IL6ST

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
Inferred from direct assayⁱ
- 12643274
ciliary neurotrophic factor receptor binding
Source: BHF-UCL
Inferred from physical interactionⁱ
- 12707266
cytokine binding
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
cytokine receptor activity
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
growth factor binding
Source: BHF-UCL
Inferred from physical interactionⁱ
- 8999038
interleukin-11 binding Source: Ensembl
interleukin-11 receptor activity Source: Ensembl
interleukin-27 receptor activity
Source: BHF-UCL
Inferred by curatorⁱ
- 14764690
protein homodimerization activity
Source: BHF-UCL
Traceable author statementⁱ
- 8390097

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

ciliary neurotrophic factor-mediated signaling pathway
Source: BHF-UCL
Inferred from direct assayⁱ
- 12643274
cytokine-mediated signaling pathway
Source: BHF-UCL
Inferred from direct assayⁱ
- 2261637
glycogen metabolic process Source: Ensembl
interleukin-27-mediated signaling pathway
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 14764690
interleukin-35-mediated signaling pathway Source: Reactome
interleukin-6-mediated signaling pathway
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 12643274
- 2261637
leukemia inhibitory factor signaling pathway
Source: BHF-UCL
Inferred from direct assayⁱ
- 12643274
- 8999038
negative regulation of apoptotic process
Source: BHF-UCL
Traceable author statementⁱ
- 17530315
negative regulation of interleukin-6-mediated signaling pathway
Source: BHF-UCL
Inferred from direct assayⁱ
- 8353278
oncostatin-M-mediated signaling pathway
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 8999038
positive regulation of acute inflammatory response
Source: BHF-UCL
Inferred by curatorⁱ
- 8999038
positive regulation of adaptive immune response
Source: BHF-UCL
Inferred by curatorⁱ
- 14764690
positive regulation of astrocyte differentiation Source: Ensembl
positive regulation of cardiac muscle hypertrophy
Source: BHF-UCL
Traceable author statementⁱ
- 10744750
positive regulation of cell proliferation
Source: BHF-UCL
Inferred from direct assayⁱ
- 2261637
positive regulation of osteoblast differentiation
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 12372336
positive regulation of T cell proliferation
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 14764690
positive regulation of tyrosine phosphorylation of STAT protein
Source: BHF-UCL
Inferred from mutant phenotypeⁱ
- 14764690
positive regulation of vascular endothelial growth factor production
Source: BHF-UCL
Traceable author statementⁱ
- 10744750
regulation of Notch signaling pathway Source: Ensembl
response to cytokine
Source: BHF-UCL
Inferred from direct assayⁱ
- 2261637
- 8999038
viral process Source: UniProtKB-KW

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Receptor
Biological process	Host-virus interaction

Enzyme and pathway databases

Reactomeⁱ	R-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
SignaLinkⁱ	P40189
SIGNORⁱ	P40189

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
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 5

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000134352.19
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:6021 IL6ST
MIMⁱ	600694 gene
neXtProtⁱ	NX_P40189

Topology

Feature key	Position(s)	DescriptionActions	Length
Topological domainⁱ	23 – 619	ExtracellularSequence analysisAdd BLAST	597
Transmembraneⁱ	620 – 641	HelicalSequence analysisAdd BLAST	22
Topological domainⁱ	642 – 918	CytoplasmicSequence analysisAdd BLAST	277

Keywords - Cellular componentⁱ

Cell membrane, Membrane, Secreted

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	172	C → S: Induces ligand-independent activation. 1 Publication	1
Mutagenesisⁱ	186 – 190	Missing : Induces ligand-independent activation. 1 Publication	5
Mutagenesisⁱ	189	V → G: Does not induce ligand-independent activation. 1 Publication	1
Mutagenesisⁱ	190	Y → G: Does not induce ligand-independent activation. 1 Publication	1
Mutagenesisⁱ	215	D → G: Induces ligand-independent activation. 1 Publication	1
Mutagenesisⁱ	252	V → G: Induces ligand-independent activation. 1 Publication	1
Mutagenesisⁱ	782	S → A: Increases cell surface expression. 1 Publication	1

Organism-specific databases

DisGeNET More...DisGeNETⁱ	3572
Open Targets More...OpenTargetsⁱ	ENSG00000134352
PharmGKBⁱ	PA29837

Chemistry databases

ChEMBLⁱ	CHEMBL3124734
IUPHAR/BPS Guide to PHARMACOLOGY More...GuidetoPHARMACOLOGYⁱ	2317

