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Protein

Interleukin-6 receptor subunit beta

Gene

IL6ST

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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:2261637). That causes phosphorylation of IL6ST tyrosine residues which in turn activates STAT3 (PubMed:19915009, PubMed:23294003). Mediates signals which regulate immune response, hematopoiesis, pain control and bone metabolism (By similarity). Has a role in embryonic development (By similarity). Does not bind IL6 (PubMed:2261637). Essential for survival of motor and sensory neurons and for differentiation of astrocytes (By similarity). Required for expression of TRPA1 in nociceptive neurons (By similarity). Required for the maintenance of PTH1R expression in the osteoblast lineage and for the stimulation of PTH-induced osteoblast differentiation (By similarity). Required for normal trabecular bone mass and cortical bone composition (By similarity).By similarity3 Publications

GO - Molecular functioni

  • ciliary neurotrophic factor receptor activity Source: BHF-UCL
  • ciliary neurotrophic factor receptor binding Source: BHF-UCL
  • growth factor binding Source: BHF-UCL
  • interleukin-11 binding Source: Ensembl
  • interleukin-11 receptor activity Source: Ensembl
  • interleukin-27 receptor activity Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL

GO - Biological processi

  • ciliary neurotrophic factor-mediated signaling pathway Source: BHF-UCL
  • cytokine-mediated signaling pathway Source: BHF-UCL
  • glycogen metabolic process Source: Ensembl
  • interleukin-27-mediated signaling pathway Source: BHF-UCL
  • interleukin-35-mediated signaling pathway Source: Reactome
  • interleukin-6-mediated signaling pathway Source: BHF-UCL
  • leukemia inhibitory factor signaling pathway Source: BHF-UCL
  • negative regulation of apoptotic process Source: BHF-UCL
  • negative regulation of interleukin-6-mediated signaling pathway Source: BHF-UCL
  • oncostatin-M-mediated signaling pathway Source: BHF-UCL
  • positive regulation of acute inflammatory response Source: BHF-UCL
  • positive regulation of adaptive immune response Source: BHF-UCL
  • positive regulation of astrocyte differentiation Source: Ensembl
  • positive regulation of cardiac muscle hypertrophy Source: BHF-UCL
  • positive regulation of cell proliferation Source: BHF-UCL
  • positive regulation of osteoblast differentiation Source: BHF-UCL
  • positive regulation of T cell proliferation Source: BHF-UCL
  • positive regulation of tyrosine phosphorylation of STAT protein Source: BHF-UCL
  • positive regulation of vascular endothelial growth factor production Source: BHF-UCL
  • regulation of Notch signaling pathway Source: Ensembl
  • response to cytokine Source: BHF-UCL
  • viral process Source: UniProtKB-KW

Keywordsi

Molecular functionReceptor
Biological processHost-virus interaction

Enzyme and pathway databases

ReactomeiR-HSA-1059683 Interleukin-6 signaling
R-HSA-110056 MAPK3 (ERK1) activation
R-HSA-112411 MAPK1 (ERK2) activation
R-HSA-6788467 IL-6-type cytokine receptor ligand interactions
R-HSA-8984722 Interleukin-35 Signalling
R-HSA-9020956 Interleukin-27 signaling
SignaLinkiP40189
SIGNORiP40189

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):
CDw130
Interleukin-6 signal transducer
Membrane glycoprotein 130
Short name:
gp130
Oncostatin-M receptor subunit alpha
CD_antigen: CD130
Gene namesi
Name:IL6ST
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000134352.19
HGNCiHGNC:6021 IL6ST
MIMi600694 gene
neXtProtiNX_P40189

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini23 – 619ExtracellularSequence analysisAdd BLAST597
Transmembranei620 – 641HelicalSequence analysisAdd BLAST22
Topological domaini642 – 918CytoplasmicSequence analysisAdd BLAST277

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi172C → S: Induces ligand-independent activation. 1 Publication1
Mutagenesisi186 – 190Missing : Induces ligand-independent activation. 1 Publication5
Mutagenesisi189V → G: Does not induce ligand-independent activation. 1 Publication1
Mutagenesisi190Y → G: Does not induce ligand-independent activation. 1 Publication1
Mutagenesisi215D → G: Induces ligand-independent activation. 1 Publication1
Mutagenesisi252V → G: Induces ligand-independent activation. 1 Publication1
Mutagenesisi782S → A: Increases cell surface expression. 1 Publication1

Organism-specific databases

DisGeNETi3572
OpenTargetsiENSG00000134352
PharmGKBiPA29837

Chemistry databases

ChEMBLiCHEMBL3124734
GuidetoPHARMACOLOGYi2317

Polymorphism and mutation databases

BioMutaiIL6ST
DMDMi215273999

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Add BLAST22
ChainiPRO_000001089923 – 918Interleukin-6 receptor subunit betaAdd BLAST896

