated signaling pathway; IMP:BHF-UCL.
DR   GO; GO:0048861; P:leukemia inhibitory factor signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; TAS:BHF-UCL.
DR   GO; GO:0070104; P:negative regulation of interleukin-6-mediated signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0038165; P:oncostatin-M-mediated signaling pathway; IMP:BHF-UCL.
DR   GO; GO:0002675; P:positive regulation of acute inflammatory response; IC:BHF-UCL.
DR   GO; GO:0002821; P:positive regulation of adaptive immune response; IC:BHF-UCL.
DR   GO; GO:0048711; P:positive regulation of astrocyte differentiation; IEA:Ensembl.
DR   GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; TAS:BHF-UCL.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL.
DR   GO; GO:0045669; P:positive regulation of osteoblast differentiation; IMP:BHF-UCL.
DR   GO; GO:0042102; P:positive regulation of T cell proliferation; IMP:BHF-UCL.
DR   GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IMP:BHF-UCL.
DR   GO; GO:0010575; P:positive regulation of vascular endothelial growth factor production; TAS:BHF-UCL.
DR   GO; GO:0008593; P:regulation of Notch signaling pathway; IEA:Ensembl.
DR   GO; GO:0034097; P:response to cytokine; IDA:BHF-UCL.
DR   GO; GO:0016032; P:viral process; IEA:UniProtKB-KW.
DR   CDD; cd00063; FN3; 2.
DR   Gene3D; 2.60.40.10; -; 6.
DR   InterPro; IPR003961; FN3_dom.
DR   InterPro; IPR036116; FN3_sf.
DR   InterPro; IPR003529; Hematopoietin_rcpt_Gp130_CS.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR010457; IgC2-like_lig-bd.
DR   InterPro; IPR015321; TypeI_recpt_CBD.
DR   Pfam; PF00041; fn3; 2.
DR   Pfam; PF09240; IL6Ra-bind; 1.
DR   Pfam; PF06328; Lep_receptor_Ig; 1.
DR   SMART; SM00060; FN3; 5.
DR   SUPFAM; SSF49265; SSF49265; 5.
DR   PROSITE; PS50853; FN3; 4.
DR   PROSITE; PS01353; HEMATOPO_REC_L_F2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cell membrane;
KW   Direct protein sequencing; Disease mutation; Disulfide bond; Glycoprotein;
KW   Host-virus interaction; Immunoglobulin domain; Membrane; Phosphoprotein;
KW   Polymorphism; Receptor; Reference proteome; Repeat; Secreted; Signal;
KW   Transmembrane; Transmembrane helix.
FT   SIGNAL          1..22
FT   CHAIN           23..918
FT                   /note="Interleukin-6 receptor subunit beta"
FT                   /id="PRO_0000010899"
FT   TOPO_DOM        23..619
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        620..641
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        642..918
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          26..120
FT                   /note="Ig-like C2-type"
FT   DOMAIN          125..216
FT                   /note="Fibronectin type-III 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT   DOMAIN          224..324
FT                   /note="Fibronectin type-III 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT   DOMAIN          329..424
FT                   /note="Fibronectin type-III 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT   DOMAIN          426..517
FT                   /note="Fibronectin type-III 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT   DOMAIN          518..613
FT                   /note="Fibronectin type-III 5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT   MOTIF           310..314
FT                   /note="WSXWS motif"
FT   MOTIF           651..659
FT                   /note="Box 1 motif"
FT   COMPBIAS        725..755
FT                   /note="Ser-rich"
FT   MOD_RES         661
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:24275569"
FT   MOD_RES         667
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:18088087,
FT                   ECO:0000244|PubMed:20068231, ECO:0000244|PubMed:23186163,
FT                   ECO:0000244|PubMed:24275569"
FT   MOD_RES         782
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:10811661"
FT   MOD_RES         789
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q00560"
FT   MOD_RES         829
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:17081983"
FT   MOD_RES         839
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:23186163"
FT   CARBOHYD        43
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:11098061,
FT                   ECO:0000269|PubMed:20489211"
FT   CARBOHYD        83
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:11098061,
FT                   ECO:0000269|PubMed:20489211"
FT   CARBOHYD        131
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:11098061"
FT   CARBOHYD        157
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:11098061"
FT   CARBOHYD        227
