ID   IL6RA_HUMAN             Reviewed;         468 AA.
AC   P08887; A8KAE8; B2R6V4; Q16202; Q53EQ7; Q5FWG2; Q5VZ23;
DT   01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1988, sequence version 1.
DT   12-AUG-2020, entry version 229.
DE   RecName: Full=Interleukin-6 receptor subunit alpha {ECO:0000305};
DE            Short=IL-6 receptor subunit alpha;
DE            Short=IL-6R subunit alpha;
DE            Short=IL-6R-alpha;
DE            Short=IL-6RA;
DE   AltName: Full=IL-6R 1;
DE   AltName: Full=Membrane glycoprotein 80;
DE            Short=gp80;
DE   AltName: CD_antigen=CD126;
DE   Contains:
DE     RecName: Full=Soluble interleukin-6 receptor subunit alpha {ECO:0000305};
DE              Short=sIL6R {ECO:0000303|PubMed:12794819, ECO:0000303|PubMed:26876177, ECO:0000303|PubMed:28060820};
DE   Flags: Precursor;
GN   Name=IL6R {ECO:0000312|HGNC:HGNC:6019};
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).
RX   PubMed=3136546; DOI=10.1126/science.3136546;
RA   Yamasaki K., Taga T., Hirata Y., Yawata H., Kawanishi Y., Seed B.,
RA   Taniguchi T., Hirano T., Kishimoto T.;
RT   "Cloning and expression of the human interleukin-6 (BSF-2/IFN beta 2)
RT   receptor.";
RL   Science 241:825-828(1988).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Yamasaki K., Taga T., Hirata Y., Yawata H., Kawanishi Y., Seed B.,
RA   Taniguchi T., Hirano T., Kishimoto T.;
RT   "Molecular structure of interleukin 6 receptor.";
RL   Proc. Jpn. Acad., B, Phys. Biol. Sci. 64:209-211(1988).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=1872801; DOI=10.1042/bj2770659;
RA   Schooltink H., Stoyan T., Lenz D., Schmitz H., Hirano T., Kishimoto T.,
RA   Heinrich P.C., Rose-John S.;
RT   "Structural and functional studies on the human hepatic interleukin-6
RT   receptor. Molecular cloning and overexpression in HepG2 cells.";
RL   Biochem. J. 277:659-664(1991).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP   ALA-358.
RC   TISSUE=Trachea;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Kidney;
RA   Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL   Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Lymph;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 313-365 (ISOFORM 2).
RX   PubMed=8056053; DOI=10.1002/eji.1830240837;
RA   Horiuchi S., Koyanagi Y., Zhou Y., Miyamoto H., Tanaka Y., Waki M.,
RA   Matsumoto A., Yamamoto M., Yamamoto N.;
RT   "Soluble interleukin-6 receptors released from T cell or
RT   granulocyte/macrophage cell lines and human peripheral blood mononuclear
RT   cells are generated through an alternative splicing mechanism.";
RL   Eur. J. Immunol. 24:1945-1948(1994).
RN   [10]
RP   PARTIAL PROTEIN SEQUENCE, GLYCOSYLATION AT ASN-55; ASN-93 AND ASN-221, LACK
RP   OF GLYCOSYLATION AT ASN-245, AND DISULFIDE BONDS.
RX   PubMed=10066782; DOI=10.1074/jbc.274.11.7207;
RA   Cole A.R., Hall N.E., Treutlein H.R., Eddes J.S., Reid G.E., Moritz R.L.,
RA   Simpson R.J.;
RT   "Disulfide bond structure and N-glycosylation sites of the extracellular
RT   domain of the human interleukin-6 receptor.";
RL   J. Biol. Chem. 274:7207-7215(1999).
RN   [11]
RP   PROTEIN SEQUENCE OF 20-49, AND SUBCELLULAR LOCATION.
RX   PubMed=2529343; DOI=10.1084/jem.170.4.1409;
RA   Novick D., Engelmann H., Wallach D., Rubinstein M.;
RT   "Soluble cytokine receptors are present in normal human urine.";
RL   J. Exp. Med. 170:1409-1414(1989).
RN   [12]
RP   MUTAGENESIS.
RX   PubMed=8467812; DOI=10.1002/j.1460-2075.1993.tb05815.x;
RA   Yawata H., Yasukawa K., Natsuka S., Murakami M., Yamasaki K., Hibi M.,
RA   Taga T., Kishimoto T.;
RT   "Structure-function analysis of human IL-6 receptor: dissociation of amino
RT   acid residues required for IL-6-binding and for IL-6 signal transduction
RT   through gp130.";
RL   EMBO J. 12:1705-1712(1993).
RN   [13]
RP   FUNCTION.
RX   PubMed=11017875;
RA   Martens A.S., Bode J.G., Heinrich P.C., Graeve L.;
RT   "The cytoplasmic domain of the interleukin-6 receptor gp80 mediates its
RT   basolateral sorting in polarized Madin-Darby canine kidney cells.";
RL   J. Cell Sci. 113:3593-3602(2000).
