UniProtKB - O18796 (IL6RA_PIG)
Interleukin-6 receptor subunit alpha
IL6R
Functioni
Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal. Signal activation necessitate an association with IL6ST. Activation leads to the regulation of the immune response, acute-phase reactions and hematopoiesis. 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.
By similaritySignaling via the membrane-bound IL6R is mostly regenerative and anti-inflammatory. Drives naive CD4+ T cells to the Th17 lineage, through 'cluster signaling' by dendritic cells.
By similaritySoluble form of IL6 receptor (sIL6R) that acts as an agonist of IL6 activity (By similarity).
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 proinflammatory properties of IL6 and an important player in the development of chronic inflammatory diseases. In complex with IL6, is required for induction of VEGF production (By similarity).
Plays a protective role during liver injury, being required for maintenance of tissue regeneration. 'Trans-signaling' in central nervous system regulates energy and glucose homeostasis (By similarity).
By similarityActivity regulationi
GO - Molecular functioni
- cytokine binding Source: GO_Central
- cytokine receptor activity Source: GO_Central
- interleukin-11 binding Source: GO_Central
- interleukin-11 receptor activity Source: GO_Central
- interleukin-6 binding Source: GO_Central
- interleukin-6 receptor activity Source: UniProtKB
GO - Biological processi
- cytokine-mediated signaling pathway Source: GO_Central
- interleukin-6-mediated signaling pathway Source: UniProtKB
- positive regulation of activation of Janus kinase activity Source: GO_Central
- positive regulation of cell population proliferation Source: GO_Central
- positive regulation of tyrosine phosphorylation of STAT protein Source: GO_Central
- T-helper 17 cell lineage commitment Source: UniProtKB
- vascular endothelial growth factor production Source: UniProtKB
Keywordsi
Molecular function | Receptor |
Names & Taxonomyi
Protein namesi | Recommended name: Interleukin-6 receptor subunit alphaShort name: IL-6 receptor subunit alpha Short name: IL-6R subunit alpha Short name: IL-6R-alpha Short name: IL-6RA Alternative name(s): IL-6R 1 CD_antigen: CD126 Cleaved into the following chain: |
Gene namesi | Name:IL6R |
Organismi | Sus scrofa (Pig) |
Taxonomic identifieri | 9823 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Artiodactyla › Suina › Suidae › Sus |
Proteomesi |
|
Subcellular locationi
Plasma membrane
- Cell membrane By similarity; Single-pass type I membrane protein Sequence analysis
Extracellular region or secreted
- Secreted By similarity
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Plasma Membrane
- external side of plasma membrane Source: GO_Central
- interleukin-6 receptor complex Source: UniProtKB
Other locations
- receptor complex Source: GO_Central
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 20 – 365 | ExtracellularSequence analysisAdd BLAST | 346 | |
Transmembranei | 366 – 386 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 387 – 467 | CytoplasmicSequence analysisAdd BLAST | 81 |
Keywords - Cellular componenti
Cell membrane, Membrane, SecretedPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 19 | By similarityAdd BLAST | 19 | |
ChainiPRO_0000010897 | 20 – 467 | Interleukin-6 receptor subunit alphaAdd BLAST | 448 | |
ChainiPRO_0000450732 | 20 – 355 | Soluble interleukin-6 receptor subunit alphaBy similarityAdd BLAST | 336 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 25 ↔ 193 | PROSITE-ProRule annotation | ||
Disulfide bondi | 47 ↔ 96 | PROSITE-ProRule annotation | ||
Glycosylationi | 55 | N-linked (GlcNAc...) asparagineBy similarity | 1 | |
Glycosylationi | 93 | N-linked (GlcNAc...) asparagineBy similarity | 1 | |
Disulfide bondi | 121 ↔ 132 | PROSITE-ProRule annotation | ||
Disulfide bondi | 165 ↔ 176 | PROSITE-ProRule annotation | ||
Glycosylationi | 221 | N-linked (GlcNAc...) asparagineBy similarity | 1 | |
Glycosylationi | 245 | N-linked (GlcNAc...) asparagineBy similarity | 1 | |
Glycosylationi | 350 | N-linked (GlcNAc...) asparagineBy similarity | 1 | |
Glycosylationi | 352 | O-linked (GlcNAc) threonineBy similarity | 1 |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 355 – 356 | Cleavage; by ADAM10 and ADAM17By similarity | 2 |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
PRIDEi | O18796 |
Expressioni
Tissue specificityi
Interactioni
Subunit structurei
Component of a hexamer of two molecules each of IL6, IL6R and IL6ST; first binds to IL6 to associate with the signaling subunit IL6ST.
Interacts (via N-terminal ectodomain) with SORL1; this interaction may affect IL6-binding to IL6R, hence decrease IL6 'classic-signaling'.
By similarityAlso interacts with SORL1; this interaction leads to soluble IL6R internalization. May form a trimeric complex with the soluble SORL1 ectodomain and circulating IL6 receptor; this interaction might stabilize circulating IL6, hence promote IL6 'trans-signaling'.