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:11098061,
FT                   ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:20489211"
FT   CARBOHYD        379
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:11098061,
FT                   ECO:0000269|PubMed:16335952"
FT   CARBOHYD        383
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:11098061,
FT                   ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:20489211"
FT   CARBOHYD        390
FT                   /note="N-linked (GlcNAc...) (complex) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19139490,
FT                   ECO:0000269|PubMed:19159218"
FT   CARBOHYD        553
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:11098061,
FT                   ECO:0000269|PubMed:20489211"
FT   CARBOHYD        564
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:11098061"
FT   DISULFID        28..54
FT                   /evidence="ECO:0000269|PubMed:11098061,
FT                   ECO:0000269|PubMed:20489211"
FT   DISULFID        48..103
FT                   /evidence="ECO:0000269|PubMed:11098061,
FT                   ECO:0000269|PubMed:20489211"
FT   DISULFID        134..144
FT                   /evidence="ECO:0000269|PubMed:11098061,
FT                   ECO:0000269|PubMed:20489211"
FT   DISULFID        172..182
FT                   /evidence="ECO:0000269|PubMed:11098061,
FT                   ECO:0000269|PubMed:20489211"
FT   DISULFID        458..466
FT                   /evidence="ECO:0000269|PubMed:11098061,
FT                   ECO:0000269|PubMed:20489211"
FT   VAR_SEQ         325..329
FT                   /note="RPSKA -> NIASF (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:10880057"
FT                   /id="VSP_001684"
FT   VAR_SEQ         330..918
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:10880057"
FT                   /id="VSP_001685"
FT   VAR_SEQ         423..483
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|Ref.3"
FT                   /id="VSP_043716"
FT   VARIANT         8
FT                   /note="L -> V (in dbSNP:rs1063560)"
FT                   /evidence="ECO:0000269|PubMed:10880057,
FT                   ECO:0000269|PubMed:2261637"
FT                   /id="VAR_047782"
FT   VARIANT         148
FT                   /note="G -> R (polymorphism; associated with increased
FT                   levels of soluble IL6RB in blood serum; dbSNP:rs2228044)"
FT                   /evidence="ECO:0000269|PubMed:24629561"
FT                   /id="VAR_047783"
FT   VARIANT         200
FT                   /note="A -> G (found in patient with lung cancer; unknown
FT                   pathological significance; dbSNP:rs199905033)"
FT                   /evidence="ECO:0000269|PubMed:25242236"
FT                   /id="VAR_074654"
FT   VARIANT         397
FT                   /note="L -> V (in dbSNP:rs2228043)"
FT                   /id="VAR_047784"
FT   VARIANT         404
FT                   /note="N -> Y (in HIES4; results in defective cytokine-
FT                   mediated signaling pathway)"
FT                   /evidence="ECO:0000269|PubMed:28747427"
FT                   /id="VAR_083197"
FT   VARIANT         415
FT                   /note="T -> I (in a colorectal cancer sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_036165"
FT   VARIANT         454
FT                   /note="I -> T (in dbSNP:rs2228046)"
FT                   /id="VAR_047785"
FT   VARIANT         498
FT                   /note="P -> L (in HIES4; results in defective cytokine-
FT                   mediated signaling pathway)"
FT                   /evidence="ECO:0000269|PubMed:30309848"
FT                   /id="VAR_083198"
FT   VARIANT         499
FT                   /note="V -> I (in dbSNP:rs34417936)"
FT                   /id="VAR_047786"
FT   MUTAGEN         172
FT                   /note="C->S: Induces ligand-independent activation."
FT                   /evidence="ECO:0000269|PubMed:23294003"
FT   MUTAGEN         186..190
FT                   /note="Missing: Induces ligand-independent activation."
FT                   /evidence="ECO:0000269|PubMed:23294003"
FT   MUTAGEN         189
FT                   /note="V->G: Does not induce ligand-independent
FT                   activation."
FT                   /evidence="ECO:0000269|PubMed:23294003"
FT   MUTAGEN         190
FT                   /note="Y->G: Does not induce ligand-independent
FT                   activation."
FT                   /evidence="ECO:0000269|PubMed:23294003"
FT   MUTAGEN         215
FT                   /note="D->G: Induces ligand-independent activation."