RN   [14]
RP   FUNCTION.
RX   PubMed=12794819; DOI=10.1002/art.11143;
RA   Nakahara H., Song J., Sugimoto M., Hagihara K., Kishimoto T., Yoshizaki K.,
RA   Nishimoto N.;
RT   "Anti-interleukin-6 receptor antibody therapy reduces vascular endothelial
RT   growth factor production in rheumatoid arthritis.";
RL   Arthritis Rheum. 48:1521-1529(2003).
RN   [15]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=16270750; DOI=10.1016/j.ejcb.2005.06.001;
RA   Buk D.M., Renner O., Graeve L.;
RT   "Increased association with detergent-resistant membranes/lipid rafts of
RT   apically targeted mutants of the interleukin-6 receptor gp80.";
RL   Eur. J. Cell Biol. 84:819-831(2005).
RN   [16]
RP   FUNCTION, AND ACTIVITY REGULATION.
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   [17]
RP   FUNCTION, AND PROTEOLYTIC CLEAVAGE.
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   [18]
RP   FUNCTION, AND INTERACTION WITH SORL1.
RX   PubMed=28265003; DOI=10.1128/mcb.00641-16;
RA   Larsen J.V., Petersen C.M.;
RT   "SorLA in Interleukin-6 Signaling and Turnover.";
RL   Mol. Cell. Biol. 37:0-0(2017).
RN   [19]
RP   FUNCTION, PROTEOLYTIC CLEAVAGE, TISSUE SPECIFICITY (ISOFORM 2),
RP   GLYCOSYLATION AT ASN-55; ASN-93; ASN-221; ASN-245; ASN-350 AND THR-352,
RP   MUTAGENESIS OF ASN-55; THR-57; ASN-93; ASN-221; ASN-245; ASN-350; THR-352;
RP   355-PRO-VAL-356; PRO-355 AND VAL-356, CHARACTERIZATION OF VARIANT ALA-358,
RP   AND SUBCELLULAR LOCATION.
RX   PubMed=28060820; DOI=10.1371/journal.pbio.2000080;
RA   Riethmueller S., Somasundaram P., Ehlers J.C., Hung C.W., Flynn C.M.,
RA   Lokau J., Agthe M., Duesterhoeft S., Zhu Y., Groetzinger J., Lorenzen I.,
RA   Koudelka T., Yamamoto K., Pickhinke U., Wichert R., Becker-Pauly C.,
RA   Raedisch M., Albrecht A., Hessefort M., Stahnke D., Unverzagt C.,
RA   Rose-John S., Tholey A., Garbers C.;
RT   "Proteolytic Origin of the Soluble Human IL-6R In Vivo and a Decisive Role
RT   of N-Glycosylation.";
RL   PLoS Biol. 15:e2000080-e2000080(2017).
RN   [20]
RP   REVIEW ON FUNCTION.
RX   PubMed=30995492; DOI=10.1016/j.immuni.2019.03.026;
RA   Kang S., Tanaka T., Narazaki M., Kishimoto T.;
RT   "Targeting Interleukin-6 Signaling in Clinic.";
RL   Immunity 50:1007-1023(2019).
RN   [21]
RP   X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 20-344.
RX   PubMed=12461182; DOI=10.1073/pnas.232432399;
RA   Varghese J.N., Moritz R.L., Lou M.-Z., Van Donkelaar A., Ji H., Ivancic N.,
RA   Branson K.M., Hall N.E., Simpson R.J.;
RT   "Structure of the extracellular domains of the human interleukin-6 receptor
RT   alpha-chain.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:15959-15964(2002).
RN   [22] {ECO:0000244|PDB:1P9M}
RP   X-RAY CRYSTALLOGRAPHY (3.65 ANGSTROMS) OF 115-315 IN COMPLEX WITH IL6 AND
RP   IL6ST, 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   [23]
RP   POLYMORPHISM, VARIANT ALA-358, AND ASSOCIATION OF VARIANT ALA-358 WITH IL6
RP   AND SOLUBLE IL6R SERUM LEVELS.
RX   PubMed=17357077; DOI=10.1086/513206;
RG   Health, Aging and Body Composition (Health ABC) Study;
RA   Reich D., Patterson N., Ramesh V., De Jager P.L., McDonald G.J., Tandon A.,
RA   Choy E., Hu D., Tamraz B., Pawlikowska L., Wassel-Fyr C., Huntsman S.,
RA   Waliszewska A., Rossin E., Li R., Garcia M., Reiner A., Ferrell R.,
RA   Cummings S., Kwok P.Y., Harris T., Zmuda J.M., Ziv E.;
RT   "Admixture mapping of an allele affecting interleukin 6 soluble receptor
RT   and interleukin 6 levels.";
RL   Am. J. Hum. Genet. 80:716-726(2007).
