IL6R
entrez
3570
canonical
uniprot
P08887
canonical
ensembl
ENSG00000160712
resolver
ensp
ENSP00000340589
resolver
ensp
ENSP00000357470
resolver
ensp
ENSP00000477739
resolver
ensp
ENSP00000528564
resolver
ensp
ENSP00000528565
resolver
ensp
ENSP00000670042
resolver
enst
ENST00000622330
resolver
genesymbol
IL6R
resolver
hgnc
HGNC:6019
resolver
uniprot
A0A087WTB5
resolver
uniprot
A0N0L5
resolver
uniprot
A8KAE8
resolver
uniprot
B2R6V4
resolver
uniprot
Q16202
resolver
uniprot
Q53EQ7
resolver
uniprot
Q5FWG2
resolver
uniprot
Q5VZ23
resolver
uniprot_entry
A0A087WTB5_HUMAN
resolver
uniprot_entry
A0N0L5_HUMAN
resolver
uniprot_entry
IL6RA_HUMAN
resolver
uniprot_sec
A8KAE8
resolver
uniprot_sec
B2R6V4
resolver
uniprot_sec
Q16202
resolver
uniprot_sec
Q53EQ7
resolver
uniprot_sec
Q5FWG2
resolver
uniprot_sec
Q5VZ23
resolver
activity_regulation
ACTIVITY REGULATION: Classic and trans-signaling are both inhibited by tocilizumab, a humanized monoclonal antibody that blocks interleukin IL6R signaling. {ECO:0000269|PubMed:21990364}.
uniprot
proteins
amino_acid_sequence
MLAVGCALLAALLAAPGAALAPRRCPAQEVARGVLTSLPGDSVTLTCPGVEPEDNATVHWVLRKPAAGSHPSRWAGMGRRLLLRSVQLHDSGNYSCYRAGRPAGTVHLLVDVPPEEPQLSCFRKSPLSNVVCEWGPRSTPSLTTKAVLLVRKFQNSPAEDFQEPCQYSQESQKFSCQLAVPEGDSSFYIVSMCVASSVGSKFSKTQTFQGCGILQPDPPANITVTAVARNPRWLSVTWQDPHSWNSSFYRLRFELRYRAERSKTFTTWMVKDLQHHCVIHDAWSGLRHVVQLRAQEEFGQGEWSEWSPEAMGTPWTESRSPPAENEVSTPMQALTTNKDDDNILFRDSANATSLPVQDSSSVPLPTFLVAGGSLAFGTLLCIAIVLRFKKTWKLRALKEGKTSMHPPYSLGQLVPERPRPTPVLVPLISPPVSPSSLGSDNTSSHNRPDARDPRSPYDISNTDYFFPR
uniprot
proteins
disease_involvement
DISEASE: Hyper-IgE syndrome 5, autosomal recessive, with recurrent infections (HIES5) [MIM:618944]: An immunologic disorder characterized by recurrent sinopulmonary and deep skin infections, mostly caused by bacteria, including H.influenza and S.aureus. Additional features include asthma, atopic dermatitis, and impaired inflammatory responses during infection. Disease onset is in early infancy. {ECO:0000269|PubMed:31235509}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to the regulation of the immune response, acute-phase reactions and hematopoiesis (PubMed:30995492, PubMed:31235509). The interaction with membrane-bound IL6R and IL6ST stimulates 'classic signaling', the restricted expression of the IL6R limits classic IL6 signaling to only a few tissues such as the liver and some cells of the immune system. Whereas the binding of IL6 and soluble IL6R to IL6ST stimulates 'trans-signaling'. Alternatively, 'cluster signaling' occurs when membrane-bound IL6:IL6R complexes on transmitter cells activate IL6ST receptors on neighboring receiver cells (Probable). {ECO:0000269|PubMed:28265003, ECO:0000269|PubMed:31235509, ECO:0000305|PubMed:30995492}.; FUNCTION: [Isoform 1]: Signaling via the membrane-bound IL6R is mostly regenerative and anti-inflammatory (Probable). Drives naive CD4(+) T cells to the Th17 lineage, through 'cluster signaling' by dendritic cells (By similarity). {ECO:0000250|UniProtKB:P22272, ECO:0000305|PubMed:30995492}.; FUNCTION: [Isoform 2]: Soluble form of IL6 receptor (sIL6R) that acts as an agonist of IL6 activity (PubMed:21990364). The IL6:sIL6R complex (hyper-IL6) binds to IL6ST/gp130 on cell surfaces and induces signaling also on cells that do not express membrane-bound IL6R in a process called IL6 'trans-signaling'. sIL6R is causative for the pro-inflammatory properties of IL6 and an important player in the development of chronic inflammatory diseases (PubMed:21990364). In complex with IL6, is required for induction of VEGF production (PubMed:12794819). Plays a protective role during liver injury, being required for maintenance of tissue regeneration (By similarity). 'Trans-signaling' in central nervous system regulates energy and glucose homeostasis (By similarity). {ECO:0000250|UniProtKB:P22272, ECO:0000269|PubMed:12794819, ECO:0000269|PubMed:21990364}.; FUNCTION: [Soluble interleukin-6 receptor subunit alpha]: Soluble form of IL6 receptor (sIL6R) that acts as an agonist of IL6 activity (PubMed:21990364). The IL6:sIL6R complex (hyper-IL6) binds to IL6ST/gp130 on cell surfaces and induces signaling also on cells that do not express membrane-bound IL6R in a process called IL6 'trans-signaling'. sIL6R is causative for the pro-inflammatory properties of IL6 and an important player in the development of chronic inflammatory diseases (PubMed:21990364). In complex with IL6, is required for induction of VEGF production (PubMed:12794819). Plays a protective role during liver injury, being required for maintenance of tissue regeneration (By similarity). 'Trans-signaling' in central nervous system regulates energy and glucose homeostasis (By similarity). {ECO:0000250|UniProtKB:P22272, ECO:0000269|PubMed:12794819, ECO:0000269|PubMed:21990364}.