Polymorphism and mutation databases

BioMutaⁱ	IL6ST
DMDMⁱ	215273999

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Signal peptideⁱ	1 – 22	Add BLAST		22
ChainⁱPRO_0000010899	23 – 918	Interleukin-6 receptor subunit betaAdd BLAST		896

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Disulfide bondⁱ	28 ↔ 54	2 Publications
Glycosylationⁱ	43	N-linked (GlcNAc...) asparagine2 Publications	1
Disulfide bondⁱ	48 ↔ 103	2 Publications
Glycosylationⁱ	83	N-linked (GlcNAc...) asparagine2 Publications	1
Glycosylationⁱ	131	N-linked (GlcNAc...) asparagine1 Publication	1
Disulfide bondⁱ	134 ↔ 144	2 Publications
Glycosylationⁱ	157	N-linked (GlcNAc...) asparagine1 Publication	1
Disulfide bondⁱ	172 ↔ 182	2 Publications
Glycosylationⁱ	227	N-linked (GlcNAc...) asparagine3 Publications	1
Glycosylationⁱ	379	N-linked (GlcNAc...) asparagine2 Publications	1
Glycosylationⁱ	383	N-linked (GlcNAc...) asparagine3 Publications	1
Glycosylationⁱ	390	N-linked (GlcNAc...) (complex) asparagine2 Publications	1
Disulfide bondⁱ	458 ↔ 466	2 Publications
Glycosylationⁱ	553	N-linked (GlcNAc...) asparagine2 Publications	1
Glycosylationⁱ	564	N-linked (GlcNAc...) asparagine1 Publication	1
Modified residueⁱ	661	PhosphoserineCombined sources	1
Modified residueⁱ	667	PhosphoserineCombined sources	1
Modified residueⁱ	782	Phosphoserine1 Publication	1
Modified residueⁱ	789	PhosphoserineBy similarity	1
Modified residueⁱ	829	PhosphoserineCombined sources	1
Modified residueⁱ	839	PhosphoserineCombined sources	1

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

EPDⁱ	P40189
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	P40189
PaxDbⁱ	P40189
PeptideAtlas More...PeptideAtlasⁱ	P40189
PRIDEⁱ	P40189
ProteomicsDBⁱ	55338 55339 [P40189-2] 55340 [P40189-3]

PTM databases

GlyConnectⁱ	649
iPTMnetⁱ	P40189
PhosphoSitePlusⁱ	P40189
SwissPalmⁱ	P40189
UniCarbKBⁱ	P40189

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

Bgeeⁱ	ENSG00000134352 Expressed in 248 organ(s), highest expression level in female gonad
CleanExⁱ	HS_IL6ST
ExpressionAtlasⁱ	P40189 baseline and differential
Genevisibleⁱ	P40189 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	CAB025784 HPA010558

HPAⁱ

CAB025784
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

With	Entry	#Exp.	IntAct	Notes
CNTF	P26441	10	EBI-1030834,EBI-1050897
JAK1	P23458	3	EBI-15742214,EBI-1383438
K2	Q2HRC7	2	EBI-1030834,EBI-9007403	From Human herpesvirus 8 type P (isolate GK18).
KCNIP3	Q9Y2W7	4	EBI-1030834,EBI-751501
LIF	P15018	2	EBI-1030834,EBI-1037189
Stat3	P42227	4	EBI-1030834,EBI-602878	From Mus musculus.

GO - Molecular functionⁱ

ciliary neurotrophic factor receptor binding
Source: BHF-UCL
Inferred from physical interactionⁱ
- 12707266
cytokine binding
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- 21873635
growth factor binding
Source: BHF-UCL
Inferred from physical interactionⁱ
- 8999038
interleukin-11 binding Source: Ensembl
protein homodimerization activity
Source: BHF-UCL
Traceable author statementⁱ
- 8390097

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	109786, 33 interactors
CORUMⁱ	P40189
Database of interacting proteins More...DIPⁱ	DIP-95N
IntActⁱ	P40189, 21 interactors
Molecular INTeraction database More...MINTⁱ	P40189
STRINGⁱ	9606.ENSP00000338799

