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Protein

Interleukin-6 receptor subunit beta

Gene

Il6st

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Signal-transducing molecule. The receptor systems for IL6, LIF, OSM, CNTF, IL11, CTF1 and BSF3 can utilize IL6ST for initiating signal transmission. Binding of IL6 to IL6R induces IL6ST homodimerization and formation of a high-affinity receptor complex, which activates Janus kinases (PubMed:1602143). That causes phosphorylation of IL6ST tyrosine residues which in turn activates STAT3 (PubMed:10661409). Mediates signals which regulate immune response, hematopoiesis, pain control and bone metabolism (PubMed:10661409, PubMed:26255596, PubMed:25057188, PubMed:8552649). Has a role in embryonic development (PubMed:10661409). Does not bind IL6 (By similarity). Essential for survival of motor and sensory neurons and for differentiation of astrocytes (PubMed:10377352). Required for expression of TRPA1 in nociceptive neurons (PubMed:25057188). Required for the maintenance of PTH1R expression in the osteoblast lineage and for the stimulation of PTH-induced osteoblast differentiation (PubMed:25228504). Required for normal trabecular bone mass and cortical bone composition (PubMed:24339143, PubMed:9348227, PubMed:26255596).By similarity9 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Receptor

Enzyme and pathway databases

ReactomeiR-MMU-1059683. Interleukin-6 signaling.
R-MMU-110056. MAPK3 (ERK1) activation.
R-MMU-112411. MAPK1 (ERK2) activation.
R-MMU-6788467. IL-6-type cytokine receptor ligand interactions.

Names & Taxonomyi

Protein namesi
Recommended name:
Interleukin-6 receptor subunit beta
Short name:
IL-6 receptor subunit beta
Short name:
IL-6R subunit beta
Short name:
IL-6R-beta
Short name:
IL-6RB
Alternative name(s):
Interleukin-6 signal transducer
Membrane glycoprotein 130
Short name:
gp130
Oncostatin-M receptor subunit alpha
CD_antigen: CD130
Gene namesi
Name:Il6st
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:96560. Il6st.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini23 – 617ExtracellularSequence analysisAdd BLAST595
Transmembranei618 – 639HelicalSequence analysisAdd BLAST22
Topological domaini640 – 917CytoplasmicSequence analysisAdd BLAST278

GO - Cellular componenti

  • cell body Source: MGI
  • ciliary neurotrophic factor receptor complex Source: MGI
  • dendrite Source: MGI
  • external side of plasma membrane Source: MGI
  • extracellular exosome Source: MGI
  • interleukin-6 receptor complex Source: MGI
  • membrane Source: MGI
  • neuronal cell body Source: MGI
  • oncostatin-M receptor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Progressively lethal between E12.5 and birth (PubMed:8552649). Embryos show hypoplastic ventricular myocardium without septal and trabecular defect, reduced numbers of pluripotential and committed hematopoietic progenitors in liver and reduced differentiated lineages in thymus (PubMed:8552649). Impaired differentiation of astrocytes and decreased number of dorsal root ganglion and motor neurons at E18.5 (PubMed:10377352). Decreased volume of mineralized trabecular bones, while number of osteoclasts is increased (PubMed:9348227, PubMed:26255596). Conditional knockout from the entire osteoblast lineage or specifically in osteocytes causes no significant skeletal or morphological defects but mice show 30% lower trabecular bone formation rate and larger cortical diameter compared to wild type (PubMed:24339143, PubMed:26255596). Conditional knockout in primary nociceptive afferents causes reduced sensitivity to mechanical stimulation due to reduced sensitivity of nociceptive neurons and reduces TRPA1 mRNA expression in dorsal root ganglion neurons (PubMed:25057188).6 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
ChainiPRO_000001090023 – 917Interleukin-6 receptor subunit betaAdd BLAST895