uniprot
proteins
mass_dalton
51548
uniprot
proteins
mutagenesis
MUTAGEN 55; /note="N->A: Strongly induces cleavage and sIL6R levels. No effect on IL6R signaling; when associated with A-93, A-221, A-245 and A-350. Loss of cleavage by ADAM17; when associated with A-93, A-221, A-245 and A-350."; /evidence="ECO:0000269|PubMed:28060820"; MUTAGEN 57; /note="T->A: Strongly induces cleavage and sIL6R levels."; /evidence="ECO:0000269|PubMed:28060820"; MUTAGEN 93; /note="N->A: No effect on cleavage or sIL6R levels. No effect on IL6R signaling; when associated with A-55, A-221, A-245 and A-350. Loss of cleavage by ADAM17; when associated with A-55, A-221, A-245 and A-350."; /evidence="ECO:0000269|PubMed:28060820"; MUTAGEN 121; /note="C->S: Complete loss of ligand-binding."; /evidence="ECO:0000269|PubMed:8467812"; MUTAGEN 122; /note="F->A: No change of ligand-binding and IL6 signaling."; /evidence="ECO:0000269|PubMed:8467812"; MUTAGEN 132; /note="C->A: Complete loss of ligand-binding."; /evidence="ECO:0000269|PubMed:8467812"; MUTAGEN 134; /note="W->L: Complete loss of ligand-binding."; /evidence="ECO:0000269|PubMed:8467812"; MUTAGEN 140; /note="P->G: No change of ligand-binding and IL6 signaling."; /evidence="ECO:0000269|PubMed:8467812"; MUTAGEN 153; /note="F->L: No change of ligand-binding and IL6 signaling."; /evidence="ECO:0000269|PubMed:8467812"; MUTAGEN 165; /note="C->L: Complete loss of ligand-binding."; /evidence="ECO:0000269|PubMed:8467812"; MUTAGEN 174; /note="F->L: No change of ligand-binding and IL6 signaling."; /evidence="ECO:0000269|PubMed:8467812"; MUTAGEN 176; /note="C->A: Complete loss of ligand-binding."; /evidence="ECO:0000269|PubMed:8467812"; MUTAGEN 184; /note="D->T: 30% decrease of ligand-binding and IL6 signaling."; /evidence="ECO:0000269|PubMed:8467812"; MUTAGEN 190; /note="V->G: 80% decrease of ligand-binding and no IL6 signaling."; /evidence="ECO:0000269|PubMed:8467812"; MUTAGEN 193; /note="C->D: Complete loss of ligand-binding."; /evidence="ECO:0000269|PubMed:8467812"; MUTAGEN 211; /note="C->A: No change of ligand-binding and IL6 signaling."; /evidence="ECO:0000269|PubMed:8467812"; MUTAGEN 217; /note="D->V: Complete loss of ligand-binding."; /evidence="ECO:0000269|PubMed:8467812"; MUTAGEN 221; /note="N->A: No effect on cleavage or sIL6R levels. No effect on IL6R signaling; when associated with A-55, A-93, A-245 and A-350. Loss of cleavage by ADAM17; when associated with A-55, A-93, A-245 and A-350."; /evidence="ECO:0000269|PubMed:28060820"; MUTAGEN 232; /note="R->S: 30% decrease of ligand-binding and IL6 signaling."; /evidence="ECO:0000269|PubMed:8467812"; MUTAGEN 233; /note="W->Q: 30% decrease of ligand-binding and increase of IL6 signaling."; /evidence="ECO:0000269|PubMed:8467812"; MUTAGEN 245; /note="N->A: Slightly induces cleavage and sIL6R levels. No effect on IL6R signaling; when associated with A-55, A-93, A-221 and A-350. Loss of cleavage by ADAM17; when associated with A-55, A-93, A-221 and A-350."; /evidence="ECO:0000269|PubMed:28060820"; MUTAGEN 254; /note="E->A: 50% decrease of ligand-binding and IL6 signaling."; /evidence="ECO:0000269|PubMed:8467812"; MUTAGEN 277; /note="C->D: 30% increase of ligand-binding and 100% increase in IL6 signaling."; /evidence="ECO:0000269|PubMed:8467812"; MUTAGEN 278; /note="V->N: 50% Decrease of ligand-binding and 50% increase in IL6 