By similarityGO - Molecular functioni
- cytokine binding Source: GO_Central
- interleukin-11 binding Source: GO_Central
- interleukin-6 binding Source: GO_Central
Protein-protein interaction databases
STRINGi | 9823.ENSSSCP00000006981 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 20 – 112 | Ig-like C2-typeAdd BLAST | 93 | |
Domaini | 113 – 217 | Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST | 105 | |
Domaini | 218 – 316 | Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST | 99 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 315 – 357 | DisorderedSequence analysisAdd BLAST | 43 | |
Regioni | 428 – 467 | DisorderedSequence analysisAdd BLAST | 40 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 303 – 307 | WSXWS motif | 5 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 315 – 338 | Polar residuesSequence analysisAdd BLAST | 24 | |
Compositional biasi | 433 – 449 | Polar residuesSequence analysisAdd BLAST | 17 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
InParanoidi | O18796 |
OrthoDBi | 783799at2759 |
Family and domain databases
CDDi | cd00063, FN3, 1 hit |
Gene3Di | 2.60.40.10, 3 hits |
InterProi | View protein in InterPro IPR003961, FN3_dom IPR036116, FN3_sf IPR003530, Hematopoietin_rcpt_L_F3_CS IPR007110, Ig-like_dom IPR036179, Ig-like_dom_sf IPR013783, Ig-like_fold IPR003599, Ig_sub IPR003598, Ig_sub2 IPR013151, Immunoglobulin IPR015321, TypeI_recpt_CBD |
Pfami | View protein in Pfam PF00047, ig, 1 hit PF09240, IL6Ra-bind, 1 hit |
SMARTi | View protein in SMART SM00060, FN3, 1 hit SM00409, IG, 1 hit SM00408, IGc2, 1 hit |
SUPFAMi | SSF48726, SSF48726, 1 hit SSF49265, SSF49265, 2 hits |
PROSITEi | View protein in PROSITE PS50853, FN3, 2 hits PS01354, HEMATOPO_REC_L_F3, 1 hit PS50835, IG_LIKE, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MLAVGCALLT ALLAAPGMAL APRGCSKLEV AQDVLTSLPG ASVTLTCPGG
60 70 80 90 100
EPGDNATIHW VLRNQVTGSP DGRPAGVGRR LLLKSVQLSD SGNYSCYQDG
110 120 130 140 150
VPAGSVRLLV DAPPEEPQLS CFRKSPLSNV GCEWRPRSPP SPTTKAVLLV
160 170 180 190 200
RKFQNSPVED FQEPCQYSLE AQRFFCQLAV PEGDNSFHIV TLCVANSAGS
210 220 230 240 250
QSSTPQTFEG YGILQPDPPV NITVSAVDRN PRWLSVTWQD PPSWNSYFYR
260 270 280 290 300
LQFELRYRAE RSKTFTTWMV KELQHHCIIH DAWSGMRHVV QLRAQEEFGH
310 320 330 340 350
GLWSEWSQEV TGIPWTESRS SPAETELPLS TQAPTTNEDD EDISSKESAN
360 370 380 390 400
ATSLPVQDSA SVPLPTFLVA GGSLAFGTLL CIGIILRFKK TGQLQALKEG
410 420 430 440 450
KTNMHPPYSL GQLVPERPKS TPVLVPLISP PVSPNSLGDN TSRNSRPEAR
460
GPQSPYDVSN RDYFFPR
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF147881 mRNA Translation: AAF73109.1 AF015116 mRNA Translation: AAB70916.1 |
RefSeqi | NP_999568.1, NM_214403.1 |
Genome annotation databases
GeneIDi | 399522 |
KEGGi | ssc:399522 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF147881 mRNA Translation: AAF73109.1 AF015116 mRNA Translation: AAB70916.1 |
RefSeqi | NP_999568.1, NM_214403.1 |
3D structure databases
SMRi | O18796 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 9823.ENSSSCP00000006981 |
Proteomic databases
PRIDEi | O18796 |
Genome annotation databases
GeneIDi | 399522 |
KEGGi | ssc:399522 |
Organism-specific databases
CTDi | 3570 |
Phylogenomic databases
InParanoidi | O18796 |
OrthoDBi | 783799at2759 |
Miscellaneous databases
ChiTaRSi | IL6R, pig |
Family and domain databases
CDDi | cd00063, FN3, 1 hit |
Gene3Di | 2.60.40.10, 3 hits |
InterProi | View protein in InterPro IPR003961, FN3_dom IPR036116, FN3_sf IPR003530, Hematopoietin_rcpt_L_F3_CS IPR007110, Ig-like_dom IPR036179, Ig-like_dom_sf IPR013783, Ig-like_fold IPR003599, Ig_sub IPR003598, Ig_sub2 IPR013151, Immunoglobulin IPR015321, TypeI_recpt_CBD |
Pfami | View protein in Pfam PF00047, ig, 1 hit PF09240, IL6Ra-bind, 1 hit |
SMARTi | View protein in SMART SM00060, FN3, 1 hit SM00409, IG, 1 hit SM00408, IGc2, 1 hit |
SUPFAMi | SSF48726, SSF48726, 1 hit SSF49265, SSF49265, 2 hits |
PROSITEi | View protein in PROSITE PS50853, FN3, 2 hits PS01354, HEMATOPO_REC_L_F3, 1 hit PS50835, IG_LIKE, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | IL6RA_PIG | |
Accessioni | O18796Primary (citable) accession number: O18796 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 1, 2000 |
Last sequence update: | December 1, 2000 | |
Last modified: | February 23, 2022 | |
This is version 124 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families