FT                   /evidence="ECO:0000269|PubMed:23294003"
FT   MUTAGEN         252
FT                   /note="V->G: Induces ligand-independent activation."
FT                   /evidence="ECO:0000269|PubMed:23294003"
FT   MUTAGEN         759
FT                   /note="Y->F: Refractory to inhibition by SOCS3."
FT                   /evidence="ECO:0000269|PubMed:25731159"
FT   MUTAGEN         782
FT                   /note="S->A: Increases cell surface expression."
FT                   /evidence="ECO:0000269|PubMed:10811661"
FT   STRAND          28..35
FT                   /evidence="ECO:0000244|PDB:1I1R"
FT   STRAND          37..39
FT                   /evidence="ECO:0000244|PDB:1I1R"
FT   STRAND          44..50
FT                   /evidence="ECO:0000244|PDB:1I1R"
FT   HELIX           52..58
FT                   /evidence="ECO:0000244|PDB:1I1R"
FT   HELIX           62..64
FT                   /evidence="ECO:0000244|PDB:1I1R"
FT   STRAND          65..69
FT                   /evidence="ECO:0000244|PDB:1I1R"
FT   HELIX           76..78
FT                   /evidence="ECO:0000244|PDB:1I1R"
FT   STRAND          80..83
FT                   /evidence="ECO:0000244|PDB:1I1R"
FT   STRAND          86..91
FT                   /evidence="ECO:0000244|PDB:1I1R"
FT   STRAND          97..107
FT                   /evidence="ECO:0000244|PDB:1I1R"
FT   TURN            108..110
FT                   /evidence="ECO:0000244|PDB:1I1R"
FT   STRAND          111..123
FT                   /evidence="ECO:0000244|PDB:1I1R"
FT   STRAND          130..137
FT                   /evidence="ECO:0000244|PDB:1BQU"
FT   STRAND          143..147
FT                   /evidence="ECO:0000244|PDB:1BQU"
FT   STRAND          157..164
FT                   /evidence="ECO:0000244|PDB:1BQU"
FT   STRAND          176..178
FT                   /evidence="ECO:0000244|PDB:1PVH"
FT   STRAND          181..183
FT                   /evidence="ECO:0000244|PDB:1BQU"
FT   STRAND          194..202
FT                   /evidence="ECO:0000244|PDB:1BQU"
FT   STRAND          205..208
FT                   /evidence="ECO:0000244|PDB:1BQU"
FT   STRAND          212..214
FT                   /evidence="ECO:0000244|PDB:1BQU"
FT   HELIX           216..218
FT                   /evidence="ECO:0000244|PDB:1BQU"
FT   STRAND          219..221
FT                   /evidence="ECO:0000244|PDB:1BQU"
FT   STRAND          226..231
FT                   /evidence="ECO:0000244|PDB:1BQU"
FT   STRAND          234..238
FT                   /evidence="ECO:0000244|PDB:1I1R"
FT   STRAND          240..245
FT                   /evidence="ECO:0000244|PDB:1BQU"
FT   HELIX           248..251
FT                   /evidence="ECO:0000244|PDB:1BQU"
FT   STRAND          255..263
FT                   /evidence="ECO:0000244|PDB:1BQU"
FT   HELIX           274..277
FT                   /evidence="ECO:0000244|PDB:1BQU"
FT   STRAND          282..286
FT                   /evidence="ECO:0000244|PDB:1BQU"
FT   STRAND          291..303
FT                   /evidence="ECO:0000244|PDB:1BQU"
FT   STRAND          317..321
FT                   /evidence="ECO:0000244|PDB:1BQU"
FT   HELIX           325..331
FT                   /evidence="ECO:0000244|PDB:1BQU"
