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 27-MAR-2024, entry version 245. 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 INTERACTION WITH ARMH4. RX PubMed=26927669; DOI=10.1172/jci84620; RA Lee D., Wang Y.H., Kalaitzidis D., Ramachandran J., Eda H., Sykes D.B., RA Raje N., Scadden D.T.; RT "Endogenous transmembrane protein UT2 inhibits pSTAT3 and suppresses RT hematological malignancy."; RL J. Clin. Invest. 126:1300-1310(2016). RN [29] 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 [30] 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 [31] 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 [32] 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 [33] {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 [34] 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 [35] 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 [36] 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 [37] 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 [38] RP VARIANT HIES4B TYR-404, INVOLVEMENT IN HIES4B, FUNCTION, AND RP CHARACTERIZATION OF VARIANT HIES4B 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 [39] RP VARIANT HIES4B LEU-498, INVOLVEMENT IN HIES4B, FUNCTION, AND RP CHARACTERIZATION OF VARIANT HIES4B 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). RN [40] RP VARIANT STWS2 281-ARG--GLN-918 DEL, INVOLVEMENT IN STWS2, AND RP CHARACTERIZATION OF VARIANT STWS2 281-ARG--GLN-918 DEL. RX PubMed=31914175; DOI=10.1084/jem.20191306; RA Chen Y.H., Grigelioniene G., Newton P.T., Gullander J., Elfving M., RA Hammarsjoe A., Batkovskyte D., Alsaif H.S., Kurdi W.I.Y., Abdulwahab F., RA Shanmugasundaram V., Devey L., Bacrot S., Brodszki J., Huber C., Hamel B., RA Gisselsson D., Papadogiannakis N., Jedrycha K., Guertl-Lackner B., RA Chagin A.S., Nishimura G., Aschenbrenner D., Alkuraya F.S., Laurence A., RA Cormier-Daire V., Uhlig H.H.; RT "Absence of GP130 cytokine receptor signaling causes extended Stueve- RT Wiedemann syndrome."; RL J. Exp. Med. 217:0-0(2020). RN [41] RP VARIANTS HIES4A 733-CYS--GLN-918 DEL; 754-SER--GLN-918 DEL AND RP 759-TYR--GLN-918 DEL, CHARACTERIZATION OF VARIANTS HIES4A 733-CYS--GLN-918 RP DEL; 754-SER--GLN-918 DEL AND 759-TYR--GLN-918 DEL, AND MUTAGENESIS OF RP 789-SER--GLN-918 AND 899-GLU--GLN-918. RX PubMed=32207811; DOI=10.1084/jem.20191804; RG Undiagnosed Diseases Network; RA Beziat V., Tavernier S.J., Chen Y.H., Ma C.S., Materna M., Laurence A., RA Staal J., Aschenbrenner D., Roels L., Worley L., Claes K., Gartner L., RA Kohn L.A., De Bruyne M., Schmitz-Abe K., Charbonnier L.M., Keles S., RA Nammour J., Vladikine N., Maglorius Renkilaraj M.R.L., Seeleuthner Y., RA Migaud M., Rosain J., Jeljeli M., Boisson B., Van Braeckel E., RA Rosenfeld J.A., Dai H., Burrage L.C., Murdock D.R., Lambrecht B.N., RA Avettand-Fenoel V., Vogel T.P., Esther C.R., Haskologlu S., Dogu F., RA Ciznar P., Boutboul D., Ouachee-Chardin M., Amourette J., Lebras M.N., RA Gauvain C., Tcherakian C., Ikinciogullari A., Beyaert R., Abel L., RA Milner J.D., Grimbacher B., Couderc L.J., Butte M.J., Freeman A.F., RA Catherinot E., Fieschi C., Chatila T.A., Tangye S.G., Uhlig H.H., RA Haerynck F., Casanova J.L., Puel A.; RT "Dominant-negative mutations in human IL6ST underlie hyper-IgE syndrome."; RL J. Exp. Med. 217:0-0(2020). RN [42] RP VARIANT IMD94 187-SER--TYR-190 DEL, CHARACTERIZATION OF VARIANT IMD94 RP 187-SER--TYR-190 DEL, AND INVOLVEMENT IN IMD94. RX PubMed=33517393; DOI=10.1093/hmg/ddab035; RA Materna-Kiryluk A., Pollak A., Gawalski K., Szczawinska-Poplonyk A., RA Rydzynska Z., Sosnowska A., Cukrowska B., Gasperowicz P., Konopka E., RA Pietrucha B., Grzywa T.M., Banaszak-Ziemska M., Niedziela M., RA Skalska-Sadowska J., Stawinski P., Sladowski D., Nowis D., Ploski R.; RT "Mosaic IL6ST variant inducing constitutive GP130 cytokine receptor RT signaling as a cause of neonatal onset immunodeficiency with RT autoinflammation and dysmorphy."; RL Hum. Mol. Genet. 