##gff-version 3 P08887 UniProtKB Signal peptide 1 19 . . . Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:2529343;Dbxref=PMID:2529343 P08887 UniProtKB Chain 20 468 . . . ID=PRO_0000010895;Note=Interleukin-6 receptor subunit alpha P08887 UniProtKB Chain 20 355 . . . ID=PRO_0000450730;Note=Soluble interleukin-6 receptor subunit alpha P08887 UniProtKB Topological domain 20 365 . . . Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 P08887 UniProtKB Transmembrane 366 386 . . . Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 P08887 UniProtKB Topological domain 387 468 . . . Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 P08887 UniProtKB Domain 26 112 . . . Note=Ig-like C2-type P08887 UniProtKB Domain 113 217 . . . Note=Fibronectin type-III 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00316 P08887 UniProtKB Domain 218 316 . . . Note=Fibronectin type-III 2;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00316 P08887 UniProtKB Region 303 328 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P08887 UniProtKB Region 421 468 . . . Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P08887 UniProtKB Motif 303 307 . . . Note=WSXWS motif P08887 UniProtKB Compositional bias 311 328 . . . Note=Polar residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite P08887 UniProtKB Site 245 245 . . . Note=Not glycosylated;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:10066782;Dbxref=PMID:10066782 P08887 UniProtKB Site 355 356 . . . Note=Cleavage%3B by ADAM10 and ADAM17;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28060820;Dbxref=PMID:28060820 P08887 UniProtKB Glycosylation 55 55 . . . Note=N-linked (GlcNAc...) asparagine;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:10066782,ECO:0000269|PubMed:28060820;Dbxref=PMID:10066782,PMID:28060820 P08887 UniProtKB Glycosylation 93 93 . . . Note=N-linked (GlcNAc...) asparagine;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:10066782,ECO:0000269|PubMed:28060820;Dbxref=PMID:10066782,PMID:28060820 P08887 UniProtKB Glycosylation 221 221 . . . Note=N-linked (GlcNAc...) asparagine;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:10066782,ECO:0000269|PubMed:28060820;Dbxref=PMID:10066782,PMID:28060820 P08887 UniProtKB Glycosylation 245 245 . . . Note=N-linked (GlcNAc...) asparagine;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28060820;Dbxref=PMID:28060820 P08887 UniProtKB Glycosylation 350 350 . . . Note=N-linked (GlcNAc...) asparagine;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28060820;Dbxref=PMID:28060820 P08887 UniProtKB Glycosylation 352 352 . . . Note=O-linked (GlcNAc) threonine;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28060820;Dbxref=PMID:28060820 P08887 UniProtKB Disulfide bond 25 193 . . . Ontology_term=ECO:0000255,ECO:0000269;evidence=ECO:0000255|PROSITE-ProRule:PRU00114,ECO:0000269|PubMed:10066782;Dbxref=PMID:10066782 P08887 UniProtKB Disulfide bond 47 96 . . . Ontology_term=ECO:0000255,ECO:0000269;evidence=ECO:0000255|PROSITE-ProRule:PRU00114,ECO:0000269|PubMed:10066782;Dbxref=PMID:10066782 P08887 UniProtKB Disulfide bond 121 132 . . . Ontology_term=ECO:0000255,ECO:0000269;evidence=ECO:0000255|PROSITE-ProRule:PRU00114,ECO:0000269|PubMed:10066782;Dbxref=PMID:10066782 P08887 UniProtKB Disulfide bond 165 176 . . . Ontology_term=ECO:0000255,ECO:0000269;evidence=ECO:0000255|PROSITE-ProRule:PRU00114,ECO:0000269|PubMed:10066782;Dbxref=PMID:10066782 P08887 UniProtKB Alternative sequence 356 365 . . . ID=VSP_001682;Note=In isoform 2. VQDSSSVPLP->GSRRRGSCGL;Ontology_term=ECO:0000303,ECO:0000303,ECO:0000303;evidence=ECO:0000303|PubMed:14702039,ECO:0000303|PubMed:15489334,ECO:0000303|PubMed:8056053;Dbxref=PMID:14702039,PMID:15489334,PMID:8056053 P08887 UniProtKB Alternative sequence 366 468 . . . ID=VSP_001683;Note=In isoform 2. Missing;Ontology_term=ECO:0000303,ECO:0000303,ECO:0000303;evidence=ECO:0000303|PubMed:14702039,ECO:0000303|PubMed:15489334,ECO:0000303|PubMed:8056053;Dbxref=PMID:14702039,PMID:15489334,PMID:8056053 P08887 UniProtKB Natural variant 279 279 . . . ID=VAR_084713;Note=In HIES5%3B decreased STAT1 and STAT3 phosphorylation. I->N;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:31235509;Dbxref=dbSNP:rs1689606931,PMID:31235509 P08887 UniProtKB Natural variant 280 280 . . . ID=VAR_084714;Note=In HIES5%3B uncertain significance%3B no effect on STAT1 and STAT3 phosphorylation. H->P;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:31235509;Dbxref=PMID:31235509 P08887 UniProtKB Natural variant 358 358 . . . ID=VAR_021995;Note=Significantly associated with circulating levels of IL6 and soluble IL6R%3B increases cleavage by