CC   -!- FUNCTION: Part of the receptor for interleukin 6. Binds to IL6 with low
CC       affinity, but does not transduce a signal (PubMed:28265003). Signal
CC       activation necessitate an association with IL6ST. Activation leads to
CC       the regulation of the immune response, acute-phase reactions and
CC       hematopoiesis (Probable). The interaction with membrane-bound IL6R and
CC       IL6ST stimulates 'classic signaling', the restricted expression of the
CC       IL6R limits classic IL6 signaling to only a few tissues such as the
CC       liver and some cells of the immune system. Whereas the binding of IL6
CC       and soluble IL6R to IL6ST stimulates 'trans-signaling'. Alternatively,
CC       'cluster signaling' occurs when membrane-bound IL6:IL6R complexes on
CC       transmitter cells activate IL6ST receptors on neighboring receiver
CC       cells (Probable). {ECO:0000269|PubMed:28265003,
CC       ECO:0000305|PubMed:30995492}.
CC   -!- FUNCTION: [Isoform 1]: Signaling via the membrane-bound IL6R is mostly
CC       regenerative and anti-inflammatory (Probable). Drives naive CD4(+) T
CC       cells to the Th17 lineage, through 'cluster signaling' by dendritic
CC       cells (By similarity). {ECO:0000250|UniProtKB:P22272,
CC       ECO:0000305|PubMed:30995492}.
CC   -!- FUNCTION: [Isoform 2]: Soluble form of IL6 receptor (sIL6R) that acts
CC       as an agonist of IL6 activity (PubMed:21990364). The IL6:sIL6R complex
CC       (hyper-IL6) binds to IL6ST/gp130 on cell surfaces and induces signaling
CC       also on cells that do not express membrane-bound IL6R in a process
CC       called IL6 'trans-signaling'. sIL6R is causative for the
CC       proinflammatory properties of IL6 and an important player in the
CC       development of chronic inflammatory diseases (PubMed:21990364). In
CC       complex with IL6, is required for induction of VEGF production
CC       (PubMed:12794819). Plays a protective role during liver injury, being
CC       required for maintenance of tissue regeneration (By similarity).
CC       'Trans-signaling' in central nervous system regulates energy and
CC       glucose homeostasis (By similarity). {ECO:0000250|UniProtKB:P22272,
CC       ECO:0000269|PubMed:12794819, ECO:0000269|PubMed:21990364}.
CC   -!- FUNCTION: [Soluble interleukin-6 receptor subunit alpha]: Soluble form
CC       of IL6 receptor (sIL6R) that acts as an agonist of IL6 activity
CC       (PubMed:21990364). The IL6:sIL6R complex (hyper-IL6) binds to
CC       IL6ST/gp130 on cell surfaces and induces signaling also on cells that
CC       do not express membrane-bound IL6R in a process called IL6 'trans-
CC       signaling'. sIL6R is causative for the proinflammatory properties of
CC       IL6 and an important player in the development of chronic inflammatory
CC       diseases (PubMed:21990364). In complex with IL6, is required for
CC       induction of VEGF production (PubMed:12794819). Plays a protective role
CC       during liver injury, being required for maintenance of tissue
CC       regeneration (By similarity). 'Trans-signaling' in central nervous
CC       system regulates energy and glucose homeostasis (By similarity).
CC       {ECO:0000250|UniProtKB:P22272, ECO:0000269|PubMed:12794819,
CC       ECO:0000269|PubMed:21990364}.
CC   -!- ACTIVITY REGULATION: Classic and trans-signaling are both inhibited by
CC       tocilizumab, a humanized monoclonal antibody that blocks interleukin
CC       IL6R signaling. {ECO:0000269|PubMed:21990364}.
CC   -!- SUBUNIT: Component of a hexamer of two molecules each of IL6, IL6R and
CC       IL6ST; first binds to IL6 to associate with the signaling subunit IL6ST
CC       (PubMed:12829785, PubMed:28265003). Interacts (via N-terminal
CC       ectodomain) with SORL1; this interaction may affect IL6-binding to
CC       IL6R, hence decrease IL6 'classic-signaling' (PubMed:28265003).
CC       {ECO:0000269|PubMed:12829785, ECO:0000269|PubMed:28265003}.
CC   -!- SUBUNIT: [Isoform 2]: Also interacts with SORL1; this interaction leads
CC       to soluble IL6R internalization. May form a trimeric complex with the
CC       soluble SORL1 ectodomain and circulating IL6 receptor; this interaction
CC       might stabilize circulating IL6, hence promote IL6 'trans-signaling,.
CC       {ECO:0000269|PubMed:28265003}.
CC   -!- SUBUNIT: [Soluble interleukin-6 receptor subunit alpha]: Also interacts
CC       with SORL1; this interaction leads to soluble IL6R internalization. May
CC       form a trimeric complex with the soluble SORL1 ectodomain and
CC       circulating IL6 receptor; this interaction might stabilize circulating
CC       IL6, hence promote IL6 'trans-signaling,.
CC       {ECO:0000269|PubMed:28265003}.