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi28 ↔ 54By similarity
Glycosylationi43N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi48 ↔ 103By similarity
Glycosylationi61N-linked (GlcNAc...)Sequence analysis1
Glycosylationi83N-linked (GlcNAc...)Sequence analysis1
Glycosylationi131N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi134 ↔ 144By similarity
Glycosylationi157N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi172 ↔ 180By similarity
Glycosylationi225N-linked (GlcNAc...)1 Publication1
Glycosylationi388N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi456 ↔ 464By similarity
Glycosylationi476N-linked (GlcNAc...)Sequence analysis1
Glycosylationi551N-linked (GlcNAc...)Sequence analysis1
Modified residuei659PhosphoserineBy similarity1
Modified residuei665PhosphoserineBy similarity1
Modified residuei780PhosphoserineBy similarity1
Modified residuei787PhosphoserineCombined sources1
Modified residuei827PhosphoserineBy similarity1
Modified residuei837PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation of Ser-780 down-regulates cell surface expression.By similarity
Heavily N-glycosylated. Glycosylation is required for protein stability and localization in plasma membrane but not for ligand binding.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ00560.
PaxDbiQ00560.
PRIDEiQ00560.

PTM databases

iPTMnetiQ00560.
PhosphoSitePlusiQ00560.
SwissPalmiQ00560.

Expressioni

Tissue specificityi

Found in tissues such as brain, heart, thymus, spleen, kidney, lung and liver. Found in all the cell lines tested except BaF-B03. Expression not restricted to IL6-responsive cells.1 Publication

Developmental stagei

In embryonic stem cells it is found from day 6 of gestation. It reaches a peak on day 8 and gradually declines during the rest of embryogenesis.1 Publication

Gene expression databases

BgeeiENSMUSG00000021756.
CleanExiMM_IL6ST.
ExpressionAtlasiQ00560. baseline and differential.
GenevisibleiQ00560. MM.

Interactioni

Subunit structurei

Component of a hexamer of two molecules each of IL6, IL6R and IL6ST. Forms heterodimers composed of LIFR and IL6ST (type I OSM receptor) which are activated by LIF and OSM. Also forms heterodimers composed of OSMR and IL6ST (type II receptor) which are activated by OSM but not by LIF. Interacts with HCK (By similarity). Interacts with INPP5D/SHIP1 (PubMed:17105399).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Il12rb2P973782EBI-3862992,EBI-6253448
Socs3O357183EBI-3862992,EBI-2659360

GO - Molecular functioni

Protein-protein interaction databases

BioGridi200643. 8 interactors.
DIPiDIP-5782N.
IntActiQ00560. 6 interactors.
MINTiMINT-3382082.
STRINGi10090.ENSMUSP00000064205.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2BBUNMR-B750-764[»]
2HMHX-ray2.00B753-763[»]
4GL9X-ray3.90I/J/K/L750-764[»]
ProteinModelPortaliQ00560.
SMRiQ00560.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ00560.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini26 – 120Ig-like C2-typeAdd BLAST95
Domaini128 – 221Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST94
Domaini222 – 322Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST101
Domaini327 – 417Fibronectin type-III 3PROSITE-ProRule annotationAdd BLAST91
Domaini422 – 515Fibronectin type-III 4PROSITE-ProRule annotationAdd BLAST94
Domaini517 – 611Fibronectin type-III 5PROSITE-ProRule annotationAdd BLAST95

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi308 – 312WSXWS motif5
Motifi649 – 657Box 1 motif9

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi723 – 741Ser-richAdd BLAST19

Domaini

The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.
The box 1 motif is required for JAK interaction and/or activation.

Sequence similaritiesi

Contains 5 fibronectin type-III domains.PROSITE-ProRule annotation

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IF1N. Eukaryota.
ENOG410YNQ4. LUCA.
GeneTreeiENSGT00550000074436.
HOGENOMiHOG000015771.
HOVERGENiHBG052119.
InParanoidiQ00560.
KOiK05060.
OMAiFKQNCSQ.
OrthoDBiEOG091G01XM.
TreeFamiTF338122.

