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   17-JUN-2020, entry version 228.
DE   RecName: Full=Interleukin-6 receptor subunit alpha;
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   Flags: Precursor;
GN   Name=IL6R;
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, 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   [15]
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   [16]
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   [17]
RP   X-RAY CRYSTALLOGRAPHY (3.65 ANGSTROMS) OF 115-315.
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   [18]
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 may lead
CC       to the regulation of the immune response, acute-phase reactions and
CC       hematopoiesis. {ECO:0000269|PubMed:28265003}.
CC   -!- FUNCTION: Low concentration of a soluble form of IL6 receptor acts as
CC       an agonist of IL6 activity.
CC   -!- SUBUNIT: Hexamer of two molecules each of IL6, IL6R and IL6ST
CC       (PubMed:28265003). Interacts (via N-terminal ectodomain) with SORL1;
CC       this interaction may affect IL6-binding to IL6R, hence decrease IL6
CC       cis-signaling (PubMed:28265003). The soluble form of IL6R also
CC       interacts with SORL1; this interaction leads to soluble IL6R
CC       internalization (PubMed:28265003). 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       (PubMed:28265003). {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]: Basolateral cell membrane; Single-
CC       pass type I membrane protein.
CC   -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1; Synonyms=Long;
CC         IsoId=P08887-1; Sequence=Displayed;
CC       Name=2; Synonyms=Short;
CC         IsoId=P08887-2; Sequence=VSP_001682, VSP_001683;
CC   -!- TISSUE SPECIFICITY: Isoform 2 is expressed in peripheral blood
CC       mononuclear cells and weakly found in urine and serum.
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 may also be released from the membrane by
CC       proteolysis.
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   iPTMnet; P08887; -.
DR   PhosphoSitePlus; P08887; -.
DR   BioMuta; IL6R; -.
DR   DMDM; 124343; -.
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; 952 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; ENOG410II5K; Eukaryota.
DR   eggNOG; ENOG4111XGC; LUCA.
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   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; 3 hits in 787 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 blood and 217 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   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   CARBOHYD        55
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:10066782"
FT   CARBOHYD        93
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:10066782"
FT   CARBOHYD        221
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:10066782"
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; dbSNP:rs2228145)"
FT                   /evidence="ECO:0000269|PubMed:14702039,
FT                   ECO:0000269|PubMed:17357077"
FT                   /id="VAR_021995"
FT   VARIANT         385
FT                   /note="V -> I (in dbSNP:rs2228146)"
FT                   /id="VAR_049166"
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         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         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   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
//