CC   -!- INTERACTION:
CC       P08887; P05231: IL6; NbExp=7; IntAct=EBI-299383, EBI-720533;
CC       P08887; Q96EQ0: SGTB; NbExp=3; IntAct=EBI-299383, EBI-744081;
CC       P08887; Q92673: SORL1; NbExp=7; IntAct=EBI-299383, EBI-1171329;
CC       P08887; Q2HRC7: K2; Xeno; NbExp=3; IntAct=EBI-299383, EBI-9007403;
CC       P08887-2; O00233: PSMD9; NbExp=3; IntAct=EBI-16630231, EBI-750973;
CC   -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC       {ECO:0000250|UniProtKB:P22272}; Single-pass type I membrane protein
CC       {ECO:0000255}.
CC   -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted
CC       {ECO:0000269|PubMed:28060820}.
CC   -!- SUBCELLULAR LOCATION: [Soluble interleukin-6 receptor subunit alpha]:
CC       Secreted {ECO:0000269|PubMed:28060820}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1; Synonyms=Long, mIL6R {ECO:0000303|PubMed:26876177};
CC         IsoId=P08887-1; Sequence=Displayed;
CC       Name=2; Synonyms=Short, sIL6R {ECO:0000303|PubMed:21990364};
CC         IsoId=P08887-2; Sequence=VSP_001682, VSP_001683;
CC   -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed in peripheral blood
CC       mononuclear cells and weakly found in urine and serum. 1%-20% of the
CC       total sIL6R in plasma is generated by alternative splicing
CC       (PubMed:28060820). {ECO:0000269|PubMed:28060820}.
CC   -!- DOMAIN: The two fibronectin type-III-like domains, contained in the N-
CC       terminal part, form together a cytokine-binding domain.
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   -!- PTM: A short soluble form is released from the membrane by proteolysis
CC       (PubMed:26876177). The sIL6R is formed mostly by limited proteolysis of
CC       membrane-bound receptors, a process referred to as ectodomain shedding,
CC       but is also directly secreted from the cells after alternative mRNA
CC       splicing (PubMed:26876177, PubMed:28060820). mIL6R is cleaved by the
CC       proteases ADAM10 and ADAM17 (PubMed:26876177, PubMed:28060820).
CC       {ECO:0000269|PubMed:26876177, ECO:0000269|PubMed:28060820}.
CC   -!- PTM: Glycosylated. Glycosylation is dispensable for transport,
CC       signaling, and cell-surface turnover. Glycosylation at Asn-55 is a
CC       protease-regulatory exosite. Glycosylation is required for ADAM17-
CC       mediated proteolysis. {ECO:0000269|PubMed:28060820}.
CC   -!- POLYMORPHISM: Genetic variations in IL6R determine soluble IL6R serum
CC       levels [MIM:614689].
CC   -!- POLYMORPHISM: Genetic variations in IL6R define the IL6 serum level
CC       quantitative trait locus [MIM:614752].
CC   -!- SIMILARITY: Belongs to the type I cytokine receptor family. Type 3
CC       subfamily. {ECO:0000305}.
DR   EMBL; X12830; CAA31312.1; -; mRNA.
DR   EMBL; X58298; CAA41231.1; -; mRNA.
DR   EMBL; AK293013; BAF85702.1; -; mRNA.
DR   EMBL; AK312730; BAG35601.1; -; mRNA.
DR   EMBL; AK223582; BAD97302.1; -; mRNA.
DR   EMBL; AL162591; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471121; EAW53200.1; -; Genomic_DNA.
DR   EMBL; BC089410; AAH89410.1; -; mRNA.
DR   EMBL; S72848; AAC60635.1; -; mRNA.
DR   CCDS; CCDS1067.1; -. [P08887-1]
DR   CCDS; CCDS1068.1; -. [P08887-2]
DR   PIR; A41242; A41242.
DR   RefSeq; NP_000556.1; NM_000565.3. [P08887-1]
DR   RefSeq; NP_001193795.1; NM_001206866.1.
DR   RefSeq; NP_852004.1; NM_181359.2. [P08887-2]
DR   PDB; 1N26; X-ray; 2.40 A; A=20-344.
DR   PDB; 1N2Q; Model; -; C/D=20-344.
DR   PDB; 1P9M; X-ray; 3.65 A; C=115-315.
DR   PDB; 2ARW; NMR; -; A=212-336.
DR   PDB; 5FUC; X-ray; 2.70 A; C/D=111-322.
DR   PDBsum; 1N26; -.
DR   PDBsum; 1N2Q; -.
DR   PDBsum; 1P9M; -.
DR   PDBsum; 2ARW; -.
DR   PDBsum; 5FUC; -.
DR   SMR; P08887; -.
DR   BioGRID; 109784; 19.
DR   DIP; DIP-162N; -.
DR   ELM; P08887; -.
DR   IntAct; P08887; 18.
DR   MINT; P08887; -.
DR   STRING; 9606.ENSP00000357470; -.
DR   ChEMBL; CHEMBL2364155; -.
DR   DrugBank; DB11767; Sarilumab.
DR   DrugBank; DB06273; Tocilizumab.