FT   STRAND          332..338
FT                   /evidence="ECO:0000244|PDB:3L5I"
FT   STRAND          345..351
FT                   /evidence="ECO:0000244|PDB:3L5I"
FT   HELIX           356..359
FT                   /evidence="ECO:0000244|PDB:3L5I"
FT   STRAND          363..372
FT                   /evidence="ECO:0000244|PDB:3L5I"
FT   STRAND          378..391
FT                   /evidence="ECO:0000244|PDB:3L5I"
FT   STRAND          396..406
FT                   /evidence="ECO:0000244|PDB:3L5I"
FT   STRAND          412..416
FT                   /evidence="ECO:0000244|PDB:3L5I"
FT   STRAND          428..435
FT                   /evidence="ECO:0000244|PDB:3L5I"
FT   STRAND          438..444
FT                   /evidence="ECO:0000244|PDB:3L5I"
FT   STRAND          452..460
FT                   /evidence="ECO:0000244|PDB:3L5I"
FT   STRAND          462..464
FT                   /evidence="ECO:0000244|PDB:3L5I"
FT   STRAND          469..474
FT                   /evidence="ECO:0000244|PDB:3L5I"
FT   STRAND          478..481
FT                   /evidence="ECO:0000244|PDB:3L5I"
FT   STRAND          491..500
FT                   /evidence="ECO:0000244|PDB:3L5I"
FT   STRAND          508..515
FT                   /evidence="ECO:0000244|PDB:3L5I"
FT   STRAND          525..530
FT                   /evidence="ECO:0000244|PDB:3L5I"
FT   STRAND          535..539
FT                   /evidence="ECO:0000244|PDB:3L5I"
FT   HELIX           544..547
FT                   /evidence="ECO:0000244|PDB:3L5I"
FT   STRAND          553..560
FT                   /evidence="ECO:0000244|PDB:3L5I"
FT   STRAND          566..571
FT                   /evidence="ECO:0000244|PDB:3L5I"
FT   STRAND          575..579
FT                   /evidence="ECO:0000244|PDB:3L5I"
FT   STRAND          587..596
FT                   /evidence="ECO:0000244|PDB:3L5I"
FT   STRAND          599..602
FT                   /evidence="ECO:0000244|PDB:3L5I"
FT   STRAND          606..609
FT                   /evidence="ECO:0000244|PDB:3L5I"
SQ   SEQUENCE   918 AA;  103537 MW;  6510A4409FFCF08C CRC64;
     MLTLQTWLVQ ALFIFLTTES TGELLDPCGY ISPESPVVQL HSNFTAVCVL KEKCMDYFHV
     NANYIVWKTN HFTIPKEQYT IINRTASSVT FTDIASLNIQ LTCNILTFGQ LEQNVYGITI
     ISGLPPEKPK NLSCIVNEGK KMRCEWDGGR ETHLETNFTL KSEWATHKFA DCKAKRDTPT
     SCTVDYSTVY FVNIEVWVEA ENALGKVTSD HINFDPVYKV KPNPPHNLSV INSEELSSIL
     KLTWTNPSIK SVIILKYNIQ YRTKDASTWS QIPPEDTAST RSSFTVQDLK PFTEYVFRIR
     CMKEDGKGYW SDWSEEASGI TYEDRPSKAP SFWYKIDPSH TQGYRTVQLV WKTLPPFEAN
     GKILDYEVTL TRWKSHLQNY TVNATKLTVN LTNDRYLATL TVRNLVGKSD AAVLTIPACD
     FQATHPVMDL KAFPKDNMLW VEWTTPRESV KKYILEWCVL SDKAPCITDW QQEDGTVHRT
     YLRGNLAESK CYLITVTPVY ADGPGSPESI KAYLKQAPPS KGPTVRTKKV GKNEAVLEWD
     QLPVDVQNGF IRNYTIFYRT IIGNETAVNV DSSHTEYTLS SLTSDTLYMV RMAAYTDEGG
     KDGPEFTFTT PKFAQGEIEA IVVPVCLAFL LTTLLGVLFC FNKRDLIKKH IWPNVPDPSK
     SHIAQWSPHT PPRHNFNSKD QMYSDGNFTD VSVVEIEAND KKPFPEDLKS LDLFKKEKIN
     TEGHSSGIGG SSCMSSSRPS ISSSDENESS QNTSSTVQYS TVVHSGYRHQ VPSVQVFSRS
     ESTQPLLDSE ERPEDLQLVD HVDGGDGILP RQQYFKQNCS QHESSPDISH FERSKQVSSV
     NEEDFVRLKQ QISDHISQSC GSGQMKMFQE VSAADAFGPG TEGQVERFET VGMEAATDEG
     MPKSYLPQTV RQGGYMPQ
//