Chemistry databases

BindingDBⁱ

P40189

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	28 – 35	Combined sources	8
Beta strandⁱ	37 – 39	Combined sources	3
Beta strandⁱ	44 – 50	Combined sources	7
Helixⁱ	52 – 58	Combined sources	7
Helixⁱ	62 – 64	Combined sources	3
Beta strandⁱ	65 – 69	Combined sources	5
Helixⁱ	76 – 78	Combined sources	3
Beta strandⁱ	80 – 83	Combined sources	4
Beta strandⁱ	86 – 91	Combined sources	6
Beta strandⁱ	97 – 107	Combined sources	11
Turnⁱ	108 – 110	Combined sources	3
Beta strandⁱ	111 – 123	Combined sources	13
Beta strandⁱ	130 – 137	Combined sources	8
Beta strandⁱ	143 – 147	Combined sources	5
Beta strandⁱ	157 – 164	Combined sources	8
Beta strandⁱ	176 – 178	Combined sources	3
Beta strandⁱ	181 – 183	Combined sources	3
Beta strandⁱ	194 – 202	Combined sources	9
Beta strandⁱ	205 – 208	Combined sources	4
Beta strandⁱ	212 – 214	Combined sources	3
Helixⁱ	216 – 218	Combined sources	3
Beta strandⁱ	219 – 221	Combined sources	3
Beta strandⁱ	226 – 231	Combined sources	6
Beta strandⁱ	234 – 238	Combined sources	5
Beta strandⁱ	240 – 245	Combined sources	6
Helixⁱ	248 – 251	Combined sources	4
Beta strandⁱ	255 – 263	Combined sources	9
Helixⁱ	274 – 277	Combined sources	4
Beta strandⁱ	282 – 286	Combined sources	5
Beta strandⁱ	291 – 303	Combined sources	13
Beta strandⁱ	317 – 321	Combined sources	5
Helixⁱ	325 – 331	Combined sources	7
Beta strandⁱ	332 – 338	Combined sources	7
Beta strandⁱ	345 – 351	Combined sources	7
Helixⁱ	356 – 359	Combined sources	4
Beta strandⁱ	363 – 372	Combined sources	10
Beta strandⁱ	378 – 391	Combined sources	14
Beta strandⁱ	396 – 406	Combined sources	11
Beta strandⁱ	412 – 416	Combined sources	5
Beta strandⁱ	428 – 435	Combined sources	8
Beta strandⁱ	438 – 444	Combined sources	7
Beta strandⁱ	452 – 460	Combined sources	9
Beta strandⁱ	462 – 464	Combined sources	3
Beta strandⁱ	469 – 474	Combined sources	6
Beta strandⁱ	478 – 481	Combined sources	4
Beta strandⁱ	491 – 500	Combined sources	10
Beta strandⁱ	508 – 515	Combined sources	8
Beta strandⁱ	525 – 530	Combined sources	6
Beta strandⁱ	535 – 539	Combined sources	5
Helixⁱ	544 – 547	Combined sources	4
Beta strandⁱ	553 – 560	Combined sources	8
Beta strandⁱ	566 – 571	Combined sources	6
Beta strandⁱ	575 – 579	Combined sources	5
Beta strandⁱ	587 – 596	Combined sources	10
Beta strandⁱ	599 – 602	Combined sources	4
Beta strandⁱ	606 – 609	Combined sources	4

Show more details

3D structure databases

ProteinModelPortalⁱ	P40189
SMRⁱ	P40189
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	P40189

EvolutionaryTraceⁱ

P40189

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Length
Domainⁱ	26 – 120	Ig-like C2-typeAdd BLAST	95
Domainⁱ	125 – 216	Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST	92
Domainⁱ	224 – 324	Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST	101
Domainⁱ	329 – 424	Fibronectin type-III 3PROSITE-ProRule annotationAdd BLAST	96
Domainⁱ	426 – 517	Fibronectin type-III 4PROSITE-ProRule annotationAdd BLAST	92
Domainⁱ	518 – 613	Fibronectin type-III 5PROSITE-ProRule annotationAdd BLAST	96

Motif

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Motifⁱ	310 – 314	WSXWS motif		5
Motifⁱ	651 – 659	Box 1 motif		9

Compositional bias

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Compositional biasⁱ	725 – 755	Ser-richAdd BLAST		31

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

Belongs to the type I cytokine receptor family. Type 2 subfamily.Curated

Keywords - Domainⁱ

Immunoglobulin domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGⁱ	ENOG410IF1N Eukaryota ENOG410YNQ4 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00550000074436
HOGENOMⁱ	HOG000015771
HOVERGENⁱ	HBG052119
InParanoidⁱ	P40189
KEGG Orthology (KO) More...KOⁱ	K05060
OMAⁱ	MMCQWDP
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G01XM
PhylomeDBⁱ	P40189
TreeFamⁱ	TF338122

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd00063 FN3, 2 hits
Gene3Dⁱ	2.60.40.10, 6 hits
InterProⁱ	View 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
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00041 fn3, 2 hits PF09240 IL6Ra-bind, 1 hit PF06328 Lep_receptor_Ig, 1 hit
SMARTⁱ	View protein in SMART SM00060 FN3, 5 hits
SUPFAMⁱ	SSF49265 SSF49265, 5 hits
PROSITEⁱ	View 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. Align Add to basket

This entry has 3 described isoforms and 4 potential isoforms that are computationally mapped.Show all Align All

Isoform 1 (identifier: P40189-1) [UniParc]FASTA Add 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]FASTA Add 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.

« 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 
CMKEDGKGYW SDWSEEASGI TYEDNIASF

Show »

Length:329

Mass (Da):37,499

Checksum:ⁱD556124C867984E4

GO

Isoform 3 (identifier: P40189-3) [UniParc]FASTA Add to basket

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

« 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 FQGNLAESKC YLITVTPVYA DGPGSPESIK 
       460        470        480        490        500
AYLKQAPPSK GPTVRTKKVG KNEAVLEWDQ LPVDVQNGFI RNYTIFYRTI 
       510        520        530        540        550
IGNETAVNVD SSHTEYTLSS LTSDTLYMVR MAAYTDEGGK DGPEFTFTTP 
       560        570        580        590        600
KFAQGEIEAI VVPVCLAFLL TTLLGVLFCF NKRDLIKKHI WPNVPDPSKS 
       610        620        630        640        650
HIAQWSPHTP PRHNFNSKDQ MYSDGNFTDV SVVEIEANDK KPFPEDLKSL 
       660        670        680        690        700
DLFKKEKINT EGHSSGIGGS SCMSSSRPSI SSSDENESSQ NTSSTVQYST 
       710        720        730        740        750
VVHSGYRHQV PSVQVFSRSE STQPLLDSEE RPEDLQLVDH VDGGDGILPR 
       760        770        780        790        800
QQYFKQNCSQ HESSPDISHF ERSKQVSSVN EEDFVRLKQQ ISDHISQSCG 
       810        820        830        840        850
SGQMKMFQEV SAADAFGPGT EGQVERFETV GMEAATDEGM PKSYLPQTVR 

QGGYMPQ

Show »

Length:857

Mass (Da):96,276

Checksum:ⁱ726208A5073B5451

GO

Computationally mapped potential isoform sequencesⁱ

There are 4 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

Entry	Entry name	Protein names	Gene names	Length	Annotation

Q5FC05	Q5FC05_HUMAN	IL6ST nirs variant 3 IL6ST nirs variant 3 (Interleukin-6 receptor subunit beta)	IL6ST	203	Annotation score:
D6RH03	D6RH03_HUMAN	Interleukin-6 receptor subunit beta Interleukin-6 receptor subunit beta	IL6ST	333	Annotation score:
Q5FC02	Q5FC02_HUMAN	IL6ST nirs variant 6 IL6ST nirs variant 6 (Interleukin-6 receptor subunit beta)	IL6ST	66	Annotation score:
Q5FC07	Q5FC07_HUMAN	IL6ST nirs variant 1 IL6ST nirs variant 1 (Interleukin-6 receptor subunit beta)	IL6ST	55	Annotation score:

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_047782	8	L → V2 PublicationsCorresponds to variant dbSNP:rs1063560Ensembl.	1
Natural variantⁱVAR_047783	148	G → R Polymorphism; associated with increased levels of soluble IL6RB in blood serum. 1 PublicationCorresponds to variant dbSNP:rs2228044Ensembl.	1
Natural variantⁱVAR_074654	200	A → G Found in patient with lung cancer; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs199905033Ensembl.	1
Natural variantⁱVAR_047784	397	L → V. Corresponds to variant dbSNP:rs2228043Ensembl.	1
Natural variantⁱVAR_036165	415	T → I in a colorectal cancer sample; somatic mutation. 1 Publication	1
Natural variantⁱVAR_047785	454	I → T. Corresponds to variant dbSNP:rs2228046Ensembl.	1
Natural variantⁱVAR_047786	499	V → I. Corresponds to variant dbSNP:rs34417936Ensembl.	1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Length
Alternative sequenceⁱVSP_001684	325 – 329	RPSKA → NIASF in isoform 2. 1 Publication	5
Alternative sequenceⁱVSP_001685	330 – 918	Missing in isoform 2. 1 PublicationAdd BLAST	589
Alternative sequenceⁱVSP_043716	423 – 483	Missing in isoform 3. 1 PublicationAdd BLAST	61