DR   DrugCentral; P08887; -.
DR   GuidetoPHARMACOLOGY; 1708; -.
DR   GlyGen; P08887; 6 sites, 2 O-linked glycans (2 sites).
DR   iPTMnet; P08887; -.
DR   PhosphoSitePlus; P08887; -.
DR   BioMuta; IL6R; -.
DR   DMDM; 124343; -.
DR   jPOST; P08887; -.
DR   MassIVE; P08887; -.
DR   MaxQB; P08887; -.
DR   PaxDb; P08887; -.
DR   PeptideAtlas; P08887; -.
DR   PRIDE; P08887; -.
DR   ProteomicsDB; 52171; -. [P08887-1]
DR   ProteomicsDB; 52172; -. [P08887-2]
DR   ABCD; P08887; 121 sequenced antibodies.
DR   Antibodypedia; 20397; 967 antibodies.
DR   DNASU; 3570; -.
DR   Ensembl; ENST00000344086; ENSP00000340589; ENSG00000160712. [P08887-2]
DR   Ensembl; ENST00000368485; ENSP00000357470; ENSG00000160712. [P08887-1]
DR   GeneID; 3570; -.
DR   KEGG; hsa:3570; -.
DR   UCSC; uc001fez.2; human. [P08887-1]
DR   CTD; 3570; -.
DR   DisGeNET; 3570; -.
DR   EuPathDB; HostDB:ENSG00000160712.12; -.
DR   GeneCards; IL6R; -.
DR   HGNC; HGNC:6019; IL6R.
DR   HPA; ENSG00000160712; Tissue enhanced (skeletal).
DR   MalaCards; IL6R; -.
DR   MIM; 147880; gene.
DR   MIM; 614689; phenotype.
DR   MIM; 614752; phenotype.
DR   neXtProt; NX_P08887; -.
DR   OpenTargets; ENSG00000160712; -.
DR   PharmGKB; PA29835; -.
DR   eggNOG; ENOG502RY0M; Eukaryota.
DR   GeneTree; ENSGT00940000161919; -.
DR   HOGENOM; CLU_051451_0_0_1; -.
DR   InParanoid; P08887; -.
DR   KO; K05055; -.
DR   OrthoDB; 783799at2759; -.
DR   PhylomeDB; P08887; -.
DR   TreeFam; TF331210; -.
DR   PathwayCommons; P08887; -.
DR   Reactome; R-HSA-1059683; Interleukin-6 signaling.
DR   Reactome; R-HSA-110056; MAPK3 (ERK1) activation.
DR   Reactome; R-HSA-112411; MAPK1 (ERK2) activation.
DR   Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling.
DR   Reactome; R-HSA-9616222; Transcriptional regulation of granulopoiesis.
DR   SignaLink; P08887; -.
DR   SIGNOR; P08887; -.
DR   BioGRID-ORCS; 3570; 4 hits in 876 CRISPR screens.
DR   ChiTaRS; IL6R; human.
DR   EvolutionaryTrace; P08887; -.
DR   GeneWiki; Interleukin-6_receptor; -.
DR   GenomeRNAi; 3570; -.
DR   Pharos; P08887; Tclin.
DR   PRO; PR:P08887; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; P08887; protein.
DR   Bgee; ENSG00000160712; Expressed in liver and 228 other tissues.
DR   ExpressionAtlas; P08887; baseline and differential.
DR   Genevisible; P08887; HS.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:BHF-UCL.
DR   GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0070110; C:ciliary neurotrophic factor receptor complex; IDA:BHF-UCL.
DR   GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR   GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
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:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR   GO; GO:0070119; F:ciliary neurotrophic factor 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:0019899; F:enzyme binding; IPI:UniProtKB.
DR   GO; GO:0019981; F:interleukin-6 binding; IPI:BHF-UCL.
DR   GO; GO:0004915; F:interleukin-6 receptor activity; IEA:Ensembl.
DR   GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL.
DR   GO; GO:0006953; P:acute-phase response; TAS:BHF-UCL.
DR   GO; GO:0070120; P:ciliary neurotrophic factor-mediated signaling pathway; IMP:BHF-UCL.
DR   GO; GO:0019221; P:cytokine-mediated signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0050829; P:defense response to Gram-negative bacterium; TAS:BHF-UCL.
DR   GO; GO:0050830; P:defense response to Gram-positive bacterium; NAS:BHF-UCL.
DR   GO; GO:0031018; P:endocrine pancreas development; IMP:BHF-UCL.
DR   GO; GO:0097191; P:extrinsic apoptotic signaling pathway; TAS:BHF-UCL.
DR   GO; GO:0002384; P:hepatic immune response; TAS:BHF-UCL.
DR   GO; GO:0070102; P:interleukin-6-mediated signaling pathway; IMP:BHF-UCL.
DR   GO; GO:0002548; P:monocyte chemotaxis; IC:BHF-UCL.
DR   GO; GO:0032966; P:negative regulation of collagen biosynthetic process; IDA:BHF-UCL.
