IL6RB_HUMAN
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 03-AUG-2022, entry version 236.
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 FUNCTION, AND IDENTIFICATION IN HUMANIN RECEPTOR COMPLEX.
RX PubMed=19386761; DOI=10.1091/mbc.e09-02-0168;
RA Hashimoto Y., Kurita M., Aiso S., Nishimoto I., Matsuoka M.;
RT "Humanin inhibits neuronal cell death by interacting with a cytokine
RT receptor complex or complexes involving CNTF receptor alpha/WSX-1/gp130.";
RL Mol. Biol. Cell 20:2864-2873(2009).
RN [19]
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 [20]
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 [21]
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 [22]
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 [23]
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 [24]
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 [25]
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 [26]
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 [27]
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 [28]
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 [29]
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 [30]
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 [31]
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 [32] {ECO:0007744|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 [33]
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 [34]
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 [35]
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 [36]
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 [37]
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 [38]
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 activates 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). Acts as a receptor for the neuroprotective peptide humanin
CC as part of a complex with IL27RA/WSX1 and CNTFR (PubMed:19386761).
CC Mediates signals which regulate immune response, hematopoiesis, pain
CC control and bone metabolism (By similarity). Has a role in embryonic
CC development (By similarity). Essential for survival of motor and
CC sensory neurons and for differentiation of astrocytes (By similarity).
CC Required for expression of TRPA1 in nociceptive neurons (By
CC similarity). Required for the maintenance of PTH1R expression in the
CC osteoblast lineage and for the stimulation of PTH-induced osteoblast
CC differentiation (By similarity). Required for normal trabecular bone
CC mass and cortical bone composition (By similarity).
CC {ECO:0000250|UniProtKB:Q00560, ECO:0000269|PubMed:19386761,
CC ECO:0000269|PubMed:19915009, ECO:0000269|PubMed:2261637,
CC ECO:0000269|PubMed:23294003, ECO:0000269|PubMed:25731159,
CC ECO:0000269|PubMed:28747427, 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). Component of a receptor complex composed of
CC IL6ST/GP130, IL27RA/WSX1 and CNTFR which interacts with the
CC neuroprotective peptide humanin (PubMed:19386761). Interacts with HCK
CC (PubMed:9406996). Interacts with INPP5D/SHIP1 (By similarity).
CC Interacts with SRC and YES (PubMed:25731159).
CC {ECO:0000250|UniProtKB:Q00560, ECO:0000269|PubMed:12829785,
CC ECO:0000269|PubMed:14527405, ECO:0000269|PubMed:19386761,
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 variants
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}.
CC ---------------------------------------------------------------------------
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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; 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; 1P9M; -.
DR PDBsum; 1PVH; -.
DR PDBsum; 3L5H; -.
DR PDBsum; 3L5I; -.
DR PDBsum; 3L5J; -.
DR AlphaFoldDB; P40189; -.
DR BMRB; P40189; -.
DR SMR; P40189; -.
DR BioGRID; 109786; 67.
DR CORUM; P40189; -.
DR DIP; DIP-95N; -.
DR IntAct; P40189; 31.
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, 18 N-linked glycans (9 sites).
DR iPTMnet; P40189; -.
DR PhosphoSitePlus; P40189; -.
DR SwissPalm; 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; 813 antibodies from 39 providers.
DR DNASU; 3572; -.
DR Ensembl; ENST00000336909.9; ENSP00000338799.5; ENSG00000134352.20. [P40189-1]
DR Ensembl; ENST00000381287.8; ENSP00000370687.4; ENSG00000134352.20. [P40189-2]
DR Ensembl; ENST00000381294.7; ENSP00000370694.3; ENSG00000134352.20. [P40189-3]
DR Ensembl; ENST00000381298.7; ENSP00000370698.2; ENSG00000134352.20. [P40189-1]
DR Ensembl; ENST00000502326.7; ENSP00000462158.1; ENSG00000134352.20. [P40189-1]
DR Ensembl; ENST00000522633.2; ENSP00000435399.1; ENSG00000134352.20. [P40189-2]
DR GeneID; 3572; -.
DR KEGG; hsa:3572; -.
DR MANE-Select; ENST00000381298.7; ENSP00000370698.2; NM_002184.4; NP_002175.2.
DR UCSC; uc003jqq.4; human. [P40189-1]
DR CTD; 3572; -.
DR DisGeNET; 3572; -.
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 VEuPathDB; HostDB:ENSG00000134352; -.
DR eggNOG; ENOG502QXEG; Eukaryota.
DR GeneTree; ENSGT00940000159608; -.
DR HOGENOM; CLU_017990_0_0_1; -.
DR InParanoid; P40189; -.
DR OMA; KPNPPRN; -.
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; 40 hits in 1096 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 parietal pleura and 211 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:0045121; C:membrane raft; IDA:ARUK-UCL.
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:0097110; F:scaffold protein binding; IPI:ARUK-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:0070102; P:interleukin-6-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0060576; P:intestinal epithelial cell development; IDA:UniProtKB.
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:0043524; P:negative regulation of neuron apoptotic process; IMP:UniProtKB.
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:0045747; P:positive regulation of Notch signaling pathway; IDA:UniProtKB.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IMP:BHF-UCL.
DR GO; GO:1901731; P:positive regulation of platelet aggregation; TAS:ARUK-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:0034097; P:response to cytokine; IDA:BHF-UCL.