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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS3971.1 [P40189-1] CCDS47209.1 [P40189-2] CCDS54856.1 [P40189-3]
PIRⁱ	A36337
NCBI Reference Sequences More...RefSeqⁱ	NP_001177910.1, NM_001190981.1 [P40189-3] NP_002175.2, NM_002184.3 [P40189-1] NP_786943.1, NM_175767.2 [P40189-2]
UniGeneⁱ	Hs.532082 Hs.706627

Genome annotation databases

Ensemblⁱ	ENST00000336909; 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]
GeneIDⁱ	3572
KEGGⁱ	hsa:3572
UCSC genome browser More...UCSCⁱ	uc003jqq.4 human [P40189-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing, Polymorphism

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
P40189-3	IL6ST isoform 4		HUMAN		857	UniRef100_A0A0A0N0L2

Protein	Similar proteins		Species	Score	Length	Source
P40189	Uncharacterized protein		RHIRO		943	UniRef90_P40189
Uncharacterized protein		MACMU		942
Uncharacterized protein		MACFA		942
Uncharacterized protein		MACNE		942
Uncharacterized protein		PAPAN		942
+53
P40189-2	Interleukin-6 receptor subunit beta		HUMAN		333	UniRef90_P40189-2
IL6ST isoform 4		PANTR		333
Uncharacterized protein		PANPA		333
Uncharacterized protein		MACMU		333
Uncharacterized protein		MACFA		333
+21
P40189-3	IL6ST isoform 7		PANTR		857	UniRef90_A0A2I3S799
Uncharacterized protein		PANPA		857
Uncharacterized protein		PAPAN		881
Uncharacterized protein		MACFA		857
Interleukin-6 receptor subunit beta isoform 3 (Fragment)		MACMU		431
+16

Protein	Similar proteins		Species	Score	Length	Source
P40189	Interleukin-6 receptor subunit beta	)	MOUSE		917	UniRef50_P40189
Interleukin-6 receptor subunit beta		RAT		918
Uncharacterized protein		RHIRO		943
Uncharacterized protein		PAPAN		942
Uncharacterized protein		MACMU		942
+275
P40189-2	IL6ST isoform 4		PANTR		333	UniRef50_P40189-2
Uncharacterized protein		PANPA		333
Uncharacterized protein		NOMLE		333
Uncharacterized protein		MACMU		333
Uncharacterized protein		MACFA		333
+40
P40189-3	Interleukin 6 signal transducer		PANTR		884	UniRef50_H2R0A7
Uncharacterized protein		PANPA		884
Interleukin 6 signal transducer		SAIBB		885
Uncharacterized protein		NOMLE		884
IL6ST isoform 3		HUMAN		884
+44

Cross-referencesⁱ

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
CCDSⁱ	CCDS3971.1 [P40189-1] CCDS47209.1 [P40189-2] CCDS54856.1 [P40189-3]
PIRⁱ	A36337
RefSeqⁱ	NP_001177910.1, NM_001190981.1 [P40189-3] NP_002175.2, NM_002184.3 [P40189-1] NP_786943.1, NM_175767.2 [P40189-2]
UniGeneⁱ	Hs.532082 Hs.706627

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	1BJ8	NMR	-	A	219-325	[»]
	1BQU	X-ray	2.00	A/B	122-333	[»]
	1I1R	X-ray	2.40	A	23-325	[»]
	1N2Q	model	-	A/B	23-324	[»]
	1P9M	X-ray	3.65	A	23-321	[»]
	1PVH	X-ray	2.50	A/C	123-323	[»]
	3L5H	X-ray	3.60	A	24-612	[»]
	3L5I	X-ray	1.90	A	323-612	[»]
	3L5J	X-ray	3.04	A/B	323-610	[»]
ProteinModelPortalⁱ	P40189
SMRⁱ	P40189
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

BioGridⁱ	109786, 33 interactors
CORUMⁱ	P40189
DIPⁱ	DIP-95N
IntActⁱ	P40189, 21 interactors
MINTⁱ	P40189
STRINGⁱ	9606.ENSP00000338799