DR   GO; GO:0032717; P:negative regulation of interleukin-8 production; NAS:BHF-UCL.
DR   GO; GO:0002446; P:neutrophil mediated immunity; TAS:BHF-UCL.
DR   GO; GO:0010536; P:positive regulation of activation of Janus kinase activity; IDA:BHF-UCL.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL.
DR   GO; GO:0032722; P:positive regulation of chemokine production; IDA:BHF-UCL.
DR   GO; GO:0072126; P:positive regulation of glomerular mesangial cell proliferation; IMP:ARUK-UCL.
DR   GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:BHF-UCL.
DR   GO; GO:0002690; P:positive regulation of leukocyte chemotaxis; TAS:BHF-UCL.
DR   GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:BHF-UCL.
DR   GO; GO:0045669; P:positive regulation of osteoblast differentiation; TAS:BHF-UCL.
DR   GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:BHF-UCL.
DR   GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IDA:BHF-UCL.
DR   GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IMP:BHF-UCL.
DR   GO; GO:0034097; P:response to cytokine; IDA:BHF-UCL.
DR   CDD; cd00063; FN3; 1.
DR   Gene3D; 2.60.40.10; -; 3.
DR   InterPro; IPR003961; FN3_dom.
DR   InterPro; IPR036116; FN3_sf.
DR   InterPro; IPR003530; Hematopoietin_rcpt_L_F3_CS.
DR   InterPro; IPR007110; Ig-like_dom.
DR   InterPro; IPR036179; Ig-like_dom_sf.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR003599; Ig_sub.
DR   InterPro; IPR003598; Ig_sub2.
DR   InterPro; IPR013151; Immunoglobulin.
DR   InterPro; IPR015321; TypeI_recpt_CBD.
DR   Pfam; PF00047; ig; 1.
DR   Pfam; PF09240; IL6Ra-bind; 1.
DR   SMART; SM00060; FN3; 1.
DR   SMART; SM00409; IG; 1.
DR   SMART; SM00408; IGc2; 1.
DR   SUPFAM; SSF48726; SSF48726; 1.
DR   SUPFAM; SSF49265; SSF49265; 2.
DR   PROSITE; PS50853; FN3; 2.
DR   PROSITE; PS01354; HEMATOPO_REC_L_F3; 1.
DR   PROSITE; PS50835; IG_LIKE; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cell membrane;
KW   Direct protein sequencing; Disulfide bond; Glycoprotein;
KW   Immunoglobulin domain; Membrane; Polymorphism; Receptor;
KW   Reference proteome; Repeat; Secreted; Signal; Transmembrane;
KW   Transmembrane helix.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000269|PubMed:2529343"
FT   CHAIN           20..468
FT                   /note="Interleukin-6 receptor subunit alpha"
FT                   /id="PRO_0000010895"
FT   CHAIN           20..355
FT                   /note="Soluble interleukin-6 receptor subunit alpha"
FT                   /id="PRO_0000450730"
FT   TOPO_DOM        20..365
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        366..386
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        387..468
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          26..112
FT                   /note="Ig-like C2-type"
FT   DOMAIN          113..217
FT                   /note="Fibronectin type-III 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT   DOMAIN          218..316
FT                   /note="Fibronectin type-III 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT   MOTIF           303..307
FT                   /note="WSXWS motif"
FT   SITE            245
FT                   /note="Not glycosylated"
FT                   /evidence="ECO:0000269|PubMed:10066782"
FT   SITE            355..356
FT                   /note="Cleavage; by ADAM10 and ADAM17"
FT                   /evidence="ECO:0000269|PubMed:28060820"
FT   CARBOHYD        55
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:10066782,
FT                   ECO:0000269|PubMed:28060820"
FT   CARBOHYD        93
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:10066782,
FT                   ECO:0000269|PubMed:28060820"
FT   CARBOHYD        221
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:10066782,
FT                   ECO:0000269|PubMed:28060820"
FT   CARBOHYD        245
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:28060820"
FT   CARBOHYD        350
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:28060820"
FT   CARBOHYD        352
FT                   /note="O-linked (GlcNAc) threonine"
FT                   /evidence="ECO:0000269|PubMed:28060820"
FT   DISULFID        25..193
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT                   ECO:0000269|PubMed:10066782"
FT   DISULFID        47..96
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT                   ECO:0000269|PubMed:10066782"
FT   DISULFID        121..132
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT                   ECO:0000269|PubMed:10066782"
FT   DISULFID        165..176
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT                   ECO:0000269|PubMed:10066782"
FT   VAR_SEQ         356..365
FT                   /note="VQDSSSVPLP -> GSRRRGSCGL (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039,
FT                   ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:8056053"
FT                   /id="VSP_001682"
FT   VAR_SEQ         366..468
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039,
FT                   ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:8056053"
FT                   /id="VSP_001683"
FT   VARIANT         358
FT                   /note="D -> A (significantly associated with circulating
FT                   levels of IL6 and soluble IL6R; increases cleavage by
FT                   ADAM17; dbSNP:rs2228145)"
FT                   /evidence="ECO:0000269|PubMed:14702039,
FT                   ECO:0000269|PubMed:17357077, ECO:0000269|PubMed:28060820"
FT                   /id="VAR_021995"
FT   VARIANT         385
FT                   /note="V -> I (in dbSNP:rs2228146)"
FT                   /id="VAR_049166"
FT   MUTAGEN         55
FT                   /note="N->A: Strongly induces cleavage and sIL6R levels. No
FT                   effect on IL6R signaling; when associated with A-93, A-221,
FT                   A-245 and A-350. Loss of cleavage by ADAM17; when
FT                   associated with A-93, A-221, A-245 and A-350."
FT                   /evidence="ECO:0000269|PubMed:28060820"
FT   MUTAGEN         57
FT                   /note="T->A: Strongly induces cleavage and sIL6R levels."
FT                   /evidence="ECO:0000269|PubMed:28060820"
FT   MUTAGEN         93
FT                   /note="N->A: No effect on cleavage or sIL6R levels. No
FT                   effect on IL6R signaling; when associated with A-55, A-221,
FT                   A-245 and A-350. Loss of cleavage by ADAM17; when
FT                   associated with A-55, A-221, A-245 and A-350."
FT                   /evidence="ECO:0000269|PubMed:28060820"
FT   MUTAGEN         121
FT                   /note="C->S: Complete loss of ligand-binding."
FT                   /evidence="ECO:0000269|PubMed:8467812"
FT   MUTAGEN         122
FT                   /note="F->A: No change of ligand-binding and IL6
FT                   signaling."
FT                   /evidence="ECO:0000269|PubMed:8467812"
FT   MUTAGEN         132
FT                   /note="C->A: Complete loss of ligand-binding."
FT                   /evidence="ECO:0000269|PubMed:8467812"
FT   MUTAGEN         134
FT                   /note="W->L: Complete loss of ligand-binding."
FT                   /evidence="ECO:0000269|PubMed:8467812"
FT   MUTAGEN         140
FT                   /note="P->G: No change of ligand-binding and IL6
FT                   signaling."
FT                   /evidence="ECO:0000269|PubMed:8467812"
FT   MUTAGEN         153
FT                   /note="F->L: No change of ligand-binding and IL6
FT                   signaling."
FT                   /evidence="ECO:0000269|PubMed:8467812"
FT   MUTAGEN         165
FT                   /note="C->L: Complete loss of ligand-binding."
FT                   /evidence="ECO:0000269|PubMed:8467812"
FT   MUTAGEN         174
FT                   /note="F->L: No change of ligand-binding and IL6
FT                   signaling."
FT                   /evidence="ECO:0000269|PubMed:8467812"
FT   MUTAGEN         176
FT                   /note="C->A: Complete loss of ligand-binding."
FT                   /evidence="ECO:0000269|PubMed:8467812"
FT   MUTAGEN         184
FT                   /note="D->T: 30% decrease of ligand-binding and IL6
FT                   signaling."
FT                   /evidence="ECO:0000269|PubMed:8467812"
FT   MUTAGEN         190
FT                   /note="V->G: 80% decrease of ligand-binding and no IL6
FT                   signaling."
FT                   /evidence="ECO:0000269|PubMed:8467812"
FT   MUTAGEN         193
FT                   /note="C->D: Complete loss of ligand-binding."
FT                   /evidence="ECO:0000269|PubMed:8467812"
FT   MUTAGEN         211
FT                   /note="C->A: No change of ligand-binding and IL6
FT                   signaling."
FT                   /evidence="ECO:0000269|PubMed:8467812"
FT   MUTAGEN         217
FT                   /note="D->V: Complete loss of ligand-binding."
FT                   /evidence="ECO:0000269|PubMed:8467812"
FT   MUTAGEN         221
FT                   /note="N->A: No effect on cleavage or sIL6R levels. No
FT                   effect on IL6R signaling; when associated with A-55, A-93,
FT                   A-245 and A-350. Loss of cleavage by ADAM17; when
FT                   associated with A-55, A-93, A-245 and A-350."
FT                   /evidence="ECO:0000269|PubMed:28060820"
FT   MUTAGEN         232
FT                   /note="R->S: 30% decrease of ligand-binding and IL6
FT                   signaling."
FT                   /evidence="ECO:0000269|PubMed:8467812"
FT   MUTAGEN         233
FT                   /note="W->Q: 30% decrease of ligand-binding and increase of
FT                   IL6 signaling."
FT                   /evidence="ECO:0000269|PubMed:8467812"
FT   MUTAGEN         245
FT                   /note="N->A: Slightly induces cleavage and sIL6R levels.No
FT                   effect on IL6R signaling; when associated with A-55, A-93,
FT                   A-221 and A-350. Loss of cleavage by ADAM17; when
FT                   associated with A-55, A-93, A-221 and A-350."
FT                   /evidence="ECO:0000269|PubMed:28060820"
FT   MUTAGEN         254
FT                   /note="E->A: 50% decrease of ligand-binding and IL6
FT                   signaling."
