IL6R

Protein identityUniProt · HPA

UniProt accession

P08887

Gene

IL6R

Ensembl

ENSG00000160712

Chromosome

1

Canonical length

468 aa

Protein class

Cancer-related genes, Candidate cardiovascular disease genes, CD markers, Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins, Predicted secreted proteins

Secretome location

Secreted to blood

OverviewNCBI Gene

This gene encodes a subunit of the interleukin 6 (IL6) receptor complex. Interleukin 6 is a potent pleiotropic cytokine that regulates cell growth and differentiation and plays an important role in the immune response. The IL6 receptor is a protein complex consisting of this protein and interleukin 6 signal transducer (IL6ST/GP130/IL6-beta), a receptor subunit also shared by many other cytokines. Dysregulated production of IL6 and this receptor are implicated in the pathogenesis of many diseases, such as multiple myeloma, autoimmune diseases and prostate cancer. Alternatively spliced transcript variants encoding distinct isoforms have been identified in this gene. A pseudogene of this gene is found on chromosome 9. [provided by RefSeq, Aug 2020]

Canonical amino-acid sequenceUniProt

468 residues, UniProt reviewed canonical sequence.

>P08887|IL6R
     1  MLAVGCALLA ALLAAPGAAL APRRCPAQEV ARGVLTSLPG DSVTLTCPGV EPEDNATVHW
    61  VLRKPAAGSH PSRWAGMGRR LLLRSVQLHD SGNYSCYRAG RPAGTVHLLV DVPPEEPQLS
   121  CFRKSPLSNV VCEWGPRSTP SLTTKAVLLV RKFQNSPAED FQEPCQYSQE SQKFSCQLAV
   181  PEGDSSFYIV SMCVASSVGS KFSKTQTFQG CGILQPDPPA NITVTAVARN PRWLSVTWQD
   241  PHSWNSSFYR LRFELRYRAE RSKTFTTWMV KDLQHHCVIH DAWSGLRHVV QLRAQEEFGQ
   301  GEWSEWSPEA MGTPWTESRS PPAENEVSTP MQALTTNKDD DNILFRDSAN ATSLPVQDSS
   361  SVPLPTFLVA GGSLAFGTLL CIAIVLRFKK TWKLRALKEG KTSMHPPYSL GQLVPERPRP
   421  TPVLVPLISP PVSPSSLGSD NTSSHNRPDA RDPRSPYDIS NTDYFFPR

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against IL6R can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.44

Highest tissue expression

91 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about IL6R.

Disease | AllUniProt

Conditions IL6R is implicated in, by any mechanism.

• Hyper-IgE syndrome 5, autosomal recessive, with recurrent infections (HIES5) MIM:618944

ReferencesPubMed · IEDB

Publications for IL6R from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.81

gnomAD pLI

0

gnomAD missense Z

0.69

DepMap mean gene effect

-0.09

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• acute-phase response
• cell surface receptor signaling pathway via STAT
• ciliary neurotrophic factor-mediated signaling pathway
• cytokine-mediated signaling pathway
• defense response to Gram-negative bacterium
• defense response to Gram-positive bacterium
• endocrine pancreas development
• extrinsic apoptotic signaling pathway
• hepatic immune response
• interleukin-6-mediated signaling pathway
• monocyte chemotaxis
• negative regulation of collagen biosynthetic process
• negative regulation of interleukin-8 production
• neutrophil mediated immunity
• positive regulation of cell population proliferation
• positive regulation of chemokine production
• positive regulation of glomerular mesangial cell proliferation
• positive regulation of interleukin-6 production
• positive regulation of leukocyte chemotaxis
• positive regulation of MAPK cascade
• positive regulation of osteoblast differentiation
• positive regulation of smooth muscle cell proliferation
• response to cytokine
• T-helper 17 cell lineage commitment
• vascular endothelial growth factor production

Molecular functions

• cytokine receptor activity
• enzyme binding
• interleukin-11 binding
• interleukin-11 receptor activity
• interleukin-6 receptor activity
• protein homodimerization activity
• ciliary neurotrophic factor binding
• interleukin-6 binding

Cellular components

• apical plasma membrane
• ciliary neurotrophic factor receptor complex
• external side of plasma membrane
• extracellular region
• extracellular space
• interleukin-6 receptor complex
• plasma membrane
• receptor complex

Protein domainsUniProt · Pfam · InterPro

• Long hematopoietin receptor, soluble alpha chain, conserved site
• Immunoglobulin subtype 2
• Immunoglobulin domain subtype
• Fibronectin type III
• Immunoglobulin-like domain
• Immunoglobulin-like beta-sandwich domain
• Immunoglobulin-like fold
• Type I cytokine receptor, cytokine-binding domain
• Fibronectin type III superfamily
• Immunoglobulin-like domain superfamily
• Immunoglobulin domain
• Interleukin-6 receptor alpha chain, binding

KeywordsUniProt

• Cell membrane
• Disulfide bond
• Glycoprotein
• Immunoglobulin domain
• Membrane
• Receptor
• Repeat
• Secreted
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of IL6R in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SORL1
• IL6