ADAM17. D->A;Ontology_term=ECO:0000269,ECO:0000269,ECO:0000269;evidence=ECO:0000269|PubMed:14702039,ECO:0000269|PubMed:17357077,ECO:0000269|PubMed:28060820;Dbxref=dbSNP:rs2228145,PMID:14702039,PMID:17357077,PMID:28060820 P08887 UniProtKB Natural variant 385 385 . . . ID=VAR_049166;Note=V->I;Dbxref=dbSNP:rs2228146 P08887 UniProtKB Mutagenesis 55 55 . . . Note=Strongly induces cleavage and sIL6R levels. No effect on IL6R signaling%3B when associated with A-93%2C A-221%2C A-245 and A-350. Loss of cleavage by ADAM17%3B when associated with A-93%2C A-221%2C A-245 and A-350. N->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28060820;Dbxref=PMID:28060820 P08887 UniProtKB Mutagenesis 57 57 . . . Note=Strongly induces cleavage and sIL6R levels. T->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28060820;Dbxref=PMID:28060820 P08887 UniProtKB Mutagenesis 93 93 . . . Note=No effect on cleavage or sIL6R levels. No effect on IL6R signaling%3B when associated with A-55%2C A-221%2C A-245 and A-350. Loss of cleavage by ADAM17%3B when associated with A-55%2C A-221%2C A-245 and A-350. N->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28060820;Dbxref=PMID:28060820 P08887 UniProtKB Mutagenesis 121 121 . . . Note=Complete loss of ligand-binding. C->S;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8467812;Dbxref=PMID:8467812 P08887 UniProtKB Mutagenesis 122 122 . . . Note=No change of ligand-binding and IL6 signaling. F->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8467812;Dbxref=PMID:8467812 P08887 UniProtKB Mutagenesis 132 132 . . . Note=Complete loss of ligand-binding. C->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8467812;Dbxref=PMID:8467812 P08887 UniProtKB Mutagenesis 134 134 . . . Note=Complete loss of ligand-binding. W->L;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8467812;Dbxref=PMID:8467812 P08887 UniProtKB Mutagenesis 140 140 . . . Note=No change of ligand-binding and IL6 signaling. P->G;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8467812;Dbxref=PMID:8467812 P08887 UniProtKB Mutagenesis 153 153 . . . Note=No change of ligand-binding and IL6 signaling. F->L;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8467812;Dbxref=PMID:8467812 P08887 UniProtKB Mutagenesis 165 165 . . . Note=Complete loss of ligand-binding. C->L;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8467812;Dbxref=PMID:8467812 P08887 UniProtKB Mutagenesis 174 174 . . . Note=No change of ligand-binding and IL6 signaling. F->L;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8467812;Dbxref=PMID:8467812 P08887 UniProtKB Mutagenesis 176 176 . . . Note=Complete loss of ligand-binding. C->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8467812;Dbxref=PMID:8467812 P08887 UniProtKB Mutagenesis 184 184 . . . Note=30%25 decrease of ligand-binding and IL6 signaling. D->T;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8467812;Dbxref=PMID:8467812 P08887 UniProtKB Mutagenesis 190 190 . . . Note=80%25 decrease of ligand-binding and no IL6 signaling. V->G;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8467812;Dbxref=PMID:8467812 P08887 UniProtKB Mutagenesis 193 193 . . . Note=Complete loss of ligand-binding. C->D;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8467812;Dbxref=PMID:8467812 P08887 UniProtKB Mutagenesis 211 211 . . . Note=No change of ligand-binding and IL6 signaling. C->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8467812;Dbxref=PMID:8467812 P08887 UniProtKB Mutagenesis 217 217 . . . Note=Complete loss of ligand-binding. D->V;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8467812;Dbxref=PMID:8467812 P08887 UniProtKB Mutagenesis 221 221 . . . Note=No effect on cleavage or sIL6R levels. No effect on IL6R signaling%3B when associated with A-55%2C A-93%2C A-245 and A-350. Loss of cleavage by ADAM17%3B when associated with A-55%2C A-93%2C A-245 and A-350. N->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28060820;Dbxref=PMID:28060820 P08887 UniProtKB Mutagenesis 232 232 . . . Note=30%25 decrease of ligand-binding and IL6 signaling. R->S;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8467812;Dbxref=PMID:8467812 P08887 UniProtKB Mutagenesis 233 233 . . . Note=30%25 decrease of ligand-binding and increase of IL6 signaling. W->Q;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8467812;Dbxref=PMID:8467812 P08887 UniProtKB Mutagenesis 245 245 . . . Note=Slightly induces cleavage and sIL6R levels.No effect on IL6R signaling%3B when associated with A-55%2C A-93%2C A-221 and A-350. Loss of cleavage by ADAM17%3B when associated with A-55%2C A-93%2C A-221 and A-350. N->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28060820;Dbxref=PMID:28060820 P08887 UniProtKB Mutagenesis 254 254 . . . Note=50%25 decrease of ligand-binding