FT                   /evidence="ECO:0000269|PubMed:8467812"
FT   MUTAGEN         277
FT                   /note="C->D: 30% increase of ligand-binding and 100%
FT                   increase in IL6 signaling."
FT                   /evidence="ECO:0000269|PubMed:8467812"
FT   MUTAGEN         278
FT                   /note="V->N: 50% Decrease of ligand-binding and 50%
FT                   increase in IL6 signaling."
FT                   /evidence="ECO:0000269|PubMed:8467812"
FT   MUTAGEN         279
FT                   /note="I->D: Complete loss of ligand-binding."
FT                   /evidence="ECO:0000269|PubMed:8467812"
FT   MUTAGEN         280
FT                   /note="H->I: No change of ligand-binding and no IL6
FT                   signaling."
FT                   /evidence="ECO:0000269|PubMed:8467812"
FT   MUTAGEN         281
FT                   /note="D->G: 70% decrease of ligand-binding and no IL6
FT                   signaling."
FT                   /evidence="ECO:0000269|PubMed:8467812"
FT   MUTAGEN         285
FT                   /note="G->D: 80% decrease of ligand-binding and no IL6
FT                   signaling."
FT                   /evidence="ECO:0000269|PubMed:8467812"
FT   MUTAGEN         291
FT                   /note="Q->K: Complete loss of ligand-binding."
FT                   /evidence="ECO:0000269|PubMed:8467812"
FT   MUTAGEN         293
FT                   /note="R->G: Complete loss of ligand-binding."
FT                   /evidence="ECO:0000269|PubMed:8467812"
FT   MUTAGEN         350
FT                   /note="N->A: No effect on IL6R signaling; when associated
FT                   with A-55, A-93, A-221 and A-245. Loss of cleavage by
FT                   ADAM17; when associated with A-55, A-93, A-221 and A-245."
FT                   /evidence="ECO:0000269|PubMed:28060820"
FT   MUTAGEN         352
FT                   /note="T->A: No effect on IL6R signaling."
FT                   /evidence="ECO:0000269|PubMed:28060820"
FT   MUTAGEN         355..356
FT                   /note="PV->IE: Abolishes cleavage by ADAM17."
FT                   /evidence="ECO:0000269|PubMed:28060820"
FT   MUTAGEN         355
FT                   /note="P->I,D: Reduces cleavage by ADAM17."
FT                   /evidence="ECO:0000269|PubMed:28060820"
FT   MUTAGEN         356
FT                   /note="V->E,G: Abolishes cleavage by ADAM17."
FT                   /evidence="ECO:0000269|PubMed:28060820"
FT   CONFLICT        210
FT                   /note="G -> D (in Ref. 5; BAD97302)"
FT                   /evidence="ECO:0000305"
FT   STRAND          34..37
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   STRAND          43..46
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   STRAND          56..63
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   STRAND          65..68
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   STRAND          72..83
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   HELIX           88..90
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   STRAND          92..101
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   STRAND          105..110
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   STRAND          120..125
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   STRAND          130..134
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   STRAND          145..157
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   STRAND          159..168
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   TURN            169..172
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   STRAND          173..178
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   STRAND          187..196
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   STRAND          199..202
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   STRAND          206..209
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   TURN            210..212
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   STRAND          220..226
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   STRAND          234..239
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   STRAND          247..249
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   STRAND          251..259
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   STRAND          266..269
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   HELIX           271..273
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   STRAND          275..281
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   STRAND          288..296
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   TURN            297..299
FT                   /evidence="ECO:0000244|PDB:1N26"
FT   STRAND          310..312
FT                   /evidence="ECO:0000244|PDB:1N26"
SQ   SEQUENCE   468 AA;  51548 MW;  62AA239FA14F1B8B CRC64;
     MLAVGCALLA ALLAAPGAAL APRRCPAQEV ARGVLTSLPG DSVTLTCPGV EPEDNATVHW
     VLRKPAAGSH PSRWAGMGRR LLLRSVQLHD SGNYSCYRAG RPAGTVHLLV DVPPEEPQLS
     CFRKSPLSNV VCEWGPRSTP SLTTKAVLLV RKFQNSPAED FQEPCQYSQE SQKFSCQLAV
     PEGDSSFYIV SMCVASSVGS KFSKTQTFQG CGILQPDPPA NITVTAVARN PRWLSVTWQD
     PHSWNSSFYR LRFELRYRAE RSKTFTTWMV KDLQHHCVIH DAWSGLRHVV QLRAQEEFGQ
     GEWSEWSPEA MGTPWTESRS PPAENEVSTP MQALTTNKDD DNILFRDSAN ATSLPVQDSS
     SVPLPTFLVA GGSLAFGTLL CIAIVLRFKK TWKLRALKEG KTSMHPPYSL GQLVPERPRP
     TPVLVPLISP PVSPSSLGSD NTSSHNRPDA RDPRSPYDIS NTDYFFPR
//