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 variant; Disulfide bond; Glycoprotein;
KW Host-virus interaction; Immunoglobulin domain; Membrane; Phosphoprotein;
KW Receptor; Reference proteome; Repeat; Secreted; Signal; Transmembrane;
KW 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 REGION 660..681
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 722..758
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 310..314
FT /note="WSXWS motif"
FT MOTIF 651..659
FT /note="Box 1 motif"
FT COMPBIAS 724..758
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 661
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 667
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|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:0007744|PubMed:17081983"
FT MOD_RES 839
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|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 (associated with increased levels of soluble
FT 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:0007829|PDB:1I1R"
FT STRAND 37..39
FT /evidence="ECO:0007829|PDB:1I1R"
FT STRAND 44..50
FT /evidence="ECO:0007829|PDB:1I1R"
FT HELIX 52..58
FT /evidence="ECO:0007829|PDB:1I1R"
FT HELIX 62..64
FT /evidence="ECO:0007829|PDB:1I1R"
FT STRAND 65..69
FT /evidence="ECO:0007829|PDB:1I1R"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:1I1R"
FT STRAND 80..83
FT /evidence="ECO:0007829|PDB:1I1R"
FT STRAND 86..91
FT /evidence="ECO:0007829|PDB:1I1R"
FT STRAND 97..107
FT /evidence="ECO:0007829|PDB:1I1R"
FT TURN 108..110
FT /evidence="ECO:0007829|PDB:1I1R"
FT STRAND 111..123
FT /evidence="ECO:0007829|PDB:1I1R"
FT STRAND 130..137
FT /evidence="ECO:0007829|PDB:1BQU"
FT STRAND 143..147
FT /evidence="ECO:0007829|PDB:1BQU"
FT STRAND 157..164
FT /evidence="ECO:0007829|PDB:1BQU"
FT STRAND 176..178
FT /evidence="ECO:0007829|PDB:1PVH"
FT STRAND 181..183
FT /evidence="ECO:0007829|PDB:1BQU"
FT STRAND 194..202
FT /evidence="ECO:0007829|PDB:1BQU"
FT STRAND 205..208
FT /evidence="ECO:0007829|PDB:1BQU"
FT STRAND 212..214
FT /evidence="ECO:0007829|PDB:1BQU"
FT HELIX 216..218
FT /evidence="ECO:0007829|PDB:1BQU"
FT STRAND 219..221
FT /evidence="ECO:0007829|PDB:1BQU"
FT STRAND 226..231
FT /evidence="ECO:0007829|PDB:1BQU"
FT STRAND 234..238
FT /evidence="ECO:0007829|PDB:1I1R"
FT STRAND 240..245
FT /evidence="ECO:0007829|PDB:1BQU"
FT HELIX 248..251
FT /evidence="ECO:0007829|PDB:1BQU"
FT STRAND 255..263
FT /evidence="ECO:0007829|PDB:1BQU"
FT HELIX 274..277
FT /evidence="ECO:0007829|PDB:1BQU"
FT STRAND 282..286
FT /evidence="ECO:0007829|PDB:1BQU"
FT STRAND 291..303
FT /evidence="ECO:0007829|PDB:1BQU"
FT STRAND 317..321
FT /evidence="ECO:0007829|PDB:1BQU"
FT HELIX 325..331
FT /evidence="ECO:0007829|PDB:1BQU"
FT STRAND 332..338
FT /evidence="ECO:0007829|PDB:3L5I"
FT STRAND 345..351
FT /evidence="ECO:0007829|PDB:3L5I"
FT HELIX 356..359
FT /evidence="ECO:0007829|PDB:3L5I"
FT STRAND 363..372
FT /evidence="ECO:0007829|PDB:3L5I"
FT STRAND 378..391
FT /evidence="ECO:0007829|PDB:3L5I"
FT STRAND 396..406
FT /evidence="ECO:0007829|PDB:3L5I"
FT STRAND 412..416
FT /evidence="ECO:0007829|PDB:3L5I"
FT STRAND 428..435
FT /evidence="ECO:0007829|PDB:3L5I"
FT STRAND 438..444
FT /evidence="ECO:0007829|PDB:3L5I"
FT STRAND 452..460
FT /evidence="ECO:0007829|PDB:3L5I"
FT STRAND 462..464
FT /evidence="ECO:0007829|PDB:3L5I"
FT STRAND 469..474
FT /evidence="ECO:0007829|PDB:3L5I"
FT STRAND 478..481
FT /evidence="ECO:0007829|PDB:3L5I"
FT STRAND 491..500
FT /evidence="ECO:0007829|PDB:3L5I"
FT STRAND 508..515
FT /evidence="ECO:0007829|PDB:3L5I"
FT STRAND 525..530
FT /evidence="ECO:0007829|PDB:3L5I"
FT STRAND 535..539
FT /evidence="ECO:0007829|PDB:3L5I"
FT HELIX 544..547
FT /evidence="ECO:0007829|PDB:3L5I"
FT STRAND 553..560
FT /evidence="ECO:0007829|PDB:3L5I"
FT STRAND 566..571
FT /evidence="ECO:0007829|PDB:3L5I"
FT STRAND 575..579
FT /evidence="ECO:0007829|PDB:3L5I"
FT STRAND 587..596
FT /evidence="ECO:0007829|PDB:3L5I"
FT STRAND 599..602
FT /evidence="ECO:0007829|PDB:3L5I"
FT STRAND 606..609
FT /evidence="ECO:0007829|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