signaling."; /evidence="ECO:0000269|PubMed:8467812"; MUTAGEN 279; /note="I->D: Complete loss of ligand-binding."; /evidence="ECO:0000269|PubMed:8467812"; MUTAGEN 280; /note="H->I: No change of ligand-binding and no IL6 signaling."; /evidence="ECO:0000269|PubMed:8467812"; MUTAGEN 281; /note="D->G: 70% decrease of ligand-binding and no IL6 signaling."; /evidence="ECO:0000269|PubMed:8467812"; MUTAGEN 285; /note="G->D: 80% decrease of ligand-binding and no IL6 signaling."; /evidence="ECO:0000269|PubMed:8467812"; MUTAGEN 291; /note="Q->K: Complete loss of ligand-binding."; /evidence="ECO:0000269|PubMed:8467812"; MUTAGEN 293; /note="R->G: Complete loss of ligand-binding."; /evidence="ECO:0000269|PubMed:8467812"; MUTAGEN 350; /note="N->A: No effect on IL6R signaling; when associated with A-55, A-93, A-221 and A-245. Loss of cleavage by ADAM17; when associated with A-55, A-93, A-221 and A-245."; /evidence="ECO:0000269|PubMed:28060820"; MUTAGEN 352; /note="T->A: No effect on IL6R signaling."; /evidence="ECO:0000269|PubMed:28060820"; MUTAGEN 355..356; /note="PV->IE: Abolishes cleavage by ADAM17."; /evidence="ECO:0000269|PubMed:28060820"; MUTAGEN 355; /note="P->I,D: Reduces cleavage by ADAM17."; /evidence="ECO:0000269|PubMed:28060820"; MUTAGEN 356; /note="V->E,G: Abolishes cleavage by ADAM17."; /evidence="ECO:0000269|PubMed:28060820
uniprot
proteins
post_translational_modification
PTM: A short soluble form is released from the membrane by proteolysis (PubMed:26876177). The sIL6R is formed mostly by limited proteolysis of membrane-bound receptors, a process referred to as ectodomain shedding, but is also directly secreted from the cells after alternative mRNA splicing (PubMed:26876177, PubMed:28060820). mIL6R is cleaved by the proteases ADAM10 and ADAM17 (PubMed:26876177, PubMed:28060820). {ECO:0000269|PubMed:26876177, ECO:0000269|PubMed:28060820}.; PTM: Glycosylated. Glycosylation is dispensable for transport, signaling, and cell-surface turnover. Glycosylation at Asn-55 is a protease-regulatory exosite. Glycosylation is required for ADAM17-mediated proteolysis. {ECO:0000269|PubMed:28060820}.
uniprot
proteins
protein_family
Type 3 subfamily
uniprot
proteins
protein_family
Type I cytokine receptor family
uniprot
proteins
pubmed
10066782
uniprot
proteins
pubmed
11017875
uniprot
proteins
pubmed
12461182
uniprot
proteins
pubmed
12794819
uniprot
proteins
pubmed
12829785
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16270750
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17357077
uniprot
proteins
pubmed
1872801
uniprot
proteins
pubmed
21990364
uniprot
proteins
pubmed
2529343
uniprot
proteins
pubmed
26876177
uniprot
proteins
pubmed
28060820
uniprot
proteins
pubmed
28265003
uniprot
proteins
pubmed
30995492
uniprot
proteins
pubmed
31235509
uniprot
proteins
pubmed
3136546
uniprot
proteins
pubmed
8056053
uniprot
proteins
pubmed
8467812
uniprot
proteins
sequence_length
468
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane {ECO:0000250|UniProtKB:P22272}; Single-pass type I membrane protein {ECO:0000255}.; SUBCELLULAR LOCATION: [Isoform 2]: Secreted {ECO:0000269|PubMed:28060820}.; SUBCELLULAR LOCATION: [Soluble interleukin-6 receptor subunit alpha]: Secreted {ECO:0000269|PubMed:28060820}.
uniprot
proteins
transmembrane_region
TRANSMEM 366..386; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins