Protein:IL6R |
Protein Summary |
 Gene summary |
| Gene name: IL6R | ASpdb.0 ID: 3570 | Gene | Gene symbol | IL6R | Gene ID | 3570 |
| Gene name | interleukin 6 receptor |
| Synonyms | CD126|HIES5|IL-1Ra|IL-6R|IL-6R-1|IL-6RA|IL6Q|IL6QTL|IL6RA|IL6RQ|gp80 |
| Cytomap | 1q21.3 |
| Type of gene | protein-coding |
| Description | interleukin-6 receptor subunit alphaCD126 antigenIL-6 receptor subunit alphamembrane glycoprotein 80 |
| Modification date | 20240416 |
| UniProtAcc | P08887 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | IL6R | GO:0004915 | interleukin-6 receptor activity | 2261637 |
| Gene | IL6R | GO:0005576 | extracellular region | 12748171 |
| Gene | IL6R | GO:0005896 | interleukin-6 receptor complex | 2261637|12829785 |
| Gene | IL6R | GO:0008284 | positive regulation of cell population proliferation | 2261637 |
| Gene | IL6R | GO:0010573 | vascular endothelial growth factor production | 12794819 |
| Gene | IL6R | GO:0016324 | apical plasma membrane | 16034137 |
| Gene | IL6R | GO:0019221 | cytokine-mediated signaling pathway | 2261637 |
| Gene | IL6R | GO:0032722 | positive regulation of chemokine production | 10510402 |
| Gene | IL6R | GO:0032755 | positive regulation of interleukin-6 production | 10510402 |
| Gene | IL6R | GO:0034097 | response to cytokine | 2261637 |
| Gene | IL6R | GO:0048661 | positive regulation of smooth muscle cell proliferation | 10510402 |
| Gene | IL6R | GO:0050731 | positive regulation of peptidyl-tyrosine phosphorylation | 11884403 |
| Gene | IL6R | GO:0070110 | ciliary neurotrophic factor receptor complex | 12643274 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P08887-1 | P08887-1_1n26_A.pdb | 1N26 | X-ray | 2.4 | A | 20 | 318 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P08887 | IL6R | P08887-1 | P08887-2 | 468 | 365 | 356 | 365 | Substitution | VQDSSSVPLP | GSRRRGSCGL | 356 | 365 |
| P08887 | IL6R | P08887-1 | P08887-2 | 468 | 365 | 366 | 468 | Deletion | none | none | 365 | 365 |
| Multiple sequence alignment of our canonical and alternatively spliced IL6R |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of IL6R |
| UniProt-id | ENSG | ENST | ENSP |
| P08887-1 | ENSG00000160712.13 | ENST00000368485.8 | ENSP00000357470.3 |
| P08887-2 | ENSG00000160712.13 | ENST00000344086.8 | ENSP00000340589.4 |
| UniProt-id | NM ID | NP ID |
| P08887-1 | NM_000565.3 | NP_000556.1 |
| P08887-2 | NM_181359.2 | NP_852004.1 |
| Amino acid sequences of our canonical and alternatively spliced IL6R |
| accession_id | Protein sequence |
| P08887-1 | MLAVGCALLAALLAAPGAALAPRRCPAQEVARGVLTSLPGDSVTLTCPGVEPEDNATVHWVLRKPAAGSHPSRWAGMGRRLLLRSVQLHD SGNYSCYRAGRPAGTVHLLVDVPPEEPQLSCFRKSPLSNVVCEWGPRSTPSLTTKAVLLVRKFQNSPAEDFQEPCQYSQESQKFSCQLAV PEGDSSFYIVSMCVASSVGSKFSKTQTFQGCGILQPDPPANITVTAVARNPRWLSVTWQDPHSWNSSFYRLRFELRYRAERSKTFTTWMV KDLQHHCVIHDAWSGLRHVVQLRAQEEFGQGEWSEWSPEAMGTPWTESRSPPAENEVSTPMQALTTNKDDDNILFRDSANATSLPVQDSS SVPLPTFLVAGGSLAFGTLLCIAIVLRFKKTWKLRALKEGKTSMHPPYSLGQLVPERPRPTPVLVPLISPPVSPSSLGSDNTSSHNRPDA |
| P08887-2 | MLAVGCALLAALLAAPGAALAPRRCPAQEVARGVLTSLPGDSVTLTCPGVEPEDNATVHWVLRKPAAGSHPSRWAGMGRRLLLRSVQLHD SGNYSCYRAGRPAGTVHLLVDVPPEEPQLSCFRKSPLSNVVCEWGPRSTPSLTTKAVLLVRKFQNSPAEDFQEPCQYSQESQKFSCQLAV PEGDSSFYIVSMCVASSVGSKFSKTQTFQGCGILQPDPPANITVTAVARNPRWLSVTWQDPHSWNSSFYRLRFELRYRAERSKTFTTWMV KDLQHHCVIHDAWSGLRHVVQLRAQEEFGQGEWSEWSPEAMGTPWTESRSPPAENEVSTPMQALTTNKDDDNILFRDSANATSLPGSRRR |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| IL6R (go to UniProt):P08887 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P08887 | Topological domain | 20 | 365 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Substitution;Start=356;End=365 |
| P08887 | Transmembrane | 366 | 386 | Note=Helical;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=366;End=468 |
| P08887 | Topological domain | 387 | 468 | Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=366;End=468 |
| P08887 | Region | 421 | 468 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=366;End=468 |
Gene Isoform Structures and Expression Levels for IL6R |
| Gene structures of our canonical and alternative spliced genes of IL6R * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P08887-1 |
| 3D view using mol* of P08887-2 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P08887-1 |
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| pLDDT distribution across the protein length of P08887-2 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P08887-1 |
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| Ramachandran plot of P08887-2 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P08887-1 | 1.014 | 99 | 1.097 | 262.738 | 0.708 | 0.601 | 0.766 | 0.793 | 0.611 | 1.297 | 1.404 | 28,29,30,31,34,64,65,66,88,89,91,92,93,107,108,109 ,110,111,112,113,114,115,134,136,138,139,140,141,1 42,143,144,174,194,197 |