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi28 ↔ 542 Publications
Glycosylationi43N-linked (GlcNAc...) asparagine2 Publications1
Disulfide bondi48 ↔ 1032 Publications
Glycosylationi83N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi131N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi134 ↔ 1442 Publications
Glycosylationi157N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi172 ↔ 1822 Publications
Glycosylationi227N-linked (GlcNAc...) asparagine3 Publications1
Glycosylationi379N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi383N-linked (GlcNAc...) asparagine3 Publications1
Glycosylationi390N-linked (GlcNAc...) (complex) asparagine2 Publications1
Disulfide bondi458 ↔ 4662 Publications
Glycosylationi553N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi564N-linked (GlcNAc...) asparagine1 Publication1
Modified residuei661PhosphoserineCombined sources1
Modified residuei667PhosphoserineCombined sources1
Modified residuei782Phosphoserine1 Publication1
Modified residuei789PhosphoserineBy similarity1
Modified residuei829PhosphoserineCombined sources1
Modified residuei839PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylation of Ser-782 down-regulates cell surface expression.1 Publication
Heavily N-glycosylated (PubMed:11098061, PubMed:16335952, PubMed:19159218, PubMed:19139490, PubMed:11251120). Glycosylation is required for protein stability and localization in plasma membrane but not for ligand binding (PubMed:19915009).6 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiP40189
MaxQBiP40189
PaxDbiP40189
PeptideAtlasiP40189
PRIDEiP40189
ProteomicsDBi55338
55339 [P40189-2]
55340 [P40189-3]

PTM databases

GlyConnecti649
iPTMnetiP40189
PhosphoSitePlusiP40189
SwissPalmiP40189
UniCarbKBiP40189

Expressioni

Tissue specificityi

Found in all the tissues and cell lines examined (PubMed:2261637). Expression not restricted to IL6 responsive cells (PubMed:2261637). Expressed in blood serum (at protein level) (PubMed:24629561).2 Publications

Inductioni

LIF and OSM activate the type I OSM receptor while only OSM can activate the type II OSM receptor.1 Publication

Gene expression databases

BgeeiENSG00000134352
CleanExiHS_IL6ST
ExpressionAtlasiP40189 baseline and differential
GenevisibleiP40189 HS

Organism-specific databases

HPAiCAB025784
HPA010558

Interactioni

Subunit structurei

Component of a hexamer of two molecules each of IL6, IL6R and IL6ST (PubMed:12829785). Forms heterodimers composed of LIFR and IL6ST (type I OSM receptor) which are activated by LIF and OSM (PubMed:8999038). Also forms heterodimers composed of OSMR and IL6ST (type II receptor) which are activated by OSM but not by LIF (PubMed:8999038). Homodimer. Interacts with HCK (PubMed:9406996). Interacts with INPP5D/SHIP1 (By similarity).By similarity4 Publications
(Microbial infection) The homodimer binds two molecules of herpes virus 8/HHV-8 protein vIL-6.2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • ciliary neurotrophic factor receptor binding Source: BHF-UCL
  • growth factor binding Source: BHF-UCL
  • interleukin-11 binding Source: Ensembl
  • protein homodimerization activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi109786, 33 interactors
CORUMiP40189
DIPiDIP-95N
IntActiP40189, 21 interactors
MINTiP40189
STRINGi9606.ENSP00000338799