30:226-233(2021). RN [43] RP VARIANT HIES4B PRO-517, AND CHARACTERIZATION OF VARIANT HIES4B PRO-517. RX PubMed=33771552; DOI=10.1016/j.jaci.2021.02.044; RG Undiagnosed Diseases Network; RA Chen Y.H., Zastrow D.B., Metcalfe R.D., Gartner L., Krause F., Morton C.J., RA Marwaha S., Fresard L., Huang Y., Zhao C., McCormack C., Bick D., RA Worthey E.A., Eng C.M., Gold J., Montgomery S.B., Fisher P.G., Ashley E.A., RA Wheeler M.T., Parker M.W., Shanmugasundaram V., Putoczki T.L., RA Schmidt-Arras D., Laurence A., Bernstein J.A., Griffin M.D.W., Uhlig H.H.; RT "Functional and structural analysis of cytokine-selective IL6ST defects RT that cause recessive hyper-IgE syndrome."; RL J. Allergy Clin. Immunol. 148:585-598(2021). 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). Interacts with ARMH4; CC this interaction prevents IL6ST protein homodimerization and bridges CC ARMH4 with IL6R and STAT3 and therefore inhibits phosphorylation of CC STAT3 at 'Tyr-705' (PubMed:26927669). {ECO:0000250|UniProtKB:Q00560, CC ECO:0000269|PubMed:12829785, ECO:0000269|PubMed:14527405, CC ECO:0000269|PubMed:19386761, ECO:0000269|PubMed:2261637, CC ECO:0000269|PubMed:25731159, ECO:0000269|PubMed:26927669, 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 syndrome 4A, autosomal dominant, with recurrent CC infections (HIES4A) [MIM:619752]: An immunologic disorder characterized CC by recurrent mainly sino-pulmonary infections associated with increased CC serum IgE. Some patients have onset of symptoms in early childhood and CC develop complications, including bronchiectasis or hemoptysis, whereas CC others have later onset of less severe infections. Immunologic workup CC usually shows normal leukocyte levels, although some patients may CC demonstrate alterations in lymphocyte subsets, including T cells. CC Affected individuals also have variable skeletal abnormalities, CC including high-arched palate, hyperextensible joints, scoliosis, and CC bone fractures. {ECO:0000269|PubMed:32207811}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- DISEASE: Hyper-IgE syndrome 4B, autosomal recessive, with recurrent CC infections (HIES4B) [MIM:618523]: An immunologic disorder characterized CC by recurrent infections, mainly affecting the respiratory tract, skin CC and 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, ECO:0000269|PubMed:33771552}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Stuve-Wiedemann syndrome 2 (STWS2) [MIM:619751]: A form of CC Stuve-Wiedemann syndrome, an autosomal recessive disease characterized CC by bowing of tubular bones and other skeletal and craniofacial CC abnormalities, respiratory distress, feeding difficulties, and CC hyperthermic episodes. Most patients do not survive past infancy. STWS2 CC patients manifest skeletal dysplasia and neonatal lung dysfunction with CC additional features such as congenital thrombocytopenia, eczematoid CC dermatitis, renal abnormalities, and defective acute-phase response. CC {ECO:0000269|PubMed:31914175}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Immunodeficiency 94 with autoinflammation and dysmorphic CC facies (IMD94) [MIM:619750]: An autosomal dominant disorder CC characterized by onset in early infancy, lymphadenopathy, CC autoinflammation, immunodeficiency with