Chemistry databases

BindingDBⁱ	P40189
ChEMBLⁱ	CHEMBL3124734
GuidetoPHARMACOLOGYⁱ	2317

PTM databases

GlyConnectⁱ	649
iPTMnetⁱ	P40189
PhosphoSitePlusⁱ	P40189
SwissPalmⁱ	P40189
UniCarbKBⁱ	P40189

Polymorphism and mutation databases

BioMutaⁱ	IL6ST
DMDMⁱ	215273999

Proteomic databases

EPDⁱ	P40189
MaxQBⁱ	P40189
PaxDbⁱ	P40189
PeptideAtlasⁱ	P40189
PRIDEⁱ	P40189
ProteomicsDBⁱ	55338 55339 [P40189-2] 55340 [P40189-3]

Protocols and materials databases

The DNASU plasmid repository More...DNASUⁱ	3572
Structural Biology Knowledgebase	Search...

Genome annotation databases

Ensemblⁱ	ENST00000336909; 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]
GeneIDⁱ	3572
KEGGⁱ	hsa:3572
UCSCⁱ	uc003jqq.4 human [P40189-1]

Organism-specific databases

CTDⁱ	3572
DisGeNETⁱ	3572
EuPathDBⁱ	HostDB:ENSG00000134352.19
GeneCardsⁱ	IL6ST
HGNCⁱ	HGNC:6021 IL6ST
HPAⁱ	CAB025784 HPA010558
MIMⁱ	600694 gene
neXtProtⁱ	NX_P40189
OpenTargetsⁱ	ENSG00000134352
PharmGKBⁱ	PA29837
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	ENOG410IF1N Eukaryota ENOG410YNQ4 LUCA
GeneTreeⁱ	ENSGT00550000074436
HOGENOMⁱ	HOG000015771
HOVERGENⁱ	HBG052119
InParanoidⁱ	P40189
KOⁱ	K05060
OMAⁱ	MMCQWDP
OrthoDBⁱ	EOG091G01XM
PhylomeDBⁱ	P40189
TreeFamⁱ	TF338122

Enzyme and pathway databases

Reactomeⁱ	R-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
SignaLinkⁱ	P40189
SIGNORⁱ	P40189

Miscellaneous databases

ChiTaRSⁱ	IL6ST human
EvolutionaryTraceⁱ	P40189
GeneWikiⁱ	Glycoprotein_130
GenomeRNAiⁱ	3572
Protein Ontology More...PROⁱ	PR:P40189
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000134352 Expressed in 248 organ(s), highest expression level in female gonad
CleanExⁱ	HS_IL6ST
ExpressionAtlasⁱ	P40189 baseline and differential
Genevisibleⁱ	P40189 HS

Family and domain databases

CDDⁱ	cd00063 FN3, 2 hits
Gene3Dⁱ	2.60.40.10, 6 hits
InterProⁱ	View 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
Pfamⁱ	View protein in Pfam PF00041 fn3, 2 hits PF09240 IL6Ra-bind, 1 hit PF06328 Lep_receptor_Ig, 1 hit
SMARTⁱ	View protein in SMART SM00060 FN3, 5 hits
SUPFAMⁱ	SSF49265 SSF49265, 5 hits
PROSITEⁱ	View protein in PROSITE PS50853 FN3, 4 hits PS01353 HEMATOPO_REC_L_F2, 1 hit
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	IL6RB_HUMAN
Accessionⁱ	P40189Primary (citable) accession number: P40189 Secondary accession number(s): A0N0L4, Q5FC04, Q9UQ41
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
	Last sequence update:	November 25, 2008
	Last modified:	November 7, 2018
	This is version 213 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any 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

Documents

SIMILARITY comments
Index of protein domains and families
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
PDB cross-references
Index of Protein Data Bank (PDB) cross-references
Human chromosome 5
Human chromosome 5: entries, gene names and cross-references to MIM
Human cell differentiation molecules
CD nomenclature of surface proteins of human leucocytes and list of entries

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UniProtKB - P40189 (IL6RB_HUMAN)

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Interleukin-6 receptor subunit beta

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

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<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

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Keywords - Coding sequence diversityi

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GO - Molecular functionⁱ

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Keywords - Cellular componentⁱ

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Keywords - PTMⁱ

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Keywords - Domainⁱ

Keywords - Coding sequence diversityⁱ

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Keywords - Technical termⁱ