Chemistry databases

BindingDBiP40189

Structurei

Secondary structure

1918
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi28 – 35Combined sources8
Beta strandi37 – 39Combined sources3
Beta strandi44 – 50Combined sources7
Helixi52 – 58Combined sources7
Helixi62 – 64Combined sources3
Beta strandi65 – 69Combined sources5
Helixi76 – 78Combined sources3
Beta strandi80 – 83Combined sources4
Beta strandi86 – 91Combined sources6
Beta strandi97 – 107Combined sources11
Turni108 – 110Combined sources3
Beta strandi111 – 123Combined sources13
Beta strandi130 – 137Combined sources8
Beta strandi143 – 147Combined sources5
Beta strandi157 – 164Combined sources8
Beta strandi176 – 178Combined sources3
Beta strandi181 – 183Combined sources3
Beta strandi194 – 202Combined sources9
Beta strandi205 – 208Combined sources4
Beta strandi212 – 214Combined sources3
Helixi216 – 218Combined sources3
Beta strandi219 – 221Combined sources3
Beta strandi226 – 231Combined sources6
Beta strandi234 – 238Combined sources5
Beta strandi240 – 245Combined sources6
Helixi248 – 251Combined sources4
Beta strandi255 – 263Combined sources9
Helixi274 – 277Combined sources4
Beta strandi282 – 286Combined sources5
Beta strandi291 – 303Combined sources13
Beta strandi317 – 321Combined sources5
Helixi325 – 331Combined sources7
Beta strandi332 – 338Combined sources7
Beta strandi345 – 351Combined sources7
Helixi356 – 359Combined sources4
Beta strandi363 – 372Combined sources10
Beta strandi378 – 391Combined sources14
Beta strandi396 – 406Combined sources11
Beta strandi412 – 416Combined sources5
Beta strandi428 – 435Combined sources8
Beta strandi438 – 444Combined sources7
Beta strandi452 – 460Combined sources9
Beta strandi462 – 464Combined sources3
Beta strandi469 – 474Combined sources6
Beta strandi478 – 481Combined sources4
Beta strandi491 – 500Combined sources10
Beta strandi508 – 515Combined sources8
Beta strandi525 – 530Combined sources6
Beta strandi535 – 539Combined sources5
Helixi544 – 547Combined sources4
Beta strandi553 – 560Combined sources8
Beta strandi566 – 571Combined sources6
Beta strandi575 – 579Combined sources5
Beta strandi587 – 596Combined sources10
Beta strandi599 – 602Combined sources4
Beta strandi606 – 609Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BJ8NMR-A219-325[»]
1BQUX-ray2.00A/B122-333[»]
1I1RX-ray2.40A23-325[»]
1N2Qmodel-A/B23-324[»]
1P9MX-ray3.65A23-321[»]
1PVHX-ray2.50A/C123-323[»]
3L5HX-ray3.60A24-612[»]
3L5IX-ray1.90A323-612[»]
3L5JX-ray3.04A/B323-610[»]
ProteinModelPortaliP40189
SMRiP40189
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP40189

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini26 – 120Ig-like C2-typeAdd BLAST95
Domaini125 – 216Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST92
Domaini224 – 324Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST101
Domaini329 – 424Fibronectin type-III 3PROSITE-ProRule annotationAdd BLAST96
Domaini426 – 517Fibronectin type-III 4PROSITE-ProRule annotationAdd BLAST92
Domaini518 – 613Fibronectin type-III 5PROSITE-ProRule annotationAdd BLAST96

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi310 – 314WSXWS motif5
Motifi651 – 659Box 1 motif9

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi725 – 755Ser-richAdd BLAST31

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

Keywords - Domaini

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IF1N Eukaryota
ENOG410YNQ4 LUCA
GeneTreeiENSGT00550000074436
HOGENOMiHOG000015771
HOVERGENiHBG052119
InParanoidiP40189
KOiK05060
OMAiFCFNKRD
OrthoDBiEOG091G01XM
PhylomeDBiP40189
TreeFamiTF338122

Family and domain databases

CDDicd00063 FN3, 2 hits
Gene3Di2.60.40.10, 6 hits
InterProiView protein in InterPro
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR003529 Hematopoietin_rcpt_Gp130_CS
IPR013783 Ig-like_fold
IPR010457 IgC2-like_lig-bd
IPR015321 TypeI_recpt_CBD
PfamiView protein in Pfam
PF00041 fn3, 2 hits
PF09240 IL6Ra-bind, 1 hit
PF06328 Lep_receptor_Ig, 1 hit
SMARTiView protein in SMART
SM00060 FN3, 5 hits
SUPFAMiSSF49265 SSF49265, 5 hits
PROSITEiView protein in PROSITE
PS50853 FN3, 4 hits
PS01353 HEMATOPO_REC_L_F2, 1 hit