Family and domain databases

CDDicd00063. FN3. 3 hits.
Gene3Di2.60.40.10. 6 hits.
InterProiIPR003961. FN3_dom.
IPR003529. Hematopoietin_rcpt_Gp130_CS.
IPR013783. Ig-like_fold.
IPR010457. IgC2-like_lig-bd.
IPR015321. TypeI_recpt_CBD.
[Graphical view]
PfamiPF00041. fn3. 2 hits.
PF09240. IL6Ra-bind. 1 hit.
PF06328. Lep_receptor_Ig. 1 hit.
[Graphical view]
SMARTiSM00060. FN3. 5 hits.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 4 hits.
PROSITEiPS50853. FN3. 5 hits.
PS01353. HEMATOPO_REC_L_F2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q00560-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSAPRIWLAQ ALLFFLTTES IGQLLEPCGY IYPEFPVVQR GSNFTAICVL
60 70 80 90 100
KEACLQHYYV NASYIVWKTN HAAVPREQVT VINRTTSSVT FTDVVLPSVQ
110 120 130 140 150
LTCNILSFGQ IEQNVYGVTM LSGFPPDKPT NLTCIVNEGK NMLCQWDPGR
160 170 180 190 200
ETYLETNYTL KSEWATEKFP DCQSKHGTSC MVSYMPTYYV NIEVWVEAEN
210 220 230 240 250
ALGKVSSESI NFDPVDKVKP TPPYNLSVTN SEELSSILKL SWVSSGLGGL
260 270 280 290 300
LDLKSDIQYR TKDASTWIQV PLEDTMSPRT SFTVQDLKPF TEYVFRIRSI
310 320 330 340 350
KDSGKGYWSD WSEEASGTTY EDRPSRPPSF WYKTNPSHGQ EYRSVRLIWK
360 370 380 390 400
ALPLSEANGK ILDYEVILTQ SKSVSQTYTV TGTELTVNLT NDRYVASLAA
410 420 430 440 450
RNKVGKSAAA VLTIPSPHVT AAYSVVNLKA FPKDNLLWVE WTPPPKPVSK
460 470 480 490 500
YILEWCVLSE NAPCVEDWQQ EDATVNRTHL RGRLLESKCY QITVTPVFAT
510 520 530 540 550
GPGGSESLKA YLKQAAPARG PTVRTKKVGK NEAVLAWDQI PVDDQNGFIR
560 570 580 590 600
NYSISYRTSV GKEMVVHVDS SHTEYTLSSL SSDTLYMVRM AAYTDEGGKD
610 620 630 640 650
GPEFTFTTPK FAQGEIEAIV VPVCLAFLLT TLLGVLFCFN KRDLIKKHIW
660 670 680 690 700
PNVPDPSKSH IAQWSPHTPP RHNFNSKDQM YSDGNFTDVS VVEIEANNKK
710 720 730 740 750
PCPDDLKSVD LFKKEKVSTE GHSSGIGGSS CMSSSRPSIS SNEENESAQS
760 770 780 790 800
TASTVQYSTV VHSGYRHQVP SVQVFSRSES TQPLLDSEER PEDLQLVDSV
810 820 830 840 850
DGGDEILPRQ PYFKQNCSQP EACPEISHFE RSNQVLSGNE EDFVRLKQQQ
860 870 880 890 900
VSDHISQPYG SEQRRLFQEG STADALGTGA DGQMERFESV GMETTIDEEI
910
PKSYLPQTVR QGGYMPQ
Length:917
Mass (Da):102,451
Last modified:October 3, 2012 - v2
Checksum:iEDA69AB865E5A6E8
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti756Q → E in CAA44515 (PubMed:1602143).Curated1
Sequence conflicti756Q → E in AAA37723 (PubMed:1602143).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X62646 mRNA. Translation: CAA44515.1.
M83336 mRNA. Translation: AAA37723.1.
AC159196 Genomic DNA. No translation available.
CH466568 Genomic DNA. Translation: EDL18412.1.
CCDSiCCDS26773.1.
PIRiI49699.
RefSeqiNP_034690.3. NM_010560.3.
UniGeneiMm.4364.