hypogammaglobulinemia, and CC dysmorphic facial features. {ECO:0000269|PubMed:33517393}. Note=The CC disease may be caused by variants affecting the gene represented in CC 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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 PDB; 7U7N; EM; 3.47 A; B=23-321. DR PDB; 8D6A; EM; 3.54 A; A=23-619. DR PDB; 8D74; EM; 3.03 A; A=23-619. DR PDB; 8D7R; EM; 3.90 A; A=23-619. DR PDB; 8D82; EM; 3.22 A; A/E=23-700. DR PDB; 8D85; EM; 3.81 A; B=23-619. DR PDB; 8DPS; EM; 3.47 A; A/D=22-324. DR PDB; 8DPT; EM; 4.00 A; A/D=22-612. DR PDB; 8DPU; X-ray; 3.78 A; A/D/G/J/M/P=22-324. 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 PDBsum; 7U7N; -. DR PDBsum; 8D6A; -. DR PDBsum; 8D74; -. DR PDBsum; 8D7R; -. DR PDBsum; 8D82; -. DR PDBsum; 8D85; -. DR PDBsum; 8DPS; -. DR PDBsum; 8DPT; -. DR PDBsum; 8DPU; -. DR AlphaFoldDB; P40189; -. DR BMRB; P40189; -. DR EMDB; EMD-26382; -. DR EMDB; EMD-27221; -. DR EMDB; EMD-27227; -. DR EMDB; EMD-27229; -. DR EMDB; EMD-27231; -. DR EMDB; EMD-27244; -. DR EMDB; EMD-27246; -. DR EMDB; EMD-27247; -. DR EMDB; EMD-27641; -. DR EMDB; EMD-27642; -. DR SASBDB; P40189; -. DR SMR; P40189; -. DR BioGRID; 109786; 72. 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 GlyCosmos; P40189; 13 sites, 18 glycans. DR GlyGen; P40189; 15 sites, 18 N-linked glycans (9 sites), 1 O-linked glycan (2 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; 9606-ENSP00000370698; -. DR PeptideAtlas; P40189; -. DR ProteomicsDB; 55338; -. [P40189-1] DR ProteomicsDB; 55339; -. [P40189-2] DR ProteomicsDB; 55340; -. [P40189-3] DR Pumba; P40189; -. DR Antibodypedia; 2448; 936 antibodies from 39 providers. DR DNASU; 3572; -. DR Ensembl; ENST00000381294.8; ENSP00000370694.3; ENSG00000134352.21. [P40189-3] DR Ensembl; ENST00000381298.7; ENSP00000370698.2; ENSG00000134352.21. [P40189-1] DR Ensembl; ENST00000502326.7; ENSP00000462158.1; ENSG00000134352.21. [P40189-1] DR Ensembl; ENST00000522633.2; ENSP00000435399.1; ENSG00000134352.21. [P40189-2] DR Ensembl; ENST00000698645.1; ENSP00000513858.1; ENSG00000134352.21. [P40189-1] 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 AGR; HGNC:6021; -. 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 MIM; 619750; phenotype. DR MIM; 619751; phenotype. DR MIM; 619752; phenotype. DR neXtProt; NX_P40189; -. DR OpenTargets; ENSG00000134352; -. DR Orphanet; 2314; Autosomal dominant hyper-IgE syndrome due to STAT3 deficiency. DR Orphanet; 641368; Autosomal recessive hyper-IgE syndrome due to ZNF341 deficiency. DR Orphanet; 3206; Stueve-Wiedemann syndrome. 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; RYILEWC; -. DR OrthoDB; 5354422at2759; -. 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; 41 hits in 1176 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 213 other cell types or tissues. DR ExpressionAtlas; P40189; baseline and differential. 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; IDA:UniProt. 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:0015026; F:coreceptor activity; IDA:UniProt. 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:0030296; F:protein tyrosine kinase activator activity; IDA:UniProt. 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:0038154; P:interleukin-11-mediated signaling pathway; IDA:UniProt. 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 GO; GO:0072540; P:T-helper 17 cell lineage commitment; ISS:UniProt. DR CDD; cd00063; FN3; 2. DR Gene3D; 2.60.40.10; Immunoglobulins; 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 PANTHER; PTHR23036; CYTOKINE RECEPTOR; 1. DR PANTHER; PTHR23036:SF83; INTERLEUKIN-6 RECEPTOR SUBUNIT BETA; 1. 