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P40189-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLTLQTWLVQ ALFIFLTTES TGELLDPCGY ISPESPVVQL HSNFTAVCVL
60 70 80 90 100
KEKCMDYFHV NANYIVWKTN HFTIPKEQYT IINRTASSVT FTDIASLNIQ
110 120 130 140 150
LTCNILTFGQ LEQNVYGITI ISGLPPEKPK NLSCIVNEGK KMRCEWDGGR
160 170 180 190 200
ETHLETNFTL KSEWATHKFA DCKAKRDTPT SCTVDYSTVY FVNIEVWVEA
210 220 230 240 250
ENALGKVTSD HINFDPVYKV KPNPPHNLSV INSEELSSIL KLTWTNPSIK
260 270 280 290 300
SVIILKYNIQ YRTKDASTWS QIPPEDTAST RSSFTVQDLK PFTEYVFRIR
310 320 330 340 350
CMKEDGKGYW SDWSEEASGI TYEDRPSKAP SFWYKIDPSH TQGYRTVQLV
360 370 380 390 400
WKTLPPFEAN GKILDYEVTL TRWKSHLQNY TVNATKLTVN LTNDRYLATL
410 420 430 440 450
TVRNLVGKSD AAVLTIPACD FQATHPVMDL KAFPKDNMLW VEWTTPRESV
460 470 480 490 500
KKYILEWCVL SDKAPCITDW QQEDGTVHRT YLRGNLAESK CYLITVTPVY
510 520 530 540 550
ADGPGSPESI KAYLKQAPPS KGPTVRTKKV GKNEAVLEWD QLPVDVQNGF
560 570 580 590 600
IRNYTIFYRT IIGNETAVNV DSSHTEYTLS SLTSDTLYMV RMAAYTDEGG
610 620 630 640 650
KDGPEFTFTT PKFAQGEIEA IVVPVCLAFL LTTLLGVLFC FNKRDLIKKH
660 670 680 690 700
IWPNVPDPSK SHIAQWSPHT PPRHNFNSKD QMYSDGNFTD VSVVEIEAND
710 720 730 740 750
KKPFPEDLKS LDLFKKEKIN TEGHSSGIGG SSCMSSSRPS ISSSDENESS
760 770 780 790 800
QNTSSTVQYS TVVHSGYRHQ VPSVQVFSRS ESTQPLLDSE ERPEDLQLVD
810 820 830 840 850
HVDGGDGILP RQQYFKQNCS QHESSPDISH FERSKQVSSV NEEDFVRLKQ
860 870 880 890 900
QISDHISQSC GSGQMKMFQE VSAADAFGPG TEGQVERFET VGMEAATDEG
910
MPKSYLPQTV RQGGYMPQ
Length:918
Mass (Da):103,537
Last modified:November 25, 2008 - v2
Checksum:i6510A4409FFCF08C
GO
Isoform 2 (identifier: P40189-2) [UniParc]FASTAAdd to basket
Also known as: GP130-RAPS

The sequence of this isoform differs from the canonical sequence as follows:
     325-329: RPSKA → NIASF
     330-918: Missing.

Show »
Length:329
Mass (Da):37,499
Checksum:iD556124C867984E4
GO
Isoform 3 (identifier: P40189-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     423-483: Missing.

Show »
Length:857
Mass (Da):96,276
Checksum:i726208A5073B5451
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0477828L → V2 PublicationsCorresponds to variant dbSNP:rs1063560Ensembl.1
Natural variantiVAR_047783148G → R Polymorphism; associated with increased levels of soluble IL6RB in blood serum. 1 PublicationCorresponds to variant dbSNP:rs2228044Ensembl.1
Natural variantiVAR_074654200A → G Found in patient with lung cancer; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs199905033Ensembl.1
Natural variantiVAR_047784397L → V. Corresponds to variant dbSNP:rs2228043Ensembl.1
Natural variantiVAR_036165415T → I in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_047785454I → T. Corresponds to variant dbSNP:rs2228046Ensembl.1
Natural variantiVAR_047786499V → I. Corresponds to variant dbSNP:rs34417936Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_001684325 – 329RPSKA → NIASF in isoform 2. 1 Publication5
Alternative sequenceiVSP_001685330 – 918Missing in isoform 2. 1 PublicationAdd BLAST589
Alternative sequenceiVSP_043716423 – 483Missing in isoform 3. 1 PublicationAdd BLAST61

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M57230 mRNA Translation: AAA59155.1
AB015706 mRNA Translation: BAA78112.1
AB102802 mRNA Translation: BAD89393.1
EF064722 Genomic DNA Translation: ABK41905.1
AC008914 Genomic DNA No translation available.
AC016596 Genomic DNA No translation available.
CH471123 Genomic DNA Translation: EAW54936.1
CCDSiCCDS3971.1 [P40189-1]
CCDS47209.1 [P40189-2]
CCDS54856.1 [P40189-3]
PIRiA36337
RefSeqiNP_001177910.1, NM_001190981.1 [P40189-3]
NP_002175.2, NM_002184.3 [P40189-1]
NP_786943.1, NM_175767.2 [P40189-2]
UniGeneiHs.532082
Hs.706627

Genome annotation databases

EnsembliENST00000336909; ENSP00000338799; ENSG00000134352 [P40189-1]
ENST00000381287; ENSP00000370687; ENSG00000134352 [P40189-2]
ENST00000381294; ENSP00000370694; ENSG00000134352 [P40189-3]
ENST00000381298; ENSP00000370698; ENSG00000134352 [P40189-1]
ENST00000502326; ENSP00000462158; ENSG00000134352 [P40189-1]
ENST00000522633; ENSP00000435399; ENSG00000134352 [P40189-2]
GeneIDi3572
KEGGihsa:3572
UCSCiuc003jqq.4 human [P40189-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiIL6RB_HUMAN
AccessioniPrimary (citable) accession number: P40189
Secondary accession number(s): A0N0L4, Q5FC04, Q9UQ41
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: November 25, 2008
Last modified: June 20, 2018
This is version 211 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

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