Genome annotation databases

EnsembliENSMUST00000070731; ENSMUSP00000064205; ENSMUSG00000021756.
ENSMUST00000183663; ENSMUSP00000138836; ENSMUSG00000021756.
ENSMUST00000184311; ENSMUSP00000139227; ENSMUSG00000021756.
GeneIDi16195.
KEGGimmu:16195.
UCSCiuc007rwg.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X62646 mRNA. Translation: CAA44515.1.
M83336 mRNA. Translation: AAA37723.1.
AC159196 Genomic DNA. No translation available.
CH466568 Genomic DNA. Translation: EDL18412.1.
CCDSiCCDS26773.1.
PIRiI49699.
RefSeqiNP_034690.3. NM_010560.3.
UniGeneiMm.4364.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2BBUNMR-B750-764[»]
2HMHX-ray2.00B753-763[»]
4GL9X-ray3.90I/J/K/L750-764[»]
ProteinModelPortaliQ00560.
SMRiQ00560.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200643. 8 interactors.
DIPiDIP-5782N.
IntActiQ00560. 6 interactors.
MINTiMINT-3382082.
STRINGi10090.ENSMUSP00000064205.

PTM databases

iPTMnetiQ00560.
PhosphoSitePlusiQ00560.
SwissPalmiQ00560.

Proteomic databases

MaxQBiQ00560.
PaxDbiQ00560.
PRIDEiQ00560.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000070731; ENSMUSP00000064205; ENSMUSG00000021756.
ENSMUST00000183663; ENSMUSP00000138836; ENSMUSG00000021756.
ENSMUST00000184311; ENSMUSP00000139227; ENSMUSG00000021756.
GeneIDi16195.
KEGGimmu:16195.
UCSCiuc007rwg.2. mouse.

Organism-specific databases

CTDi3572.
MGIiMGI:96560. Il6st.

Phylogenomic databases

eggNOGiENOG410IF1N. Eukaryota.
ENOG410YNQ4. LUCA.
GeneTreeiENSGT00550000074436.
HOGENOMiHOG000015771.
HOVERGENiHBG052119.
InParanoidiQ00560.
KOiK05060.
OMAiFKQNCSQ.
OrthoDBiEOG091G01XM.
TreeFamiTF338122.

Enzyme and pathway databases

ReactomeiR-MMU-1059683. Interleukin-6 signaling.
R-MMU-110056. MAPK3 (ERK1) activation.
R-MMU-112411. MAPK1 (ERK2) activation.
R-MMU-6788467. IL-6-type cytokine receptor ligand interactions.

Miscellaneous databases

EvolutionaryTraceiQ00560.
PROiQ00560.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000021756.
CleanExiMM_IL6ST.
ExpressionAtlasiQ00560. baseline and differential.
GenevisibleiQ00560. MM.

Family and domain databases

CDDicd00063. FN3. 3 hits.
Gene3Di2.60.40.10. 6 hits.
InterProiIPR003961. FN3_dom.
IPR003529. Hematopoietin_rcpt_Gp130_CS.
IPR013783. Ig-like_fold.
IPR010457. IgC2-like_lig-bd.
IPR015321. TypeI_recpt_CBD.
[Graphical view]
PfamiPF00041. fn3. 2 hits.
PF09240. IL6Ra-bind. 1 hit.
PF06328. Lep_receptor_Ig. 1 hit.
[Graphical view]
SMARTiSM00060. FN3. 5 hits.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 4 hits.
PROSITEiPS50853. FN3. 5 hits.
PS01353. HEMATOPO_REC_L_F2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiIL6RB_MOUSE
AccessioniPrimary (citable) accession number: Q00560
Secondary accession number(s): G5E8D2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: October 3, 2012
Last modified: November 30, 2016
This is version 159 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.