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; Fibronectin type III; 5. DR PROSITE; PS50853; FN3; 4. DR PROSITE; PS01353; HEMATOPO_REC_L_F2; 1. DR Genevisible; P40189; HS. 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 (correlated with increased levels of soluble FT IL6RB in blood serum; dbSNP:rs2228044)" FT /evidence="ECO:0000269|PubMed:24629561" FT /id="VAR_047783" FT VARIANT 187..190 FT /note="Missing (in IMD94; results in constitutively active FT IL6-mediated signaling and constitutive phosphorylation of FT STAT3 in patient cells)" FT /evidence="ECO:0000269|PubMed:33517393" FT /id="VAR_086950" FT VARIANT 200 FT /note="A -> G (found in patient with lung cancer; uncertain FT significance; dbSNP:rs199905033)" FT /evidence="ECO:0000269|PubMed:25242236" FT /id="VAR_074654" FT VARIANT 281..918 FT /note="Missing (in STWS2; results in impaired FT cytokine-mediated signaling pathway with loss of response FT to IL-6, IL-11, IL-27, OSM and LIF; does not localize to FT the cell membrane)" FT /evidence="ECO:0000269|PubMed:31914175" FT /id="VAR_086951" FT VARIANT 397 FT /note="L -> V (in dbSNP:rs2228043)" FT /id="VAR_047784" FT VARIANT 404 FT /note="N -> Y (in HIES4B; results in defective FT cytokine-mediated signaling pathway with loss of response FT to IL-6, IL-11, IL-27, OSM but not LIF)" 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 HIES4B; results in defective FT cytokine-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 VARIANT 517 FT /note="A -> P (in HIES4B; results in impaired FT cytokine-mediated signaling pathway with loss of response FT to IL-6, IL-11, IL-27 and reduced response to OSM, CNTF and FT LIF)" FT /evidence="ECO:0000269|PubMed:33771552" FT /id="VAR_086952" FT VARIANT 733..918 FT /note="Missing (in HIES4A; results in impaired FT cytokine-mediated signaling pathway with loss of response FT to IL-6, IL-11, OSM and LIF and a weak response to IL-27)" FT /evidence="ECO:0000269|PubMed:32207811" FT /id="VAR_086953" FT VARIANT 754..918 FT /note="Missing (in HIES4A; results in impaired FT cytokine-mediated signaling pathway with loss of response FT to IL-6, IL-11, OSM and LIF and a weak response to IL-27)" FT /evidence="ECO:0000269|PubMed:32207811" FT /id="VAR_086954" FT VARIANT 759..918 FT /note="Missing (in HIES4A; results in impaired FT cytokine-mediated signaling pathway with loss of response FT to IL-6, IL-11, OSM, LIF and a weak response to IL-27)" FT /evidence="ECO:0000269|PubMed:32207811" FT /id="VAR_086955" 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 MUTAGEN 789..918 FT /note="Missing: Results in impaired cytokine-mediated FT signaling pathway with loss of response to IL-6 and IL-11. FT Weak response to IL-27, OSM and LIF." FT /evidence="ECO:0000269|PubMed:32207811" FT MUTAGEN 899..918 FT /note="Missing: Results in impaired cytokine-mediated FT signaling pathway with loss of response to IL-6 and IL-11. FT Weak response to IL-27, OSM and LIF." FT /evidence="ECO:0000269|PubMed:32207811" 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 165..168 FT /evidence="ECO:0007829|PDB:7U7N" FT STRAND 176..178 FT /evidence="ECO:0007829|PDB:1PVH" FT STRAND 181..183 FT /evidence="ECO:0007829|PDB:1BQU" FT STRAND 190..192 FT /evidence="ECO:0007829|PDB:8D74" 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 306..308 FT /evidence="ECO:0007829|PDB:8D82" 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 373..375 FT /evidence="ECO:0007829|PDB:8D74" 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 531..533 FT /evidence="ECO:0007829|PDB:8D82" 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 //