and IL6 signaling. E->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8467812;Dbxref=PMID:8467812 P08887 UniProtKB Mutagenesis 277 277 . . . Note=30%25 increase of ligand-binding and 100%25 increase in IL6 signaling. C->D;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8467812;Dbxref=PMID:8467812 P08887 UniProtKB Mutagenesis 278 278 . . . Note=50%25 Decrease of ligand-binding and 50%25 increase in IL6 signaling. V->N;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8467812;Dbxref=PMID:8467812 P08887 UniProtKB Mutagenesis 279 279 . . . Note=Complete loss of ligand-binding. I->D;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8467812;Dbxref=PMID:8467812 P08887 UniProtKB Mutagenesis 280 280 . . . Note=No change of ligand-binding and no IL6 signaling. H->I;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8467812;Dbxref=PMID:8467812 P08887 UniProtKB Mutagenesis 281 281 . . . Note=70%25 decrease of ligand-binding and no IL6 signaling. D->G;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8467812;Dbxref=PMID:8467812 P08887 UniProtKB Mutagenesis 285 285 . . . Note=80%25 decrease of ligand-binding and no IL6 signaling. G->D;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8467812;Dbxref=PMID:8467812 P08887 UniProtKB Mutagenesis 291 291 . . . Note=Complete loss of ligand-binding. Q->K;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8467812;Dbxref=PMID:8467812 P08887 UniProtKB Mutagenesis 293 293 . . . Note=Complete loss of ligand-binding. R->G;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:8467812;Dbxref=PMID:8467812 P08887 UniProtKB Mutagenesis 350 350 . . . Note=No effect on IL6R signaling%3B when associated with A-55%2C A-93%2C A-221 and A-245. Loss of cleavage by ADAM17%3B when associated with A-55%2C A-93%2C A-221 and A-245. N->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28060820;Dbxref=PMID:28060820 P08887 UniProtKB Mutagenesis 352 352 . . . Note=No effect on IL6R signaling. T->A;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28060820;Dbxref=PMID:28060820 P08887 UniProtKB Mutagenesis 355 356 . . . Note=Abolishes cleavage by ADAM17. PV->IE;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28060820;Dbxref=PMID:28060820 P08887 UniProtKB Mutagenesis 355 355 . . . Note=Reduces cleavage by ADAM17. P->I%2CD;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28060820;Dbxref=PMID:28060820 P08887 UniProtKB Mutagenesis 356 356 . . . Note=Abolishes cleavage by ADAM17. V->E%2CG;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:28060820;Dbxref=PMID:28060820 P08887 UniProtKB Sequence conflict 210 210 . . . Note=G->D;Ontology_term=ECO:0000305;evidence=ECO:0000305 P08887 UniProtKB Beta strand 34 37 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Beta strand 43 46 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Beta strand 56 63 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Beta strand 65 68 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Beta strand 72 83 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Helix 88 90 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Beta strand 92 101 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Beta strand 105 110 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Beta strand 120 125 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Beta strand 130 134 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Beta strand 145 157 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Beta strand 159 168 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Turn 169 172 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Beta strand 173 178 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Beta strand 187 196 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Beta strand 199 202 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Beta strand 206 209 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Turn 210 212 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Beta strand 220 226 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Beta strand 234 239 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Beta strand 247 249 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Beta strand 251 259 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Beta strand 266 269 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Helix 271 273 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Beta strand 275 281 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Beta strand 288 296 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Turn 297 299 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26 P08887 UniProtKB Beta strand 310 312 . . . Ontology_term=ECO:0007829;evidence=ECO:0007829|PDB:1N26