| P08887-2 | 0.98 | 128 | 1.032 | 294.98 | 0.645 | 0.61 | 0.827 | 0.478 | 0.839 | 0.57 | 1.28 | 34,65,88,91,92,93,107,108,109,110,111,112,113,114, 115,134,136,138,139,140,141,142,143,144,145,146,16 5,166,167,169,174,194,196 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P08887-1_P08887-1_1n26_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P08887-1_1n26_A_P08887-2.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P08887-1_P08887-2.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P08887-1_vs_P08887-2.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P08887-1_vs_P08887-2.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to IL6R |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P08887 | IL6R | DB11767 | Sarilumab | approved, investigational | antagonist, antibody |
| P08887 | IL6R | DB15762 | Satralizumab | approved | binder, antibody |
| P08887 | IL6R | DB06273 | Tocilizumab | approved | inhibitor, antibody |
Related Diseases to IL6R |
| Previous studies relating to the alternative splicing of IL6R and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| IL6R | 12008038 | Soluble interleukin-6 receptor enhanced by oncostatin M induces major changes in gene expression profile of human hepatoma cells. | Interleukin-6 (IL-6) binds to a receptor complex consisting of an 80 kDa binding unit (IL-6R) and gp130 responsible for signal transduction. Due to alternative splicing and/or proteolytic digestion IL-6R occurs in soluble form (sIL-6R), as well. Soluble IL-6R is able to bind to gp130 expressing on nucleated cells, thus sIL-6R makes most cells responsive to IL-6. In this study we found that oncostatin M (OSM), an other gp130 dependent cytokine with proliferation inhibitory potential, increases the expression of both membrane-bound IL-6R and sIL-6R generated by alternative splicing in hepatic and mammary carcinoma cell lines. Furthermore, we studied the functional relevance of the presence and binding of soluble IL-6R to HepG2 cells. Using a cDNA expression array, mRNA levels of about 580 human genes were tested by differential display analysis. Our findings suggest, that elevation of surface density of IL-6R by attachment of sIL-6R induces major modulation in gene expression profile of the hepatoma cells. Soluble IL-6R alone has minor effect, it rather decreases expression of some genes, while incubation with IL-6 and sIL-6R together induces major changes in the mRNA pattern of HepG2 cells. These data strongly suggest that presence and binding of soluble cytokine receptors are important elements of inter-cytokine cross talk and affects actual gene expression profile of responding cells. | D006528 | Carcinoma, Hepatocellular |
| IL6R | 12008038 | Soluble interleukin-6 receptor enhanced by oncostatin M induces major changes in gene expression profile of human hepatoma cells. | Interleukin-6 (IL-6) binds to a receptor complex consisting of an 80 kDa binding unit (IL-6R) and gp130 responsible for signal transduction. Due to alternative splicing and/or proteolytic digestion IL-6R occurs in soluble form (sIL-6R), as well. Soluble IL-6R is able to bind to gp130 expressing on nucleated cells, thus sIL-6R makes most cells responsive to IL-6. In this study we found that oncostatin M (OSM), an other gp130 dependent cytokine with proliferation inhibitory potential, increases the expression of both membrane-bound IL-6R and sIL-6R generated by alternative splicing in hepatic and mammary carcinoma cell lines. Furthermore, we studied the functional relevance of the presence and binding of soluble IL-6R to HepG2 cells. Using a cDNA expression array, mRNA levels of about 580 human genes were tested by differential display analysis. Our findings suggest, that elevation of surface density of IL-6R by attachment of sIL-6R induces major modulation in gene expression profile of the hepatoma cells. Soluble IL-6R alone has minor effect, it rather decreases expression of some genes, while incubation with IL-6 and sIL-6R together induces major changes in the mRNA pattern of HepG2 cells. These data strongly suggest that presence and binding of soluble cytokine receptors are important elements of inter-cytokine cross talk and affects actual gene expression profile of responding cells. | D008113 | Liver Neoplasms |
| IL6R | 23375120 | Alternative splicing and proteolytic rupture contribute to the generation of soluble IL-6 receptors (sIL-6R) in rheumatoid arthritis. | To describe the relationship between the two mechanisms involved in sIL6R generation in rheumatoid arthritis (RA). | D001172 | Arthritis, Rheumatoid |
| IL6R | 23375120 | Alternative splicing and proteolytic rupture contribute to the generation of soluble IL-6 receptors (sIL-6R) in rheumatoid arthritis. | To describe the relationship between the two mechanisms involved in sIL6R generation in rheumatoid arthritis (RA). | D020022 | Genetic Predisposition to Disease |
Clinically important variants in IL6R |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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